Gene Therapy for Malignant and Benign Gynaecological Disorders: A Systematic Review of an Emerging Success Story.
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ABSTRACT:
SUBMITTER: Drakopoulou E
PROVIDER: S-EPMC9265289 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chemoimmunotherapy has been the standard of care for patients with chronic lymphocytic leukemia (CLL) over the last decade. Advances in monoclonal antibody technology have resulted in the development of newer generations of anti-CD20 antibodies with improved therapeutic effectiveness. In parallel, our knowledge about the distinctive biological characteristics of CLL has progressively deepened and has revealed the importance of B-cell receptor (BCR) signaling and upregulated antiapoptotic proteins for survival and expansion of malignant cell clones. This knowledge provided the basis for development of novel targeted agents that revolutionized treatment of CLL. Ibrutinib and idelalisib inhibit the Bruton tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) delta, respectively, thus interfering with supportive signals coming from the microenvironment via the BCR. These drugs induce egress of CLL cells from secondary lymphoid organs and remarkably improve clinical outcomes, especially for patients with unmutated immunoglobulin heavy-chain genes or with p53 abnormalities that do not benefit from classical treatment schemes. Latest clinical trial results have established ibrutinib with or without anti-CD20 antibodies as the preferred first-line treatment for most CLL patients, which will reduce the use of chemoimmunotherapy in the imminent future. Further advances are achieved with venetoclax, a BH3-mimetic that specifically inhibits the antiapoptotic B-cell lymphoma 2 protein and thus causes rapid apoptosis of CLL cells, which translates into deep and prolonged clinical responses including high rates of minimal residual disease negativity. This review summarizes recent advances in the development of targeted CLL therapies, including new combination schemes, novel BTK and PI3K inhibitors, spleen tyrosine kinase inhibitors, immunomodulatory drugs, and cellular immunotherapy.
| S-EPMC6746030 | biostudies-literature
Project description:Chimeric antigen receptor (CAR) T cells are genetically engineered autologous cells that express an activating receptor targeted towards one or more tumoral antigens. After ex vivo production and re-infusion, they are able to proliferate in the host and to recognize and kill tumor cells. Together with checkpoint inhibition, this new therapy is already being celebrated as a major medical breakthrough in recent years, due to the substantial benefit observed in clinical trials with patients with chemotherapy-refractory B?cell malignancies. These results have led to the recent approval of two CAR T?cell products by the Food and Drug Administration (FDA) in the United States. The list of targetable antigens and possible indications is continuously being expanded, as are the modifications to the CAR structure and the final cell products currently under investigation. In some patients, CAR T?cell therapy may lead to substantial toxicity including the cytokine release syndrome (CRS). In summary, CAR T?cell therapy has already provided clinical benefit to patients with B?cell malignancies unresponsive to conventional treatment. Yet, the therapy is still in an early stage of development, and the many opportunities for improvement in its various aspects as well as its future role in relation to conventional therapy will set the pace in the field of hematology for the next years or even decades.
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Project description:Background: Eating disorders (EDs) during the transition to adulthood can derail social, psychological, and vocational development. Effective treatment is of paramount importance, yet young adults' treatment needs are typically less well met than those of adolescents. In recent years, there has been a considerable shift in how developmental psychologists understand the transition to adulthood, with this life-phase reconceptualized as "emerging adulthood" (EA) (~18-25 years). Engagement with burgeoning developmental research is likely key to providing more effective care for young people experiencing EDs. Aims: To review ED research which has utilized the concept of EA, and to assess the usefulness of this concept for ED research and practice. Methods: A systematic scoping review was conducted in accordance with the Joanna Briggs Institute guidelines for scoping reviews. Three databases (Psychinfo, PubMed, Embase) were searched for papers which explicitly focused on EDs during EA. No restrictions as to publication type, language, study design, or participants were applied. Included studies were assessed for developmental "informedness," and findings were qualitatively synthesized. Results: Thirty-six studies (N = 25,475) were included in the review. Most studies used quantitative methodologies, were cross-sectional in design and focused on identifying psychological and social factors which contribute to etiology of EDs. Many studies (N = 22) used well-defined samples of emerging adults (EAs); few studies (N = 8) included developmental measures relevant to EAs. Findings indicate that whilst factors implicated in EDs in adolescence and adulthood are relevant to EAs, EA-specific factors (e.g., identity exploration) may also contribute. Conventional ED services and treatments present difficulties for EAs, whilst those adapted to EAs' needs are feasible, acceptable, and more effective than treatment-as-usual. Directions for future research and clinical implications are discussed. Conclusion: Existing research indicates that the EA concept is relevant for understanding EDs during the transition to adulthood, and ED services should implement adaptations which exploit the opportunities and overcome the challenges of this developmental stage. EA is currently an underused concept in ED research, and future engagement with the developmental literature by both researchers and clinicians may be key to understanding and treating EDs during transition to adulthood.
