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1.
Cancer Metastasis Rev ; 41(2): 281-299, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35511379

RESUMEN

Esophageal cancer (EC) is frequently considered a lethal malignancy and is often identified at a later stage. It is one of the major causes of cancer-related deaths globally. The conventional treatment methods like chemotherapy, radiotherapy, and surgery offer limited efficacy and poor clinical outcome with a less than 25% 5-year survival rate. The poor prognosis of EC persists despite the growth in the development of diagnostic and therapeutic modalities to treat EC. This underlines the need to elucidate the complex molecular mechanisms that drive esophageal oncogenesis. Apart from the role of the tumor microenvironment and its structural and cellular components in tumorigenesis, mounting evidence points towards the involvement of the esophageal microbiome, inflammation, and their cross-talk in promoting esophageal cancer. The current review summarizes recent research that delineates the underlying molecular mechanisms by which the microbiota and inflammation promote the pathophysiology of esophageal cancer, thus unraveling targets for potential therapeutic intervention.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Microbiota , Carcinogénesis , Carcinoma de Células Escamosas/patología , Transformación Celular Neoplásica , Humanos , Inflamación , Microambiente Tumoral
2.
J Transl Med ; 21(1): 449, 2023 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-37420216

RESUMEN

Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)-T cell therapy, however, leverages the immune system's T-cells to recognize and attack tumor cells. T-cells are isolated from patients and modified to target tumor-associated antigens. CAR-T therapy has achieved FDA approval for treating blood cancers like B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma by targeting CD-19 and B-cell maturation antigens. Bi-specific chimeric antigen receptors may contribute to mitigating tumor antigen escape, but their efficacy could be limited in cases where certain tumor cells do not express the targeted antigens. Despite success in blood cancers, CAR-T technology faces challenges in solid tumors, including lack of reliable tumor-associated antigens, hypoxic cores, immunosuppressive tumor environments, enhanced reactive oxygen species, and decreased T-cell infiltration. To overcome these challenges, current research aims to identify reliable tumor-associated antigens and develop cost-effective, tumor microenvironment-specific CAR-T cells. This review covers the evolution of CAR-T therapy against various tumors, including hematological and solid tumors, highlights challenges faced by CAR-T cell therapy, and suggests strategies to overcome these obstacles, such as utilizing single-cell RNA sequencing and artificial intelligence to optimize clinical-grade CAR-T cells.


Asunto(s)
Neoplasias Hematológicas , Mieloma Múltiple , Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Inteligencia Artificial , Neoplasias/terapia , Inmunoterapia Adoptiva , Antígenos de Neoplasias , Microambiente Tumoral , Tratamiento Basado en Trasplante de Células y Tejidos
3.
J Transl Med ; 21(1): 286, 2023 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-37118828

RESUMEN

BACKGROUND: Osteosarcoma is a type of bone cancer that predominantly affects young individuals, including children and adolescents. The disease progresses through heterogeneous genetic alterations, and patients often develop pulmonary metastases even after the primary tumors have been surgically removed. Ubiquitin-specific peptidases (USPs) regulate several critical cellular processes, such as cell cycle progression, transcriptional activation, and signal transduction. Various studies have revealed the significance of USP37 in the regulation of replication stress and oncogenesis. METHODS: In this study, the Cancer Genome Atlas (TCGA) database was analyzed to investigate USP37 expression. RNA sequencing was utilized to assess the impact of USP37 overexpression and depletion on gene expression in osteosarcoma cells. Various molecular assays, including colony formation, immunofluorescence, immunoprecipitation, and DNA replication restart, were employed to examine the physical interaction between USP37 and PCNA, as well as its physiological effects in osteosarcoma cells. Additionally, molecular docking studies were conducted to gain insight into the nature of the interaction between USP37 and PCNA. Furthermore, immunohistochemistry was performed on archived tissue blocks from osteosarcoma patients to establish a correlation between USP37 and PCNA expression. RESULTS: Analysis of the TCGA database revealed that increased expression of USP37 was linked to decreased progression-free survival (PFS) in osteosarcoma patients. Next-generation sequencing analysis of osteosarcoma cells demonstrated that overexpression or knockdown of USP37 led to the expression of different sets of genes. USP37 overexpression provided a survival advantage, while its depletion heightened sensitivity to replication stress in osteosarcoma cells. USP37 was found to physically interact with PCNA, and molecular docking studies indicated that the interaction occurs through unique residues. In response to genotoxic stress, cells that overexpressed USP37 resolved DNA damage foci more quickly than control cells or cells in which USP37 was depleted. The expression of USP37 varied in archived osteosarcoma tissues, with intermediate expression seen in 52% of cases in the cohort examined. CONCLUSION: The results of this investigation propose that USP37 plays a vital role in promoting replication stress tolerance in osteosarcoma cells. The interaction between USP37 and PCNA is involved in the regulation of replication stress, and disrupting it could potentially trigger synthetic lethality in osteosarcoma. This study has expanded our knowledge of the mechanism through which USP37 regulates replication stress, and its potential as a therapeutic target in osteosarcoma merits additional exploration.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Niño , Humanos , Adolescente , Antígeno Nuclear de Célula en Proliferación , Endopeptidasas/genética , Endopeptidasas/metabolismo , Simulación del Acoplamiento Molecular , Proteasas Ubiquitina-Específicas , Osteosarcoma/genética , Neoplasias Óseas/genética
4.
J Transl Med ; 20(1): 534, 2022 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-36401282

