Risultati per: L’inibizione di un enzima uccide selettivamente le cellule di melanoma

To the Editor We read the work of Pellacani et al with great interest. They reported the effects of adjunct reflectance confocal microscopy (RCM) in equivocal lesions for the diagnosis of melanoma in a prospective, multicenter randomized clinical trial against standard therapeutic care, which comprised either immediate excision or digital dermoscopy follow-up (DDF) after clinical and dermoscopic evaluation. They showed that RCM halved the number needed to excise.

This case report describes an ulcerated, erythematous, and hyperpigmented periurethral nodule with surrounding irregular macular hyperpigmentation.

Introduction
The benefits of patient-reported feedback, using questionnaires that allow patients to report how they feel and function without any interpretation from healthcare professionals, are well established. However, patient-reported outcomes measures (PROMs) are not routinely collected in patients with melanoma in Australia. The aim of this study is to evaluate the feasibility and acceptability of implementing electronic PROMs (ePROMs) into routine care from the perspectives of patients with stage III melanoma and their treating clinical team.

Methods and analysis
A minimum of 50 patients and 5 clinicians will be recruited to this prospective, longitudinal pilot study (ePROMs-MELanoma). The study uses a mixed-methods approach (quantitative PROMs questionnaires and end-of-study surveys with qualitative interviews) and commenced in May 2021 in surgical and medical melanoma clinics at two sites in metropolitan Sydney, Australia. The primary outcomes are measures of feasibility and acceptability, comprising descriptive questionnaire completion statistics, and proportion of patients who reported that these PROMs were easy to complete and measured items they considered important. Clinician and clinic staff views will be canvassed on the appropriateness of these PROMs for their patients, change in referral practice and uptake and incorporation into routine practice. Secondary aims include measurement of improvements in patients’ emotional and physical health and well-being, and utility of real-time data capture and clinician feedback. All participants will complete the Distress Thermometer and EQ-5D-5L questionnaires in the clinic using a tablet computer at baseline and two to three subsequent follow-up appointments. Participants who report a score of 4 or higher on the Distress Thermometer will be triaged to complete an additional three questionnaires: the QLQ-C30, Depression, Anxiety and Stress Scale and Melanoma Concerns Questionnaire-28. Results will be generated in real time; patients with psychosocial distress or poor quality of life will discuss possible referral to appropriate allied health services with their clinician. Thematic analysis of interviews will be conducted.

Ethics and dissemination
Ethics approval obtained from St Vincent’s Hospital Human Research Ethics Committee on 19 September 2019 (2019/ETH10558), with amendments approved on 8 June 2022. Patient consent is obtained electronically prior to questionnaire commencement. Dissemination strategies will include publication in peer-reviewed journals and presentation at international conferences, tailored presentations for clinical societies and government bodies, organisational reporting through multidisciplinary meetings and research symposia for local clinicians and clinic staff, and more informal, lay reports and presentations for consumer melanoma representative bodies and patient participants and their families.

Trial registration number
ACTRN12620001149954.

Vaccini in sviluppo ma ancora in fase iniziale sperimentazione

New England Journal of Medicine, Volume 387, Issue 23, Page 2113-2125, December 2022.

This cohort study investigates the association among different immunosuppressive regimens for grade 3 and higher immune-related adverse events with overall survival and progression-free survival in a homogeneous cohort of patients with advanced melanoma who were treated with first-line ipilimumab and nivolumab.

This cohort study aims to identify lifetime trajectories of sunburns and compare the association between these trajectories and subsequent risk of cutaneous melanoma and squamous cell carcinoma.

This economic evaluation aims to determine the cost-effectiveness of ipilimumab discontinuation for patients with interim imaging-confirmed tumor response in the treatment of advanced melanoma.

