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The intersection of HIV and melanoma presents a complex and unique challenge, marked by distinct patterns in incidence, mortality, and treatment response. Higher mortality rates among people with HIV who develop melanoma underscore an urgent need to identify the factors influencing these outcomes. Investigating immune system dynamics, the effects of anti-retroviral drugs, and the evolving landscape of cancer immunotherapy in this population holds promise for new insights, though significant uncertainties remain. Over the past 25 years, melanoma research has demonstrated that a robust immune response is critical for effective treatment. In the context of chronic HIV infection, viral reservoirs enable the virus to persist despite anti-retroviral therapy and foster dysregulated myeloid and T cell compartments. The resulting chronic inflammation weakens the immune system and damages tissues, potentially creating “cold” tumor microenvironments that are less responsive to therapy. In this challenging context, animal models become invaluable for uncovering underlying biological mechanisms. While these models do not fully replicate human HIV infection, they provide essential insights into critical questions and inform the development of tailored treatments for this patient population. Clinically, increasing trial participation and creating a centralized, accessible repository for HIV and cancer samples and data are vital. Achieving these goals requires institutions to address barriers to research participation among people with HIV, focusing on patient-centered initiatives that leverage biomedical research to improve their outcomes and extend their lives. [ABSTRACT FROM AUTHOR]

Mitral valve regurgitation is one of the most common heart valve diseases that can occur when the structural composition of the mitral valve is affected. Mitral valve repair, typically performed in a minimally invasive setting, is a complex surgery that aims to reinstate the structural integrity of the valve and thereby restore normal valve function. The current practice lacks quantification of geometrical changes and interactive 3D visualization that could enhance the understanding of pathomorphological changes and impact of surgical correction. This work presents functionalities from smartMVR, a quantitative tool to measure, compare, and analyse changes in mitral valve geometry from data captured on-demand using an RGB-D camera. The feasibility of the approach is demonstrated on a silicone replica of a pathological mitral valve that is iteratively corrected using common surgical techniques. [ABSTRACT FROM AUTHOR]

The United States government makes a substantial investment in biomedical training programs each year. However, for most trainees, these opportunities do not translate into career progression in academic research pathways. Only about one-fifth of postdoctoral fellows eventually secure a tenure-track faculty position, and even among these candidates, attrition is high. Although a number of factors govern career choices and career longevity, the transition from trainee to faculty is a challenging process and requires knowledge and skills that are not necessarily developed during a traditional university experience. Many postdoctoral fellows receive adequate training in research skills and scientific communication, but new faculty report not being sufficiently prepared for the job search process and for starting their labs. To address this critical training gap, the ITERT core (Interdisciplinary Translational Education and Research Training) and the Office of Postdoctoral Fellows at the University of Texas MD Anderson Cancer Center implemented a structured course for both postdoctoral fellows and senior PhD students to provide formalized training for successfully navigating academic positions in biomedical research. Here we report on the pilot Navigating Academic Careers course conducted in 2021–2022 for 30 PhD students and postdocs. The nine-module course was conducted over 13 weeks in 25.5 h instructional sessions. The key educational objectives included 1) navigating the job application and the interview/negotiation process, 2) hiring, leading, and mentoring lab personnel and program support staff, 3) project administration and financial stewardship, 4) managing time and work-life balance and 5) developing collaborations, branding, personalized niche, and networking. Survey-based analysis at the time of the course was used to capture the participants' assessment of the course content, organization, and delivery, with a follow-up survey conducted approximately 2 years post-course (2024) to evaluate longer-term impacts of the training. Initial in-course assessment revealed that 89.9% of respondents found the scope and instructional content appropriate, and 91.1% found the course relevant and applicable to their career needs. Longer-term post-course evaluation indicated that 80% of respondents applied the learnings of the course, that 80% reported feeling more confident in navigating an academic job search, and that 66.6% continued to report agreement with the course preparing them for their current role/ongoing job search, with 46.7% already securing jobs in academic research, including as independent faculty. The outcomes of this pilot course suggest that integrating this into the broader postdoctoral training curriculum can enhance both the transition and early-career success of talented scientists-in-training into working professionals in biomedical careers, as faculty and science-trained staff. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Minimally invasive mitral valve repair (MVR) is considered one of the most challenging operations in cardiac surgery and requires much practice and experience. Simulation-based surgical training might be a method to support the learning process and help to flatten the steep learning curve of novices. The purpose of this study was to show the possible effects on learning of surgical training using a high-fidelity simulator with patient-specific mitral valve replicas. METHODS Twenty-five participants were recruited to perform MVR on anatomically realistic valve models during different training sessions. After every session their performance was evaluated by a surgical expert regarding accuracy and duration for each step. A second blinded rater similarly assessed the performance after the study. Through repeated documentation of those parameters, their progress in learning was analysed, and gains in proficiency were evaluated. RESULTS Participants showed significant performance enhancements in terms of both accuracy and time. Their surgical skills showed sizeable improvements after only 1 session. For example, the time to implant neo-chordae decreased by 24.64% (354 s-264 s, P  < 0.001) and the time for annuloplasty by 4.01% (54 s-50 s, P  = 0.165), whereas the number of irregular stitches for annuloplasty decreased from 52% to 24%. The significance of simulation-based surgical training as a tool for acquiring and training surgical skills was reviewed positively. CONCLUSIONS The results of this study indicate that simulation-based surgical training is a valuable and effective method for learning reconstructive techniques of minimally invasive MVR and overall general dexterity. The novel learning and training options should be implemented in the surgical traineeship for systematic teaching of various surgical skills. [ABSTRACT FROM AUTHOR]

