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1.
Ann Med Surg (Lond) ; 86(2): 689-696, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38333329

RESUMO

Background: The authors systematically appraise a large database of continuous professional development (CPD) and continuous medical education (CME) events against the European Accreditation Council for Continuous Medical Education (EACCME) framework. Methods: The authors performed a retrospective observational study of all CPD or CME events within the European Union of Medical Specialists (UEMS) database between 2017 and 2019, including 91 countries and 6034 events. Assessment of event design, quality and outcomes was evaluated against a validated, expert-derived accreditation framework, using thematic analysis to extract distinct themes, and subsequent quantitative analysis. Results: The authors included 5649 live educational events (LEEs) and 385 e-learning materials (ELMs). Three thousand seven hundred sixty-two [3762 (62.3%)] of the events did not report clear justification in their needs assessment process. Most accreditation applications claimed covering a single educational need [1603/2277 (70.3%)]. Needs assessments were reported to be similar across conferences, courses and other types of events (P<0.01); 5642/6034 events (93.5%) had clearly documented expected learning outcomes; only 978/6034 (16.2%) reported a single expected learning outcome while the rest report 2-10 outcomes. Providers who declared more than one educational need also declared multiple learning outcomes (ρ=0.051, P<0.01). Conclusions: Despite EACCME providing a robust framework for the CPD/CME accreditation process, reporting quality can still be improved, as more than 1 in 2 events fail to provide a clear description of their needs assessment. To the authors' knowledge, this is the largest educational LEE/ELM database, which can be a starting to revisit the CME/CPD accreditation process.

2.
Cancer Diagn Progn ; 4(1): 1-8, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38173660

RESUMO

In the past decade, immune checkpoint inhibitors (ICIs) have entered the treatment landscape of non-small-cell lung cancer, signalling a paradigm shift within the field characterized by significant survival benefits for patients with advanced and metastatic disease, and especially those with non-targetable genetic oncogenic driver mutations. However, the shift towards immune-based treatments has created new challenges in oncology. Atypical immunotherapy response patterns, including pseudo-progression and hyperprogressive disease, as well as immune-related adverse events have generated the need for new methods to predict patient response to treatment. Hence, new versions of the traditional Response Evaluation Criteria for Solid Tumors (RECIST) have emerged to help characterise with better accuracy radiological findings concerning patient response classification to immunotherapy. This review discusses response evaluation criteria relevant to unique radiological findings observed in patients treated with immunotherapy for non-small-cell lung cancer.

3.
Epigenomics ; 15(10): 593-613, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37535320

RESUMO

Aim: This study aimed to critically appraise the evidence of the diagnostic effectiveness of miRNAs for the detection of cervical cancer. Methods & materials: A systematic review and meta-analysis was performed, searching PubMed, EMBASE and Web of Science. An umbrella meta-analysis of meta-analyses of individual biomarkers was performed. A Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment of evidence was also performed. Results: A total of 52 miRNAs were included. Umbrella meta-analysis revealed significant heterogeneity in terms of sensitivity, specificity, receiver operating characteristic (ROC), positive predictive value and/or negative predictive value. Umbrella effects were 0.76 (95% CI: 0.73-0.78), 0.78 (95% CI: 0.75-0.81), 0.77 (95% CI: 0.75-0.80), 0.75 (95% CI: 0.71-0.79) and 0.76 (95% CI: 0.74-0.79), respectively. Conclusion: Moderate quality evidence suggested miR199a-5p, miR21-5p and miR-141a had excellent diagnostic performance.


miRNAs are small chemical messengers that play a role in the regulation of protein produced inside the cytoplasm of cells, including cancer cells. In cervical cancer cells, miRNAs become dysregulated ­ that is, their levels become increased or decreased ­ and therefore detecting their relative abundance or absence in test samples may enable identification of cervical cancer. This study aimed to systematically collect and appraise the evidence for the diagnostic ability of miRNAs for detection of cervical cancer. A systematic appraisal of the evidence was conducted by searching three research databases (PubMed, EMBASE and Web of Science) to collect evidence published up to 13 November 2022. Results for diagnostic performance of 52 miRNAs were extracted from 20 relevant studies. An assessment of risk of bias for each study was performed using a standardized checklist, which identified one high-quality study, 18 moderate-quality studies and one low-quality study. Results for each individual biomarker were assessed by meta-analytic methods, which generated weighted averages for 38 of 52 miRNAs. All 52 miRNAs were then compared using an umbrella meta-analysis (a weighted average of all miRNA biomarkers), which identified significant differences in diagnostic ability between miRNAs. Sensitivity analyses suggested that these differences were partly explained by differences in grades of cervical cancer and differences in types of sample used for testing. A GRADE assessment of the overall evidence quality suggested that moderate-quality evidence supported further investigation of three miRNA biomarkers (miR-199a-5p, miR-21-5p and miR-141a), which performed excellently (i.e., better than the umbrella weighted average) across five performance parameters, including sensitivity, specificity, receiver operator characteristic, positive predictive value and negative predictive value. In summary, this study suggested miR-199a-5p, miR-21-5p and miR-141a had excellent diagnostic performance for detection of cervical cancer and recommends further investigation of these miRNAs in randomized controlled trials.