RESUMEN

Gene editing has great potential in treating diseases caused by well-characterized molecular alterations. The introduction of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-based gene-editing tools has substantially improved the precision and efficiency of gene editing. The CRISPR/Cas9 system offers several advantages over the existing gene-editing approaches, such as its ability to target practically any genomic sequence, enabling the rapid development and deployment of novel CRISPR-mediated knock-out/knock-in methods. CRISPR/Cas9 has been widely used to develop cancer models, validate essential genes as druggable targets, study drug-resistance mechanisms, explore gene non-coding areas, and develop biomarkers. CRISPR gene editing can create more-effective chimeric antigen receptor (CAR)-T cells that are durable, cost-effective, and more readily available. However, further research is needed to define the CRISPR/Cas9 system's pros and cons, establish best practices, and determine social and ethical implications. This review summarizes recent CRISPR/Cas9 developments, particularly in cancer research and immunotherapy, and the potential of CRISPR/Cas9-based screening in developing cancer precision medicine and engineering models for targeted cancer therapy, highlighting the existing challenges and future directions. Lastly, we highlight the role of artificial intelligence in refining the CRISPR system's on-target and off-target effects, a critical factor for the broader application in cancer therapeutics.


Asunto(s)
Sistemas CRISPR-Cas , Neoplasias , Humanos , Sistemas CRISPR-Cas/genética , Inteligencia Artificial , Edición Génica/métodos , Inmunoterapia , Neoplasias/genética , Neoplasias/terapia
5.
Gynecol Oncol ; 162(2): 382-388, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34088513

RESUMEN

BACKGROUND: Treatment of patients with platinum resistant/refractory epithelial ovarian cancer (EOC) is an unmet need. We evaluated the role of oral metronomic therapy in this setting. PATIENTS AND METHODS: Between October 2017 and September 2019 seventy five patients with platinum resistant/refractory EOC were enrolled. Patients received oral etoposide (50 mg, day 1 to 14, cyclophosphamide 50 mg, day 1 to 28, every 4 weeks (Arm A, n = 38). Patients in Arm- B (n = 37) received Pazopanib (400 mg once daily) in addition to etoposide and cyclophosphamide. Quality of life (QoL) was evaluated using the EORTC questionnaire. Serum VEGF and PDGF were estimated at baseline, after 3rd and 6th cycle. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and QoL. RESULTS: Patients characteristics were well matched. Median PFS was higher in arm B, 5.1 months (95% CI 3.13 to10.33) compared to 3.4 months (95% CI 3.0 to 6.53) in arm A, p = 0.045. Median OS has 'not reached' in Arm B compared to 11.2 months (95% CI, 5.66 - not reached) in arm A, p = 0.032. Therapy was tolerated well; oral mucositis (p = 0.36) and fatigue (p = 0.08) being more in arm B. QoL assessment revealed modest improvement in 'symptom scales' in Arm B. Serum VEGF and PDGF levels decreased with therapy in both arms (Arm A-p < 0.0001, Arm B-p < 0.016). CONCLUSION: Addition of pazopanib to etoposide and cyclophosphamide could be a novel oral combination for metronomic therapy for platinum resistant/refractory EOC. TRIAL REGISTRATION: CTRI/2017/10/010219.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Indazoles/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Pirimidinas/administración & dosificación , Sulfonamidas/administración & dosificación , Administración Metronómica , Administración Oral , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Epitelial de Ovario/mortalidad , Carcinoma Epitelial de Ovario/patología , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Resistencia a Antineoplásicos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Indazoles/efectos adversos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Supervivencia sin Progresión , Pirimidinas/efectos adversos , Calidad de Vida , Sulfonamidas/efectos adversos
6.
Int Ophthalmol ; 41(2): 575-580, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33165653