Purpose: Minimally invasive mitral valve surgery (MIMVS) and transcatheter edge-to-edge repair (TEER) are complex procedures used to treat mitral valve (MV) pathologies, but with limited training opportunities available. To enable training, a realistic hemodynamic environment is needed. In this work we aimed to develop and validate a simulator that enables investigation of MV pathologies and their repair by MIMVS and TEER in a hemodynamic setting. Methods: Different MVs were installed in the simulator, and pressure, flow, and transesophageal echocardiographic measurements were obtained. To confirm the simulator's physiological range, we first installed a biological prosthetic, a mechanical prosthetic, and a competent excised porcine MV. Subsequently, we inserted two porcine MVs—one with induced chordae tendineae rupture and the other with a dilated annulus, along with a patient-specific silicone valve extracted from echocardiography with bi-leaflet prolapse. Finally, TEER and MIMVS procedures were conducted by experts to repair the MVs. Results: Systolic pressures, cardiac outputs, and regurgitations volumes (RVol) with competent MVs were 119 ± 1 mmHg, 4.78 ± 0.16 l min−1, and 5 ± 3 ml respectively, and thus within the physiological range. In contrast, the pathological MVs displayed increased RVols. MIMVS and TEER resulted in a decrease in RVols and mitigated the severity of mitral regurgitation. Conclusion: Ex-vivo modelling of MV pathologies and repair procedures using the described simulator realistically replicated physiological in-vivo conditions. Furthermore, we showed the feasibility of performing MIMVS and TEER at the simulator, also at patient-specific level, thus providing new clinical perspectives in terms of training modalities and personalized planning. [ABSTRACT FROM AUTHOR]

Background: Transvenous laser lead extraction (TLE) for cardiac implantable electric devices (CIED) is a challenging procedure especially if performed in octogenarians. In this study we evaluated the safety and efficacy of transvenous laser lead extraction in elderly patients. Methods: This is a retrospective study of octogenarian patients who underwent laser-assisted lead extraction (LLE) (GlideLight laser sheath, Philips, San Diego, USA). 270 Consecutive patients were included. Patients were divided into two groups. Octogenarian group and non-octogenarian group. The Data was gathered from patients treated between September 2013 and January 2020 and is retrospectively analyzed. Results: Of 270 consecutive patients, 38 (14.0%) were 80 years old or more. The total number of the extracted leads was 556 among which 84(15.0%) from the Octogenarian group. From these leads were 155 single coil leads, 82 dual coil leads, 129 right ventricular pacing leads, 155 right atrial leads, and 35 left ventricular leads. In the Octogenarian group the number of removed leads was as follows: 13 single coil leads, 10 dual coil leads, 28 right ventricular pacing leads, 28 right atrial leads and 5 left ventricular leads. No mortality was recorded in the Octogenarian group. One patient in the YG suffered from a superior vena cava tear and one patient suffered from pulmonary embolism. Conclusion: In octogenarian laser assisted lead extraction patients is a safe and effective procedure. No increase in morbidity, mortality or perioperative complication could be recorded in this group. Age should not be a limiting factor to perform this procedure. [ABSTRACT FROM AUTHOR]

