RESUMEN
BACKGROUND: Lung cancer, accounting for a significant proportion of global cancer cases and deaths, poses a considerable health burden. Non-small cell lung cancer (NSCLC) patients have a poor prognosis and limited treatment options due to late-stage diagnosis and drug resistance. Dysregulated of the mitogen-activated protein kinase (MAPK) pathway, which is implicated in NSCLC pathogenesis, underscores the potential of MEK inhibitors such as binimetinib. Despite promising results in other cancers, comprehensive studies evaluating the safety and efficacy of binimetinib in lung cancer are lacking. This systematic review aimed to investigate the safety and efficacy of binimetinib for lung cancer treatment. METHODS: We searched PubMed, Scopus, Web of Science, and Google Scholar until September 2023. Clinical trials evaluating the efficacy or safety of binimetinib for lung cancer treatment were included. Studies were excluded if they included individuals with conditions unrelated to lung cancer, investigated other treatments, or had different types of designs. The quality assessment was conducted utilizing the National Institutes of Health tool. RESULTS: Seven studies with 228 participants overall were included. Four had good quality judgments, and three had fair quality judgments. The majority of patients experienced all-cause adverse events, with diarrhea, fatigue, and nausea being the most commonly reported adverse events of any grade. The objective response rate (ORR) was up to 75%, and the median progression-free survival (PFS) was up to 9.3 months. The disease control rate after 24 weeks varied from 41% to 64%. Overall survival (OS) ranged between 3.0 and 18.8 months. Notably, treatment-related adverse events were observed in more than 50% of patients, including serious adverse events such as colitis, febrile neutropenia, and pulmonary infection. Some adverse events led to dose limitation and drug discontinuation in five studies. Additionally, five studies reported cases of death, mostly due to disease progression. The median duration of treatment ranged from 14.8 weeks to 8.4 months. The most common dosage of binimetinib was 30 mg or 45 mg twice daily, sometimes used in combination with other agents like encorafenib or hydroxychloroquine. CONCLUSIONS: Only a few studies have shown binimetinib to be effective, in terms of improving OS, PFS, and ORR, while most of the studies found nonsignificant efficacy with increased toxicity for binimetinib compared with traditional chemotherapy in patients with lung cancer. Further large-scale randomized controlled trials are recommended.
Asunto(s)
Bencimidazoles , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Bencimidazoles/uso terapéutico , Bencimidazoles/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Supervivencia sin ProgresiónRESUMEN
Aim: The current systematic review and meta-analysis aimed to assess the association between Gastrointestinal (GI) cancers and opium use. Background: GI malignancies are a global public health issue and are associated with many risk factors including genetic and lifestyle factors. Methods: PubMed, Web of Science, Embase and Scopus and the Google Scholar search engine in addition to Persian databases including Magiran and SID were searched using relevant keywords. The associations of opium use, long duration of opium use, high daily amount opium use and high cumulative opium use and GI cancer and various subtypes of GI cancers were estimated and pooled in format of odds ratios (OR) and their corresponding 95% confidence intervals (CI) with a random effects model. Results: 22 articles that were published between 1983 and 2022 entered the analyses. There were significant relationships between opium use based on crude effect sizes (OR: 2.53, 1.95-3.29) and adjusted effect sizes (OR: 2.64, 1.99-3.51), high daily opium use (or: 3.41, 1.92-6.06), long duration of opium use (OR: 3.03, 1.90-4.84) and high cumulative opium use (OR: 3.88, 2.35-6.41), all compared to never opium use, and GI cancer. The results were not sensitive to sensitivity analyses and no influential publication biases were found in these analyses. Conclusion: Our meta-analysis showed that opium use could be associated with increased risk of overall and some particular GI cancers including oropharyngeal, gastric, pancreatic and colorectal cancers. Opium use as a potentially modifiable factor, therefore, should be more emphasized.
