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1.
World J Clin Oncol ; 15(7): 848-858, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39071455

RESUMO

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPis) are approved as first-line therapies for breast cancer gene (BRCA)-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. They are also effective for new and recurrent ovarian cancers that are BRCA- or homologous recombination deficiency (HRD)-positive. However, data on these mutations and PARPi use in the Middle East are limited. AIM: To assess BRCA/HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian cancer. METHODS: This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations, and 25 of 65 ovarian cancer patients tested for HRD. These adult patients participated in at least four visits to the oncology service at our center between August 2021 and May 2023. Data were summarized using descriptive statistics and compared using counts and percentages. Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors criteria. RESULTS: Among the 472 breast cancer patients, 12.1% underwent BRCA testing, and 38.5% of 65 ovarian cancer patients received HRD testing. Pathogenic mutations were found in 25.6% of the tested patients: 26.3% breast cancers had germline BRCA (gBRCA) mutations and 24.0% ovarian cancers showed HRD. Notably, 40.0% of gBRCA-positive breast cancers and 66.0% of HRD-positive ovarian cancers were Middle Eastern and Asian patients, respectively. PARPi treatment was used in 5 (33.3%) gBRCA-positive breast cancer patients as first-line therapy (n = 1; 7-months progression-free), for maintenance (n = 2; > 15-months progression-free), or at later stages due to compliance issues (n = 2). Four patients (66.6%) with HRD-positive ovarian cancer received PARPi and all remained progression-free. CONCLUSION: Lower testing rates but higher BRCA mutations in breast cancer were found. Ethnicity reflected United Arab Emirates demographics, with breast cancer in Middle Eastern and ovarian cancer in Asian patients.

2.
Cureus ; 15(10): e48077, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38046499

RESUMO

In a world characterized by rapid technological evolution, the integration of quantum technologies into the realm of healthcare has emerged as a transformative force. This narrative review explores the journey of quantum innovations in medicine, delving into the fundamental principles of quantum mechanics that underpin quantum computing, sensing, and communication. From the birth of quantum theory to the advent of practical quantum applications, we journey through historical milestones that have paved the way for a quantum-powered future in healthcare. The narrative unfolds to reveal the profound implications of quantum technologies in healthcare, ranging from accelerated drug discovery and genomic analysis to secure data transmission and telemedicine. Real-world case studies illuminate successful applications, while the review addresses the ethical, societal, and regulatory considerations that accompany this quantum revolution. As we peer into the future, we contemplate the challenges that lie ahead and offer recommendations for researchers and policymakers to forge a harmonious and equitable synergy between quantum and medicine. In a world where innovation outpaces the tick of the clock, this narrative review serves as a timely guide for those poised to shape the quantum healthcare landscape, where precision and compassion converge and the possibilities are limitless.

3.
Cureus ; 15(11): e49339, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38143595

RESUMO

Obesity, a widespread health concern characterized by the excessive accumulation of body fat, is a complex condition influenced by genetics, environment, and social determinants. Recent research has increasingly focused on the role of gut microbiota in obesity, highlighting its pivotal involvement in various metabolic processes. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, interacts with the host in a myriad of ways, impacting energy metabolism, appetite regulation, inflammation, and the gut-brain axis. Dietary choices significantly shape the gut microbiota, with diets high in fat and carbohydrates promoting the growth of harmful bacteria while reducing beneficial microbes. Lifestyle factors, like physical activity and smoking, also influence gut microbiota composition. Antibiotics and medications can disrupt microbial diversity, potentially contributing to obesity. Early-life experiences, including maternal obesity during pregnancy, play a vital role in the developmental origins of obesity. Therapeutic interventions targeting the gut microbiota, including prebiotics, probiotics, fecal microbiota transplantation, bacterial consortium therapy, and precision nutrition, offer promising avenues for reshaping the gut microbiota and positively influencing weight regulation and metabolic health. Clinical applications of microbiota-based therapies are on the horizon, with potential implications for personalized treatments and condition-based interventions. Emerging technologies, such as next-generation sequencing and advanced bioinformatics, empower researchers to identify specific target species for microbiota-based therapeutics, opening new possibilities in healthcare. Despite the promising outlook, microbiota-based therapies face challenges related to microbial selection, safety, and regulatory issues. However, with ongoing research and advances in the field, these challenges can be addressed to unlock the full potential of microbiota-based interventions.