Multi-point tracking is a challenging task that involves detecting points in the scene and tracking them across time. Here, metrics from Multi-object tracking (MOT) methods are shown to perform better than frame-based F-measures. The recently proposed HOTA metric, used for benchmarks such as the KITTI dataset, better evaluates the performance over metrics like MOTA, DetA, and IDF1. While HOTA takes into account temporal associations, it does not provide a tailored means to analyse the spatial associations of a dataset in a multi-camera setup. Moreover, there are differences in evaluating the detection task for points vs. objects (point distances vs. bounding box overlap). Therefore, we propose a multi-view higher-order tracking metric mvHOTA , to determine the accuracy of multi-point (multi-instance and multi-class) tracking methods while taking into account temporal and spatial associations. We demonstrate its use in evaluating the tracking performance on an endoscopic point detection dataset from a previously organised surgical data science challenge. Furthermore, we compare with other adjusted MOT metrics for this use-case, discuss the properties of mvHOTA, and show how the proposed multi-view Association and the Occlusion index (OI) facilitate analysis of methods with respect to handling of occlusions. The code is available at . [ABSTRACT FROM AUTHOR]

Purpose: Minimally invasive surgeries have restricted surgical ports, demanding a high skill level from the surgeon. Surgical simulation potentially reduces this steep learning curve and additionally provides quantitative feedback. Markerless depth sensors show great promise for quantification, but most such sensors are not designed for accurate reconstruction of complex anatomical forms in close-range. Methods: This work compares three commercially available depth sensors, namely the Intel D405, D415, and the Stereolabs Zed-Mini in the range of 12–20 cm, for use in surgical simulation. Three environments are designed that closely mimic surgical simulation, comprising planar surfaces, rigid objects, and mitral valve models of silicone and realistic porcine tissue. The cameras are evaluated on Z-accuracy, temporal noise, fill rate, checker distance, point cloud comparisons, and visual inspection of surgical scenes, across several camera settings. Results: The Intel cameras show sub-mm accuracy in most static environments. The D415 fails in reconstructing valve models, while the Zed-Mini provides lesser temporal noise and higher fill rate. The D405 could reconstruct anatomical structures like the mitral valve leaflet and a ring prosthesis, but performs poorly for reflective surfaces like surgical tools and thin structures like sutures. Conclusion: If a high temporal resolution is needed and lower spatial resolution is acceptable, the Zed-Mini is the best choice, whereas the Intel D405 is the most suited for close-range applications. The D405 shows potential for applications like deformable registration of surfaces, but is not yet suitable for applications like real-time tool tracking or surgical skill assessment. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a malignant prognosis. GBM is characterized by high cellular heterogeneity and its progression relies on the interaction with the central nervous system, which ensures the immune-escape and tumor promotion. This interplay induces metabolic, (epi)-genetic and molecular rewiring in both domains. In the present study, we aim to characterize the time-related changes in the GBM landscape, using a syngeneic mouse model of primary GBM. GL261 glioma cells were injected in the right striatum of immuno-competent C57Bl/6 mice and animals were sacrificed after 7, 14, and 21 days (7D, 14D, 21D). The tumor development was assessed through 3D tomographic imaging and brains were processed for immunohistochemistry, immunofluorescence, and western blotting. A human transcriptomic database was inquired to support the translational value of the experimental data. Our results showed the dynamic of the tumor progression, being established as a bulk at 14D and surrounded by a dense scar of reactive astrocytes. The GBM growth was paralleled by the impairment in the microglial/macrophagic recruitment and antigen-presenting functions, while the invasive phase was characterized by changes in the extracellular matrix, as shown by the analysis of tenascin C and metalloproteinase-9. The present study emphasizes the role of the molecular changes in the microenvironment during the GBM progression, fostering the development of novel multi-targeted, time-dependent therapies in an experimental model similar to the human disease. [ABSTRACT FROM AUTHOR]