RESUMEN
Portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) are two distinct entities that are frequently mistaken with each other, because they present with similar manifestations. This issue may cause catastrophic outcomes, as each one of them has a unique pathophysiology, thereby making their management approaches completely different. There are clinical clues that help physicians distinguish these two. Direct vision via upper endoscopy is often mandatory to establish the diagnosis, and sometimes biopsy is required. In this review, we sought to discuss different aspects of both conditions and highlight clinical evidence that may help in identifying and managing the disease appropriately.
RESUMEN
Background and Aims: Bowel preparation affects the quality of colonoscopy. Reaching the optimal preparation has been a challenge for years. Polyethylene glycol (PEG) is the sole FDA-approved substance for this purpose. However, patients find it unpleasant and often complain about its adverse effects. In this study, we aimed to reduce these complaints by lowering the amount of PEG and adding senna which is an herbal stimulant laxative. Methods: Four hundred and eighty-six patients were admitted for colonoscopy. Finally, 382 patients were enrolled in the study and we divided them into two groups; 186 patients were placed in which conventional high volume PEG-alone regimen was consumed and 196 patients in which low volume PEG plus senna regimen was offered. The quality of colon preparation was compared between the two groups by independent two samples t-test (or its corresponding nonparametric test), Fisher's exact, or χ 2 test in SPSS software version 22. Results: The colon preparation quality was equally efficient in the two groups as 69.36% in the high volume PEG group and 71.94% in PEG plus senna group had adequate bowel preparation (p = 0.58). Adverse effects, like nausea, bloating, headache, and sleeplessness were significantly less in the low volume PEG plus senna group. Conclusion: Besides the fact that bowel preparation by low volume PEG plus senna combination was noninferior to the conventional high volume PEG-alone regimen, the side effects were much less common with the low volume PEG plus senna regimen.
RESUMEN
Early detection of diseases is very important to increase the life quality and reduce the treatment cost for the patient. MicroRNAs have been introduced in recent years as an efficient class of biomarkers for detecting the risky situation of many diseases such as cancers, Multiple sclerosis (MS), and heart attacks, and other diseases. Now, real-time PCR has been used to profile the microRNA expression, which is expensive, time-consuming, and has low accuracy. Most recently, DNA logic gates are used to detect the MicroRNA expression level that is more accurate and faster than previous methods. In this paper, we improved the design of multi-threshold and multi-input DNA-based logic gates in response to specific microRNA (miRNA) inputs. The proposed design style can simultaneously recognize multiple miRNAs with different rising and falling thresholds. The proposed structure in this paper is used to diagnose Multiple Sclerosis (MS) as a case study. We simulated this system to understand its performance and compare it with other existing methods. The simulation results show the efficiency of the proposed method in terms of accuracy, efficiency, and speed. In this analysis, unwanted reactions, fault positive, and the probability of generating the final output using the formal method are investigated in depth. Finally, the proposed solutions are improved based on the results of these analyses. The analytic approach of this paper helps to design the DNA-based logic gates for real diseases.
RESUMEN
Tramadol is a synthetic analogue of codeine that is often prescribed for the treatment of mild to moderate pains. It has a number of side effects including emotional instability and anxiety. In this study, we focus on the structural and functional changes of prefrontal cortex under chronic exposure to tramadol. At the cellular level, the amounts of ROS and annexin V in PC12 cells were evidently increased upon exposure to tramadol (at a concentration of 600 µM for 48 h). To this end, the rats were daily treated with tramadol at doses of 50 mg/kg for 3 weeks. Our findings reveal that tramadol provokes atrophy and apoptosis by the induction of apoptotic markers such as Caspase 3 and 8, pro-inflammatory markers, and downregulation of GDNF. Moreover, it triggers microgliosis and astrogliosis along with neuronal death in the prefrontal cortex. Behavioral disturbance and cognitive impairment are other side effects of tramadol. Overall, our results indicate tramadol-induced neurodegeneration in the prefrontal cortex mainly through activation of neuroinflammatory response.
