Search Results for: Raccomandazioni cliniche per il melanoma cutaneo

Introduction
Long-term population-based safety studies, applying advanced causal inference techniques, including an active comparator with new-user design, are needed to investigate skin cancer outcomes among individuals with multiple sclerosis (MS) treated with fingolimod. This study aims to describe a protocol for investigating the relationship between fingolimod use and the incidence of skin cancer among individuals with MS.

Methods and analysis
We will use population-based administrative health data from two Canadian provinces (British Columbia and Alberta) to conduct an observational cohort ‘trial emulation’ study with an active comparator and new-user design. Individuals with MS aged ≥18 years will be identified using a validated algorithm. Incident users of fingolimod and active comparators (natalizumab, alemtuzumab, dimethyl fumarate, teriflunomide) will then be identified. The outcome of interest will be skin cancer (melanoma and non-melanoma skin cancers). Survival analysis will be used to estimate HRs and corresponding 95% CIs, adjusted for potential confounders.

Ethics and dissemination
Ethics approval for this study was obtained from the University of British Columbia Clinical Research Ethics Board (H24-03199). No personal identifying information will be made available as part of this study. Findings will be disseminated through presentations and peer-reviewed publications.

Trial registration number
NCT06705608.

Rallenta la ricerca sui farmaci in Italia che con le sperimentazioni cliniche – passate nel 2023 a 611 dalle 663 dell’anno prima (-7,8%) – muove ogni anno 700-800 milioni di…

Ascierto, il 50% dei pazienti metastatici sopravvive a 10 anni dalla diagnosi

Introduction
The sun is one of the primary natural sources of ultraviolet radiation (UVR) and a known human carcinogen. It has been related to melanoma and several skin cancers, such as squamous cell carcinoma and basal cell carcinoma. Non-melanoma skin cancers are prevalent in South Africa, with high reported incidence rates in both genders. Due to its diversified population, South Africa experiences extreme ultraviolet index (UVI) levels, reaching 13 in the summer (a UVI of 11+ is considered extreme). Most summer workdays expose outdoor workers to repeated UVR exposure, which can lead to health risks like sunburn, premature ageing, cataracts, and an increased risk of skin cancer. This study aims to evaluate UV radiation exposure among outdoor military workers.

Methods and analysis
A cross-sectional quantitative study will occur at the Lohatla military base in Kathu, Northern Cape province of South Africa, using personal electronic dosimeters for solar UVR assessment. Additionally, a self-administered questionnaire will assist in assessing health effects and perceived exposure behaviours. The study addresses a critical public health concern, exploring significant risks associated with UVR exposure among outdoor military workers across different demographics.

Ethics and dissemination
The ethical approval for this study was obtained from the Health Sciences Research Committees of the University of Free State (UFS-HSD2023/1227/2811). The confidential data will be accessed by the named researchers and stored in secure password-protected platforms. In addition, the findings will be disseminated through high-impact publications in various formats to government departments and the broader scientific community.

New England Journal of Medicine, Volume 392, Issue 1, Page 81-82, January 2, 2025.

Introduction
A diagnosis of melanoma in situ presents negligible risk to a person’s lifespan or physical well-being, but existing terminology makes it difficult for patients to distinguish these from higher risk invasive melanomas. This study aims to explore whether using an alternative label for melanoma in situ may influence patients’ management choices and anxiety levels.

Methods and analysis
This study is a between-subjects randomised online experiment, using hypothetical scenarios. Following consent, eligible participants will be randomised 1:1:1 to three labels: ‘melanoma in situ’ (control), ‘low-risk melanocytic neoplasm’ (intervention 1) and ‘low-risk melanocytic neoplasm, in situ’ (intervention 2). The required sample size is 1668 people. The co-primary outcomes are (1) choice between no further surgery or further surgery to ensure clear histological margins greater than 5 mm and (2) choice between patient-initiated clinical follow-up when needed (patient-led surveillance) and regular routinely scheduled clinical follow-up (clinician-led surveillance). Secondary outcomes include diagnosis anxiety, perceived risk of invasive melanoma and of dying from melanoma and management choice anxiety (after surgery choice and follow-up choice). We will make pairwise comparisons across the three diagnostic label groups using regression models (univariable and multivariable).

Ethics and dissemination
The study has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12624000740594). Ethics approval has been received from The University of Sydney Human Research Ethics Committee (2024/HE000019). The results of the study will be published in a peer-reviewed medical journal, and a plain language summary of the findings will be shared on the Wiser Healthcare publication page (https://www.wiserhealthcare.org.au/category/publications/).

Trial registration number
Australian New Zealand Clinical Trials Registry (ID 386943).

Objective
Fat mass and obesity-associated protein (FTO), an eraser of N 6-methyadenosine (m6A), plays oncogenic roles in various cancers. However, its role in hepatocellular carcinoma (HCC) is unclear. Furthermore, small extracellular vesicles (sEVs, or exosomes) are critical mediators of tumourigenesis and metastasis, but the relationship between FTO-mediated m6A modification and sEVs in HCC is unknown.

Design
The functions and mechanisms of FTO and glycoprotein non-metastatic melanoma protein B (GPNMB) in HCC progression were investigated in vitro and in vivo. Neutralising antibody of syndecan-4 (SDC4) was used to assess the significance of sEV-GPNMB. FTO inhibitor CS2 was used to examine the effects on anti-PD-1 and sorafenib treatment.

Results
FTO expression was upregulated in patient HCC tumours. Functionally, FTO promoted HCC cell proliferation, migration and invasion in vitro, and tumour growth and metastasis in vivo. FTO knockdown enhanced the activation and recruitment of tumour-infiltrating CD8+ T cells. Furthermore, we identified GPNMB to be a downstream target of FTO, which reduced the m6A abundance of GPNMB, hence, stabilising it from degradation by YTH N 6-methyladenosine RNA binding protein F2. Of note, GPNMB was packaged into sEVs derived from HCC cells and bound to the surface receptor SDC4 of CD8+ T cells, resulting in the inhibition of CD8+ T cell activation. A potential FTO inhibitor, CS2, suppresses the oncogenic functions of HCC cells and enhances the sensitivity of anti-PD-1 and sorafenib treatment.

Conclusion
Targeting the FTO/m6A/GPNMB axis could significantly suppress tumour growth and metastasis, and enhance immune activation, highlighting the potential of targeting FTO signalling with effective inhibitors for HCC therapy.

Several studies have highlighted the significance of targeting fat mass and obesity-associated protein (FTO) in gastrointestinal cancers including hepatocellular carcinoma (HCC) .1 The recent study from the group of Irene Oi-Lin Ng presented in Gut by Chen et al2 introduces new insights into the molecular dynamics of HCC, focusing on the pivotal role of FTO in the disease’s pathophysiology. Functioning as an eraser of N6-methyladenosine (m6A), FTO modulates RNA stability and translation. In the context of HCC, FTO’s activity leads to the stabilisation of oncogenic transcripts, thereby promoting cancer cell proliferation and survival.3 The study identifies glycoprotein non-metastatic melanoma protein B (GPNMB) as a downstream effector of FTO (figure 1). By diminishing the m6A modification on GPNMB, FTO enhances its stability, thereby protecting it from YTHDF2-mediated degradation. This stabilisation facilitates the incorporation of GPNMB into small extracellular vesicles (sEVs), which are…

Ascierto, +25% di sopravvivenza in forme malattia avanzate

Ascierto, ‘dai raggi solari ci si deve difendere anche in inverno’