mRNA export and cancer

This PhD focuses on the relationship between mRNA export and cancer

E-cigarettes and urologic health: a collaborative review of toxicology, epidemiology, and potential risks

Context: Use of electronic cigarettes (ECs) is on the rise in most high-income countries. Smoking conventional cigarettes is a known risk factor for urologic malignancy incidence, progression, and mortality, as well as for other urologic health indicators. The potential impact of EC use on urologic health is therefore of clinical interest to the urology community. Objective: To review the available data on current EC use, including potential benefits in urologic patients, potential issues linked to toxicology of EC constituents, and how this might translate into urologic health risks. Evidence acquisition: A Medline search was carried out in August 2016 for studies reporting urologic health outcomes and EC use. Snowballing techniques were also used to identify relevant studies from recent systematic reviews. A narrative synthesis of data around EC health outcomes, toxicology, and potential use in smoking cessation and health policy was carried out. Evidence synthesis: We found no studies to date that have been specifically designed to prospectively assess urologic health risks, even in an observational setting. Generating such data would be an important contribution to the debate on the role of ECs in public health and clinical practice. There is evidence from a recent Cochrane review of RCTs that ECs can support smoking cessation. There are emerging data indicating that potentially harmful components of ECs such as tobacco-specific nitrosamines, polyaromatic hydrocarbons, and heavy metals could be linked to possible urologic health risks. Conclusions: ECs might be a useful tool to encourage cessation of conventional cigarette smoking. However, data collection around the specific impact of ECs on urologic health is needed to clarify the possible patient benefits, outcomes, and adverse events. Patient summary: While electronic cigarettes might help some people to stop smoking, their overall impact on urologic health is not clear. While electronic cigarettes might help some people to stop smoking, it is not clear if they may be bad for urologic health

Luzp4 defines a new mRNA export pathway in cancer cells

Cancer testis antigens (CTAs) represented a poorly characterized group of proteins whose expression is normally restricted to testis but are frequently up-regulated in cancer cells. Here we show that one CTA, Luzp4, is an mRNA export adaptor. It associates with the TREX mRNA export complex subunit Uap56 and harbours a Uap56 binding motif, conserved in other mRNA export adaptors. Luzp4 binds the principal mRNA export receptor Nxf1, enhances its RNA binding activity and complements Alyref knockdown in vivo. Whilst Luzp4 is up-regulated in a range of tumours, it appears preferentially expressed in melanoma cells where it is required for growth

Orchidopexy for Testicular Torsion : A Systematic Review of Surgical Technique

Peer reviewedPostprin

Influência da incorporação da HAp e β-TCP no cimento ósseo wollastonita/ brushita

O elevado número de pacientes com problemas de saúde por doenças ósseas ou traumas tem promovido o desenvolvimentode pesquisas em biomateriais de modo a garantir uma melhor qualidade de vida. Dentre os diversosbiomateriais, os cimentos ósseos poliméricos (PMMA) ou cerâmicos (fosfatos e silicatos de cálcio) destacam-se para aplicações em cirurgias ortopédicas e odontológicas, tais como: reconstrução óssea, artoplastia.Diante do exposto o objetivo da pesquisa foi avaliar a influência da incorporação de fosfatos de cálcio (β-TCP(amostra 1 - A1) e hidroxiapatita – HAp (amostra 2 – A2) na proporção de 2% (m/m) para a formação de cimentoósseo de silicato de cálcio (wollastonita/brushita) pelo método de dissolução/precipitação. A mistura dopó (wollastonita) foi homogeneizada, posteriormente uma solução de ácido fosfórico adicionada para formaçãodo cimento ósseo, foram colocadas em um molde de teflon baseado com a norma ABNT NBR ISO 5833, e finalmentedeixados a 25ºC por 24 horas obtendo os corpos de prova. A análise por DRX das amostras indicarama presença das fases cristalinas do fosfato de cálcio (β-TCP e HAp) e silicato de cálcio (wollastonita e Brushita).As imagens das amostras por MEV apresentaram tamanho de partículas características da wollastonita/brushita/HAp/β-TCP. Foi realizado uma análise granulométrica a partir das micrografias, onde se observouque a incorporação dos fosfatos influencio na aglomeração dos tamanhos das partículas quando comparados aocimento ósseo puro. O ensaio de compressão indica que a incorporação dos fosfatos melhora a propriedade mecânica,devido à redução das partículas o qual provoca uma maior compactação. Conclui-se que a A2 com aincorporação da HAp essa melhora da resistência mecânica foi mais intensa em relação a A1, no entanto, àsduas amostras tiveram melhorias significativas em comparação ao cimento ósseo de silicato de cálcio.Palavras-chave: Cimento ósseo. Brushita. Hidroxiapatita. β-TCP. Wollastonita

Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors

CONTEXT Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external and internal factors) contribute significantly to the development of BC. Therefore, establishing a clear understanding of these risk factors is the key to prevention. OBJECTIVE To perform an up-to-date systematic review of BC's epidemiology and external risk factors. EVIDENCE ACQUISITION Two reviewers (I.J. and S.O.) performed a systematic review using PubMed and Embase in January 2022 and updated it in September 2022. The search was restricted to 4 yr since our previous review in 2018. EVIDENCE SYNTHESIS Our search identified 5177 articles and a total of 349 full-text manuscripts. GLOBOCAN data from 2020 revealed an incidence of 573 000 new BC cases and 213 000 deaths worldwide in 2020. The 5-yr prevalence worldwide in 2020 was 1 721 000. Tobacco smoking and occupational exposures (aromatic amines and polycyclic aromatic hydrocarbons) are the most substantial risk factors. In addition, correlative evidence exists for several risk factors, including specific dietary factors, imbalanced microbiome, gene-environment risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. CONCLUSIONS We present a contemporary overview of the epidemiology of BC and the current evidence for BC risk factors. Smoking and specific occupational exposures are the most established risk factors. There is emerging evidence for specific dietary factors, imbalanced microbiome, gene-external risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. Further high-quality evidence is required to confirm initial findings and further understand cancer prevention. PATIENT SUMMARY Bladder cancer is common, and the most substantial risk factors are smoking and workplace exposure to suspected carcinogens. On-going research to identify avoidable risk factors could reduce the number of people who get bladder cancer

Diagnosis, treatment, and survival from kidney cancer: real‐world National Health Service England data between 2013 and 2019

Objectives: To report the NHS Digital (NHSD) data for patients diagnosed with kidney cancer (KC) in England. We explore the incidence, route to diagnosis (RTD), treatment, and survival patterns from 2013 to 2019. Materials and Methods: Data was extracted from the Cancer Data NHSD portal for International Classification of Diseases, 10th edition coded KC; this included Cancer Registry data, Hospital Episode Statistics, and cancer waiting times data. Results: Registrations included 66 696 individuals with KC. Incidence of new KC diagnoses increased (8998 in 2013, to 10 232 in 2019), but the age‐standardised rates were stable (18.7–19.4/100 000 population). Almost half of patients (30 340 [45.5%]) were aged 0–70 years and the cohort were most frequently diagnosed with Stage 1–2 KC (n = 26 297 [39.4%]). Most patients were diagnosed through non‐urgent general practitioner referrals (n = 16 814 [30.4%]), followed by 2‐week‐wait (n = 15 472 [28.0%]) and emergency routes (n = 11 796 [21.3%]), with older patients (aged ≥70 years), Stage 4 KCs, and patients with non‐specified renal cell carcinoma being significantly more likely to present through the emergency route (all P < 0.001). Invasive treatment (surgery or ablation), radiotherapy, or systemic anti‐cancer therapy use varied with disease stage, patient factors, and treatment network (Cancer Alliance). Survival outcomes differed by Stage, histological subtype, and social deprivation class (P < 0.001). Age‐standardised mortality rates did not change over the study duration, although immunotherapy usage is likely not captured in this study timeline. Conclusion: The NHSD resource provides useful insight about the incidence, diagnostic pathways, treatment, and survival of patients with KC in England and a useful benchmark for the upcoming commissioned National Kidney Cancer Audit. The RTD data may be limited by incidental diagnoses, which could confound the high proportion of ‘emergency’ diagnoses. Importantly, survival outcomes remained relatively unchanged

Diagnosis, treatment and survival from bladder, upper urinary tract and urethral cancers: Real world findings from NHS England between 2013 and 2019

Objective We report NHS England data for patients with bladder cancer (BC), upper tract urothelial cancer (UTUC: renal pelvic and ureteric), and urethral cancers from 2013 to 2019. Materials and Methods Hospital episode statistics, waiting times, and cancer registrations were extracted from NHS Digital. Results Registrations included 128 823 individuals with BC, 16 018 with UTUC, and 2533 with urethral cancer. In 2019, 150 816 persons were living with a diagnosis of BC, of whom 113 067 (75.0%) were men, 85 117 (56.5%) were aged >75 years, and 95 553 (91.7%) were Caucasian. Incidence rates were stable (32.7–34.3 for BC, 3.9–4.2 for UTUC and 0.6–0.7 for urethral cancer per 100 000 population). Most patients 52 097 (mean [range] 41.3% [40.7–42.0%]) were referred outside the 2-week-wait pathway and 15 340 (mean [range] 12.2% [11.7–12.6%]) presented as emergencies. Surgery, radiotherapy, chemotherapy, or multimodal treatment use varied with disease stage, patient factors and Cancer Alliance. Between 27% and 29% (n = 6616) of muscle-invasive BCs did not receive radical treatment. Survival rates reflected stage, grade, location, and tumour histology. Overall survival rates did not improve over time (relative change: 0.97, 95% confidence interval 0.97–0.97) at 2 years in contrast to other cancers. Conclusion The diagnostic pathway for BC needs improvement. Increases in survival might be delivered through greater use of radical treatment. NHS Digital data offers a population-wide picture of this disease but does not allow individual outcomes to be matched with disease or patient features and key parameters can be missing or incomplete

A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer

CONTEXT: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain.OBJECTIVE: To perform a systematic review to determine the benefits and harms of EBRT-BT.EVIDENCE ACQUISITION: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs).EVIDENCE SYNTHESIS: Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p &lt; 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs.CONCLUSIONS: EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control.PATIENT SUMMARY: We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.</p