4.
Cureus ; 15(11): e49235, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38143712

RESUMO

Introduction Lower limb fractures frequently require immobilization with backslabs to promote healing. This study investigates a novel approach involving the incorporation of a single ridge to enhance backslab strength while maintaining cost-effectiveness. Objective The aim of this study was to assess the mechanical performance of ridged backslabs in comparison to traditional non-ridged backslabs, specifically focusing on their load-bearing capacity and cost-effectiveness when used in lower limb fractures. Methods This experimental study, conducted between January 2023 and June 2023, compares three groups of backslabs with varying layers (eight, ten, and twelve) that were fabricated, each consisting of four ridged and four non-ridged specimens. These backslabs, constructed from six-inch plaster of Paris rolls, were 190 cm in length. A three-point bending test was conducted on both groups using a Hounsfield H100KS Universal Testing Machine (Tinius Olsen Ltd., Redhill, UK), with a crosshead speed of 5 mm/min and a span distance of 190 mm between supports. Results Significant differences in mean maximum force endured were observed between the ten-layered and twelve-layered flat and ridged backslabs (p-values: 0.003 and 0.004, respectively). Ten-layered ridged backslabs exhibited a 56 N higher load-bearing capacity, while twelve-layered ridged backslabs withstood 73.9 N more force than their flat counterparts, underscoring the superior strength of ridged lower limb backslabs. Conclusion Ridged backslabs outperformed non-ridged backslabs in terms of strength when subjected to external forces. These findings support the potential adoption of ridged backslabs as a lightweight, cost-effective, and robust alternative for immobilization in lower limb fractures.

5.
Cureus ; 15(9): e46176, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37908951

RESUMO

Heart transplantation (HTx) stands as a life-saving intervention for patients with end-stage heart disease, but the field is fraught with numerous challenges that span from the scarcity of donor organs to long-term complications arising from immunosuppressive therapies. This comprehensive review article offers an in-depth exploration of the multifaceted aspects of HTx. The review covers groundbreaking advancements in xenotransplantation, enabled by cutting-edge genetic engineering techniques, and the promising role of stem cell therapies, particularly porcine mesenchymal stem cells, in cardiac regeneration. It also delves into the evolution and limitations of immunosuppressive therapies and the revolutionary potential of artificial intelligence (AI) and machine learning (ML) in enhancing donor-recipient matching and predicting patient outcomes. Economic considerations, especially in the context of rising healthcare costs, are examined to assess the sustainability of these advancements. The article further discusses the significant improvements in patient outcomes over the years, while highlighting persisting challenges, such as graft failure, rejection, and infection. It underscores the importance of experience and specialized training, evidenced by the presence of an institutional learning curve. The review concludes by advocating for a multifaceted, collaborative approach involving clinicians, researchers, and policymakers to overcome existing challenges. Through coordinated efforts that consider medical, ethical, and economic factors, the field of HTx is poised for further evolution, offering renewed hope for improved patient care and outcomes.

6.
Cureus ; 15(10): e46998, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37965396

RESUMO

This article provides an in-depth review of the current state of management for diabetes, hypertension, and cardiovascular disease, focusing on advancements from genomics to robotics. It explores the role of genomic markers in personalized medicine, offering tailored treatment options for these chronic conditions. The article also examines the efficacy of various pharmacological and surgical interventions, including bariatric surgery for diabetes and device-based treatments for hypertension. A comparative analysis is presented to evaluate the cost-effectiveness and patient outcomes between medical and surgical approaches. The review concludes that while personalized medicine and minimally invasive surgical techniques show promise, more high-quality comparative research is needed. The ultimate goal is to integrate these emerging technologies within a framework of evidence-based medicine to improve patient outcomes and health equity.