Melanoma cells display distinct intrinsic phenotypic states. Here, we seek to characterize the molecular regulation of these states using multi-omic analyses of whole exome, transcriptome, microRNA, long non-coding RNA and DNA methylation data together with reverse-phase protein array data on a panel of 68 highly annotated early passage melanoma cell lines. We demonstrate that clearly defined cancer cell intrinsic transcriptomic programs are maintained in melanoma cells ex vivo and remain highly conserved within melanoma tumors, are associated with distinct immune features within tumors, and differentially correlate with checkpoint inhibitor and adoptive T cell therapy efficacy. Through integrative analyses we demonstrate highly complex multi-omic regulation of melanoma cell intrinsic programs that provide key insights into the molecular maintenance of phenotypic states. These findings have implications for cancer biology and the identification of new therapeutic strategies. Further, these deeply characterized cell lines will serve as an invaluable resource for future research in the field. The regulation of the distinct intrinsic phenotypic states in melanoma remain poorly characterised. Here, multi-omics analysis for a panel of 68 early passage melanoma cell lines reveals that cancer cell intrinsic transcriptomic programs are associated with distinct immune features. [ABSTRACT FROM AUTHOR]

The CycleGAN framework allows for unsupervised image-to-image translation of unpaired data. In a scenario of surgical training on a physical surgical simulator, this method can be used to transform endoscopic images of phantoms into images which more closely resemble the intra-operative appearance of the same surgical target structure. This can be viewed as a novel augmented reality approach, which we coined Hyperrealism in previous work. In this use case, it is of paramount importance to display objects like needles, sutures or instruments consistent in both domains while altering the style to a more tissue-like appearance. Segmentation of these objects would allow for a direct transfer, however, contouring of these, partly tiny and thin foreground objects is cumbersome and perhaps inaccurate. Instead, we propose to use landmark detection on the points when sutures pass into the tissue. This objective is directly incorporated into a CycleGAN framework by treating the performance of pre-trained detector models as an additional optimization goal. We show that a task defined on these sparse landmark labels improves consistency of synthesis by the generator network in both domains. Comparing a baseline CycleGAN architecture to our proposed extension (DetCycleGAN), mean precision (PPV) improved by $+61.32$ , mean sensitivity (TPR) by $+37.91$ , and mean $F_1$ score by $+0.4743$. Furthermore, it could be shown that by dataset fusion, generated intra-operative images can be leveraged as additional training data for the detection network itself. [ABSTRACT FROM AUTHOR]

Purpose: Mitral valve repair is a complex minimally invasive surgery of the heart valve. In this context, suture detection from endoscopic images is a highly relevant task that provides quantitative information to analyse suturing patterns, assess prosthetic configurations and produce augmented reality visualisations. Facial or anatomical landmark detection tasks typically contain a fixed number of landmarks, and use regression or fixed heatmap-based approaches to localize the landmarks. However in endoscopy, there are a varying number of sutures in every image, and the sutures may occur at any location in the annulus, as they are not semantically unique. Method: In this work, we formulate the suture detection task as a multi-instance deep heatmap regression problem, to identify entry and exit points of sutures. We extend our previous work, and introduce the novel use of a 2D Gaussian layer followed by a differentiable 2D spatial Soft-Argmax layer to function as a local non-maximum suppression. Results: We present extensive experiments with multiple heatmap distribution functions and two variants of the proposed model. In the intra-operative domain, Variant 1 showed a mean F 1 of + 0.0422 over the baseline. Similarly, in the simulator domain, Variant 1 showed a mean F 1 of + 0.0865 over the baseline. Conclusion: The proposed model shows an improvement over the baseline in the intra-operative and the simulator domains. The data is made publicly available within the scope of the MICCAI AdaptOR2021 Challenge https://adaptor2021.github.io/, and the code at https://github.com/Cardio-AI/suture-detection-pytorch/. [ABSTRACT FROM AUTHOR]