Assuntos
MicroRNAs , Neoplasias do Colo do Útero , Feminino , Humanos , MicroRNAs/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Biomarcadores , Curva ROC , Biomarcadores Tumorais/genética
4.
Eur J Surg Oncol ; 49(4): 682-687, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36646615

RESUMO

BACKGROUND: Tumors of mixed neuroendocrine and nonneuroendocrine histology are classified as collision, combined, or amphicrine and can occur in most organs, including the hepato-pancreato-biliary tract. Given the rarity of mixed adenoneuroendocrine carcinoma (MANEC) of the ampulla of Vater, the patient characteristics, management, and outcomes remain unclear. We sought to systematically review the worldwide literature on ampullary MANECs. METHODS: Eligible studies were identified through a systematic search of the MEDLINE (via PubMed), Scopus, and Cochrane Library databases (end-of-search-date: January 5th, 2022), according to the PRISMA 2020 statement. RESULTS: A total of 39 studies reporting on 56 patients with ampullary MANEC were included. The median age was 63.0 (interquartile range [IQR]: 51.0-69.0) years and 55.6% were male (n = 25/45). Most had combined tumors (64.4%; n = 29/45), followed by collision (24.4%; n = 11/45), and amphicrine tumors (11.1%; n = 5/45). More than half had lymph node metastasis (56.8%; n = 25/44), yet only 7.9% had distant metastasis (n = 3/38). Tumor resection (i.e., mostly pancreaticoduodenectomy) was performed in 96.3% (n = 52/54), followed by adjuvant chemotherapy in 61.8% (n = 21/34). Nearly half experienced disease recurrence (47.2%; n = 17/36) over a median follow-up of 12.0 (IQR: 3.0-16.0) months, and 42.1% (n = 16/38) died over a median follow-up of 12.0 (IQR: 4.0-18.0) months. The most common cause of death was disease progression/recurrence in 81.3% (n = 13/16). CONCLUSION: Early diagnosis and management of ampullary MANEC is challenging yet crucial to improve outcomes since many patients are diagnosed at an advanced disease stage and have unfavorable outcomes. Multicenter granular data are warranted to further understand and improve outcomes in these patients.


Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Carcinoma Neuroendócrino , Neoplasias do Ducto Colédoco , Neoplasias Gastrointestinais , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Ampola Hepatopancreática/patologia , Recidiva Local de Neoplasia/patologia , Adenocarcinoma/patologia , Pancreaticoduodenectomia , Neoplasias Gastrointestinais/patologia , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias do Ducto Colédoco/diagnóstico , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/diagnóstico , Estudos Multicêntricos como Assunto
5.
Future Oncol ; 18(29): 3349-3365, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36172856

RESUMO

Cytokines are soluble proteins that mediate intercellular signaling regulating immune and inflammatory responses. Cytokine modulation represents a promising cancer immunotherapy approach for immune-mediated tumor regression. However, redundancy in cytokine signaling and cytokines' pleiotropy, narrow therapeutic window, systemic toxicity, short half-life and limited efficacy represent outstanding challenges for cytokine-based cancer immunotherapies. Recently, there has been interest in the paradoxical role of IL-10 in cancer, its controversial prognostic utility and novel strategies to enhance its therapeutic profile. Here, the authors review the literature surrounding the role of IL-10 within the tumor microenvironment, its prognostic correlates to cancer patient outcomes and its pro- and antitumor effects, and they assess the legitimacy of potential therapeutic strategies harnessing IL-10 by outlining the notable preclinical and clinical evidence to date.


