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Background: Fibrosis is a pathological scarring process characterized by persistent myofibroblast activation with excessive accumulation of extracellular matrix (ECM). Fibrotic disorders represent an increasing burden of disease-associated morbidity and mortality worldwide for which there are limited therapeutic options. Reversing fibrosis requires the elimination of myofibroblasts, remodeling of the ECM, and regeneration of functional tissue. Multipotent mesenchymal stromal cells (MSC) have antifibrotic properties mediated by secreted factors present in their conditioned medium (MSC-CM). However, there are no standardized in vitro assays to predict the antifibrotic effects of human MSC. As a result, we lack evidence on the effect of cytokine priming on MSC's antifibrotic effects. We hypothesize that the MSC-CM promotes fibrosis resolution in vitro and that this effect is enhanced following MSC cytokine priming., Methods: We compared the antifibrotic effects of resting versus interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) primed MSC-CM in four in vitro assays: prevention of fibroblast activation, myofibroblasts deactivation, ECM degradation and fibrosis resolution in lung explant cultures. Furthermore, we performed transcriptomic analysis of myofibroblasts treated or not with resting or primed MSC-CM and proteomic characterization of resting and primed MSC-CM., Results: We isolated MSC from adipose tissue of 8 donors, generated MSC-CM and tested each MSC-CM independently. We report that MSC-CM treatment prevented TGF-β induced fibroblast activation to a similar extent as nintedanib but, in contrast to nintedanib, MSC-CM reduced fibrogenic myofibroblasts (i.e. transcriptomic upregulation of apoptosis, senescence, and inflammatory pathways). These effects were larger when primed rather than resting MSC-CM were used. Priming increased the ability of MSC-CM to remodel the ECM, reducing its content of collagen I and fibronectin, and reduced the fibrotic load in TGF-β treated lung explant cultures. Priming increased the following antifibrotic proteins in MSC-CM: DKK1, MMP-1, MMP-3, follistatin and cathepsin S. Inhibition of DKK1 reduced the antifibrotic effects of MSC-CM., Conclusions: In vitro, MSC-CM promote fibrosis resolution, an effect enhanced following MSC cytokine priming. Specifically, MSC-CM reduces fibrogenic myofibroblasts through apoptosis, senescence, and by enhancing ECM degradation. Future studies will establish the in vivo relevance of MSC priming to fibrosis resolution., (© 2024. The Author(s).)

Health care workers (HCWs) are at high risk for SARS-CoV-2. In addition, pre-symptomatic or asymptomatic transmission accounts for around half of the cases. Saliva testing is an option to detect SARS-CoV-2 infection. To determine the performance of saliva samples for screening, HCWs were tested for SARS-CoV-2 by RT-PCR. Those with a positive result in saliva were tested by nasopharyngeal swabbing for viral RNA detection and blood collection to search for the presence of specific antibodies. In September-October 2020, 100 HCWs were enrolled and followed up. Six subjects (6%) tested positive in saliva. Of them, 5/6 were positive in a subsequent nasopharyngeal swab and 4/6 developed signs and symptoms compatible with COVID-19. Among the latter, 3 seroconverted while asymptomatic HCWs remained seronegative. Saliva screening was helpful for identifying SARS-CoV-2 infection in HCWs. This screening permitted rapid personnel isolation avoiding further transmission of the virus in the hospital setting., (Copyright © 2022 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

The potential increased risk of immune-related adverse events (irAEs) post-influenza vaccine is a concern in patients receiving immune checkpoint inhibitors (ICI). We conducted a systematic review with meta-analysis of studies reporting the effects of influenza vaccination in patients with cancer during ICI treatment. We searched five electronic databases until 01/2022. Two authors independently selected studies, appraised their quality, and collected data. The primary outcome was the determination of pooled irAE rates. Secondary outcomes included determination of immunogenicity and influenza infection rates and cancer-related outcomes. Nineteen studies (26 publications, n = 4705) were included; 89.5% were observational. Vaccinated patients reported slighter lower rates of irAEs compared to unvaccinated patients (32% versus 41%, respectively). Seroprotection for influenza type A was 78%-79%, and for type B was 75%. Influenza and irAE-related death rates were similar between groups. The pooled proportion of participants reporting a laboratory-confirmed infection was 2% (95% CI 0% to 6%), and influenza-like illness was 14% (95% CI 2% to 32%). No differences were reported on the rates of laboratory-confirmed infection between vaccinated and unvaccinated patients. Longer progression-free and overall survival was also observed in vaccinated compared with unvaccinated patients. Current evidence suggests that influenza vaccination is safe in patients receiving ICIs, does not increase the risk of irAEs, and may improve survival.