Background: The implantation of cardiac implantable electronic devices (CIED) has increased in the last decades with improvement in the quality of life of patients with cardiac rhythm disorders. The presence of bilateral subclavian, innominate or superior vena cava obstruction is a major limitation to device revision and/or upgrade. Methods and material: This is retrospective study of patients who underwent laser-assisted lead extraction (LLE) (GlideLight laser sheath, Spectranetics Corporation, Colorado Springs, USA) with lead revision or upgrade using the laser sheath as a guide rail. Patients with known occlusion, severe stenosis or functional obstruction of the venous access vessels with indwelling leads were included in this study. Results: 106 patients underwent percutaneous LLE with lead revision and/or upgrade. Preoperative known complete occlusion or severe stenosis of access veins was present in 23 patients (21.5%). More patients with implantable cardioverter-defibrillator (ICD) underwent LLE (64.1%) than patients with CRT-Ds (24.5%) and pacemaker patients (11.3%). In total 172 leads were extracted: 79 (45.9%) single-coil defibrillator leads, 35 (20.3%) dual-coil defibrillator leads, 31 (18.0%) right atrial leads, 24 (13.9%) right ventricular leads and three (1.7%) malfunctional coronary sinus left ventricular pacing leads. The mean age of leads was 99.2±65.6 months. The implantation of new leads after crossing the venous stenosis/obstruction was successful in 98 (92.4%) cases. Postoperative complications were pocket hematoma in two cases and wound infection in one case. No peri-operative and no immediate postoperative death was recorded. One intraoperative superior vena cava tear was treated by immediate thoracotomy and surgical repair. Conclusion: In a single-center study on LLE in the presence of supra-cardiac occlusion of the central veins for CIED lead upgrade and revision we could demonstrate a low procedural complication rate with no procedural deaths. Most of the leads could be completely extracted to revise or upgrade the system. Our study showed a low complication rate, with acceptable mortality rates. [ABSTRACT FROM AUTHOR]

Purpose: Intensive planning and analysis from echocardiography are a crucial step before reconstructive surgeries are applied to malfunctioning mitral valves. Volume visualizations of echocardiographic data are often used in clinical routine. However, they lack a clear visualization of the crucial factors for decision making. Methods: We build upon patient-specific mitral valve surface models segmented from echocardiography that represent the valve's geometry, but suffer from self-occlusions due to complex 3D shape. We transfer these to 2D maps by unfolding their geometry, resulting in a novel 2D representation that maintains anatomical resemblance to the 3D geometry. It can be visualized together with color mappings and presented to physicians to diagnose the pathology in one gaze without the need for further scene interaction. Furthermore, it facilitates the computation of a Pathology Score, which can be used for diagnosis support. Results: Quality and effectiveness of the proposed methods were evaluated through a user survey conducted with domain experts. We assessed pathology detection accuracy using 3D valve models in comparison with the novel visualizations. Classification accuracy increased by 5.3% across all tested valves and by 10.0% for prolapsed valves. Further, the participants' understanding of the relation between 3D and 2D views was evaluated. The Pathology Score is found to have potential to support discriminating pathologic valves from normal valves. Conclusions: In summary, our survey shows that pathology detection can be improved in comparison with simple 3D surface visualizations of the mitral valve. The correspondence between the 2D and 3D representations is comprehensible, and color-coded pathophysiological magnitudes further support the clinical assessment. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the fourth cause of death from cancer worldwide mainly due to the high incidence of drug‐resistance. During a screen for new actionable targets in drug‐resistant tumours we recently identified p65BTK – a novel oncogenic isoform of Bruton's tyrosine kinase. Studying three different cohorts of patients here we show that p65BTK expression correlates with histotype and cancer progression. Using drug‐resistant TP53‐null colon cancer cells as a model we demonstrated that p65BTK silencing or chemical inhibition overcame the 5‐fluorouracil resistance of CRC cell lines and patient‐derived organoids and significantly reduced the growth of xenografted tumours. Mechanistically, we show that blocking p65BTK in drug‐resistant cells abolished a 5‐FU‐elicited TGFB1 protective response and triggered E2F‐dependent apoptosis. Taken together, our data demonstrated that targeting p65BTK restores the apoptotic response to chemotherapy of drug‐resistant CRCs and gives a proof‐of‐concept for suggesting the use of BTK inhibitors in combination with 5‐FU as a novel therapeutic approach in CRC patients. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: According to literature, interruptions during drug administration lead to a significant proportion of medication errors. Evidence on the effectiveness of interventions to reduce interruption is still limited. The purpose of this paper is to explore main reasons for interruptions during drug administration rounds in a geriatric ward of an Italian secondary hospital and test the effectiveness of a combined intervention.Design/methodology/approach: This is a pre and post-intervention observational study based on direct observation. All nurse staff (24) participated to the study that lead to observe a total of 44 drug dispensing rounds with 945 drugs administered to 491 patients in T0 and 994 drugs to 506 patients in T1.Findings: A significant reduction of raw number of interruptions (mean per round from 17.31 in T0 to 9.09 in T1, p<0.01), interruptions/patient rate (from 0.78 in T0 to 0.40 in T1, p<0.01) and interruptions/drugs rate (from 0.44 in T0 to 0.22 in T1, p<0.01) were observed. Needs for further improvements were elicited (e.g. a greater involvement of support staff).Practical Implications: Nurse staff should be adequately trained on the risks related to interruptions during drug administration since routine activity is at high risk of distractions due to its repetitive and skill-based nature.Originality/value: A strong involvement of both MB and leadership, together with the frontline staff, helped to raise staff motivation and guide a bottom-up approach, able to identify tailored interventions and serve concurrently as training instrument tool. [ABSTRACT FROM AUTHOR]