Assuntos
Interleucina-10 , Neoplasias , Humanos , Imunoterapia , Inflamação , Interleucina-10/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Microambiente Tumoral
6.
Epigenomics ; 14(18): 1055-1072, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36169190

RESUMO

Background: The aim of this systematic review and meta-analysis was to assess the evidence for the diagnostic effectiveness of human papillomavirus (HPV) methylation biomarkers for detection of cervical cancer. Methods: PubMed, Embase and Web of Science were searched. Nine articles focusing on HPV methylation for detection of precancerous and cancerous cervical lesions were included. The QUADAS-2 tool was used for quality assessment. The receiver operating characteristic (ROC) was the main diagnostic performance parameter extracted. Results: Of the nine articles included in this study, seven were of moderate quality and two were of high quality. A meta-analysis of the ROC for 27 HPV methylation biomarkers revealed an overall pooled ROC of 0.770 (95% CI: 0.720-0.819; I2: 98.4%; Q: 1537.4; p < 0.01). Four methylation biomarkers had strong diagnostic ability (ROC > 0.900), 17 were moderate (ROC: 0.7000-0.8999) and six were poor (ROC < 0.700). Conclusion: HPV methylation biomarkers hold significant promise as independent screening tests for the detection of cervical precancerous and cancerous lesions.


This study reviewed the literature to assess the available evidence for the ability of biomarkers based on human papillomavirus (HPV) methylation (i.e., the detection of methyl groups in HPV DNA in cervical specimens) to screen for cervical precancerous and cancerous lesions. Scientific databases were searched, and abstracts screened for relevance. The quality of the included articles was assessed using a quality assessment tool called QUADAS-2. The main diagnostic performance parameter extracted from the included articles was the receiver operating characteristic (ROC), a measure of the ability of a biomarker to detect all true cases (true positives) while excluding all true non-cases (true negatives). After screening, nine articles were included, of which seven were of moderate quality and two were of high quality. ROC data were extracted for 27 biomarkers, of which four methylation biomarkers had high diagnostic ability (i.e., ROC > 0.900), 17 had moderate diagnostic ability (ROC: 0.7000­0.8999) and six had low diagnostic ability (ROC < 0.700). An umbrella meta-analysis (i.e., a weighted-average ROC for all HPV methylation biomarkers) revealed an ROC consistent with moderate diagnostic ability (0.770). The main conclusion from this study was that HPV methylation biomarkers, especially ones with high diagnostic ability, hold significant promise as independent screening tests for the detection of cervical precancerous and cancerous lesions.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Lesões Pré-Cancerosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Biomarcadores , Detecção Precoce de Câncer , Feminino , Humanos , Metilação , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Displasia do Colo do Útero/diagnóstico
7.
World J Clin Oncol ; 13(6): 448-472, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35949435

RESUMO

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. HCC is an inflammation-associated immunogenic cancer that frequently arises in chronically inflamed livers. Advanced HCC is managed with systemic therapies; the tyrosine kinase inhibitor (TKI) sorafenib has been used in 1st-line setting since 2007. Immunotherapies have emerged as promising treatments across solid tumors including HCC for which immune checkpoint inhibitors (ICIs) are licensed in 1st- and 2nd-line treatment setting. The treatment field of advanced HCC is continuously evolving. Several clinical trials are investigating novel ICI candidates as well as new ICI regimens in combination with other therapeutic modalities including systemic agents, such as other ICIs, TKIs, and anti-angiogenics. Novel immunotherapies including adoptive cell transfer, vaccine-based approaches, and virotherapy are also being brought to the fore. Yet, despite advances, several challenges persist. Lack of real-world data on the use of immunotherapy for advanced HCC in patients outside of clinical trials constitutes a main limitation hindering the breadth of application and generalizability of data to this larger and more diverse patient cohort. Consequently, issues encountered in real-world practice include patient ineligibly for immunotherapy because of contraindications, comorbidities, or poor performance status; lack of response, efficacy, and safety data; and cost-effectiveness. Further real-world data from high-quality large prospective cohort studies of immunotherapy in patients with advanced HCC is mandated to aid evidence-based clinical decision-making. This review provides a critical and comprehensive overview of clinical trials and real-world data of immunotherapy for HCC, with a focus on ICIs, as well as novel immunotherapy strategies underway.