Background: Cutaneous angiosarcoma (cAS) is a highly aggressive malignancy that challenges the radicality of surgical treatment. Electrochemotherapy (ECT), a skin-directed treatment based on cytotoxic chemotherapy combined with local electric pulses, may be an intraoperative adjunct and a new opportunity in the therapeutic strategy. This cohort study reports the experience with ECT as an option., Methods: Data on patients with locally-advanced/metastatic cAS who underwent ECT between October 2013 and October 2018 at eight European centres were prospectively submitted to the InspECT (International network for sharing practices of ECT) register. Patients received therapy according to the European Standard Operating Procedures of ECT (ESOPE). Treatment feasibility was assessed based on tumour coverage with electrodes and recorded tissue current; treatment toxicity and tumour response were graded according to CTCAE v5.0 and RECIST v1.1 criteria, respectively; patient-reported outcomes (PRO) were evaluated using a visual analogue score (VAS) for pain, acceptance of retreatment and the EQ-5D questionnaire., Results: We enrolled 20 patients with advanced cAS in the scalp/face (n = 7), breast/trunk (n = 10) or limbs (n = 3). Target tumours (n = 51) had a median size of 2.3 cm (range, 1-20). We administered 24 ECT courses using 1-4 cm treatment safety margin around tumours. In five patients, ECT was combined/sequenced with surgery. Median tissue current was 3 A (range, 1.5-10), tumour margins coverage rate was 75% (15/20 patients). The objective response rate (ORR) was 80% (complete, 40%). Grade-3 toxicity included skin ulceration (15%) and pain (10%), with no significant change of PRO scores. Bleeding control was achieved in 13/14 patients with ulcerated tumours. With a median overall survival of 12.5 months, the local progression-free survival (LPFS) was 10.9 months., Conclusion: ECT produces sustained response rate with minimal side effects and should be considered an option for advanced cAS. Palliative benefits include patient tolerability, local haemostasis and durable local control. Definition of optimal timing, treatment safety margins and combination with surgery need further investigation., (Copyright © 2019 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Metastatic extraorbital sebaceous carcinoma is a rare event that could involve the head and neck. The treatment of choice for the initial stage of the disease is surgery and/or radiotherapy. The treatment of recurrent or advanced disease is still controversial., Material and Methods: Extensive literature search was done, and the treatment options are discussed., Results: Results. The literature search found several treatment modalities in use for the treatment of metastatic extraorbital sebaceous carcinoma. Electrochemotherapy was not included in the reported treatments. We used this technique for a man of 85 years old with a recurrent and locally metastatic extraorbital sebaceous carcinoma of the scalp. During the period of 8 months, two sessions of electrochemotherapy were employed, which resulted in an objective response of the tumour and good quality of life., Conclusions: Electrochemotherapy has shown to be a interesting tools for treatment of metastatic extraorbital sebaceous carcinoma when other radical options are not available or convenient.

In patients with cancer, tumor- and treatment-induced immunosuppression are responsible for a four-fold increase in morbidity and mortality caused by influenza and invasive Streptococcus pneumoniae infections compared to the general population. The main oncology societies strongly recommend vaccination in patients with cancer to prevent these infections. However, vaccine hesitancy is a main concern in this population. The aim of this study was to assess the feasibility of in-hospital vaccination for patients under anticancer treatment and their family members (FMs) against influenza and pneumococcal infections during the COVID-19 pandemic in order to increase vaccine coverage. This was a single-center, prospective, observational study conducted at the Department of Oncology of Luigi Sacco University Hospital (Milan, Italy) between October 2020 and April 2021. The main primary outcome was the incidence of influenza-like illness (ILI) and pneumococcal infections. The main secondary outcome was safety. A total of 341 subjects were enrolled, including 194 patients with cancer and 147 FMs. The incidence of ILI was higher among patients than among FMs (9% vs. 2.7%, OR 3.92, p = 0.02). Moreover, two subjects were diagnosed with pneumococcal pneumonia. The most frequent vaccine-related AEs were pain in the injection site (31%) and fatigue (8.7%). In conclusion, this hospital-based vaccination strategy was feasible during the COVID-19 pandemic, representing a potential model to maximize vaccine coverage during a public health emergency. [ABSTRACT FROM AUTHOR]

Background: Migrants face barriers accessing healthcare, risking delays in cancer diagnosis. Diagnostic delays result in later stage diagnosis which is associated with poorer cancer survival. This review aims to compare the differences in cancer stage at diagnosis between migrants and non-migrants., Methods: We conducted a systematic review and meta-analysis of three databases from 2000 to 2023 for studies conducted in OECD countries that compared stage at diagnosis between migrants and non-migrants. Meta-analysis compared odds ratios (OR) for early (stage I and II) stage at diagnosis. The Risk of Bias in Non-randomised Studies of Exposure tool was used to assess study quality., Results: 41 of the 11,549 studies identified were included; 34 studies had suitable data for meta-analysis. Overall, migrants were significantly less likely to be diagnosed with early stage cancer compared with non-migrants (OR 0.84; 95% CI 0.78-0.91). This difference was maintained across cancer types, although only statistically significant for breast (OR 0.78; 95% CI 0.70-0.87) and prostate cancer (OR 0.92; 95% CI 0.85-0.99)., Discussion: Published studies indicate that migrants are less likely to be diagnosed with early stage cancer. Variation by cancer type, study location and region of origin highlights the need for further research to understand these differences., Competing Interests: Competing interests Harvey-Sullivan, Ali, Dhesi, and Painter are NIHR-funded academic clinical fellows. Otherwise, the authors declare no conflict of interest. Ethics approval and consent to participate Ethical approval was not requested because this study retrieved and synthesised data from already published studies., (© 2024. The Author(s).)