7.
Cureus ; 15(9): e45996, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37900524

RESUMO

Focal cortical dysplasia (FCD) is a prominent neurological disorder characterized by disruptions in localized brain cell organization and development. This narrative review delineates the multi-faceted nature of FCD, emphasizing its correlation with drug-resistant epilepsy, predominantly in children and young adults. We explore the historical context of FCD, highlighting its indispensable role in shaping our comprehension of epilepsy and cortical anomalies. The clinical spectrum of FCD is broad, encompassing diverse seizure patterns, cognitive impairments, and associated neuropsychiatric disorders. We underscore the importance of differential diagnosis, with techniques ranging from electroencephalogram (EEG) interpretations to microscopic evaluations, and discuss advanced diagnostic modalities, such as the 3T magnetic resonance imaging (MRI) epilepsy protocols. Therapeutically, while anti-seizure medications are often first-line interventions, surgically refractory cases necessitate more invasive procedures, underscoring the importance of individualized treatment. Furthermore, the review touches upon the prognostic aspects of FCD, highlighting the importance of personalized care regimens, and provides insights into emerging therapeutic avenues, including the potential of the mammalian target of rapamycin (mTOR) pathway. Conclusively, this review accentuates the complex relationship between brain development and epileptogenicity inherent to FCD and underscores the promise of future research in enhancing patient outcomes.

8.
Cureus ; 15(9): e44694, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37674761

RESUMO

Soft tissue sarcomas (STSs) are a heterogeneous group of malignancies that have long posed challenges in terms of diagnosis, treatment, and management. This narrative review provides a comprehensive exploration into the multifaceted realm of STS, spanning from its historical origins to the latest advancements in research and clinical care. We delve into the molecular intricacies of STS, highlighting the genetic and epigenetic aberrations that drive these tumors. The review emphasizes the neurological implications of STS, a relatively underexplored area, shedding light on the interplay between tumor biology and neural processes. The evolving therapeutic landscape is discussed, with a focus on the promise of targeted therapies, immunotherapy, and precision medicine. A significant portion is dedicated to the patient-centric approach, underscoring the importance of holistic care that addresses both the physical and psychological needs of STS patients. Furthermore, we highlight the gaps in current research and clinical practices, offering insights into potential avenues for future exploration. This review serves as a valuable resource for clinicians, researchers, and the broader scientific community, encapsulating the current state of STS knowledge and pointing toward future directions in this dynamic field.

9.
Cureus ; 15(8): e44374, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37664359

RESUMO

This narrative review delves into the potential of artificial intelligence (AI) in predicting, stratifying risk, and personalizing treatment planning for congenital heart disease (CHD). CHD is a complex condition that affects individuals across various age groups. The review highlights the challenges in predicting risks, planning treatments, and prognosticating long-term outcomes due to CHD's multifaceted nature, limited data, ethical concerns, and individual variabilities. AI, with its ability to analyze extensive data sets, presents a promising solution. The review emphasizes the need for larger, diverse datasets, the integration of various data sources, and the analysis of longitudinal data. Prospective validation in real-world clinical settings, interpretability, and the importance of human clinical expertise are also underscored. The ethical considerations surrounding privacy, consent, bias, monitoring, and human oversight are examined. AI's implications include improved patient outcomes, cost-effectiveness, and real-time decision support. The review aims to provide a comprehensive understanding of AI's potential for revolutionizing CHD management and highlights the significance of collaboration and transparency to address challenges and limitations.