8.
Cancer Genomics Proteomics ; 19(4): 390-414, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35732328

RESUMO

Brain tumours are the leading cause of paediatric cancer-associated death worldwide. High-grade glioma (HGG) represents a main cause of paediatric brain tumours and is associated with poor prognosis despite surgical and chemoradiotherapeutic advances. The molecular genetics of paediatric HGG (pHGG) are distinct from those in adults, and therefore, adult clinical trial data cannot be extrapolated to children. Compared to adult HGG, pHGG is characterised by more frequent mutations in PDGFRA, TP53 and recurrent K27M and G34R/V mutations on histone H3. Ongoing trials are investigating novel targeted therapies in pHGG. Promising results have been achieved with BRAF/MEK and PI3K/mTOR inhibitors. Combination of PI3K/mTOR, EGFR, CDK4/6, and HDAC inhibitors are potentially viable options. Inhibitors targeting the UPS proteosome, ADAM10/17, IDO, and XPO1 are more novel and are being investigated in early-phase trials. Despite preclinical and clinical trials holding promise for the discovery of effective pHGG treatments, several issues persist. Inadequate blood-brain barrier penetration, unfavourable pharmacokinetics, dose-limiting toxicities, long-term adverse effects in the developing child, and short-lived duration of response due to relapse and resistance highlight the need for further improvement. Future pHGG management will largely depend on selecting combination therapies which work synergistically based on a sound knowledge of the underlying molecular target pathways. A systematic investigation of multimodal therapy with chemoradiotherapy, surgery, target agents and immunotherapy is paramount. This review provides a comprehensive overview of pHGG focusing on molecular genetics and novel targeted therapies. The diagnostics, genetic discrepancies with adults and their clinical implications, as well as conventional treatment approaches are discussed.


Assuntos
Neoplasias Encefálicas , Glioma , Adulto , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Criança , Glioma/tratamento farmacológico , Glioma/genética , Histonas , Humanos , Biologia Molecular , Fosfatidilinositol 3-Quinases/metabolismo
9.
Epigenomics ; 14(11): 699-709, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35574589

RESUMO

Cancer epigenetic mechanisms support the acquisition of hallmark characteristics during oncogenesis. EZH2 - an important histone methyltransferase that writes histone H3 lysine 27 trimethylation marks - is known to be dysregulated in cancer cells. However, the interactions between EZH2 and miRNAs that form a complex network of cross-talk and reciprocal regulation that enable cancer cells to acquire hallmark characteristics have been relatively poorly appreciated. The specific functions of EZH2 appear to be regulated by a vast array of miRNAs, which direct EZH2 toward regulation over the development of specific hallmark characteristics. This review discusses recent advances in the understanding of EZH2, focusing on its collaboration with miRNAs to orchestrate oncogenesis. These epigenetic processes promote the evasion of apoptosis/cell cycle arrest, cellular dedifferentiation and the establishment of a tumor microenvironment that facilitates local cancer cell invasion, anti-cancer drug resistance and evasion of the immune response.


Cancer epigenetics involves cellular processes that ensure that gene expression changes that enable cancer cells to outcompete their neighboring normal tissues are passed on from one cancer cell to the next. One key epigenetic player is called EZH2, which is an enzyme that transfers methyl (CH3) groups from donor molecules to the histone proteins around which DNA is coiled. The transfer of methyl groups to histones ­ a process called histone methylation ­ silences the production of proteins from the genes coded in DNA. To achieve this goal, EZH2 is directed to affect specific genes through interactions with other molecules consisting of short sequences of RNA (a molecule similar in structure to DNA). The specific RNA molecules in question are called miRNAs or non-coding RNAs. These EZH2/miRNA interactions form a complex web of circuits that enables cancer cells to gain characteristics that give them a competitive advantage over their normal tissue neighbors. This review discusses recent advances in the understanding of the role of EZH2 in cancer formation, focusing on the interactions it has with miRNAs (and other non-coding RNAs) to organize many different processes linked with cancer formation. These processes include the avoidance of cell death or cell growth arrest, the development of stem cell properties and the formation of an environment around tumor cells that allows them to invade adjacent normal tissue (i.e., metastasize) and avoid being killed by anti-cancer drugs and the immune system.