Electrochemotherapy is a novel, locoregional therapy that is used to treat cutaneous and deep-seated tumors. The electric pulses used in electrochemotherapy increase the permeability of the cell membranes of the target lesion and thus enhance the delivery of low-permeant cytotoxic drugs to the cells, leading to their death. It has also been postulated that electrochemotherapy acts as an in situ vaccination by inducing immunogenic cell death. This in turn leads to an enhanced systemic antitumor response, which could be further exploited by immunotherapy. However, only a few clinical studies have investigated the role of combined treatment in patients with melanoma, breast cancer, hepatocellular carcinoma, and cutaneous squamous cell carcinoma. In this review, we therefore aim to review the published preclinical evidence on combined treatment and to review clinical studies that have investigated the combined role of electrochemotherapy and immunotherapy. [ABSTRACT FROM AUTHOR]

Copyright of Estudios sobre el Mensaje Periodistico is the property of Universidad Complutense de Madrid and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Cutaneous squamous cell carcinoma (cSCC) is the second most frequent cancer in humans, and it is especially common in fragile, elderly people. Surgery is the standard treatment for cSCC but intralesional treatments can be an alternative in those patients who are either not candidates or refuse to undergo surgery. Classic intralesional treatments, including methotrexate or 5-fluorouracil, have been implemented, but there is now a landscape of active research to incorporate intralesional immunotherapy and oncolytic virotherapy into the scene, which might change the way we deal with cSCC in the future. In this review, we focus on intralesional treatments for cSCC (including keratoacanthoma), from classic to very novel strategies. Cutaneous squamous cell carcinoma (cSCC) is the second most frequent cancer in humans and has the potential to progress locally, metastasize, and cause death in a subset of patients. cSCC is especially common in the elderly, and it will probably represent a major health concern in the near future. Surgery is the standard treatment for cSCC, but intralesional therapies can sometimes be considered for certain patients and under certain circumstances. The choice of intralesional treatment depends on the patient′s characteristics and the clinician′s previous experience and expertise. Here we are reviewing intralesional treatments for cSCC and keratoacanthoma (KA). We have started with some classic drugs, such as methotrexate and 5-fluorouracil, bleomycin, interferon, and cryosurgery, but also comment on electrochemotherapy. Finally, we have focused on novel therapies, some of which are under development, and future perspectives, including intralesional immunotherapy and oncolytic viruses. [ABSTRACT FROM AUTHOR]

Global agreement on 30×30 means an unprecedented last push to define how much nature will be left on the planet. At the same time that space for nature is being defined, climate change will be moving nature around. Species are now on the move to track climate change both on land and in the oceans, a process that is accelerating under dramatic new extreme events. This is an opportune time to review conservation recommendations made early in the millennium, to see how many have been taken on board over the past 20 years, and how much is left to be done to adapt to climate change as conservation pushes toward 30×30. The history of Climate Change–Integrated Conservation Strategies begins with two papers published by a group of prominent climate change biologists in 2002. The importance of including adaptation to climate change in conservation was underscored by the first estimates of extinction risk due to climate change in 2004. Subsequent literature has developed concepts such as velocity of climate change and assisted migration. Regional modeling of biodiversity change, expanding protected areas to facilitate species range movements, and managing productive landscapes to facilitate species movements are all now considered "business as usual" for conservation planning for climate change. Regional coordination of conservation efforts to ensure that species on the move are managed for climate change consistently across their range, on the other hand, is under-represented in literature and practice. Improving both theory and practice of regional coordination for climate change is an important priority for conservation now and in the future. Conservation for climate change has focused mostly on warming scenarios, but failure to act on climate change emissions reduction means that meeting Paris Agreement targets will almost certainly have to include both warming past those targets and subsequent cooling back to the target. Managing this double transition is a second critical point of emphasis for climate change biology as the world moves to 30×30. [ABSTRACT FROM AUTHOR]

In order to detect the effects of different stressors on the littoral diatom assemblages and biodiversity of the lentic systems in two different basins in Türkiye, 15 lentic systems in the Akarçay and Asi basins were sampled three times (spring, summer, and fall) for littoral diatoms and environmental variables. The biological assessment of these sites was also evaluated using 9 different river and lake diatom indices. Based on the total phosphorus (TP), total nitrogen (TN), electrical conductivity (EC), salinity (SAL) values, and dominant diatom species, three lentic systems in Akarçay Basin (Lake Eber, 26 Ağustos Pond, and Lake Karamık) were more eutrophic and under the pressure of anthropogenic and climatic (precipitation) stressors. Trophic diatom index for lakes (TDIL) showed a higher correlation with TN and TP and was the most effective index in explaining ecological quality in 15 lentic systems. The species richness of diatoms was also negatively affected by EC and SAL values. The lentic systems of the two basins were separated from each other based on the species composition and the distribution of the dominant species with the effect of altitude (ALT). Considering the distribution of diatom assemblage of the lentic systems in these two basins, anthropogenic, climatic, and geographical factors have become prominent to shape the diatom community structure. [ABSTRACT FROM AUTHOR]

Cyanobacteria can form blooms and pose a threat to the functioning of freshwater ecosystems. Cyanobacterial invasions are expected to increase due to climate change. Alien species cause a decline in biodiversity by displacing native species, lead to extinctions, affect food webs, and produce cyanotoxins which potentially impact the environment and human health. Three species, Raphidiopsis raciborskii, Sphaerospermospis aphanizomenoides and Chrysosporum bergii, are considered non-native to European waters. Recently, they have expanded their native habitats and become established in temperate lakes. In this article, we provide a detailed overview of the countries where they are distributed and the occurrence of the blooms in Europe. We discuss the biotic and abiotic environmental factors that influence their establishment, as well as the characteristics of the species that make them so adaptable in non-native habitats. Understanding the interplay of these factors will allow us to better recognise patterns of invasiveness and predict their future threats to ecosystems. [ABSTRACT FROM AUTHOR]

