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1.
J Eval Clin Pract ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38993013

RESUMO

OBJECTIVES: This review aimed to synthesize the available evidence on exploring various factors that affect knowledge, attitudes, and practices (KAP) in colorectal cancer (CRC) screening. METHODS: A systematic search across five databases was performed to identify factors influencing KAP scores towards CRC screening. The PRISMA guidelines were used to conduct the literature search, and the time spanned is from March to June 2023. The search included observational studies published between January 2000 and June 2023 that met the predetermined review criteria. Data were extracted following the Joanna Briggs Institute (JBI) appraisal checklist to evaluate the quality of the articles. RESULTS: Out of 16,904 records, 1174 articles were reviewed in full text, resulting in 43 high-quality studies included based on the JBI checklist. These studies assessed knowledge (42), attitudes (26), and practices (11) related to CRC screening. Key factors to improving KAP towards CRC screening in the general public were sociodemographic, social media influence, and physician recommendations. For healthcare professionals, factors promoting KAP included screening methods, guidelines, qualifications, and understanding of CRC screening. Educators lacked awareness of CRC symptoms and needed training to teach CRC screening and prevention. Pharmacists showed positive attitudes towards early CRC detection but had varying knowledge levels. CONCLUSIONS: KAP towards CRC screening is suboptimal among the general public, healthcare professionals, students, educators, and pharmacists worldwide. Routine CRC screening counselling is paramount to improving screening rates. Continuous medical education and training programmes are essential for healthcare professionals to enhance their KAP towards CRC screening. Students and university teachers should be educated and trained about CRC screening to improve their knowledge and foster positive behavioural changes. These comprehensive measures are critical for establishing an effective screening programme.

2.
Asian Pac J Cancer Prev ; 25(6): 2193-2201, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38918683

RESUMO

The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector molecule (ERK) are important in the carcinogenesis of many tumors. The activation of these protooncogenes in prostate cancer is still under investigation. The aim of this work was to study EGFR, HER2- neu, inactive (non-phosphorylated) and active (phosphorylated) ERK expression in prostatic adenocarcinomas in correlation to the clinical and pathological parameters. METHODS: Immunohistochemistry- using tissue microarrays- for EGFR, HER2/neu, non-phosphorylated, and phosphor-ERK, was performed on tissues from 166 patients- with primary prostatic adenocarcinoma with no prior treatment-. The results of different markers expression were correlated with the clinical and pathological parameters and were analyzed statistically. RESULTS: The prostatic tissue showed EGFR, HER2 neu, phosphorylated and non-phosphorylated ERK expression in 8.4%, 1.4%, 78.2%, and 83.4% respectively whether low (patchy) or high expression (diffuse).  There were no significant correlations found between patient characteristics and expression of the tested markers. The negative immune reactivity for non-phosphorylated ERK and EGFR- was significantly correlated with high tumor stage (p values 0.03 and 0.01, respectively). CONCLUSION: EGFR and HER2/neu may play a limited role in prostatic adenocarcinoma as they showed positive expression in a limited number of the examined tissues specifically HER2neu. The expression of non-phosphorylated ERK (mostly weak to moderate) and phosphorylated ERK (mostly moderate to strong)- was appreciated in most cases. Thus, we suggest that anti-EGFR drugs may have a limited role in the treatment of castrate-resistant prostate cancer, but anti-MEK/ERK drugs may have more promising role as a target therapy. It is recommended to perform further molecular testing to elucidate the exact mechanism and significance of these markers.


Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Receptores ErbB , Neoplasias da Próstata , Receptor ErbB-2 , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Receptores ErbB/metabolismo , Receptor ErbB-2/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/tratamento farmacológico , Biomarcadores Tumorais/metabolismo , Idoso , Pessoa de Meia-Idade , Prognóstico , Fosforilação , Quinases raf/metabolismo , Seguimentos , Sistema de Sinalização das MAP Quinases , Proteínas ras/metabolismo , Idoso de 80 Anos ou mais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Transdução de Sinais
3.
Macromol Biosci ; 24(6): e2300530, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38319279