Assuntos
MicroRNAs , Carcinogênese , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Histona Metiltransferases , Histonas , Humanos , MicroRNAs/genética , Microambiente Tumoral
10.
J Cancer Educ ; 37(4): 1053-1065, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33242159

RESUMO

The mounting global cancer burden has generated an increasing demand for oncologists to join the workforce. Yet, students report limited oncology exposure in undergraduate medical curricula, while undergraduate oncology mentorships remain underutilised. We established an undergraduate oncology society-led mentorship programme aimed at medical students across several UK universities to increase medical student oncology exposure. We electronically recruited and paired oncologist mentors and medical student mentees and distributed a dedicated questionnaire (pre- and post-mentorship) to compare mentees' self-reported cancer specialty knowledge and oncology career motivation after undertaking a 6-week mentorship. We also determined students' interest across specialties and subspecialties and measured mentor availability via percentage programme uptake. Statistical analysis included univariate inferential tests on SPSS software. Twentynine (23.4%) of 124 oncology specialists agreed to become mentors. The mentorship was completed by 30 students across three medical schools: 16 (53.3%) Barts, 10 (33.3%) Birmingham, and 4 (13.3%) King's; 11 (36.7%) mentored by medical oncologists, 10 (33.3%) by clinical/radiation oncologists, and 9 (30%) by surgical oncologists. The mentorship generated a statically significant increase in students' knowledge of the multidisciplinary team and all oncology-related specialties including academia/research but not interest towards a career in oncology. Undergraduate oncology mentoring is an effective educational, networking and motivational tool for medical students. Student societies are a valuable asset in cultivating medical student oncology interest by connecting students to faculty and increasing mentor accessibility. Further research should focus on developing an optimal mentorship structure and evaluating long-term outcomes of such educational initiatives.


Assuntos
Tutoria , Estudantes de Medicina , Humanos , Oncologia , Mentores , Faculdades de Medicina
12.
Front Immunol ; 12: 737862, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777347

RESUMO

Background: Several studies report the role of Regulatory T-cells (Tregs) in the pathophysiology of pregnancy adverse outcomes. Objective: The aim of this systematic review and meta-analysis was to determine whether there is an association between regulatory T cell levels and pregnancy adverse outcomes (PAOs), including pre-eclampsia and preterm birth (PTB). Method: Literature searches were conducted in PubMed/MEDLINE, Embase, and Cochrane CENTRAL databases. Inclusion criteria were original articles (clinical trials, case-control studies and cohort studies) comparing Tregs, sampled from the decidua or maternal blood, in healthy pregnant women versus women with pre-eclampsia or PTB. The outcome was standardised mean difference (SMD) in Treg numbers. The tau-squared (Tau²), inconsistency index (I²), and chi-squared (χ²) test quantified heterogeneity among different studies. Analyses were performed in RevMan software V.5.4.0 for Mac using a random-effects model with outcome data reported with 95% confidence intervals (CI). This study was prospectively registered with PROSPERO (CRD42020205469). PRISMA guidelines were followed. Results: From 4,085 unique studies identified, 36 were included in qualitative synthesis, and 34 were included in quantitative synthesis (meta-analysis). In total, there were 1,783 participants in these studies: healthy controls=964, pre-eclampsia=759, PTB=60. Thirty-two studies compared Tregs in healthy pregnant women and women with pre-eclampsia, and 30 of these sampled Tregs from peripheral blood showing significantly higher Treg numbers in healthy pregnancies (SMD; 1.46; 95% CI, 1.03-1.88; I²=92%). Four studies sampled Tregs from the maternal decidua showing higher Tregs in healthy pregnancies (SMD, 0.76; 95% CI, -0.13-1.65; I²=84%). No difference was found in the number of Tregs between early versus late pre-eclampsia (SMD,-1.17; 95% CI, -2.79-0.44; I²=94%). For PTB, two studies compared Tregs sampled from the peripheral blood with a tendency for higher Tregs in healthy pregnancies but this did not reach significance (SMD, 2.18; 95% CI, -1.34-5.70; I²=96%). Subcohort analysis using Treg analysis (flow cytometry vs. qPCR vs. immunofluorescence tissue staining) showed similar associations. Conclusion: Lower Tregs in pregnancy, sampled from the maternal peripheral blood, are associated with pre-eclampsia. There is a need for further studies to confirm a relationship between low Tregs and PTB. As the precise mechanisms by which Tregs may mediate pre-eclampsia and PTB remain unclear, further fundamental research is necessary to elucidate the underlying processes and highlight the causative link. Systematic Review Registration: PROSPERO, identifier CRD42020205469.


