Multiscale Modeling of Spheroid Tumors: Effect of Nutrient Availability on Tumor Evolution

Recent years have revealed a large number of complex mechanisms and interactions that drive the development of malignant tumors. Tumor evolution is a framework that explains tumor development as a process driven by survival of the fittest, with tumor cells of different properties competing for limited available resources. To predict the evolutionary trajectory of a tumor, knowledge of how cellular properties influence the fitness of a subpopulation in the context of the microenvironment is required and is often inaccessible. Computational multiscale-modeling of tissues enables the observation of the full trajectory of each cell within the tumor environment. Here, we model a 3D spheroid tumor with subcellular resolution. The fitness of individual cells and the evolutionary behavior of the tumor are quantified and linked to cellular and environmental parameters. The fitness of cells is solely influenced by their position in the tumor, which in turn is influenced by the two variable parameters of our model: cell–cell adhesion and cell motility. We observe the influence of nutrient independence and static and dynamically changing nutrient availability on the evolutionary trajectories of heterogeneous tumors in a high-resolution computational model. Regardless of nutrient availability, we find a fitness advantage of low-adhesion cells, which are favorable for tumor invasion. We find that the introduction of nutrient-dependent cell division and death accelerates the evolutionary speed. The evolutionary speed can be increased by fluctuations in nutrients. We identify a distinct frequency domain in which the evolutionary speed increases significantly over a tumor with constant nutrient supply. The findings suggest that an unstable supply of nutrients can accelerate tumor evolution and, thus, the transition to malignancy

Photopolymerizable platelet lysate hydrogels for customizable 3D cell culture platforms

3D cell culture platforms have emerged as a setting that resembles in vivo environments replacing the traditional 2D platforms. Over the recent years, an extensive effort has been made on the development of more physiologically relevant 3D cell culture platforms. Extracellular matrix-based materials have been reported as a bioactive and biocompatible support for cell culture. For example, human plasma derivatives have been extensively used in cell culture. Despite all the promising results, in most cases these types of materials have poor mechanical properties and poor stability in vitro. Here plasma-based hydrogels with increased stability are proposed. Platelet lysates are modified by addition of methacryloyl groups (PLMA) that polymerize in controlled geometries upon UV light exposure. The hydrogels could also generate porous scaffolds after lyophilization. The results show that PLMA materials have increased mechanical properties that can be easily adjusted by changing PLMA concentration or modification degree. Cells readily adhere, proliferate, and migrate, exhibiting high viability when encapsulated in PLMA hydrogels. The innovation potential of PLMA materials is based on the fact that it is a complete xeno-free solution for human cell culture, thus an effective alternative to the current gold standards for 3D cell culture based on animal products.publishe

How I treat anaplastic glioma without 1p/19q codeletion

Anaplastic astrocytoma without 1p/19q codeletion is a rare primary central nervous system tumour occurring primarily in middle-aged adults and associated with a median survival of 5–10 years. The major corner stone of treatment is maximal safe neurosurgical resection, followed by radiotherapy and chemotherapy. Several clinical trials addressed the optimal adjuvant treatment; however, interpretation has been challenged by the recent molecular marker-based reclassification of tumour. The interim study of the CATNON trial strongly suggests the addition of 12 adjuvant cycles of temozolomide in addition to radiotherapy after maximal safe resection in patients with anaplastic astrocytoma without 1p/19q codeletion. Based on more recently presented data from the second interim analysis of the CATNON trial and from the molecular analysis, benefit from temozolomide during and after radiotherapy is limited to patients with isocitrate dehydrogenase-mutated anaplastic astrocytoma. Given the small patient number in the single subgroups and the so far missing neurocognitive and quality of life data, more mature analyses needs to be awaited to draw final conclusions on the application of concurrent temozolomide treatment for the daily routine in patients who already are scheduled for adjuvant temozolomide. Further molecular analysis is ongoing to define personalised treatment approaches in patients with anaplastic astrocytom

Challenges in oncology career: are we closing the gender gap? Results of the new ESMO Women for Oncology Committee survey

Discrimination; Gender equity; OncologyDiscriminació; Equitat de gènere; OncologiaDiscriminación; Equidad de género; OncologíaBackground Following a European Society for Medical Oncology Women for Oncology (ESMO W4O) survey in 2016 showing severe under-representation of female oncologists in leadership roles, ESMO launched a series of initiatives to address obstacles to gender equity. A follow-up survey in October 2021 investigated progress achieved. Materials and methods The W4O questionnaire 2021 expanded on the 2016 survey, with additional questions on the impact of ethnicity, sexual orientation and religion on career development. Results were analysed according to respondent gender and age. Results The survey sample was larger than in 2016 (n = 1473 versus 482), especially among men. Significantly fewer respondents had managerial or leadership roles than in 2016 (31.8% versus 51.7%). Lack of leadership development for women and unconscious bias were considered more important in 2021 than in 2016. In 2021, more people reported harassment in the workplace than in 2016 (50.3% versus 41.0%). In 2021, ethnicity, sexual orientation and religion were considered to have little or no impact on professional career opportunities, salary setting or related potential pay gap. However, gender had a significant or major impact on career development (25.5% of respondents), especially in respondents ≤40 years of age and women. As in 2016, highest ranked initiatives to foster workplace equity were promotion of work–life balance, development and leadership training and flexible working. Significantly more 2021 respondents (mainly women) supported the need for culture and gender equity education at work than in 2016. Conclusions Gender remains a major barrier to career progression in oncology and, although some obstacles may have been reduced since 2016, we are a long way from closing the gender gap. Increased reporting of discrimination and inappropriate behaviour in the workplace is a major, priority concern. The W4O 2021 survey findings provide new evidence and highlight the areas for future ESMO interventions to support equity and diversity in oncology career development.This work was supported by the European Society for Medical Oncology (no grant number)