To the Editor We agree with the title of the Editorial by Swerlick, but it omits the considerable efforts to mount a randomized clinical trial in Australia. We assessed melanoma screening in 1992, recommending a randomized clinical trial at ages 45 to 69 years to assess mortality. Subsequently, a similar trial based on whole-body examinations by primary care practitioners (PCPs) was proposed. A pilot phase showing that screening increased enough to allow detection of a 20% reduction in mortality over 15 years was reported in 2002. The trial cost approximately $8.4 million; after national and international peer review, the research costs were approved, which were approximately half the total. However, the other costs, including payments to PCPs for the screening examinations, were not funded. Thus, the full trial was not conducted.

In Reply I thank Elwood et al for highlighting their previous efforts to develop more robust evidence to guide melanoma screening efforts. However, their work found similar findings as Matsumoto et al, with increased thin melanoma ascertainment in patients who had undergone screening skin examinations. While they modeled possible associations with mortality based on thickness data, their work did not look at actual mortality, either all cause or melanoma related.

This cross-sectional ecological study assesses the association of proxies for UV radiation exposure and diagnostic scrutiny with geographical patterns of melanoma incidence in the US.

Circulation, Volume 146, Issue Suppl_1, Page A15638-A15638, November 8, 2022. Epidemiological studies have shown that the incidence of various cancers, such as malignant melanoma is higher in patients with heart failure (both HFrEF and HFpEF) than in age-matched population, but the underlying mechanisms remain unknown. We hypothesized that in HFpEF a chronic systemic inflammation promotes malignant melanoma progression. To test this hypothesis orthotopic melanoma xenograft model was employed in a mouse model of HFpEF. Mice with uninephrectomy, aldosterone infusion (UNX-Aldo) with osmotic minipump (Alzet, 0.30 μg/h), and high salt ingestion (1% in drinking water) develop left ventricle diastolic dysfunction as indicated by a significantly (p

Circulation, Volume 146, Issue Suppl_1, Page A11801-A11801, November 8, 2022. Introduction:The accumulation of senescent cells during aging relates to the development of various age-related pathologies including atherosclerosis and heart failure, which can be improved by specific elimination of senescent cells, so called “senolysis”. We have identified glycoprotein nonmetastatic melanoma protein B (GPNMB) as an antigen specifically expressed by senescent endothelial cells, so called “seno-antigen”. Also, we previously developed the vaccine against Gpnmb, eliminated senescent cells in mice, leading to an improvement of age-related pathologies. However, detailed function of GPNMB in senescent cells is still uncertain.Purpose:To elucidate the role of GPNMB in senescent cells and cardiovascular-related pathologies.Methods:Overexpression or depletion of GPNMB in endothelial cells (ECs) were generated. Cellular senescence was induced in ECs by doxorubicin. Gpnmb-knockout or overexpressed (Gp-KO or Gp-OE) mice were generated and imposed to hind-limb ischemia treatment or high-fat-diet feeding to evaluate vascular functions. Double transgenic mice (ApoE-KO and Gp-KO or Gp-OE) were also generated and imposed to high-fat diet to develop atherosclerosis.Results:The depletion of GPNMB in ECs was proved to shorten their replicative lifespan, and increase the expression of negative cell cycle regulators including p53, p21 and p16. Conversely, overexpressed GPNMB protected ECs from senescence stress.In vivostudies showed the impairment of vascular function, atherogenesis, and endothelium-dependent vasodilatation were enhanced in Gp-KO mice, but attenuated in Gp-OE mice. Furthermore, GPNMB was found to localize on lysosomal membrane. Cells with depleted GPNMB demonstrated the accumulation of dysfunctional lysosomes, indicated the contribution of GPNMB in maintaining lysosome integrity. Under senescence-associated lysosomal stress, elevated GPNMB expression was detected, contributing to senescent cells survival.Conclusions:GPNMB acts as a protective factor to senescent cells. Seno-antigen targeting GPNMB is possibly considered as an efficient strategy against cardiovascular diseases and other age-associated disorders with higher selectivity and fewer off-target effects.

Speranze dalle terapie cellulari, presto sperimentazioni su uomo