Assuntos
Complicações na Gravidez/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Contagem de Linfócito CD4 , Feminino , Humanos , Fenótipo , Valor Preditivo dos Testes , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/fisiopatologia , Resultado da Gravidez , Medição de Risco , Fatores de Risco , Linfócitos T Reguladores/metabolismo
14.
Adv Med Educ Pract ; 12: 995-1002, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512069

RESUMO

An increasing emphasis on simulation has become evident in the last three decades following fundamental shifts in the medical profession. Simulation-based learning (SBL) is a wide term that encompasses several means for imitating a skill, attitude, or procedure to train personnel in a safe and adaptive environment. A classic example has been the use of live animal tissue, named in vivo SBL. We aimed to review all published evidence on in vivo SBL for undergraduate medical students; this includes both teaching concepts as well as focused assessment of students on those concepts. We performed a systematic review of published evidence on MEDLINE. We also incorporated evidence from a series of systematic reviews (eviCORE) focused on undergraduate education which have been outputs from our dedicated research network (eMERG). In vivo SBL has been shown to be valuable at undergraduate level and should be considered as a potential educational tool. Strict adherence to 3R (Reduce, Refine, Replace) principles in order to reduce animal tissue usage, should always be the basis of any curriculum. In vivo SBL could potentially grant an extra mile towards medical students' inspiration and aspiration to become safe surgeons; however, it should be optimised and supported by a well-designed curriculum which enhances learning via multi-level fidelity SBL.

16.
Anticancer Res ; 41(7): 3247-3252, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230118

RESUMO

Cancer immunotherapy is an evolving field of research. Cytokines have been conceptualized as an anticancer therapy for longer than most other cancer immunotherapy modalities. Yet, to date, only two cytokines are FDA-approved: IFN-α and IL-2. Despite the initial breakthrough, both agents have been superseded by other, more efficacious agents such as immune checkpoint inhibitors. Several issues persist with cytokine-based cancer therapies; these are broadly categorised into a) high toxicity and b) low efficacy. Despite the only moderate benefits with early cytokine-based cancer therapies, advances in molecular engineering, genomics, and molecular analysis hold promise to optimise and reinstate cytokine-based therapies in future clinical practice. This review considers five important concepts for the successful clinical application of cytokine-based cancer therapies including: (i) improving pharmacokinetics and pharmacodynamics, (ii) improving local administration strategies, (iii) understanding context-dependent interactions in the tumour-microenvironment, (iv) elucidating the role of genetic polymorphisms, and (v) optimising combination therapies. IL-10 has been the focus of attention in recent years and is discussed herein as an example.


Assuntos
Citocinas/farmacologia , Citocinas/uso terapêutico , Interleucina-10/farmacologia , Interleucina-10/uso terapêutico , Neoplasias/imunologia , Neoplasias/terapia , Animais , Humanos , Imunoterapia/métodos , Polimorfismo Genético/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
17.
Eur Urol Focus ; 7(4): 717-721, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33994170

RESUMO

T-cell immunotherapy and molecular targeted therapies have become standard-of-care treatments for renal cell carcinoma (RCC). There is a need to develop robust biomarkers that predict patient outcomes to targeted therapies to personalise treatment. In recent years, quantitative analysis of imaging features, termed radiomics, has been used to extract tumour features. This narrative mini review summarises the evidence for radiomics prediction of immunotherapy and molecular targeted therapy outcomes in RCC. Radiomics may predict survival, treatment response, and disease progression in RCC treated with tyrosine kinase inhibitors (eg, sunitinib) and immune checkpoint inhibitors (eg, nivolumab). Further validation is necessary in large-scale studies. PATIENT SUMMARY: We summarise evidence on the ability of features extracted from CT (computed tomography) scans to predict patient outcomes from new treatments for kidney cancer. Although these features can predict treatment outcomes for patients, including survival, treatment response, and cancer progression, further research is necessary before this technology can be applied clinically.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/terapia , Humanos , Imunoterapia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Nivolumabe , Tomografia Computadorizada por Raios X/métodos
18.
Anticancer Res ; 41(3): 1123-1141, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788704

RESUMO

Haematology has been at the vanguard of cancer immunotherapy. Immune checkpoint inhibitors (ICIs), bispecific T-cell engagers (BiTEs), allogeneic haematopoietic stem cell transplantation (allo-HSCT) and donor lymphocyte infusion (DLI), as well as adoptive T-cell therapies outside the setting of allo-HSCT, have been approved for distinct haematologic malignancies producing durable responses in otherwise untreatable patients. Despite recent advances, immunotherapies do not benefit most patients, due to resistance or lack of response, and are only approved in specific settings. Moreover, immunotherapies are expensive and may produce severe immune related adverse reactions. Combination therapy complicates the picture and requires further evaluation. This review considers the current status and future perspectives of ICIs and BiTEs approved for haematological malignancies by analysing their strengths, weaknesses, opportunities and threats (SWOT). The biological rationale for anti-cancer mechanisms, clinical data for specific haematological cancers, efficacy, toxicity, response and resistance profiles, novel strategies to improve these characteristics as well as the potential targets to enhance or expand the application of ICIs and BiTEs are also discussed.