Has COVID-19 had a greater impact on female than male oncologists? Results of the ESMO Women for Oncology (W4O) Survey

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Desigualtats; DonaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Desigualdades; MujerCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV Inequalities; WomanBackground European Society for Medical Oncology Women for Oncology (ESMO W4O) research has previously shown under-representation of female oncologists in leadership roles. As early reports suggested disproportionate effects of the COVID-19 pandemic on women, the ESMO W4O Committee initiated a study on the impact of the pandemic on the lives of female and male oncologists. Methods A questionnaire was sent to ESMO members and put on the ESMO website between 8 June 2020 and 2 July 2020. Questions focused on the working (hospital tasks, laboratory tasks, science) and home (household management, childcare, parent care, personal care) lives of oncologists during and after COVID-19-related lockdowns. Results Of 649 respondents, 541 completed the questionnaire. Of these, 58% reported that COVID-19 had affected their professional career, 83% of whom said this was in a negative way (85% of women versus 76% of men). Approximately 86% reported that COVID-19 had changed their personal life and 82% their family life. Women were again significantly more affected than men: personal life (89% versus 78%; P = 0.001); family life (84% versus 77%; P = 0.037). During lockdowns, women reported increased time spent on hospital and laboratory tasks compared with men (53% versus 46% and 33% versus 26%, respectively) and a significantly higher proportion of women than men spent less time on science (39% versus 25%) and personal care (58% versus 39%). After confinement, this trend remained for science (42% versus 23%) and personal care (55% versus 36%). Conclusions The COVID-19 pandemic has adversely affected the professional and home lives of oncologists, especially women. Reduced research time for female oncologists may have long-lasting career consequences, especially for those at key stages in their career. The gender gap for promotion to leadership positions may widen further as a result of the pandemic.This work was supported by the European Society for Medical Oncology (ESMO)

Young oncologists' perspective on the role and future of the clinician-scientist in oncology

Jóvenes oncólogos; OncologíaJoves oncòlegs; OncologiaYoung oncologists; OncologyThe clinician-scientist, or more commonly known as physician-scientist in North America, covers a wide spectrum of roles, but is essentially an individual who holds a medical degree and usually a postgraduate scientific qualification (e.g. MS/MSc/MRes and PhD) and is primarily dedicated to pursuing their academic research interests, which can range from basic science to more translational or clinical research. Clinician-scientists are important players within the contemporary multidisciplinary and interprofessional teamscience approach to cancer research and cancer care. Clinical experience alongside rigorous training in research and scientific methodologies provides a strong foundation for clinician-scientists to conduct and lead research advancing the way we understand and treat patients with cancer.European Society for Medical Oncology (ESMO) (no grant number)

High-Throughput Proteomics Identifies Proteins With Importance to Postantibiotic Recovery in Depolarized Persister Cells

Bacterial populations produce phenotypic variants called persisters to survive harmful conditions. Persisters are highly tolerant to antibiotics and repopulate environments after the stress has vanished. In order to resume growth, persisters have to recover from the persistent state, but the processes behind recovery remain mostly elusive. Deciphering these processes is an essential step toward understanding the persister phenomenon in its entirety. High-throughput proteomics by mass spectrometry is a valuable tool to assess persister physiology during any stage of the persister life cycle, and is expected to considerably contribute to our understanding of the recovery process. In the present study, an Escherichia coli strain, that overproduces the membrane-depolarizing toxin TisB, was established as a model for persistence by the use of high-throughput proteomics. Labeling of TisB persisters with stable isotope-containing amino acids (pulsed-SILAC) revealed an active translational response to ampicillin, including several RpoS-dependent proteins. Subsequent investigation of the persister proteome during postantibiotic recovery by label-free quantitative proteomics identified proteins with importance to the recovery process. Among them, AhpF, a component of alkyl hydroperoxide reductase, and the outer membrane porin OmpF were found to affect the persistence time of TisB persisters. Assessing the role of AhpF and OmpF in TisB-independent persisters demonstrated that the importance of a particular protein for the recovery process strongly depends on the physiological condition of a persister cell. Our study provides important insights into persister physiology and the processes behind recovery of depolarized cells

Large-scale database mining reveals hidden trends and future directions for cancer immunotherapy

LLC Cancer immunotherapy has fundamentally changed the landscape of oncology in recent years and significant resources are invested into immunotherapy research. It is in the interests of researchers and clinicians to identify promising and less promising trends in this field in order to rationally allocate resources. This requires a quantitative large-scale analysis of cancer immunotherapy related databases. We developed a novel tool for text mining, statistical analysis and data visualization of scientific literature data. We used this tool to analyze 72002 cancer immunotherapy publications and 1469 clinical trials from public databases. All source codes are available under an open access license. The contribution of specific topics within the cancer immunotherapy field has markedly shifted over the years. We show that the focus is moving from cell-based therapy and vaccination towards checkpoint inhibitors, with these trends reaching statistical significance. Rapidly growing subfields include the combination of chemotherapy with checkpoint blockade. Translational studies have shifted from hematological and skin neoplasms to gastrointestinal and lung cancer and from tumor antigens and angiogenesis to tumor stroma and apoptosis. This work highlights the importance of unbiased large-scale database mining to assess trends in cancer research and cancer immunotherapy in particular. Researchers, clinicians and funding agencies should be aware of quantitative trends in the immunotherapy field, allocate resources to the most promising areas and find new approaches for currently immature topics