RESUMEN

BACKGROUND: The high-density silicone oil (Densiron), a mixture of F6H8 with silicone oil, has been used in the management of retinal detachment (RD) complicated by the presence of proliferative vitreoretinopathy (PVR) with varying rate of anatomical success and visual outcomes. METHODS: We conducted a prospective interventional case series of 22 eyes in 22 children less than 18 years diagnosed with complicated retinal detachment complicated by the presence of PVR in inferior quadrant. RESULTS: The mean age of the patients was 8.45 ± 3.36 years. There were 14 male and 8 female children. Five patients presented with total RD, 5 had subtotal RD and remaining 10 with inferior retinal detachment. There were 8 children with PVR C1, 13 with PVR C2, 3 with PVR C3. All patient's had macula off RD at presentation. The anatomical success in the form of attached retina was achieved in 21 (95.45%) eyes. Standard three-port pars plana vitrectomy without scleral buckling under general anesthesia was surgical technique employed in all cases. CONCLUSION: Densiron can be an important tamponade agent in pediatric retinal detachment complicated by PVR with increased success rate of retinal re-attachment.


Asunto(s)
Desprendimiento de Retina , Vitreorretinopatía Proliferativa , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Prospectivos , Desprendimiento de Retina/cirugía , Aceites de Silicona , Resultado del Tratamiento , Agudeza Visual , Vitrectomía , Vitreorretinopatía Proliferativa/complicaciones , Vitreorretinopatía Proliferativa/cirugía
7.
Parasitol Res ; 119(10): 3347-3357, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32833051

RESUMEN

A total of 57 tissue samples of domestic pigs (Sus scrofa) were collected from the meat outlets of five north Indian states and examined for sarcocystosis by histological and molecular methods. The genomic DNA extracted from five representative positive isolates was subjected to PCR amplification of the partial 18S rRNA gene followed by cloning and sequencing. Sequence analysis of the newly generated Indian isolates recorded 96.9-100.0% identity with published sequences of Sarcocystis suihominis. Two new haplotypes that have not been previously described manifested 99.5-100.0% nucleotide homology within themselves. In the phylogenetic analysis, Indian isolates of S. suihominis grouped together with S. suihominis originating from Italy, and they collectively formed a sister clade with Sarcocystis miescheriana within a clade containing various Sarcocystis spp. of ruminants having felids as final hosts. At the same time, this clade separated from a sister clade containing Sarcocystis spp. of bovid or cervid ruminants using canids as known or surmised definitive host. The current study established the phylogenetic relationship of Indian isolates of S. suihominis with various Sarcocystis spp. as well as with other taxa of Sarcocystidae family based on 18S rRNA gene for the first time.


Asunto(s)
Sarcocystis/clasificación , Sarcocystis/genética , Sarcocistosis/veterinaria , Sus scrofa/parasitología , Enfermedades de los Porcinos/parasitología , Animales , Haplotipos , India/epidemiología , Filogenia , ARN Ribosómico 18S/genética , Sarcocystis/aislamiento & purificación , Sarcocistosis/epidemiología , Sarcocistosis/parasitología , Porcinos , Enfermedades de los Porcinos/epidemiología
8.
J Evid Based Dent Pract ; 19(3): 283-294, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31732104