RESUMO

Postoperative adhesion can cause complications, such as pain and organ blockage, in the abdominal regions. To address this issue, surgical techniques and antiadhesive treatments are applied. Given the significant role of vascularization in adhesion band formation, Avastin (Ava) that targets vascular endothelial growth factor (VEGF) can be applied to prevent peritoneal adhesion bands. Moreover, Alginate (Alg), a natural polysaccharide, is a promising physical barrier to prevent adhesion bands. Incorporating Ava into Alg hydrogel in a form of 3D-printed scaffold (Alg/Ava) has potential to suppress inflammation and angiogenesis, leading to reduce peritoneal adhesion bands. Following physical, morphological, and biocompatibility evaluations, the efficacy of Alg and Ava alone and their combination in Alg/Ava on the formation of postsurgical adhesions is evaluated. Upon confirming physical stability and sustained release of Ava, the Alg/Ava scaffold effectively diminishes both the extent and strength of adhesion bands. Histopathological examination shows that the reduction in fibrosis and inflammation is responsible for preventing adhesion bands by the Alg/Ava scaffold. Additionally, the cytokine assessment reveals that this is due to the inhibition in the secretion of VEGF and Interleukin 6 suppressing vascularization and inflammatory pathways. This study suggests that a 3D-printed Alg/Ava scaffold has great potential to prevent the postsurgical adhesion bands.


Assuntos
Alginatos , Bevacizumab , Impressão Tridimensional , Alicerces Teciduais , Fator A de Crescimento do Endotélio Vascular , Alginatos/química , Alginatos/farmacologia , Aderências Teciduais/prevenção & controle , Animais , Alicerces Teciduais/química , Bevacizumab/farmacologia , Bevacizumab/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ratos , Complicações Pós-Operatórias/prevenção & controle , Humanos , Hidrogéis/química , Hidrogéis/farmacologia
4.
Int J Surg Pathol ; 32(2): 374-379, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37248556

RESUMO

Malignant gastrointestinal neuroectodermal tumor (GNET), also referred to as clear cell sarcoma-like tumor of the GI tract is a rare mesenchymal tumor of the gastrointestinal tract. It has to be distinguished from various mimickers including gastrointestinal stromal tumor (GIST) due to its aggressive course and different natural history and therapeutic approach. Here we report a case of GNET arising in the small intestine with aberrant DOG1 expression posing a diagnostic challenge. In this context, the combination of clinical, histomorphological, immunohistochemical, and molecular features helped to establish a proper diagnosis.


Assuntos
Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Humanos , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/cirurgia , Intestino Delgado/cirurgia , Tumores do Estroma Gastrointestinal/diagnóstico
5.
Histochem Cell Biol ; 161(3): 239-253, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37943325

RESUMO

Diabetes mellitus is a chronic metabolic disease characterized by persistent hyperglycemia, revealing a decrease in insulin efficiency. The sustained glucotoxic pancreatic microenvironment increases reactive oxygen species generation, resulting in chronic oxidative stress responsible for massive DNA damage. This triggers PARP-1 activation with both NAD+ and ATP depletion, affecting drastically pancreatic beta cells' energy storage and leading to their dysfunction and death. The aim of the present study is to highlight the main histological changes observed in pancreatic islets pre-treated with a unique NADH intraperitoneal injection in a streptozotocin-(STZ)-induced diabetes model. In order to adjust NADH doses, a preliminary study with three different doses, 500 mg/kg, 300 mg/kg, and 150 mg/kg, respectively, was conducted. Subsequently, and on the basis of the results of the aforementioned study, Wistar rats were randomly divided into four groups: non-diabetic control group, diabetics (STZ 45 mg/kg), NADH-treated group (150 mg/kg) 15 min before STZ administration, and NADH-treated group (150 mg/kg) 15 min after STZ administration. The effect of NADH was assessed by blood glucose level, TUNEL staining, histo-morphological analysis, and immunohistochemistry. The optimum protective dose of NADH was 150 mg/kg. NADH effectively decreased hyperglycemia and reduced diabetes induced by STZ. Histologically, NADH pre-treatment revealed a decrease in beta cell death favoring apoptosis over necrosis and therefore preventing inflammation with further beta cell destruction. Our data clearly demonstrate that NADH prior or post-treatment could effectively prevent the deleterious loss of beta cell mass in STZ-induced diabetes in rats and preserve the normal pancreatic islet's function.