Finite element analysis is used in this study to investigate the effect of media inhomogeneity on the electric field distribution in a sample composed of cells and their extracellular matrix. The sample is supposed to be subjected to very high pulsed electric field. Numerically computed electric field distribution and transmembrane potential at the cell membrane in electroporation conditions are considered in order to study cell behavior at different degrees of inhomogeneity. The different inhomogeneity grade is locally obtained using a representative model of fixed volume with cell–cell distance varying in the range of 1–283 um. The conductivity of the extracellular medium was varied between plain collagen and a gel-like myxoid matrix through combinations of the two, i.e., collagen and myxoid. An increase in the transmembrane potential was shown in the case of higher aggregate. The results obtained in this study show the effect of the presence of the cell aggregates and collagen on the transmembrane potential. In particular, by increasing the cell aggregation in the two cases, the transmembrane potential increased. Finally, the simulation results were compared to experimental data obtained by culturing HCC1954 cells in a hyaluronic acid-based scaffold. The experimental validation confirmed the behavior of the transmembrane potential in presence of the collagen: an increase in electroporation at a lower electric field intensity was found for the cells cultured in the scaffolds where there is the formation of collagen areas. [ABSTRACT FROM AUTHOR]

Influenza vaccines are designed to mimic natural influenza virus exposure and stimulate a long-lasting immune response to future infections. The evolving nature of the influenza virus makes vaccination an important and efficacious strategy to reduce healthcare-related complications of influenza. Several lines of evidence indicate that influenza vaccination may induce nonspecific effects, also referred to as heterologous or pleiotropic effects, that go beyond protection against infection. Different explanations are proposed, including the upregulation and downregulation of cytokines and epigenetic reprogramming in monocytes and natural killer cells, imprinting an immunological memory in the innate immune system, a phenomenon termed "trained immunity". Also, cross-reactivity between related stimuli and bystander activation, which entails activation of B and T lymphocytes without specific recognition of antigens, may play a role. In this review, we will discuss the possible nonspecific effects of influenza vaccination in cardiovascular disease, type 1 diabetes, cancer, and Alzheimer's disease, future research questions, and potential implications. A discussion of the potential effects on infections by other pathogens is beyond the scope of this review. [ABSTRACT FROM AUTHOR]

T-cell malignancy is a broad term used for a diverse group of disease subtypes representing dysfunctional malignant T cells transformed at various stages of their clonal evolution. Despite having similar clinical manifestations, these disease groups have different disease progressions and diagnostic parameters. The effective diagnosis and prognosis of such a diverse disease group demands testing of molecular entities that capture footprints of the disease physiology in its entirety. MicroRNAs (miRNAs) are a group of noncoding RNA molecules that regulate the expression of genes and, while doing so, leave behind specific miRNA signatures corresponding to cellular expression status in an altered stage of a disease. Using miRNAs as a diagnostic tool is justified, as they can effectively distinguish expressional diversity between various tumors and within subtypes of T-cell malignancies. As global attention for cancer diagnosis shifts toward liquid biopsy, diagnosis using miRNAs is more relevant in blood cancers than in solid tumors. We also lay forward the diagnostic significance of miRNAs that are indicative of subtype, progression, severity, therapy response, and relapse. This review discusses the potential use and the role of miRNAs, miRNA signatures, or classifiers in the diagnosis of major groups of T-cell malignancies like T-cell acute lymphoblastic lymphoma (T-ALL), peripheral T-cell lymphoma (PTCL), extranodal NK/T-cell lymphoma (ENKTCL), and cutaneous T-cell lymphoma (CTCL). The review also briefly discusses major diagnostic miRNAs having prominent metabolic roles in these malignancies to highlight their importance among other dysregulated miRNAs. [ABSTRACT FROM AUTHOR]

The primary aim of this study was to analyze studies that use electrochemotherapy (ECT) in "deep-seated" tumors in solid organs (liver, kidney, bone metastasis, pancreas, and abdomen) and understand the similarities between patient selection, oncologic selection, and use of new procedures and technology across the organ systems to assess response rates. A literature search was conducted using the term "Electrochemotherapy" in the title field using publications from 2017 to 2023. After factoring in inclusion and exclusion criteria, 29 studies were analyzed and graded based on quality in full. The authors determined key patient and oncologic selection characteristics and ECT technology employed across organ systems that yielded overall responses, complete responses, and partial responses of the treated tumor. It was determined that key selection factors included: the ability to be administered bleomycin, life expectancy greater than three months, unrespectability of the lesion being treated, and a later stage, more advanced cancer. Regarding oncologic selection, all patient cohorts had received chemotherapy or surgery previously but had disease recurrence, making ECT the only option for further treatment. Lastly, in terms of the use of technology, the authors found that studies with better response rates used the ClinporatorTM and updated procedural guidelines by SOP. Thus, by considering patient, oncologic, and technology selection, ECT can be further improved in treating lesions in solid organs. [ABSTRACT FROM AUTHOR]