RESUMEN

OBJECTIVE: The objective of this study was to assess the quality of reporting of full-text articles of dental diagnostic accuracy studies published in eight leading speciality dental journals in relation to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement. METHODS: The full articles of all included studies were assessed for their adherence to the 30-item STARD checklist by two researchers independently. A score of 0-2 was attributed to each item. Inter-rater agreement was assessed. Univariate and multivariate linear regression analyses were carried out to evaluate differences in reporting qualities between journals and whether certain variables influenced reporting qualities. RESULTS: A total of 145 articles were identified. Full-article STARD checklist items relating to methodology and results were poorly reported. The overall mean quality score for full articles was 28.75. Articles published in the Journal of Cranio-Maxillofacial Surgery obtained the highest quality score. In the multivariate analysis, articles published in the Journal of Cranio-Maxillofacial Surgery had significantly higher reporting quality scores than those published in the European Journal of Orthodontics (ß = -6.97, 95% confidence interval [CI]: -11.62, -2.30, P < .05), the Journal of Prosthetic Dentistry (ß = -8.01, 95% CI: -14.60, -1.41, P < .05) and Oral Diseases (ß = -6.72, 95% CI: -11.57, -1.86, P < .05). Reporting quality improved each year (P < .028). CONCLUSION: Adherence of full articles to the STARD is suboptimal in dental journals.


Asunto(s)
Publicaciones Periódicas como Asunto , Edición , Lista de Verificación , Humanos , Proyectos de Investigación
10.
Emerg Med J ; 35(6): 389-395, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29572386

RESUMEN

Terrorist attacks are increasing each year as are the number of deaths associated with them. Recent incidents have seen a shift in tactics with the use of multiple terrorists across multiple locations with firearms or knives, referred to as the marauding terrorist attack. These methods are becoming more prevalent alongside the use of vehicles deliberately aimed at pedestrians. Management of these incidents can be challenging. Not only it involves a large number of casualties but also the management of a dynamic scene in terms of both location and threat from attack. In order to improve response, and potentially outcomes, a system or response needs to have preplanned and practised procedures in place. This article reviews major incident management for those unfamiliar with current prehospital practice and details some of the findings from recent marauding terrorist firearm attacks, in particular the evolution of newer scene management tools such as 3 Echo and THREAT. It highlights the importance of haemorrhage control and the public initiatives focusing on actions during a terrorist incident.


Asunto(s)
Servicios Médicos de Urgencia/métodos , Terrorismo/psicología , Planificación en Desastres/métodos , Planificación en Desastres/organización & administración , Servicios Médicos de Urgencia/tendencias , Hemorragia/terapia , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Terrorismo/historia , Terrorismo/estadística & datos numéricos
11.
Evid Based Dent ; 17(1): 17-8, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27012571

RESUMEN

DATA SOURCES: Embase, Medline, Cochrane Central, Biomed Central and Open Grey databases and bibliographies of identified studies. STUDY SELECTION: Randomised controlled trials investigating humans with primary caries lesions receiving operative treatment involving caries removal and restoration, with minimum two treatment groups comparing different cavity treatments before restoration (no lining versus lining) were included. DATA EXTRACTION AND SYNTHESIS: Data were extracted independently by two reviewers and study quality assessed using the Cochrane risk of bias tool. Random effect meta-analysis was carried out. RESULTS: Three studies involving a total of 89 patients were included. All the studies involved primary teeth and were conducted in Brazil. Follow-up periods ranged from 26-53 months. All the studies were considered to be at high risk of bias. Restoring the cavity without lining did not significantly affect the risk of failure. The quality of the evidence was low. CONCLUSIONS: Current evidence does not support strong recommendations to use or not to use liners after caries removal and before restoring cavities. Our findings are restricted to primary teeth after selective excavation, with only one liner (calcium hydroxide) being used for comparison.


Asunto(s)
Caries Dental , Diente Primario , Hidróxido de Calcio , Atención Odontológica , Recubrimiento de la Cavidad Dental , Humanos
12.
Evid Based Dent ; 16(4): 114-5, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26680522

RESUMEN

DATA SOURCES: PubMed, the Cochrane Library and the databases of the Centre for Reviews and Dissemination were searched. STUDY SELECTION: Prospective randomised controlled trials (RCTs), clinical controlled trials (CCTs) and observational studies of Class I and/or Class II resin composite restorations with a sample size of more than 40 individuals or teeth and longer than four years follow-up were considered. RESULTS: Eight studies involving a total of 910 restorations in 420 patients were included. Seven of the eight studies were completed by the same research group with follow-up times ranging from four to 12 years. There were 80 failures of restorations in total, ranging from two to 17 per study. A majority of the fractures of the restoration or the tooth and endodontic complications occurred during the first three years of follow-up. Caries occurred later, more than 75% after three years in service. The overall incidence rate for all causes of failure was 1.55 lost restorations per 100 restoration years. Survival rate at four years = 0.93 (95% CI; 0.91- 0.95). One study (74 teeth) provided data at 12 years with a survival rate = 0.86 (95% CI; 0.82;0.89). The most common biological reason for failure (a total of 31 restorations) was secondary caries, with or without fracture of the restoration. The overall quality of the evidence was low. CONCLUSIONS: The overall survival proportion of posterior resin composite restorations is high. The major reasons for failure are secondary caries and restoration fracture, which supports the importance of adequate follow-up time as secondary caries often occurred after three years or later.