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Project description:Background/aimThe insulin-like growth factor bioregulation system is implicated in cancer biology. Herein, we aim to review the evidence on the expression of the insulin-like growth factor 1 and 2 (IGF1 and IGF2), their receptors (IGF-Rs) and IGF-binding proteins (IGFBPs) in thyroid tissue and their possible association with benign and malignant thyroid nodular diseases.Materials and methodsWe systematically reviewed Pubmed and Scopus databases up to May 2020. A total of 375 articles were retrieved and analyzed.ResultsAmong 375 articles, 45 were included in this systematic review study. IGF1 was investigated in 31 studies, IGF2 in 1, IGF1 receptor in 15 and IGF-binding proteins in 13 articles. IGF1 expression in humans was dependent on the number and compound of benign nodules as well as the method of measurement. In differentiated thyroid carcinoma, a positive correlation between IGF1 and immunohistological stage was documented in some studies while in others only a positive trend was observed. IGF-1R and IGFBPs expression was higher in malignant rather than benign lesions. There was only a positive trend for increased IGF2 expression in malignancy, while IGFBPs were in most studies statistically increased in various cancer types compared to benign nodular disease.ConclusionThe present data demonstrate that in most studies there is statistically positive expression of IGF-1 and less of IGF-2 in thyroid cancer compared to normal thyroid tissue.
| S-EPMC7811675 | biostudies-literature
Project description:ObjectivesThe use of magnetic resonance (MR) imaging in differentiation between benign and malignant adnexal masses in children and adolescents might be of great value in the diagnostic workup of sonographically indeterminate masses, since preserving fertility is of particular importance in this population. This systematic review evaluates the diagnostic value of MR imaging in children with an ovarian mass.MethodsThe review was made according to the PRISMA Statement. PubMed and EMBASE were systematically searched for studies on the use of MR imaging in differential diagnosis of ovarian masses in both adult women and children from 2008 to 2018.ResultsSixteen paediatric and 18 adult studies were included. In the included studies, MR imaging has shown good diagnostic performance in differentiating between benign and malignant ovarian masses. MR imaging techniques including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging seem to further improve the diagnostic performance.ConclusionThe addition of DWI with apparent diffusion coefficient (ADC) values measured in enhancing components of solid lesions and DCE imaging may further increase the good diagnostic performance of MR imaging in the pre-operative differentiation between benign and malignant ovarian masses by increasing specificity. Prospective age-specific studies are needed to confirm the high diagnostic performance of MR imaging in children and adolescents with a sonographically indeterminate ovarian mass.Key points• MR imaging, based on several morphological features, is of good diagnostic performance in differentiating between benign and malignant ovarian masses. Sensitivity and specificity varied between 84.8 to 100% and 20.0 to 98.4%, respectively. • MR imaging techniques like diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging seem to improve the diagnostic performance. • Specific studies in children and adolescents with ovarian masses are required to confirm the suggested increased diagnostic performance of DWI and DCE in this population.