Background and Aim Of the Study: Cardiac implantable electronic device (CIED) implantation is associated with an increase in CIED infection. For pacemaker-dependent patients, temporary pacemaker leads are implanted until infection remission, which allows new CIED implantation. We compared the outcome of pacemaker-dependent patients with infected CIED based on whether a combined single procedure of epicardial pacemaker implantation with system extraction or a temporary transjugular pacemaker implantation with interval system implantation was performed.Methods: This retrospective study included pacemaker-dependent patients with CIED infection who were divided into two groups: the Tempo and Epi groups. The Tempo group received temporary transvenous pacemaker connected to an external pulse generator. After infection remission, a new permanent pacemaker was implanted, and the temporary pacemaker leads were removed. The Epi group received implantable epicardial right-ventricular pacemaker through infrasternal inferior pericardiotomy, and a permanent pulse generator was implanted through the same incision between the subcutaneous tissue and abdominal fascia.Results: Sixty-six patients were included. Forty-two patients with epicardial pacemakers were discharged after 9.5 ± 8.8 days without infection of the newly implanted epicardial pacemaker. Patients with temporary transjugular pacemaker lead were discharged 23 ± 15 days after receiving permanent pacemakers. No serious complications were recorded in the Epi group.Conclusions: CIED infections in pacemaker-dependent patients can be treated through epicardial pacemaker implantation that allows early patient mobility and reduces hospital stay with no risk of epicardial pacemaker infection. Epicardial pacemakers can be used as a bridge until permanent intravenous CIED is implanted or as a replacement for permeant intravenous CIED. [ABSTRACT FROM AUTHOR]