Assuntos
Diabetes Mellitus Experimental , Hiperglicemia , Células Secretoras de Insulina , Ratos , Animais , NAD/efeitos adversos , Ratos Wistar , Estreptozocina/efeitos adversos , Injeções Intraperitoneais , Insulina/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperglicemia/induzido quimicamente , Hiperglicemia/prevenção & controle , Diabetes Mellitus Experimental/metabolismo , Glicemia/metabolismo
6.
Cureus ; 15(6): e40647, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37476110

RESUMO

Alveolar soft part sarcoma (ASPS) is a rare type of soft tissue sarcoma that typically affects adolescents and young adults, though it can occur at any age. We report a case of ASPS of the tongue, which is extremely rare at this location. The patient presented with a polypoidal lesion on the tongue, a biopsy of which showed granular and alveolar morphology. A definitive diagnosis was not rendered due to limited tissue. The case was discussed with the treating surgeon, and excision was recommended with clear margins. Excision of the lesion showed typical ASPS. A TFE-3 immunohistochemical stain was done, which showed strong immunoreactivity, thereby confirming the diagnosis of ASPS. This tumour is rare, and its presence in the tongue makes it extremely infrequent.

7.
Eur J Obstet Gynecol Reprod Biol X ; 16: 100172, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36440057

RESUMO

Background: Endometrial carcinoma (EC) is the most common gynaecological cancer worldwide. The Cancer Genome Atlas molecular grouping of a given case of EC could be assessed by POLE gene mutation, mismatch repair (MMR) 'to reflect microsatellite instability' and p53 status, which has proved to be of prognostic value. Programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) are playing a progressively important role in tumour immunology and cancer treatment. Objectives: To investigate PD-L1 immunohistochemical expression in EC in relation to MMR and p53 status. Associations between marker expression and different histopathological parameters were also investigated. Methods: This retrospective study was performed on archival biopsies of 170 cases of EC using a tissue microarray model. Immunohistochemical staining was applied using antibodies against PD-L1, MLH1, MSH2 and p53. Results: The percentages of positivity were as follows: PD-L1, 19.6%; MLH1, 79.5%; MSH2, 78.5%; and p53 mutant, 13.8%. There was significant correlation between MLH1 expression and MSH2 expression (p = 0.008). Tumour grade was significantly correlated with stage (p = 0.005) and p53 mutant expression (p = 0.008). Combined PD-L1 positivity and MMR deficiency showed significant correlation with the presence of lymphovascular space invasion (p = 0.014). MSH2 negativity was significantly associated with poorer overall survival (p = 0.014). Conclusions: A panel of immunohistochemical markers (PD-L1, MLH1, MSH2 and p53) could help to predict the prognosis and plan the treatment of patients with EC. MMR deficiency seems to be a good predictor for PD-L1 status, and therefore the response to potential PD-1/PD-L1 inhibitor therapy.

8.
J Tradit Complement Med ; 12(4): 367-374, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35747348

RESUMO

Background: and purpose: The formation of postoperative intra-abdominal adhesion band formation may lead to severe complications. This study aimed to evaluate the preventive effect of local administration of frankincense n-hexane extract (FHE) on the formation of postsurgical adhesion bands. Materials and methods: FHE was extracted from the resin of a Boswellia sacra tree and its components were identified by gas chromatography-mass spectrometry (GC-MS). In an animal model, the expression levels of TNF-α and TGF-ß1 cytokines after application of FHE were assessed to check the inflammatory and fibrotic cues, respectively. Results: Following FHE compound analysis, in vivo experiments demonstrated that intraoperative local administration of FHE resulted in the prevention of adhesion band formation. The adhesion grades in the FHE-treated group were significantly lower than those in the negative control (NC) and the positive control (Interceed). The infiltration of inflammatory cells observed by histopathology revealed a significant anti-inflammatory potential of FHE. Furthermore, the gene expression results proved that significant suppression of TNF-α and TGF-ß1 was responsible for its antiadhesion properties. Conclusions: The study reported the potential of FHE as an ointment for the prevention of adhesion bands.