Simple Summary: Locoregional therapies play an ever-increasing role in contemporary oncology. This review provides an up-to-date, informed analysis of locoregional therapies harnessing electric pulses. Irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are integral to the therapeutic strategy in several solid tumours, ranging from skin cancers to visceral and bone metastases. Still, despite consolidated credibility and a favourable trade-off between efficacy and side effects, these therapies face fragmentation, as shown by differences in the stage of development and regulatory approval worldwide. Here, leading experts convened at the 4th World Congress of Electroporation (Copenhagen, 9–13 October 2022) provide a coherent, updated snapshot of this field. Hopefully, these techniques' common scientific and technological ground will allow researchers to overcome knowledge barriers and develop synergistic strategies to improve patient outcomes. The 4th World Congress of Electroporation (Copenhagen, 9–13 October 2022) provided a unique opportunity to convene leading experts in pulsed electric fields (PEF). PEF-based therapies harness electric fields to produce therapeutically useful effects on cancers and represent a valuable option for a variety of patients. As such, irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are on the rise. Still, their full therapeutic potential remains underappreciated, and the field faces fragmentation, as shown by parallel maturation and differences in the stages of development and regulatory approval worldwide. This narrative review provides a glimpse of PEF-based techniques, including key mechanisms, clinical indications, and advances in therapy; finally, it offers insights into current research directions. By highlighting a common ground, the authors aim to break silos, strengthen cross-functional collaboration, and pave the way to novel possibilities for intervention. Intriguingly, beyond their peculiar mechanism of action, PEF-based therapies share technical interconnections and multifaceted biological effects (e.g., vascular, immunological) worth exploiting in combinatorial strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Electroporation is a method of treatment in which electrical pulses are generated and applied to a cell, resulting in temporary (reversible electroporation, RE) or permanent (irreversible electroporation, IRE) changes to the structure of the cell, depending on the pulse parameters applied. There has been increasing interest in manipulating the pulse parameters used to deliver successful electroporation for cutaneous malignancies in order to reduce muscle contractions and pain associated with traditional low-frequency electrochemotherapy (LF-ECT), which often requires general anaesthesia. Higher-frequency electroporation with biphasic waves successfully permeabilises the cell membrane, usually without causing these side effects, thus allowing treatment to be delivered under local anaesthetic. This permits a wide range of patients to be safely treated, including those for which general anaesthetic is a contra-indication. This article aims to demonstrate the safety and efficacy of high-frequency electroporation, as well as equivalence and good tolerability in comparison to traditional electrochemotherapy. High-frequency electroporation (HF-EP) with chemotherapy is a novel therapy proposed for both curative and palliative treatment of cutaneous malignancies. The use of high-frequency biphasic pulses is thought to reduce the painful muscle contractions associated with traditional electrochemotherapy (ECT), allowing treatment administration under local anaesthesia. This proof-of-concept study investigated the efficacy and tolerability of HF-EP protocols on a variety of cutaneous malignancies. A total of 97 lesions of five different histological subtypes were treated across 25 patients. At 12 weeks post-treatment, a 91.3% overall lesion response rate was observed (complete response: 79%; partial response: 12.3%), with excellent intraprocedural patient tolerability under local anaesthetic. HF-EP with chemotherapy shows promising results regarding tumour response rates for cutaneous malignancies of varying histological subtypes when compared to traditional ECT protocols. Improved patient tolerability is important, increasing the possibility of treatment delivery under local anaesthesia and potentially broadening the treatment envelope for patients with cutaneous malignancies. [ABSTRACT FROM AUTHOR]