Asunto(s)
Resinas Compuestas , Caries Dental/terapia , Restauración Dental Permanente , Odontología Basada en la Evidencia , Humanos , Recurrencia , Factores de Tiempo
14.
RSC Adv ; 14(8): 5461-5471, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38352690

RESUMEN

Though significant advances have been made in developing therapeutic strategies for cancer, suitable in vitro models for mechanistically identifying relevant drug targets and understanding disease progression are still lacking. Most studies are generally performed using two-dimensional (2D) models, since these models can be readily established and allow high throughput assays. However, these models have also been reported as the reason for unreliable pre-clinical information. To avoid this discrepancy, three-dimensional (3D) cell culture models have been established and have demonstrated the potential to provide alternative ways to study tissue behavior. However, most of these models first require optimization and cell cultures with a certain density, thus adding a prepping step in the platform before it can be used for any studies. This limits their use in studies where the fundamental understanding of biological processes must be carried out in a short time frame. In this study, we developed a 3D cell culture system that tests a less explored cancer therapeutic target-the deubiquitinating enzyme ubiquitin specific peptidase 37 (USP37)-in different cancer cell lines using sensitive carbon dot pH nanosensors, which provides a rapid model for studies compared to the parallel model available commercially. This enzyme is found to be elevated in different cancers and has been reported to play a role in cell cycle regulation, oncogenesis and metastasis. However, the confirmation of the role of USP37 downregulation in cellular proliferation via appropriate in vitro 3D models has not been demonstrated. To establish the applicability of the developed 3D platform in studying such oncogenes, classical 2D models have been used in this study for identifying the role of USP37 in tumor progression and metastasis. The data clearly suggests that this ingeniously developed 3D cell culture system is a better alternative to 2D models to study the growth and migration of different cancer cell lines on depletion of oncogenic proteins like USP37 and its effect on epithelial-mesenchymal transition (EMT) markers, and it can further be targeted as a viable therapeutic option.

15.
Sci Rep ; 14(1): 15287, 2024 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961106

RESUMEN

Cervical cancer is still the leading cause of cancer mortality worldwide even after introduction of vaccine against Human papillomavirus (HPV), due to low vaccine coverage, especially in the developing world. Cervical cancer is primarily treated by Chemo/Radiotherapy, depending on the disease stage, with Carboplatin/Cisplatin-based drug regime. These drugs being non-specific, target rapidly dividing cells, including normal cells, so safer options are needed for lower off-target toxicity. Natural products offer an attractive option compared to synthetic drugs due to their well-established safety profile and capacity to target multiple oncogenic hallmarks of cancer like inflammation, angiogenesis, etc. In the current study, we investigated the effect of Bergenin (C-glycoside of 4-O-methylgallic acid), a natural polyphenol compound that is isolated from medicinal plants such as Bergenia crassifolia, Caesalpinia digyna, and Flueggea leucopyrus. Bergenin has been shown to have anti-inflammatory, anti-ulcerogenic, and wound healing properties but its anticancer potential has been realized only recently. We performed a proteomic analysis of cervical carcinoma cells treated with bergenin and found it to influence multiple hallmarks of cancers, including apoptosis, angiogenesis, and tumor suppressor proteins. It was also involved in many different cellular processes unrelated to cancer, as shown by our proteomic analysis. Further analysis showed bergenin to be a potent-angiogenic agent by reducing key angiogenic proteins like Galectin 3 and MMP-9 (Matrix Metalloprotease 9) in cervical carcinoma cells. Further understanding of this interaction was carried out using molecular docking analysis, which indicated MMP-9 has more affinity for bergenin as compared to Galectin-3. Cumulatively, our data provide novel insight into the anti-angiogenic mechanism of bergenin in cervical carcinoma cells by modulation of multiple angiogenic proteins like Galectin-3 and MMP-9 which warrant its further development as an anticancer agent in cervical cancer.