Bruton's tyrosine-kinase (BTK) is a non-receptor tyrosine kinase recently associated with glioma tumorigenesis and a novel prognostic marker for poor survival in patients with glioma. The p65BTK is a novel BTK isoform involved in different pathways of drug resistance of solid tumors, thus we aimed to investigate the expression and the putative role of p65BTK in tumors of the central nervous system (CNS). We selected a large cohort of patients with glial tumors (n = 71) and analyzed the expression of p65BTK in different histotypes and correlation with clinical parameters. Sections were stained with glial fibrillary acidic protein (GFAP), p53, epidermal growth factor receptor (EGFR), S100, vimentin, and epithelial membrane antigen (EMA) antibodies. Glioma stem cell (GSC) lines, isolated from glioblastoma multiforme (GBM), were treated with different concentrations of ibrutinib, a specific inhibitor of BTK, in order to evaluate their metabolic activity, mitotic index and mortality. Moreover, an orthotopic xenotransplant of GSC from human GBM was used to evaluate the expression of p65BTK in the brain of immunodeficient mice. p65BTK was expressed in GSC and in gemistocytes in human gliomas at different histological grade. We found a significant correlation between BTK expression and low-grade (LG) tumors (p ≤ 0.05) and overall survival (OS) of patients with grade III gliomas (p ≤ 0.05), suggestive of worst prognosis. Interestingly, the expression of p65BTK remained restricted exclusively to gemistocytic cells in the xenograft mouse model. Ibrutinib administration significantly reduced metabolic activity and mitotic index and increased mortality in GSC, highlighting the specific role of p65BTK in cell proliferation and survival. In conclusion, our data demonstrated that p65BTK is expressed in glioma tumors, restricted to gemistocytic cells, has a key role in GSC and has a bad prognostic value, thus highlighting the importance of future research for targeted therapy of human gliomas. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has shown impressive clinical results in the last decade, improving both solid and hematologic cancer patients’ overall survival. Nevertheless, most of the molecular aspects underlying the response to this approach are still under investigation. miRNAs in particular have been described as regulators of a plethora of different immunologic processes and thus have the potential to be key in the future developments of immunotherapy. In this review, we summarize and discuss the emerging role of miRNAs in the diagnosis and therapeutics of the four principal cancer immunotherapy approaches: immune checkpoint blockade, adoptive cell therapy, cancer vaccines, and cytokine therapy. In particular, this review is focused on potential roles for miRNAs to be adjuvants in soluble factor- and cell-based therapies, with the aim of helping to increase specificity and decrease toxicity, and on the potential for rationally identified miRNA-based diagnostic approaches to aid in precision clinical immunooncology. [ABSTRACT FROM AUTHOR]

miRNAs are central players in cancer biology and they play a pivotal role in mediating the network communication between tumor cells and their microenvironment. In melanoma, miRNAs can impair or facilitate a wide array of processes, and here we will focus on: the epithelial to mesenchymal transition (EMT), the immune milieu, and metabolism. Multiple miRNAs can affect the EMT process, even at a distance, for example through exosome-mediated mechanisms. miRNAs also strongly act on some components of the immune system, regulating the activity of key elements such as antigen presenting cells, and can facilitate an immune evasive/suppressive phenotype. miRNAs are also involved in the regulation of metabolic processes, specifically in response to hypoxic stimuli where they can mediate the metabolic switch from an oxidative to a glycolytic metabolism. Overall, this review discusses and summarizes recent findings on miRNA regulation in the melanoma tumor microenvironment, analyzing their potential diagnostic and therapeutic applications. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common form of malignant brain tumor in adults. GBM remains one of the most fatal and least successfully treated solid tumors: current therapies provide a median survival of 12–15 months after diagnosis, due to the high recurrence rate. Glioma Stem Cells (GSCs) are believed to be the real driving force of tumor initiation, progression and relapse. Therefore, better therapeutic strategies GSCs-targeted are needed. Resveratrol is a polyphenolic phytoalexin found in fruits and vegetables displaying pleiotropic health benefits. Many studies have highlighted its chemo-preventive and chemotherapeutic activities in a wide range of solid tumors. In this work, we analyzed the effects of Resveratrol exposure on cell viability, proliferation and motility in seven GSC lines isolated from GBM patients. For the first time in our knowledge, we investigated Resveratrol impact on Wnt signaling pathway in GSCs, evaluating the expression of seven Wnt signaling pathway-related genes and the protein levels of c-Myc and β-catenin. Finally, we analyzed Twist1 and Snail1 protein levels, two pivotal activators of epithelial-mesenchymal transition (EMT) program. Results showed that although response to Resveratrol exposure was highly heterogeneous among GSC lines, generally it was able to inhibit cell proliferation, increase cell mortality, and strongly decrease cell motility, modulating the Wnt signaling pathway and the EMT activators. Treatment with Resveratrol may represent a new interesting therapeutic approach, in order to affect GSCs proliferation and motility, even if further investigations are needed to deeply understand the GSCs heterogeneous response. [ABSTRACT FROM AUTHOR]

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