Simple Summary: Accumulating studies have highlighted the critical roles of microRNAs in tumorigenesis and cancer treatment responses. Here, we systematically review the scientific publications describing the roles of microRNAs in the development and progression of prostate cancer. Numerous studies have demonstrated that microRNAs target and regulate critical genes involved in prostate cancer aggressiveness and drug resistance. However, the molecular mechanisms underlying microRNA involvement in the advanced and treatment-resistant prostate cancers remain unclear. This review aims to highlight the current understanding and knowledge gap related to the deregulation of microRNAs in prostate cancer diseases. Furthermore, we summarize the promising progress on the development of microRNA-based diagnostic/prognostic biomarkers and therapies for prostate cancer. Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer deaths among American men. Complex genetic and epigenetic mechanisms are involved in the development and progression of PCa. MicroRNAs (miRNAs) are short noncoding RNAs that regulate protein expression at the post-transcriptional level by targeting mRNAs for degradation or inhibiting protein translation. In the past two decades, the field of miRNA research has rapidly expanded, and emerging evidence has revealed miRNA dysfunction to be an important epigenetic mechanism underlying a wide range of diseases, including cancers. This review article focuses on understanding the functional roles and molecular mechanisms of deregulated miRNAs in PCa aggressiveness and drug resistance based on the existing literature. Specifically, the miRNAs differentially expressed (upregulated or downregulated) in PCa vs. normal tissues, advanced vs. low-grade PCa, and treatment-responsive vs. non-responsive PCa are discussed. In particular, the oncogenic and tumor-suppressive miRNAs involved in the regulation of (1) the synthesis of the androgen receptor (AR) and its AR-V7 splice variant, (2) PTEN expression and PTEN-mediated signaling, (3) RNA splicing mechanisms, (4) chemo- and hormone-therapy resistance, and (5) racial disparities in PCa are discussed and summarized. We further provide an overview of the current advances and challenges of miRNA-based biomarkers and therapeutics in clinical practice for PCa diagnosis/prognosis and treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Electrochemotherapy has proven to be an efficient treatment for cutaneous metastases of various cancers including breast cancer (BC). The large number of patients collected within the INSPECT database provides the possibility of a differentiated analysis on BC with different receptor statuses (estrogen receptor and HER2 receptor). Patients with BC presenting cutaneous metastases were retrieved from the INSPECT database and divided by their receptor status: HER2+, HR+ (ER/PgR+), and TN (triple negative). ECT treatment is equally effective among groups, despite different conditions, age, time since diagnosis, previous or concomitant treatments, and treatment characteristics. Response and local tumor control seem to be better in multiple small lesions than in big armor-like lesions, suggesting that treating smaller, even multiple, lesions at the time of occurrence is more effective than treating bigger long-lasting armor-like cutaneous lesions. Electrochemotherapy has been proven to be an efficient treatment for cutaneous metastases of various cancers. Data on breast cancer (BC) patients with cutaneous metastases were retrieved from the INSPECT database. Patients were divided by their receptor status: HER2+, HR+ (ER/PgR+), and TN (triple negative). Groups were similar for histological subtype and location of the nodules. Most patients were previously treated with surgery/systemic therapy/radiotherapy. We found no differences in the three groups in terms of response ratio (OR per patient 86% HER2+, 80% HR+, 76% TN, p = 0.8664). The only factor positively affecting the complete response rate in all groups was small tumor size (<3 cm, p = 0.0105, p = 0.0001, p = 0.0266, respectively). Local progression-free survival was positively impacted by the achievement of complete response in HER2+ (p = 0.0297) and HR+ (p = 0.0094), while overall survival was affected by time to local progression in all groups (p = 0.0065 in HER2+, p < 0.0001 in HR+, p = 0.0363 in TN). ECT treatment is equally effective among groups, despite different receptor status. Response and local tumor control seem to be better in multiple small lesions than in big armor-like lesions, suggesting that treating smaller, even multiple, lesions at the time of occurrence is more effective than treating bigger long-lasting armor-like cutaneous lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: A prospective institutional study was conducted at the Institute of Oncology in Ljubljana. The main objective of the study is to determine the safety and feasibility of electrochemotherapy in the treatment of vulvar cancer recurrence. From July 2020 to January 2023, 10 patients with vulvar cancer recurrence were enrolled in our study. Patients were treated with an intravenous application of bleomycin, and 8 min later, electric pulses were applied locally to the tumor to increase the cytotoxicity of bleomycin. The treatment could be performed in all patients, demonstrating its feasibility, and no adverse effects were documented, proving that the treatment is safe. In conclusion, this is the first prospective study of electrochemotherapy in the treatment of local vulvar cancer recurrence conducted for nonpalliative purposes, demonstrating its safety and feasibility. Electrochemotherapy is a local ablative therapy used for the treatment of various superficial and deep-seated tumors. Electrochemotherapy involves the application of electric pulses locally to tumors to destabilize cell membranes and facilitate the entry of cytotoxic drugs, thereby enhancing their cytotoxicity locally. The aim of our study is to investigate the safety and feasibility of electrochemotherapy in patients with vulvar cancer recurrence used for nonpalliative purposes. Ten patients with single local vulvar cancer recurrence were treated with intravenous bleomycin, followed by a local application of electric pulses (electrochemotherapy) to the tumor. Adverse events were determined using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The feasibility of treating vulvar cancer with electrochemotherapy was determined by an appropriate selection of electrodes based on the size and location of the tumor with safety margins included. Electrochemotherapy was feasible in all patients. No electrochemotherapy-related or other serious adverse events occurred. Our data suggest that electrochemotherapy is a feasible and safe technique for the treatment of vulvar cancer recurrence for nonpalliative purposes. Based on our results, electrochemotherapy might be a viable therapeutic tool for patients who would otherwise undergo surgery involving a mutilation of the external genitalia. [ABSTRACT FROM AUTHOR]

Electrochemotherapy (ECT) has evolved significantly during the last decade, expanding treatment indications from superficial skin lesions to advanced-stage, deep-seated tumors in hard-to-reach areas. Electrodes have also shown steady technological improvement throughout the years. Besides standard and VEG (variable geometry electrode) electrodes, the introduction of laparoscopic electrodes has brought on a new era in ECT treatment, making the minimally invasive approach a reality. The exact role of ECT in the oncological dashboard is yet to be determined; however, increased tumor response, pain relief, and a low number of adverse events may yield the way for more widespread application of the technique with possible further inclusion of ECT in international oncological guidelines. The aim of this review is to give an overview on the current status of ECT in deep-seated tumor treatment and shed light on its emerging role in local anticancer therapy. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma is a highly aggressive form of skin cancer. The development of immune checkpoint inhibitors (ICIs) has revolutionized the management of advanced melanoma, led to durable responses, and improved overall survival. However, the success of ICIs in melanoma treatment is influenced by the tumor microenvironment (TME) which plays a critical role in regulating the immune response to the tumor. Understanding the mechanisms underlying this interaction is crucial to optimizing the efficiency of ICIs. Electrochemotherapy (ECT) has been shown to enhance the efficacy of ICIs in melanoma treatment by inducing tumor cell death and facilitating the release of tumor antigens which can subsequently be recognized and targeted by the immune system. Moreover, ECT has been reported to modulate the TME, leading to increased infiltration of immune cells and a more favorable immunological profile. In this review, we summarize the available knowledge of changes in TME after ECT of melanoma cutaneous metastasis and highlight the differences in tumor-infiltrating immune cells between immunocompetent and immunosuppressed organisms. In addition, we showed that ECT can be an effective and safe procedure for organ transplant recipients. Furthermore, repeated ECT may enhance immune activation and probably induce a bystander effect by trained immunity. [ABSTRACT FROM AUTHOR]