Asunto(s)
Apoptosis/efectos de los fármacos , Neuronas/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Tramadol/toxicidad , Animales , Anexina A5/efectos de los fármacos , Anexina A5/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/patología , Atrofia , Caspasa 3/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 8/efectos de los fármacos , Caspasa 8/metabolismo , Muerte Celular , Factor Neurotrófico Derivado de la Línea Celular Glial/efectos de los fármacos , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Gliosis/inducido químicamente , Gliosis/metabolismo , Gliosis/patología , Masculino , Microglía/efectos de los fármacos , Microglía/patología , Neuronas/metabolismo , Neuronas/patología , Células PC12 , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Deregulation of microRNAs expression is symptomatic of cancer disease and occurs before the awareness of cancer signs. Early detection of cancer disease can improve or drop the disease entirely. DNA computing is an emerging field of detecting microRNAs based on toehold-mediated strand displacement reactions, which is a more efficient method than the commonly used method like real-time PCR. Accuracy and cost of diagnostic applications are essential criteria that are achieved by using the DNA logic gates based on the DNA computing method. In this study, the authors proposed the multi-input liver cancer biosensor with the RNA secondary structure motifs as the computational module and two approaches are suggested.
Asunto(s)
Biomarcadores de Tumor/análisis , Técnicas Biosensibles , Computadores Moleculares , MicroARNs/análisis , Técnicas de Diagnóstico Molecular , Humanos , Neoplasias Hepáticas/diagnóstico , LógicaRESUMEN
To date, no certain cure has been found for patients with degenerative cerebellar disease. In this trial, we examined the in vivo and in vitro neuroprotective effects of Sertoli cells (SCs) on alleviating the symptoms of cerebellar ataxia. Testicular cells from an immature male rat were isolated and characterized by immunocytochemical analysis for somatic cell markers (anti-Mullerian hormone, vimentin). The protein assessment had already confirmed the expression of neurotrophic factors of glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial factor (VEGF). In vitro neuroprotective impact of SCs was determined after exposing PC12 cells to Sertoli cell-conditioned media (SC-CM) and H2O2, simultaneously. Afterwards, ataxia rat models were induced by a single dose of 3-AP (3-acetylpyridin), and 3 days later, SCs were bilaterally implanted. Motor and neuromuscular activity test were conducted following SC transplantation. Finally, immunohistochemistry against RIPK3 and Iba-1 was done in our generation. The in vivo results revealed substantial improvement in neuromuscular response, while ataxia group exhibited aggravated condition over a 28-day period. Our results suggested enhanced motor function and behavioral characteristics due to the ability of SCs to suppress necroptosis and consequently extend cell survival. Nevertheless, more studies are required to affirm the therapeutic impacts of SC transplantation in human cerebellar ataxia. In vitro data indicated cell viability was increased as a result of SC-CM with a significant reduction in ROS.
Asunto(s)
Ataxia Cerebelosa/terapia , Movimiento , Necroptosis , Células de Sertoli/trasplante , Trasplante de Células Madre/métodos , Animales , Células Cultivadas , Ataxia Cerebelosa/etiología , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Masculino , Células PC12 , Piridinas/toxicidad , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Células de Sertoli/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Vimentina/genética , Vimentina/metabolismoRESUMEN
Cerebellar ataxia (CA) is a form of ataxia that adversely affects the cerebellum. Cell replacement therapy (CRT) has been considered as a potential treatment for neurological disorders. In this report, we investigated the neuro-restorative effects of human chorionic stem cells (HCSCs) transplantation on rat model of CA induced by 3-acetylpyridine (3-AP). In this regard, HCSCs were isolated and phenotypically determined. Next, a single injection of 3-AP was administered for ataxia induction, and bilateral HCSCs implantation was conducted 3 days after 3-AP injection, followed by expression analysis of a number of apoptotic, autophagic and inflammatory genes as well as vascular endothelial growth factor (VEGF) level, along with assessment of cerebellar neurodegeneration, motor coordination and muscle activity. The findings revealed that grafting of HCSCs in 3-AP model of ataxia decreased the expression levels of several inflammatory, autophagic and apoptotic genes and provoked the up-regulation of VEGF in the cerebellar region, prevented the degeneration of Purkinje cells caused by 3-AP toxicity and ameliorated motor coordination and muscle function. In conclusion, these data indicate in vivo efficacy of HCSCs in the reestablishment of motor skills and reversal of CA.