Asunto(s)
Benzopiranos , Proliferación Celular , Galectina 3 , Metaloproteinasa 9 de la Matriz , Neoplasias del Cuello Uterino , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Benzopiranos/farmacología , Femenino , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Galectina 3/metabolismo , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Galectinas/metabolismo , Galectinas/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Apoptosis/efectos de los fármacos , Células HeLa , Proteínas Sanguíneas
17.
Rev Bras Ortop (Sao Paulo) ; 58(2): 211-221, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37252308

RESUMEN

Objective Extended curettage with adjuvants of giant cell tumors of bone is associated with a lower rate of recurrence of the tumor while preserving the adjacent joint. The present study was conducted to estimate the recurrence rate and functional outcome after using argon beam as an adjuvant for extended curettage. Methods We selected 50 patients with giant cell tumors, meeting all the inclusion criteria, who underwent extended curettage using high speed burr and argon beam photocoagulation between July 2016 to January 2019. On their follow-up visit, they were assessed for any complaints of pain and signs like tenderness, locally raised temperature, and decreased range of motion of the adjacent joint. Radiologically, the patients were assessed for any increased lucency around the cement mantle and uptake of the subarticular graft. Musculoskeletal Tumor Society Score (MSTS) was administered to the patients, and range of motion of the adjacent joint was compared with the contralateral joint. Results Recurrence was found in 4 patients, that is, an 8% recurrence rate. Twenty-six out of 28 patients with a tumor in the lower limb had a grade-5 weight bearing status 6 months from the surgery, and their range of motion was comparable to contralateral healthy joint with an average MSTS score of 27 (18-30). Conclusion Extended curettage of giant cell tumors using argon beam coagulation is associated with low recurrence rates of the tumor and is an effective modality in the treatment of these tumors besides having a functional outcome comparable to the healthy limb.

18.
Adv Protein Chem Struct Biol ; 135: 21-55, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37061333

RESUMEN

Regulated cell division is one of the fundamental phenomena which is the basis of all life on earth. Even a single base pair mutation in DNA leads to the production of the dysregulated protein that can have catastrophic consequences. Cell division is tightly controlled and orchestrated by proteins called cyclins and cyclin-dependent kinase (CDKs), which serve as licensing factors during different phases of cell division. Dysregulated cell division is one of the most important hallmarks of cancer and is commonly associated with a mutation in cyclins and CDKs along with tumor suppressor proteins. Therefore, targeting the component of the cell cycle which leads to these characteristics would be an effective strategy for treating cancers. Specifically, Cyclin-dependent kinases (CDKs) involved in cell cycle regulation have been identified to be overexpressed in many cancers. Many studies indicate that oncogenesis occurs in cancerous cells by the overactivity of different CDKs, which impact cell cycle progression and checkpoint dysregulation which is responsible for development of tumor. The development of CDK inhibitors has emerged as a promising and novel approach for cancer treatment in both solid and hematological malignancies. Some of the novel CDK inhibitors have shown remarkable results in clinical trials, such as-Ribociclib®, Palbociclib® and Abemaciclib®, which are CDK4/6 inhibitors and have received FDA approval for the treatment of breast cancer. In this chapter, we discuss the molecular mechanism through which cyclins and CDKs regulate cell cycle progression and the emergence of cyclins and CDKs as rational targets in cancer. We also discuss recent advances in developing CDK inhibitors, which have emerged as a novel class of inhibitors, and their associated toxicities in recent years.


Asunto(s)
Neoplasias de la Mama , Quinasas Ciclina-Dependientes , Humanos , Femenino , Ciclo Celular , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Ciclinas
19.
Indian J Ophthalmol ; 70(11): 3879-3882, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36308119