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The role and durability of the immunogenicity of the BNT162b2 mRNA vaccine against severe acute respiratory virus 2 (SARS-CoV-2), in cancer patients one year after receiving the third dose have to be elucidated. We have prospectively evaluated the long-term immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 mRNA vaccine in 55 patients undergoing active treatment. Neutralizing antibody (NT Ab) titers against Omicron variants and total anti-trimeric S IgG levels were measured one year after the third dose. Heparinized whole-blood samples were used for the assessment of the SARS-CoV-2 interferon-γ release assay (IGRA). Thirty-seven patients (67.3%) showed positive total anti-trimeric S IgG one year after the third dose. Looking at the T-cell response against the spike protein, the frequency of responder patients did not decrease significantly between six and twelve months after the third dose. Finally, less than 20% of cancer patients showed an undetectable NT Ab titer against BA.1 and BA.5 variants of concern (VOCs). Underlying therapies seem to not affect the magnitude or frequency of the immune response. Our work underlines the persistence of humoral and cellular immune responses against BNT162b2 in a cohort of cancer patients one year after receiving the third dose, regardless of the type of underlying therapy. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab monotherapy or pembrolizumab plus chemotherapy has become an important frontline treatment for advanced non-small cell lung cancer (NSCLC). To date, it remains unclear how the coronavirus disease 2019 (COVID-19) pandemic impacted the treatment outcome. Methods: A quasi-experimental study was conducted based on a real-world database, comparing pandemic with pre-pandemic patient cohorts. The pandemic cohort consisted of patients who initiated treatment from March to July 2020, with follow-up through March 2021. The pre-pandemic cohort consisted of those initiating treatment between March and July 2019.The outcome was overall real-world survival. Multivariable Cox-proportional hazard models were constructed. Results: Analyses included data from 2090 patients: 998 in the pandemic cohort and 1092 in the pre-pandemic cohort. Baseline characteristics were comparable, with 33% of patients having PD-L1 expression level ≥50% and 29% of patients receiving pembrolizumab monotherapy. Among those treated with pembrolizumab monotherapy (N = 613), there was a differential impact of the pandemic on survival by PD-L1 expression levels (p-interaction = 0.02). For those with PD-L1 level < 50%, survival was better in the pandemic cohort than the pre-pandemic cohort: hazard ratio (HR) 0.64 (95% CI: 0.43–0.97, p = 0.03). However, for those with PD-L1 level ≥ 50%, survival was not better in the pandemic cohort: HR 1.17 (95% CI: 0.85–1.61, p = 0.34). We found no statistically significant impact of the pandemic on survival among patients treated with pembrolizumab plus chemotherapy. Conclusions: The COVID-19 pandemic was associated with an increase in survival among patients with lower PD-L1 expression who were treated with pembrolizumab monotherapy. This finding suggests an increased efficacy of immunotherapy due to viral exposure in this population. [ABSTRACT FROM AUTHOR]

A novel virus named SARS-CoV-2 has caused a worldwide pandemic, resulting in a disastrous impact to the public health since 2019. The disease is much more lethal among patients with malignant disease. Vaccination plays an important role in the prevention of infection and subsequent severe COVID-19. However, the efficacy and safety of vaccines for cancer patients needs further investigation. Encouragingly, there have been important findings deduced from research so far. In this review, an overview of the immunogenicity, effectiveness, and safeness of COVID-19 vaccines in patients with cancer to date is to be shown. We also highlight important questions to consider and directions that could be followed in future research. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma (CM) is a highly aggressive malignancy with a dimal prognosis and limited treatment options. Anoikis is believed to involve in the regeneration, migration, and metastasis of tumor. The exact role of anoikis-related genes (ARGs) in the development and progression of cutaneous melanoma, however, remains elusive. Four ARGs (SNAI2, TFDP1, IKBKG, and MCL1) with significant differential expression were selected through Cox regression and LASSO analyses. Data for internal and external cohorts validated the accuracy and clinical utility of the prognostic risk model based on ARGs. The Kaplan-Meier curve indicated a much better overall survival rate of low-risk patients. Notably, we also found that the action of ARGs in the CM was mediated by immune-related signaling pathways. Consensus clustering and TIME landscape analysis also indicated that the low-risk score patients have excellent immune status. Moreover, the results of immunotherapy response and drug sensitivity also confirmed the potential implications of informing individualized immune therapeutic strategies for CM. Collectively, the predictive risk model constructed based on ARGs provides an excellent and accurate prediction tool for CM patients. This present research provides a rationale for the joint application of targeted therapy and immunotherapy in CM treatment. The approach could have great therapeutic value and make a contribution to personalized medicine therapy. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyse papers describing the use of Electrochemotherapy (ECT) in local treatment of primary and secondary liver tumours located at different sites and with different histologies. Other Local Ablative Therapies (LAT) are also discussed. Analyses of these papers demonstrate that ECT use is safe and effective in lesions of large size, independently of the histology of the treated lesions. ECT performed better than other thermal ablation techniques in lesions > 6 cm in size and can be safely used to treat lesions distant, close, or adjacent to vital structures. ECT spares vessel and bile ducts, is repeatable, and can be performed between chemotherapeutic cycles. ECT can fill the gap in local ablative therapies due to being lesions too large or localized in highly challenging anatomical sites. [ABSTRACT FROM AUTHOR]