Asunto(s)
Ataxia Cerebelosa/terapia , Cerebelo/patología , Actividad Motora/fisiología , Degeneración Nerviosa/terapia , Trasplante de Células Madre , Células Madre/metabolismo , Animales , Apoptosis/fisiología , Ataxia Cerebelosa/inducido químicamente , Ataxia Cerebelosa/metabolismo , Ataxia Cerebelosa/fisiopatología , Cerebelo/metabolismo , Cerebelo/fisiopatología , Modelos Animales de Enfermedad , Humanos , Inflamación/metabolismo , Inflamación/patología , Inflamación/fisiopatología , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/fisiopatología , Piridinas , Ratas , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Early detection of cancer is very critical because it can reduce the treatment risk and cost. MicroRNAs (miRNAs) have been introduced in recent years as an efficient class of biomarkers for cancer early detection. Now, real-time polymerase chain reaction has been used to profile the miRNA expression, which is costly, time consuming and low accuracy. Most recently, DNA logic gates are used to detect the miRNA expression level that is more accurate and faster than previous methods. The DNA-based logic gates face with serious challenges such as the large complexity and low scalability. In this study, the authors proposed a methodology to design multi-threshold and multi-input DNA-based logic gates in response to specific miRNA inputs in live mammalian cells. The proposed design style can simultaneously recognise multiple miRNAs with different rising and falling thresholds. The design style has been evaluated on the lung cancer biomarkers and the experimental results show the efficiency of the proposed method in terms of accuracy, efficiency and speed.
Asunto(s)
Biomarcadores de Tumor/genética , Computadores Moleculares , ADN de Neoplasias/análisis , Perfilación de la Expresión Génica/métodos , MicroARNs/genética , Neoplasias/genética , ADN de Neoplasias/genética , Detección Precoz del Cáncer/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Lógica , Reproducibilidad de los Resultados , Proyectos de Investigación , Sensibilidad y Especificidad , TranscriptomaRESUMEN
The current study aimed to develop PEGylated trimethyl chitosan (TMC) coated emulsomes (EMs) conjugated with octreotide for targeted delivery of sorafenib to hepatocellular carcinoma cells (HCC) of HepG2. Sorafenib loaded TMC coated EMs were prepared by the emulsion evaporation method and characterized concerning particle size, zeta potential, drug encapsulation efficiency, and in vitro drug release. Synthesized EMs were then conjugated to octreotide. The cytotoxicity of the targeted and non-targeted EMs was determined by cellular uptake and MTT assay on HepG2 cell. Cell cycle assay was also studied using flow cytometry. The results showed the optimized EMs had the particle size of 127 nm, zeta potential of -5.41 mV, loading efficiency of 95%, and drug release efficiency of 62% within 52 h. Octreotide was attached efficiently to the surface of EMs as much as 71%. MTT assay and cellular uptake studies showed that targeted EMs had more cytotoxicity than free sorafenib and non-targeted EMs. Cell cycle analyses revealed that there was a significant more accumulation of targeted EMs treated HepG2 cells in the G1 phase than free sorafenib and non-targeted EMs. The results indicate that designed EMs may be promising for the treatment of hepatocellular carcinoma.