10.
Cureus ; 15(12): e51351, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38288195

RESUMO

Diabetic retinopathy (DR) is a leading cause of global visual impairment, necessitating a comprehensive understanding of its vascular and neural components for effective therapeutic interventions. While vascular pathology is well-established, recent evidence suggests a neurodegenerative role in DR. Vascular endothelial growth factor (VEGF), traditionally implicated in angiogenesis, has emerged as a key player with neuroprotective potential. This systematic review evaluates the literature to shed light on molecular mechanisms and clinical implications in this regard. The review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, encompassing a thorough search strategy across multiple databases. Three in vitro studies met the inclusion criteria, highlighting the limited research in this evolving field. Findings suggest VEGF's neuroprotective effects on retinal ganglion cells (RGCs) and retinal neurons, unveiling potential therapeutic avenues. However, concerns arise regarding anti-VEGF therapies' impact on RGC survival. The review discusses the need for further research to delineate specific isoforms and signaling pathways responsible for VEGF-mediated neuroprotection. The delicate balance between angiogenesis and neuroprotection poses challenges in therapeutic development, emphasizing the importance of targeted interventions. Despite limitations, this review provides valuable insights into the intricate relationship between VEGF and neuroprotection in DR, paving the way for future investigations and redefining therapeutic strategies.

11.
Environ Sci Pollut Res Int ; 29(19): 28005-28019, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34985632

RESUMO

With the recent increase in demand for high-strength concrete, higher cement content is utilized, which has increased the need for cement. The cement industry is one of the most energy-consuming sectors globally, contributing to 10% of global carbon dioxide (CO2) gas emissions and global warming. Similarly, with rapid urbanization and industrialization, a vast number of by-products and waste materials are being generated in abundance, which causes environmental and health issues. Focusing on these two issues, this study aimed to develop an M50-grade eco-friendly high-strength concrete incorporating waste materials like marble dust powder (MDP) and fly ash (FA) as partial cement replacement. 2.5%, 5%, 7.5%, and 10% MDP and FA by weight of total binder was utilized combinedly, such that the 5%, 10%, 15%, and 20% cement content was replaced, respectively. The fresh state properties in terms of workability and hardened state properties in terms of compressive and flexural strengths were evaluated at 7, 14, 28, 56, and 90 days. Furthermore, to assess the environmental impact of MDP and FA, the embodied carbon and eco-strength efficiency were calculated. Based upon the results, it was observed that a combined 10% (5% MDP and 5% FA) achieved the highest strength; however, 15% (7.5% MDP and 7.5% FA) substitution could be optimal. Furthermore, the combined utilization of FA and MDP also enabled a reduction in the total embodied carbon. It decreased the cost of concrete, resulting in an eco-friendly, high-strength concrete.


Assuntos
Cinza de Carvão , Materiais de Construção , Carbonato de Cálcio , Poeira , Pós , Resíduos
12.
Membranes (Basel) ; 11(10)2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34677531

RESUMO

In petroleum refineries, naphtha reforming units produce reformate streams and as a by-product, hydrogen (H2). Naphtha reforming units traditionally deployed are designed as packed bed reactors (PBR). However, they are restrained by a high-pressure drop, diffusion limitations in the catalyst, and radial and axial gradients of temperature and concentration. A new design using the fluidized bed reactor (FBR) surpasses the issues of the PBR, whereby the incorporation of the membrane can improve the yield of products by selectively removing hydrogen from the reaction side. In this work, a sequential modular simulation (SMS) approach is adopted to simulate the hydrodynamics of a fluidized bed membrane reactor (FBMR) for catalytic reforming of naphtha in Aspen Plus. The reformer reactor is divided into five sections of plug flow reactors and a continuous stirrer tank reactor with the membrane module to simulate the overall FBMR. Similarly, a fluidized bed reactor (FBR), without membrane permeation phenomenon, is also modelled in the Aspen Plus environment for a comparative study with FBMR. In FBMR, the continuous elimination of permeated hydrogen enhanced the production of aromatics compound in the reformate stream. Moreover, the exergy and economic analyses were carried out for both FBR and FBMR.