10.
J Mol Histol ; 52(3): 621-633, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33847878

RESUMO

Breast cancer is the leading cancer worldwide among women. Traditional clinicopathological prognostic and predictive markers need refining to improve clinical outcomes. This study explored the association between traditional clinicopathological factors and the expression of Akt1 and E2F1 transduction proteins and their phosphorylated forms in breast cancer, to determine their value as novel biomarkers and potential therapeutic targets. Tumor tissues from 94 female breast cancer patients were examined for immunophenotypic expression of total Akt1, pAkt1 (Serine 473), pAkt1 (Threonine 308), total E2F1, pE2F1 (Thr433) and pE2F1 (Ser337). The expression of pAkt1 (Ser473) was significantly associated with ER/PR positive status and total E2F1 with older age (> 50), lymph node involvement and HER2 positivity. There was a significant association between triple negative cancers and total and pAkt1 (Thr308). pAkt1 (Ser473) showed an inverse relationship with Luminal B cancers and pE2F1 (Thr433) showed an inverse association with triple negative cancers. Higher expression of pE2F1 (Ser337) was associated with better OS. Both pAkt1 (Ser473 and Thr308) proteins showed significant association with poorer patient outcomes. E2F1 (Ser337) showed a significant positive correlation with response to chemotherapy. The study suggests that a pAkt1-/pE2F1+ phenotype could indicate an opportunity to minimize chemotherapeutic options in older women; conversely a pAkt1+/pE2F1- phenotype could prompt a more aggressive regimen. Further exploration of this phenotype in younger women with breast cancer and triple-negative breast cancers is warranted.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Fator de Transcrição E2F1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Fosforilação , Análise de Sobrevida
11.
Carbohydr Polym ; 262: 117921, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33838800

RESUMO

The aim of this study was to evaluate a bioactive multilayer wound dressing, based on chitosan and alginate. To enhance healing potential, Dracaena Cinnabari and Aloe Vera were loaded as separate layers into the scaffold. The bare and bioactive multilayered scaffolds were fabricated by an iterative layering freeze-drying technique. Following of topographical, chemical, and physical assessment, the performance of the scaffolds was evaluated in vitro and in vivo. The results revealed adequate attachment, and proliferation of human foreskin fibroblasts, indicating excellent biocompatibility of the bioactive scaffold. In vivo, the performance of the multi-layered scaffold loaded with the bioactive materials was comparable with Comfeel plus®. The wounds treated with the bioactive scaffold exhibited superior hypergranulation, fibroblast maturation, epithelization, and collagen deposition, with minimal inflammation, and crust formation. It is concluded that the synergism of extracellular matrix-mimicking multi-layered scaffolding with Aloe Vera and Dracaena Cinnabari could be considered as a supportive wound dressing.


Assuntos
Alginatos/química , Bandagens , Quitosana/química , Extratos Vegetais/farmacologia , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacos , Alginatos/farmacologia , Aloe/química , Animais , Proliferação de Células/efeitos dos fármacos , Quitosana/farmacologia , Colágeno/metabolismo , Dracaena/química , Matriz Extracelular/metabolismo , Fibroblastos/efeitos dos fármacos , Prepúcio do Pênis/patologia , Humanos , Masculino , Microscopia Eletrônica de Varredura/métodos , Extratos Vegetais/química , Ratos , Ratos Wistar
12.
Naunyn Schmiedebergs Arch Pharmacol ; 392(8): 1005-1013, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31025143