Assuntos
Anticorpos Biespecíficos/imunologia , Neoplasias Hematológicas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Linfócitos T/imunologia , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/uso terapêutico , Antígeno CTLA-4/fisiologia , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/farmacologia , Receptor de Morte Celular Programada 1/fisiologia
19.
Anticancer Res ; 41(3): 1143-1156, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788705

RESUMO

Haematology has been at the forefront of cancer immunotherapy advancements. Allogeneic haematopoietic stem cell transplant (allo-HSCT) is one of the earliest forms of cancer immunotherapy and continues to cure thousands of patients. Donor lymphocyte infusion (DLI) increases allo-HSCT efficacy and reduces graft-versus-host disease (GVHD). In recent years, chimeric antigen receptor (CAR)-T-cells have been approved for the treatment of distinct haematologic malignancies, producing durable response in otherwise untreatable patients. New target antigen identification and technological advances have enabled the structural and functional evolution of CARs, broadening their applications. Despite successes, adoptive T-cell (ATC) therapies are expensive, can cause severe adverse reactions and their use is restricted to few patients. This review considers the current status and future perspectives of allogeneic transplant and donor lymphocytes, as well as novel ATC therapies, such as CAR-T-cells in haematological malignancies by analysing their strengths, weaknesses, opportunities, and threats (SWOT). The biological rationale for anti-cancer mechanisms and development; current clinical data in specific haematological malignancies; efficacy, toxicity, response and resistance profiles; novel strategies to improve these characteristics; and potential targets to enhance or expand the application of these therapies are discussed.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Imunoterapia Adotiva/métodos , Imunoterapia/métodos , Linfócitos T/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos CD19/uso terapêutico , Produtos Biológicos , Humanos , Imunoterapia Adotiva/efeitos adversos , Transfusão de Linfócitos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/imunologia , Doadores de Tecidos
20.
BMC Med Educ ; 21(1): 82, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33530974

RESUMO

BACKGROUND: One in 2 people born in the UK after 1960 are expected to require oncology input in their lifetime. However, only 36% of UK medical schools provide dedicated oncology placements and teaching indicating a discordance between public health impact and training. We designed a UK-wide survey to capture medical students' views on current oncology teaching and the potential role of a national undergraduate oncology symposium as an educational, networking and motivational tool. METHODS: We undertook a national cross-sectional survey of UK medical students' views in oncology and satisfaction with teaching using pre-designed questionnaires. We also distributed a dedicated survey (pre and post-conference) to compare medical students' motivation towards a career in oncology after attending the national symposium. This study was prospectively approved by QMUL Ethics Committee (Reference number QMREC2348). Statistical analysis included univariate inferential tests on SPSS and GraphPad software. RESULTS: The national survey was completed by 166 students representing 22 UK medical schools. Students reported limited interest, knowledge and exposure to oncology, lack of confidence in skills, and teaching dissatisfaction. Oncology was perceived as a challenging specialty (mean 4.5/5 ± 0.7), yet most students estimate receiving only 1-2 weeks of dedicated oncology teaching. The national symposium generated a statically significant increase in students' interest, knowledge, and confidence in skills surrounding oncology, improving students' perceived ability to cope with the emotional challenges in this field. CONCLUSION: Students' views towards oncology alongside their teaching dissatisfaction underpin the need to revisit and strive to improve current undergraduate oncology curricula. Increasing medical student oncology exposure by proposing outcome-based guidelines and adopting a standardised undergraduate oncology curriculum should be the foremost priority in inspiring future oncologists to ensure excellent cancer patient care.


Assuntos
Educação de Graduação em Medicina , Oncologistas , Estudantes de Medicina , Estudos Transversais , Currículo , Humanos , Responsabilidade Social , Inquéritos e Questionários , Reino Unido
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