13.
J Pak Med Assoc ; 64(6): 670-4, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25252487

RESUMO

OBJECTIVE: To observe the difference in dimension of teeth among adult females with and without malocclusion. METHODS: The cross-sectional study was conducted at Dr. Ishrat-ul-Ebad Khan Institute of Oral Health Sciences, Dow University of Health Sciences, Karachi, from April 2011 to April 2013, and used non-probability consecutive sampling. Mesiodistal and buccolingual crown dimensions were measured on study casts by using digital sliding caliper in 2 groups of females. Group 1 had 150 subjects with normal occlusion, while Group 2 had 234 with malocclusion. Independent t test was conducted to evaluate the difference between the dimensions of teeth of the two groups. Statistical analysis was done on SPSS version 16, and p value was considered significant at 0.05. RESULTS: Overall, the difference between the groups showed a greater tooth dimension in the malocclusion group of population compared to the normal group, and the most significant difference was observed in the mesiodistal dimension of maxillary 2nd premolar, which was 0.9 +/- 0.6801mm greater in dimension in the malocclusion group compared to the normal group. The least difference was observed in the buccolingual dimension of the mandibular central incisor where the malocclusion group had only 0.08 +/- 0.5247mm larger mandibular central incisors in the buccolingual dimension compared to the normal group. CONCLUSION: Mesiodistal and buccolingual crown dimensions were characteristically larger in the malocclusion group.


Assuntos
Má Oclusão/epidemiologia , Odontometria , Dente/anatomia & histologia , Adulto , Estudos Transversais , Feminino , Humanos , Modelos Dentários , Paquistão/epidemiologia
14.
Environ Toxicol Pharmacol ; 38(2): 653-62, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25218093

RESUMO

Catechins (flavan-3-ol) are a type of natural phenol and well-studied antioxidants. Catechin hydrate, also known as taxifolin; is non-mutagenic, low in toxicity compared to other immunomodulator antioxidants. We aimed to determine the potential of catechin hydrate to prevent the cyto-genotoxic effects of cadmium in lymphocytes; demonstrate the immuno-protective activity of catechin hydrate. Our previous study indicated that cadmium is apoptogenic. Lymphocytes were treated with catechin hydrate or cadmium and catechine hydrate combinations (range 0.1-100µM) to determine their effects on cell viability. Lymphocytes treated with 100µM catechin hydrate and 100µM cadmium showed cell viability 70.65±6.92% and 5.69±2.27%, respectively. In our previous study cadmium (10 and 20µM) induced apoptosis in 31.8% and 44.4% of lymphocytes, respectively. However, the percentage of apoptotic cells after treatment with the combination of cadmium and catechin hydrate was not significantly different from that of catechin hydrate (P>0.05). Only 7.3% and 10.5% of the lymphocytes were apoptotic after treatment with 10µM cadmium+10µM catechin hydrate and 20µM cadmium+20µM catechin hydrate, respectively. The anti-geno-cytotoxic and immuno-protective potential of catechin hydrate was also demonstrated by the non-significant expression of apoptosis-related genes after treatment with catechin hydrate.


Assuntos
Cádmio/toxicidade , Catequina/farmacologia , Linfócitos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fragmentação do DNA/efeitos dos fármacos , Interações Medicamentosas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Linfócitos/citologia
15.
Asian Pac J Cancer Prev ; 14(10): 5671-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24289560

RESUMO

Incidence of breast cancer shows geographical variation, even within areas of ethnic homogeneity. Saudi Arabia has witnessed an increase in occurrence of breast cancer in its unexplored ethnic populations over the past few years. We aimed at determining whether any association exists between single nucleotide polymorphisms in breast cancer associated gene 1 (BRCA1) and breast cancer associated gene 2 (BRCA2) and the risk of breast cancer. TaqMan based Real Time Polymerase chain reaction genotyping assays were used to determine the frequency of single nucleotide polymorphisms in BRCA1 (rs799917) and BRCA2 (rs144848) in a group of 100 breast cancer patients and unaffected age matched controls of Saudi Arabian origin. The present data revealed that neither BRCA1 nor the BRCA2 studied variant show any significant association with the disease. This study failed to find any role of the concerned variants in breast cancer either as risk or as prognostic factors. The small number of patients registered was one of the limitations of this study. In summary, comparison of mutation profile with other ethnic populations and regions reflected both differences and similarities indicating co-exposure to a unique set of risk factors. The differences could be due to exposure to particular environmental carcinogens; different lifestyle, reproductive pattern; dietary or cultural practices of Saudi Arabian women that need further investigations.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Neoplasias da Mama/epidemiologia , Etnicidade/genética , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Risco , Fatores de Risco , Arábia Saudita
16.
Asian Pac J Cancer Prev ; 14(10): 5783-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24289578