RESUMO

The aim of this study was to examine the effect of tocilizumab, an interleukin-6 (IL-6) inhibitor on streptozotocin-induced diabetic nephropathy. Male Sprague-Dawley rats (n = 36) were distributed into six groups and treated for 4 weeks. Groups 1, 3, 5 received either saline, tocilizumab (2 mg/kg), or tocilizumab (8 mg/kg) injection intraperitoneally (i.p.), every 2 weeks, respectively. Groups 2, 4, 6 were rendered diabetic by a single i.p. injection of streptozotocin (65 mg/kg) and were treated as in groups 1, 3, 5, respectively. Biochemical parameters were measured in plasma, urine, and kidneys. In the untreated diabetic group, there was a significant decrease in body weight, polyuria, and increased kidney weight. There was increased urinary albumin/creatinine ratio (UACR) and N-acetyl-ß-D-glucosaminidase (NAG)/creatinine ratio (UNCR). Streptozotocin also induced a significant increase in creatinine clearance. In addition, diabetes was associated with increased oxidative stress [reduced renal glutathione reductase (GR), superoxide dismutase (SOD), catalase activities, and increased malondialdhyde (MDA)] and increased plasma tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) concentrations. Kidneys from streptozotocin-treated rats showed marked vacuolation of the proximal tubular epithelium with focal tubular necrosis and the glomeruli showing increase in mesangial cells. Tocilizumab significantly mitigated the increase in UACR and UNCR, renal MDA, plasma TNF-α, IL-6 and NO levels, and the decrease in renal SOD and catalase activities in diabetic rats. Tocilizumab did not significantly improve creatinine clearance; however, it attenuated the histopathological changes induced by streptozotocin. This study shows that tocilizumab was able to ameliorate some of the changes seen in streptozotocin-induced early diabetic nephropathy in rats. This is mainly due to its anti-inflammatory and antioxidative effects.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/prevenção & controle , Hipoglicemiantes/farmacologia , Interleucina-6/antagonistas & inibidores , Animais , Anti-Inflamatórios/farmacologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Antioxidantes/farmacologia , Peso Corporal/efeitos dos fármacos , Nefropatias Diabéticas/patologia , Hipoglicemiantes/administração & dosagem , Injeções Intraperitoneais , Rim/patologia , Masculino , Tamanho do Órgão , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
13.
Toxicol Rep ; 6: 232-238, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30886824

RESUMO

We investigated the effect of levosimendan on cisplatin (Cis)-induced nephrotoxicity. Rats were divided into four groups (n = 6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) cisplatin (6 mg/kg) on day 7, respectively. The third and fourth groups received a single intraperitoneal (i.p.) injection of Cis on day 7 and levosimendan (1 mg/kg/day, orally) or vehicle for 10 days, respectively. At day 11, animals were anaesthetized and blood collected and kidneys removed. Another four groups were treated the same as the previous four groups to measure renal blood flow. Cis induced nephrotoxicity as evidenced by biochemical, histopathological and hemodynamic changes. Levosimendan partially reduced Cis-induced increase in plasma urea, creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels and decrease in creatinine clearance. Levosimendan partially reduced Cis-induced increase in urinary albumin/creatinine ratio, N-Acetyl-ß-D-Glucosaminidase (NAG) and kidney Injury Molecule-1 (KIM-1). Levosimendan significantly attenuated the effect of Cis on plasma concentration of plasma tumor necrosis factor-alpha (TNF-α), antioxidant indices [catalase and superoxide dismutase (SOD)] and lipid peroxidation. Cis induced acute tubular necrosis with tubular dilatation, interstitial edema and congestion. Levosimendan attenuated the remarkable renal damage and reduced renal blood flow induced by Cis. In conclusion this study shows that levosimendan has a partial protective effect on Cis-induced nephrotoxicity. The protective effect of levosimendan is shown to be related to its anti-inflammatory, antioxidant and vasodilator effects.

14.
Sultan Qaboos Univ Med J ; 19(4): e277-e283, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31897310

RESUMO

Programmed death ligand 1 (PD-L1) is an inhibitory molecule expressed by cancer cells to supress T-cell activity and escape anti-tumour immunity. The role of PD-L1 in cancer has been studied extensively as it is considered an important immune checkpoint against immune over-activation through its interaction with Programmed death receptor 1 (PD-1) expressed on activated lymphocytes. PD-L1 expression was found to be enhanced by chemotherapy through different proliferation pathways. However, the predictive and prognostic value for PD-L1 expression in cancer patients treated with neoadjuvant chemotherapy (NAC) is not yet established. This review focused on the potential effects of chemotherapy on PD-L1 expression and the role of PD-L1 as a prognostic and predictive marker in NAC-treated cancer patients. In addition, the potential use of this marker in clinical practice is discussed.