| S-EPMC6957553 | biostudies-literature
Project description:ObjectiveTo conduct a meta-analysis of the effectiveness of creative story therapy versus routine nursing alone for the treatment of dementia.MethodsWe manually searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China VIP Database (VIP), China Biomedical Literature Database (CBM), and Wanfang Data up to May 2023. Randomized controlled trials (RCTs) of creative story therapy combined with routine nursing versus routine nursing for the treatment of dementia were included.ResultsA total of 597 participants were enrolled in the 9 RCTs. Among them, 296 were in the creative story therapy group, and 301 were in the routine nursing group. We found statistically significant effects of creative story therapy combined with routine nursing on cognitive function [standardized mean difference (SMD) = 0.99, 95% CI 0.57, 1.41, P < 0.00001], CSDD score [mean difference (MD) = - 1.71, 95% CI - 3.27, - 0.14, P < 0.00001], quality of life [SMD = 0.97, 95% CI 0.04, 1.90, P = 0.04], and social communication [MD = 0.46, 95% CI 0.17, 0.74, P < 0.00001] between the creative story therapy group and routine nursing groups; no significant difference in change in basic needs communication [MD = 0.09, 95% CI - 0.58, 0.76, P < 0.00001].ConclusionThis meta-analysis shows that creative story therapy combined with routine nursing has significant effectiveness in improving cognitive function and depression in people with dementia. More high-quality RCTs are required to validate these results.
| S-EPMC10500921 | biostudies-literature
Project description:The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%-51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogenicity, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies.
| S-EPMC5187785 | biostudies-literature
Project description:ObjectivesTo systematically review the value of apparent diffusion coefficient (ADC) measurement in the differentiation between benign and malignant lesions.MethodsA systematic search of the Medline/Pubmed and Embase databases revealed 109 relevant studies. Quality of these articles was assessed using the Quality Assessment of the Studies of Diagnostic Accuracy Included in Systematic Reviews (QUADAS) criteria. Reported ADC values of benign and malignant lesions were compared per organ.ResultsThe mean quality score of the reviewed articles was 50%. Comparison of ADC values showed marked variation among studies and between benign and malignant lesions in various organs. In several organs, such as breast, liver, and uterus, ADC values discriminated well between benign and malignant lesions. In other organs, such as the salivary glands, thyroid, and pancreas, ADCs were not significantly different between benign and malignant lesions.ConclusionThe potential utility of ADC measurement for the characterisation of tumours differs per organ. Future well-designed studies are required before ADC measurements can be recommended for the differentiation of benign and malignant lesions. These future studies should use standardised acquisition protocols and provide complete reporting of study methods, to facilitate comparison of results and clinical implementation of ADC measurement for tumour characterisation.
| S-EPMC3481080 | biostudies-literature
Project description:This study aimed at evaluating hybrid multispectral optoacoustic tomography/ultrasound for imaging of thyroid disorders, including Graves' disease and thyroid nodules. Methods: The functional biomarkers and tissue parameters deoxygenated hemoglobin, oxygenated hemoglobin, total hemoglobin, saturation of hemoglobin, fat content, and water content were analyzed in thyroid lobes affected by Graves' disease (n = 6), thyroid lobes with healthy tissue (n = 8), benign thyroid nodules (n = 13), and malignant thyroid nodules (n = 3). Results: In Graves' disease, significantly higher deoxygenated hemoglobin (3.18 ± 0.52 vs. 2.13 ± 0.62; P = 0.0055) and total hemoglobin (8.34 ± 0.88 vs. 6.59 ± 1.16; P = 0.0084) and significantly lower fat content (0.64 ± 0.37 vs. 1.69 ± 1.25; P = 0.0293) were found than in healthy controls. Malignant thyroid nodules showed significantly lower saturation of hemoglobin (55.4% ± 2.6% vs. 60.8% ± 7.2%; P = 0.0393) and lower fat content (0.62 ± 0.19 vs. 1.46 ± 0.87; P = 0.1295) than benign nodules. Conclusion: This pilot study showed the applicability and the potential of hybrid multispectral optoacoustic tomography/ultrasound to semiquantitatively provide tissue characterization and functional parameters in thyroid disorders for improved noninvasive diagnostics of thyroid diseases.
| S-EPMC6785793 | biostudies-literature