RESUMO

Trigonella foenum in graecum (Fenugreek) is a traditional herbal plant used to treat disorders like diabetes, high cholesterol, wounds, inflammation, gastrointestinal ailments, and it is believed to have anti-tumor properties, although the mechanisms for the activity remain to be elucidated. In this study, we prepared a methanol extract from Fenugreek whole plants and investigated the mechanism involved in its growth-inhibitory effect on MCF- 7 human breast cancer cells. Apoptosis of MCF-7 cells was evidenced by investigating trypan blue exclusion, TUNEL and Caspase 3, 8, 9, p53, FADD, Bax and Bak by real-time PCR assays inducing activities, in the presence of FME at 65 µg/mL for 24 and 48 hours. FME induced apoptosis was mediated by the death receptor pathway as demonstrated by the increased level of Fas receptor expression after FME treatment. However, such change was found to be absent in Caspase 3, 8, 9, p53, FADD, Bax and Bak, which was confirmed by a time-dependent and dose-dependent manner. In summary, these data demonstrate that at least 90% of FME induced apoptosis in breast cell is mediated by Fas receptor-independently of either FADD, Caspase 8 or 3, as well as p53 interdependently.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Extratos Vegetais/farmacologia , Trigonella/química , Receptor fas/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Proteína de Domínio de Morte Associada a Fas/metabolismo , Humanos , Células MCF-7 , Extratos Vegetais/química , Plantas Medicinais/química , Proteína Supressora de Tumor p53/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
17.
Environ Toxicol Pharmacol ; 36(3): 1033-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24100270

RESUMO

Cadmium (Cd) is a major pollutant of environment. It can be fatal to human. In spite of bulk of research and literatures, the mechanism of a fatality against human is still not understood completely. Toxic and carcinogenic effects of Cd in rodents and humans are well known. However, effects of Cd on induction of apoptosis are still elusive. This study indicates immunosuppression and immunotoxicity due to Cd exposure. Present study was undertaken to determine the mechanism of cell death in vitro in human peripheral blood lymphocytes induced by Cd. Our findings suggest the toxicity due to Cd is attributed to programmed cell death-apoptosis. IC50 was calculated at 21.74 µM. A significant increase of expression of the pro-apoptotic genep53, Fas and Caspase-3 in human lymphocytes was found. Cd induced p53-dependent apoptosis through cooperation between Bak upregulation without changing the Bcl-2 and Bax expression. Data of this study compel to speculate that apoptosis may also be attributed to CD95/Fas complex formation, and p53 direct apoptogenic potential at mitochondria. It was confirmed by the increased expression of Caspase-3. Although, this work does not address all the questions regarding the mechanism of Cd induced apoptosis, but these findings establish an important role of p53 and mitochondrial function during apoptosis in human lymphocyte. Moreover, based upon our findings, the role of Fas in Cd induced apoptosis is also undeniable. Hence further investigations are required to understand the different mechanism involved into apoptosis of lymphocytes due to Cd exposure.


Assuntos
Apoptose/efeitos dos fármacos , Cádmio/toxicidade , Caspase 3/fisiologia , Linfócitos/efeitos dos fármacos , Proteína Supressora de Tumor p53/fisiologia , Receptor fas/fisiologia , Cádmio/sangue , Caspase 3/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Corantes , Fragmentação do DNA/efeitos dos fármacos , Humanos , Marcação In Situ das Extremidades Cortadas , Técnicas In Vitro , Linfócitos/enzimologia , Reação em Cadeia da Polimerase em Tempo Real , Sais de Tetrazólio , Tiazóis , Transcrição Gênica/efeitos dos fármacos , Proteína Supressora de Tumor p53/efeitos dos fármacos , Receptor fas/efeitos dos fármacos
18.
Cancer Epidemiol ; 37(5): 762-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23725642