Assuntos
Linfócitos do Interstício Tumoral/imunologia , Terapia Neoadjuvante , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Humanos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Neoplasias/imunologia , Resultado do Tratamento
15.
Naunyn Schmiedebergs Arch Pharmacol ; 392(1): 45-53, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30206656

RESUMO

Canagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor that is currently available for the management of type 2 diabetes mellitus. The present study investigated the effect of canagliflozin on cisplatin (CP)-induced nephrotoxicity in mice. The animals were divided into four groups (n = 6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) cisplatin (20 mg/kg) on day 7, respectively. The third and fourth groups were given a single intraperitoneal (i.p.) injection of CP (20 mg/kg) on day 7 and canagliflozin (10 mg/kg/day) and (30 mg/kg/day), for 10 days, respectively. At day 11, animals were anesthetized and blood collected and kidneys were removed. CP significantly increased the plasma urea, creatinine, cystatin C, and clusterin concentrations and neutrophil gelatinase-associated lipocalin (NGAL) activity. In addition, CP increased urinary albumin/creatinine ratio, N-acetyl-ß-D-glucosaminidase (NAG) activity, and liver-type fatty acid-binding protein (L-FABP) concentrations and reduced creatinine clearance. CP also significantly increased the plasma concentration of inflammatory cytokines [plasma tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1ß)] and significantly reduced antioxidant indices [catalase, glutathione reductase (GR), and superoxide dismutase (SOD)]. Histopathologically, CP caused a remarkable renal damage compared with control. Canagliflozin significantly ameliorated CP-induced biochemical and histopathological changes. The protective effect of canagliflozin is most likely due to anti-inflammatory and antioxidant effects. Our results show that administration of canagliflozin reversed the biochemical and histopathological indices of CP-induced nephrotoxicity in mice.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antineoplásicos/toxicidade , Antioxidantes/uso terapêutico , Canagliflozina/uso terapêutico , Cisplatino/toxicidade , Nefropatias/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Canagliflozina/farmacologia , Catalase/metabolismo , Clusterina/sangue , Creatinina/sangue , Cistatina C/sangue , Citocinas/sangue , Glutationa Redutase/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Lipocalina-2/sangue , Lipocalina-2/urina , Masculino , Camundongos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Superóxido Dismutase/metabolismo , Ureia/sangue , Ácido Úrico/sangue
16.
Pathology ; 50(7): 730-736, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30389219

RESUMO

The role of Notch pathway in hepatocarcinogenesis is unclear with conflicting results reported from different researchers. This study aimed to investigate the exact role of Notch1 in hepatocarcinogenesis and its influence on survival and to determine the possibility of it being a target therapy. Differential immunohistochemical expression of Notch1 in 100 cases of hepatocellular carcinoma (HCC) and adjacent non-neoplastic liver tissue was performed. The results showed that expression of Notch1 was significantly higher in the non-neoplastic hepatic tissues than in HCC tissues (p < 0.001), but there was no significant difference in Notch1 expression between cirrhotic and non-cirrhotic liver tissue (p = 0.197). Notch1 expression was higher in low grade than in high grade HCC (p = 0.036). Notch1 expression showed reverse correlation with mitotic count (p = 0.008), and necrosis (p = 0.005). The disease free survival was shorter in patients displaying low levels of Notch1 expression (p = 0.045). The overall survival showed no significant difference between high and low levels of Notch1 expression; however, it was somewhat longer in patients with high Notch1 expression (p = 0.220). In conclusion, the tumour suppressor role of Notch1 was supported and the use of Notch1 agonists may have a role in improving the prognosis of HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Receptor Notch1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese , Carcinoma Hepatocelular/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Receptor Notch1/genética , Estudos Retrospectivos , Análise Serial de Tecidos
17.
Biomed Res Int ; 2017: 9290425, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28536704

RESUMO

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer in which calpain system plays an important role in its cellular processes including apoptosis and proliferation. Although such roles have been assessed in tumor pathogenesis, the correlation of its expression to the proliferating/apoptotic index has not been studied yet. Immunohistochemical staining of calpain-1 was performed on paraffin-embedded tissues to correlate its expression with clinicopathological variables and outcome. The proliferation activity was determined by calculating the percentage of cells expressing the Ki-67 antigen. The apoptotic index was assessed morphologically and biochemically using Haematoxylin & Eosin method and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, respectively. Calpain-1 was significantly expressed in TNBC tissues varying from low to high with a significant correlation to lymph node status but not with the other clinicopathological variables, suggesting its role as a prognostic factor. In addition, a positive correlation was found between both apoptotic counts assays (P < 0.001, r = 0.547) as well as with proliferation (P = 0.045). Calpain-1 expression had no significant correlation with either proliferation (P = 0.29) or apoptotic indices (P = 0.071 and P = 0.100). Determining calpain-1 expression may provide relevant prognostic value for TNBC cancer patients.