RESUMEN

Purpose: Comparative study of intraoperative and postoperative complications, visual outcomes, and cost-effectiveness between conventional and 4-mm manual small-incision cataract surgery with MVR blade. Methods: In total, 600 patients having nuclear sclerosis grade I-IV were operated under peribulbar anesthesia and were divided into two groups of 300 each. In group A (300), conventional small-incision cataract surgery was done, whereas in group B (300), 4-mm manual small-incision cataract surgery was performed through a 4-mm sclerocorneal tunnel. A wire vectis was passed through the 4-mm incision below the nucleus to stabilize it, and a 20-G MVR blade was introduced from 11o'clock limbus and nucleus was bisected into two halves, which were removed through main incision. Cortical wash was given, and foldable IOL was implanted. Intraoperative and postoperative complications between the two groups were compared. Postoperative visual outcome and surgically induced astigmatism between the two groups was studied. Results: The most common intraoperative complication was hyphema (11.33%) and irido-dialysis (8.00%), whereas postoperatively, striate keratopathy (36.33%) and hyphema (19.33%) were common. Short-term complications such as striate keratopathy, hyphema, and irido-dialysis were significantly more in group B, and long-term results in terms of visual outcome and surgically induced astigmatism were significantly less in group B. Conclusion: Although intraoperative and short-term postoperative complications were observed more in 4-mm manual small-incision cataract surgery, it was found to be more effective in terms of surgically induced astigmatism and final visual outcome. In addition, it is cost-effective as compared to phacoemulsification.


Asunto(s)
Astigmatismo , Extracción de Catarata , Catarata , Herida Quirúrgica , Humanos , Astigmatismo/etiología , Implantación de Lentes Intraoculares/métodos , Hipema , Extracción de Catarata/efectos adversos , Catarata/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Herida Quirúrgica/complicaciones
20.
Curr Drug Deliv ; 18(6): 825-832, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33267762

RESUMEN

INTRODUCTION: In the working age population, Diabetic Macular Edema (DME) is the most common cause of visual loss. PURPOSE: The present study is aimed to assess the safety and efficacy of intravitreal injection of Ranibizumab (IVR) versus intravitreal Dexamethasone implant (IVD) in patients with DME in a tertiary care centre upto 4 months. METHODS: This is a comparative, prospective, randomized study that was done on 140 patients with macular edema confirmed on optical coherence tomography (OCT). IVD group received Ozurdex® (Allergan, Inc, Ireland) while the IVR group received Lucentis® (Novartis, Basel, Switzerland); the groups were followed up at day-1 and weeks 4, 8, 12, 16. Patients were divided into Group A, in which patients were given 3 doses (monthly) of IVR 0.3 mg in 0.05 ml (n=70). Group B patients were given a single dose of IVD implant 0.7 mg (n=70). RESULTS: The mean number of injections given was 1 Ozurdex® per patient vs. 3 Lucentis® per patient. The maximum reduction in central macular thickness (CMT) with IVD was 167.8 µm and 138.8µm in the 2nd and 3rd months, respectively, with IVR. The mean best-corrected visual acuity (BCVA) in the 4th month was 0.34 logMAR and 0.33 logMAR, in IVD and IVR groups, respectively, with consistent improvement. Patients with 0-5 letters, 6-10 letters and 10-15 letters, and >15 letters visibility in IVD group were 9.5, 20.6, 4.8, 6.4%, and 20.4, 18.8, 20.3 20.3% in IVR groups, respectively. The maximum intraocular pressure (IOP) rise with IVD was found to be 16 mmHg in 2 patients (3.17%). IOP rise >10 mmHg was observed in 14/63 patients (22.22%); the majority of patients indicated a high rise at 2nd month with all returning to baseline by 4th month. No reports of infectious endophthalmitis or new cataracts were detected in either of the treated groups. CONCLUSION: Both intravitreal Ranibizumab injection and Dexamethasone implants were found to be safe and effective in lowering CMT and improving BCVA at the 4-month follow up in patients with DME. Since there was no recurrence of CMT in the Dexamethasone implant group, we suggest that early administration before the 4th month may indicate superior efficacy over the ranibizumab injection. Further randomized trials in a large sample size with a longer period follow- up would be performed to justify the obtained results in the present study.


Asunto(s)
Dexametasona/administración & dosificación , Retinopatía Diabética , Inyecciones Intravítreas , Edema Macular , Ranibizumab/administración & dosificación , Dexametasona/uso terapéutico , Diabetes Mellitus , Retinopatía Diabética/tratamiento farmacológico , Implantes de Medicamentos/uso terapéutico , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Humanos , Edema Macular/tratamiento farmacológico , Estudios Prospectivos , Ranibizumab/uso terapéutico , Resultado del Tratamiento , Agudeza Visual
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