Asunto(s)
Antineoplásicos/química , Quitosano/química , Nanocápsulas/química , Octreótido/química , Polietilenglicoles/química , Sorafenib/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Permeabilidad de la Membrana Celular , Supervivencia Celular/efectos de los fármacos , Preparaciones de Acción Retardada/química , Composición de Medicamentos , Liberación de Fármacos , Emulsiones/química , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/farmacología , Propiedades de SuperficieRESUMEN
BACKGROUND: Poly(methyl vinyl ether-maleic acid) (PMVEMA) is a water-soluble, biodegradable polymer used for drug delivery. The aim of the present study was to prepare nanofibers of this polymer as a fast-dissolving carrier for montelukast. MATERIALS AND METHODS: Polymeric nanofibers were spun by electrospinning method using different ratios of biodegradable polymer of PMVEMA. The processing variables including voltage, distance of the needle to rotating screen, and flow rate of the solution were optimized based on the diameter of the nanofibers, drug content, and release efficiency by a Taguchi design. The morphology, diameter, and diameter distribution of the nanofibers were studied by scanning electron microscopy (SEM). Drug loading and its release rate from the nanofibers were analyzed spectrophotometrically. The possible molecular between the polymer and the drug was characterized with Fourier-transform-infrared spectroscopy. RESULTS: The results showed the best situation for electrospinning of the polymer obtained at the polymer concentration of 37%, the distance of the needle to rotating screen of 19 cm, the voltage of 120 kV, and the rate of injection of 0.2 ml/h. In these situations, the fiber diameter and drug loading efficiency percentage were 273 nm and 83%, respectively. These nanofibers released the total loaded drug within 1-3 s with no residue in the dissolution medium. SEM results showed that the optimized nanofibers were quite smooth and without beads. CONCLUSIONS: The results indicated that the nanofibers of PMVEMA could dissolve the drug very rapidly and can be adopted for fast-dissolving dosage forms.
RESUMEN
Research in human vision suggests that in a single fixation, humans can extract a significant amount of information from a natural scene, e.g. the semantic category, spatial layout, and object identities. This ability is useful, for example, for quickly determining location, navigating around obstacles, detecting threats, and guiding eye movements to gather more information. In this paper, we ask a new question: What can we see at a glance at a web page - an artificial yet complex "real world" stimulus? Is it possible to notice the type of website, or where the relevant elements are, with only a glimpse? We find that observers, fixating at the center of a web page shown for only 120 milliseconds, are well above chance at classifying the page into one of ten categories. Furthermore, this ability is supported in part by text that they can read at a glance. Users can also understand the spatial layout well enough to reliably localize the menu bar and to detect ads, even though the latter are often camouflaged among other graphical elements. We discuss the parallels between web page gist and scene gist, and the implications of our findings for both vision science and human-computer interaction.
RESUMEN
Digital microfluidic is an emerging technology to reduce the cost and time of experiments and improve the flexibility, automate-ability and correctness of biochemical assays. In many of applications such as drug discovery and DNA profiling, a large number of bio-operations (e.g. the chemical operations used in biology applications) must be done. In these applications, parallelising the operations will be critical in accuracy and cost of the process and digital microfluidic biochips can be considered as a reasonable platform. In this study, a new microfluidic architecture and the corresponding CAD flow is introduced to parallelise the assays on this platform. The authors implemented the proposed architecture and evaluated it using the large real bioassays. The authors' simulations show that the degree-of-parallelism and speed of bioassays are increased more than 4× and the improvements will be better for larger assays. This contribution can open new horizons in drug testing, biology experiments and medical diagnosis operations that contain iterative, time-consuming and labour experiments.
Asunto(s)
Algoritmos , Bioensayo/instrumentación , Bioensayo/métodos , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Diseño Asistido por Computadora , Diseño de Equipo , Dispositivos Laboratorio en un Chip , Reacción en Cadena de la Polimerasa , Factores de TiempoRESUMEN
DNA is known as the building block for storing the life codes and transferring the genetic features through the generations. However, it is found that DNA strands can be used for a new type of computation that opens fascinating horizons in computational medicine. Significant contributions are addressed on design of DNA-based logic gates for medical and computational applications but there are serious challenges for designing the medium and large-scale DNA circuits. In this paper, a new microarchitecture and corresponding design flow is proposed to facilitate the design of multistage large-scale DNA logic systems. Feasibility and efficiency of the proposed microarchitecture are evaluated by implementing a full adder and, then, its cascadability is determined by implementing a multistage 8-bit adder. Simulation results show the highlight features of the proposed design style and microarchitecture in terms of the scalability, implementation cost, and signal integrity of the DNA-based logic system compared to the traditional approaches.