Assuntos
Biomarcadores Tumorais/genética , Calpaína/genética , Prognóstico , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Apoptose/genética , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/genética , Pessoa de Meia-Idade , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Proteína Supressora de Tumor p53/genética
18.
Front Physiol ; 8: 158, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28420996

RESUMO

There is a global increase in the popularity of water-pipe tobacco smoking including in Europe and North America. Nevertheless, little is known about the male reproductive effects of water-pipe smoke (WPS), especially after long-term exposure. Here, we assessed effects of WPS exposure (30 min/day) in male mice for 6 months. Control mice were exposed to air-only for the same period of time. Twenty-four hours after the last exposure, testicular histopathology, and markers of inflammation and oxidative stress, and the tyrosine-protein kinase vascular endothelial growth factor receptor 1 (VEGFR1) were assessed in testicular homogenates. Moreover, plasma testosterone, estradiol, and luteinizing hormone (LH) concentrations were also measured. Chronic WPS exposure induced a significant decrease of testosterone and estradiol, and a slight but significant increase of LH. Glutathione reductase, catalase, and ascorbic acid were significantly decreased following WPS exposure. Plasma concentration of leptin was significantly decreased by WPS exposure, whereas that of tumor necrosis factor α and interleukin 6 was significantly increased. Histopathological analysis of the testes revealed the presence of a marked reduction in the diameter of the seminiferous tubules with reduced spermatogenesis. Transmission electron microscopy examination showed irregular thickening and wrinkling of the basement membranes with abnormal shapes and structures of the spermatozoa. VEGFR1 was overexpressed in the testis of the mice exposed to WPS and was not detected in the control. The urine concentration of cotinine, the predominant metabolite of nicotine, was significantly increased in the WPS-exposed group compared with the control group. We conclude that chronic exposure to WPS induces damaging effects to the reproductive system in male mice. If this can be confirmed in humans, it would be an additional concern to an already serious public health problem, especially with the increased use of WPS use all over the world, especially in young adults.

19.
J Pak Med Assoc ; 67(1): 12-14, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28065946

RESUMO

OBJECTIVE: To analyse morphological types, location in the large bowel and demographic characteristics of colonic polyps. METHODS: The retrospective descriptive study was conducted at the Department of Pathology, Sultan Qaboos University Hospital, Muscat, Oman, and comprised biopsy specimens of colonic polyps from patients related to a two-year period from 2011 to 2012. Demographic data, types of polyps, anatomical location and grade of dysplasia were analysed. SPSS 20 was used for statistical analysis. RESULTS: There were 160 biopsy specimens from 143 patients. Of the patients, 91(63.6 %) were male and 52(36.4%) were female. The mean age was 55.27+-14.2 years. Of the 160 polyps, 37((23.1%) were in the rectum. The most common type was the adenomatous polyp in 88(55.0%) cases followed by hyperplastic polyps 51(31.9%) and inflammatory polyps 21(13.1%). Of the 88 adenomatous polyps, 23(26%) showed high-grade dysplasia. CONCLUSIONS: The commonest colon polyp type was adenomatous polyp. Screening programmes, such as stool occult blood testing and colonoscopies, are recommended.


Assuntos
Pólipos do Colo/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Omã/epidemiologia , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto Jovem
20.
Asian Pac J Cancer Prev ; 17(11): 4867-4868, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28030913

RESUMO

Prostatic adenocarcinoma is the commonest solid malignancy seen in Omani elderly males 60-80 years of age. The Gleason grade is the most widely used grading system for prostatic carcinoma and is recommended by the World Health Organization. A peer review was carried out at the Pathology Department of Sultan Qaboos University Hospital (SQUH), Oman, to assess the quality of reporting at the center. The aim of this study was to determine inter-observer variation among 7 pathologists working at a tertiary care center in Oman. A total of 47 consecutive prostatic biopsies were interdependently reviewed by seven pathologists and the results obtained were compared with each other and the original diagnosis. This peer review indicated a fair inter-observer agreement (0.482) among 7 pathologists in the department, with fair to moderate agreement when the results were compared to the reported diagnosis, comparable to the published literature. Dual and sub-specialty reporting are being instituted to improve the performance in this vital aspect of pathology.

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