Diagnosis of Mycosis Fungoides (MF) may be challenging, due to its polymorphic nature. The use of miRNAs as biomarkers to assist in diagnosis has been investigated, mainly in skin lesion biopsies. The purpose of this study is to evaluate the plasma levels of miR-146a and miR-155 in MF patients and to investigate their association with SNPs of their genes. Plasma miRNAs were quantified by RT-qPCR. Genomic DNA was used for SNPs' genotyping by Sanger sequencing. Plasma levels of miR-146a and miR-155 were significantly higher in patients vs. controls, in early MF patients vs. controls, and in advanced vs. early MF patients. Both miRNAs' levels were significantly higher in stage IIB vs. early-stage patients. miR-155 plasma levels were significantly higher in patients with skin tumors or erythroderma. CC genotype (rs2910164 C>G) was significantly more frequent in healthy controls and associated with lower MF risk and lower miR-146a levels. The AA genotype (rs767649 T>A) was significantly more frequent in patients and correlated with increased MF risk and increased miR-155 levels. The combination of GG+AA was only detected in patients and was correlated with higher MF susceptibility. Increased mir-146a and mir-155 plasma levels in MF is an important finding to establish putative noninvasive biomarkers. The presence of SNPs is closely associated with miRs' expression, and possibly with disease susceptibility. [ABSTRACT FROM AUTHOR]

Simple Summary: This review provides a summary of the head-and-neck squamous cell carcinoma (HNSCC) biological characteristics and its current treatments. Furthermore, insight and outlook on the relationship between electroporation and its implementation (combination with nanotechnology and immunotherapy) in the treatment of H&N cancers are provided. Squamous cell carcinoma is the most common malignancy that arises in the head-and-neck district. Traditional treatment could be insufficient in case of recurrent and/or metastatic cancers; for this reason, more selective and enhanced treatments are in evaluation in preclinical and clinical trials to increase in situ concentration of chemotherapy drugs promoting a selectively antineoplastic activity. Among all cancer treatment types (i.e., surgery, chemotherapy, radiotherapy), electroporation (EP) has emerged as a safe, less invasive, and effective approach for cancer treatment. Reversible EP, using an intensive electric stimulus (i.e., 1000 V/cm) applied for a short time (i.e., 100 μs), determines a localized electric field that temporarily permealizes the tumor cell membranes while maintaining high cell viability, promoting cytoplasm cell uptake of antineoplastic agents such as bleomycin and cisplatin (electrochemotherapy), calcium (Ca2+ electroporation), siRNA and plasmid DNA (gene electroporation). The higher intracellular concentration of antineoplastic agents enhances the antineoplastic activity and promotes controlled tumor cell death (apoptosis). As secondary effects, localized EP (i) reduces the capillary blood flow in tumor tissue ("vascular lock"), lowering drug washout, and (ii) stimulates the immune system acting against cancer cells. After years of preclinical development, electrochemotherapy (ECT), in combination with bleomycin or cisplatin, is currently one of the most effective treatments used for cutaneous metastases and primary skin and mucosal cancers that are not amenable to surgery. To reach this clinical evidence, in vitro and in vivo models were preclinically developed for evaluating the efficacy and safety of ECT on different tumor cell lines and animal models to optimize dose and administration routes of drugs, duration, and intensity of the electric field. Improvements in reversible EP efficacy are under evaluation for HNSCC treatment, where the focus is on the development of a combination treatment between EP-enhanced nanotechnology and immunotherapy strategies. [ABSTRACT FROM AUTHOR]

Malignant adnexal tumors of the skin are rare. Sebaceous carcinoma (SC) is an aggressive malignant tumor of the sebaceous glands. It is traditionally classified into periocular and extraocular types. We present a rare case of extraocular SC of a 38-year-old female who presented with nontender swelling over the right flank for 1 year. Clinically, it was diagnosed with a sebaceous cyst. The tumor was excised and sent for histopathological examination. Sections showed sheets and lobules of tumor cells separated by fibrovascular stroma. Individual tumor cells were atypical basaloid to clear cells with prominent pleomorphism. Mitosis was brisk with areas of necrosis. On immunohistochemistry, the tumor cells were focally positive for epithelial membrane antigen and negative for S100 and PAX8 with a high Ki-67 index of 80%. Her postoperative period and follow-up for 1 year have been uneventful. This case is being reported for its rarity. [ABSTRACT FROM AUTHOR]

This prospective registry-based study aims to describe electrochemotherapy (ECT) modalities in basal cell carcinoma (BCC) patients and evaluate its efficacy, safety, and predictive factors. The International Network for Sharing Practices of Electrochemotherapy (InspECT) multicentre database was queried for BCC cases treated with bleomycin-ECT between 2008 and 2019 (n = 330 patients from seven countries, with 623 BCCs [median number: 1/patient; range: 1–7; size: 13 mm, range: 5–350; 85% were primary, and 80% located in the head and neck]). The procedure was carried out under local anaesthesia in 68% of cases, with the adjunct of mild sedation in the remaining 32%. Of 300 evaluable patients, 242 (81%) achieved a complete response (CR) after a single ECT course. Treatment naïvety (odds ratio [OR] 0.35, 95% confidence interval [C.I.] 0.19–0.67, p = 0.001) and coverage of deep tumour margin with electric pulses (O.R. 5.55, 95% C.I. 1.37–21.69, p = 0.016) predicted CR, whereas previous radiation was inversely correlated (O.R. 0.25, p = 0.0051). Toxicity included skin ulceration (overall, 16%; G3, 1%) and hyperpigmentation (overall, 8.1%; G3, 2.5%). At a 17-month follow-up, 28 (9.3%) patients experienced local recurrence/progression. Despite no convincing evidence that ECT confers improved outcomes compared with standard surgical excision, it can still be considered an opportunity to avoid major resection in patients unsuitable for more demanding treatment. Treatment naïvety and coverage of the deep margin predict tumour clearance and may inform current patient selection and management. [ABSTRACT FROM AUTHOR]