RESUMO

Chemotherapy has been used widely to treat cancer, both as a systemic therapy and as a local treatment. Unfortunately, many types of cancer are still refractory to chemotherapy. The mechanisms of anticancer drug resistance have been extensively explored but have not been fully characterized. This study analyzed the occurrences of polymorphism (SNP) in the MDR1 gene in breast cancer patients and determined a possible association with chemotherapy. The study group included one hundred breast carcinoma patients who subsequently received chemotherapy (the regimen generally consisted of commonly used drugs such as cyclophosphamide, adriamycin, 5-fluorouracil, docetaxel and their combinations). Blood samples from 100 healthy individuals are used, as controls were also genotyped for the MDR1 gene. This investigation revealed a significant correlation with response to various regimens of chemotherapy showing a low response to therapy with the CT/TT genotype at (exon 12) 1236 codon (p<0.001). These findings demonstrate, for the first time, that the polymorphisms in (exon 12) 1236 codon of the MDR1 gene greatly influence the drug response in patients from the Arab population of Saudi Arabia.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias da Mama/metabolismo , Códon , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Arábia Saudita
19.
Nanomedicine ; 9(8): 1328-35, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23727099

RESUMO

Luminescent functionalized mesoporous SiO2@Eu(OH)3 core-shell microspheres (LFMCSMs) were prepared by coating of europium hydroxide (Eu(OH)3) shell on mesoporous silica (SiO2) nanospheres via a facile one-pot process at low temperature. The FETEM images revealed that a well-defined luminescent europium hydroxide shell was successfully grafted on the surface of mesoporous silica nanospheres. These experimental results showed that the LFMCSM has a typical diameter of ca. 392 nm consisting of the silica core with about 230 nm in diameter and europium hydroxide shell with an average thickness of about 162 nm. LFMCSMs exhibited strong red emission peak upon irradiation with ultraviolet light, which originated from the electric-dipole transition (5)D0 → (7)F2 (614 nm) of Eu(3+) ion. The biocompatibility of the synthesized LFMCSMs was evaluated in vitro by assessing their cytotoxic and genotoxic effect on human hepatoblastoma (HepG2) cells using MTT, TUNEL, fluorescent staining, DNA ladder and Gene expression assays respectively. FROM THE CLINICAL EDITOR: This paper describes the development of a one-pot synthesis of luminescent mesoporous SiO2@Eu(OH)3 core-shell microspheres and evaluates their favorable in vitro cyto-toxicity and geno-toxicity, and their applications in bio-imaging of these particles that emit bright red signal under UV exposure.


Assuntos
Európio/toxicidade , Hidróxidos/toxicidade , Substâncias Luminescentes/toxicidade , Imagem Óptica , Dióxido de Silício/toxicidade , Európio/análise , Európio/química , Células Hep G2 , Humanos , Hidróxidos/análise , Hidróxidos/química , Substâncias Luminescentes/análise , Substâncias Luminescentes/química , Microesferas , Testes de Mutagenicidade , Dióxido de Silício/análise , Dióxido de Silício/química , Raios Ultravioleta
20.
Nat Prod Commun ; 8(2): 213-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23513732

RESUMO

Nigella sativa (NS), also known as black cumin, has long been used in traditional medicine for treating various cancer conditions. In this study, we sought to investigate the potential anti-cancer effects of NS extract using SiHa human cervical cancer cells. NS showed an 88.3% inhibition of proliferation of SiHa human cervical cancer cells at a concentration of 125 microL/mL methanolic extract at 24 h, and an IC50 value 93.2 microL/mL. NS exposure increased the expression of caspase-3, -8 and -9 several-fold. The analysis of apoptosis by Dead End terminal transferase-mediated dUTP-digoxigenin end labeling (TUNEL) assay was used to further confirm that NS induced apoptosis. Thus, NS was concluded to induce apoptosis in SiHa cell through both p53 and caspases activation. NS could potentially be an alternative source of medicine for cervical cancer therapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Nigella sativa , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Caspases/análise , Feminino , Humanos , Sementes/química , Proteína Supressora de Tumor p53/fisiologia , Neoplasias do Colo do Útero/patologia
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