BACKGROUND: The fear of taking away hope hinders clinicians' willingness to share serious news with patients with advanced disease. Unrealistic illness expectations, on the other hand, can complicate decision making and end-of-life care outcomes. Exploration of the association between hope and illness expectations can support clinicians in better communication with their patients. AIM: The aim of this study was to explore whether realistic illness expectations are associated with reduced hope in people with advanced cancer. DESIGN: This is a cross-sectional secondary analysis of baseline data from a primary palliative care cluster-randomized trial CONNECT (data collected from July 2016 to October 2020). Hope was measured by Herth Hope Index. Illness expectations were measured by assessing patients' understanding of their treatment goals, life expectancy, and terminal illness acknowledgement. Multivariable regression was performed, adjusting for demographical and clinical confounders. SETTING/PARTICIPANTS: Adult patients with advanced solid cancers recruited across 17 oncology clinics. RESULTS: Data from 672 patients were included in the study, with mean age of 69.3 years (±10.2), 53.6% were female. Proportion of patients indicating realistic expectations varied based on which question was asked from 10% to 46%. Median level of hope was 39 (IQR = 36-43). Multivariate non-inferiority regression did not find any significant differences in hope between patients with more and less realistic illness expectations. CONCLUSIONS: Our results suggest that hope can be sustained while holding both realistic and unrealistic illness expectations. Communication about serious news should focus on clarifying the expectations as well as supporting people's hopes.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- motivace MeSH
- naděje MeSH
- nádory * terapie MeSH
- paliativní péče metody MeSH
- péče o umírající * MeSH
- průřezové studie MeSH
- randomizované kontrolované studie jako téma MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The application of lipid-based nanoparticles for COVID-19 vaccines and transthyretin-mediated amyloidosis treatment have highlighted their potential for translation to cancer therapy. However, their use in delivering drugs to solid tumors is limited by ineffective targeting, heterogeneous organ distribution, systemic inflammatory responses, and insufficient drug accumulation at the tumor. Instead, the use of lipid-based nanoparticles to remotely activate immune system responses is an emerging effective strategy. Despite this approach showing potential for treating hematological cancers, its application to treat solid tumors is hampered by the selection of eligible targets, tumor heterogeneity, and ineffective penetration of activated T cells within the tumor. Notwithstanding, the use of lipid-based nanoparticles for immunotherapy is projected to revolutionize cancer therapy, with the ultimate goal of rendering cancer a chronic disease. However, the translational success is likely to depend on the use of predictive tumor models in preclinical studies, simulating the complexity of the tumor microenvironment (e.g., the fibrotic extracellular matrix that impairs therapeutic outcomes) and stimulating tumor progression. This review compiles recent advances in the field of antitumor lipid-based nanoparticles and highlights emerging therapeutic approaches (e.g., mechanotherapy) to modulate tumor stiffness and improve T cell infiltration, and the use of organoids to better guide therapeutic outcomes.
- MeSH
- familiární amyloidové neuropatie * MeSH
- imunoterapie MeSH
- lidé MeSH
- lipidy MeSH
- nádorové mikroprostředí MeSH
- nádory * terapie MeSH
- vakcíny proti COVID-19 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Klíčová slova
- Mediately,
- MeSH
- digitální zdraví * MeSH
- lidé MeSH
- mobilní aplikace MeSH
- nádory prsu diagnóza MeSH
- nádory terapie MeSH
- protinádorové látky imunologicky aktivní aplikace a dávkování škodlivé účinky MeSH
- telemedicína MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- rozhovory MeSH
Nanoparticles are commonly used in diagnostics and therapy. They are also increasingly being implemented in cancer immunotherapy because of their ability to deliver drugs and modulate the immune system. However, the effect of nanoparticles on immune cells involved in the anti-tumor immune response is not well understood. The study reported here showed that nickel-doped maghemite nanoparticles (FN NP) are differentially cytotoxic to cultured mouse and human cancer cell lines, causing their death without negatively impacting the subsequent anticancer immune response. It also found that FN NP induced cell death in the mouse colorectal cancer cell line CT26 and human prostate cancer cell line PC-3, but not in the human prostate cancer cell line LNCaP. The induced cancer cell death did not affect the phenotype and responsivity of the isolated mouse peritoneal macrophages, or ex vivo-generated mouse bone marrow-derived, or human monocyte-derived dendritic cells. Additionally, the induced cancer cell death did not prevent the ex vivo-generated mouse or human dendritic cells from stimulating lymphocytes and enriching cell cultures with cancer cell-reactive T-cells. In conclusion, this study shows that FN NP could be a valuable platform for targeting cancer cells without causing immunosuppressive effects on the subsequent anticancer immune response.
- MeSH
- buňky PC-3 MeSH
- dendritické buňky * imunologie MeSH
- imunoterapie * metody MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory prostaty imunologie terapie MeSH
- nádory imunologie terapie MeSH
- nikl * chemie imunologie MeSH
- železité sloučeniny chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Despite significant improvement in the survival of pediatric patients with cancer, treatment outcomes for high-risk, relapsed, and refractory cancers remain unsatisfactory. Moreover, prolonged survival is frequently associated with long-term adverse effects due to intensive multimodal treatments. Accelerating the progress of pediatric oncology requires both therapeutic advances and strategies to mitigate the long-term cytotoxic side effects, potentially through targeting specific molecular drivers of pediatric malignancies. In this report, we present the results of integrative genomic and transcriptomic profiling of 230 patients with malignant solid tumors (the "primary cohort") and 18 patients with recurrent or otherwise difficult-to-treat nonmalignant conditions (the "secondary cohort"). The integrative workflow for the primary cohort enabled the identification of clinically significant single nucleotide variants, small insertions/deletions, and fusion genes, which were found in 55% and 28% of patients, respectively. For 38% of patients, molecularly informed treatment recommendations were made. In the secondary cohort, known or potentially driving alteration was detected in 89% of cases, including a suspected novel causal gene for patients with inclusion body infantile digital fibromatosis. Furthermore, 47% of findings also brought therapeutic implications for subsequent management. Across both cohorts, changes or refinements to the original histopathological diagnoses were achieved in 4% of cases. Our study demonstrates the efficacy of integrating advanced genomic and transcriptomic analyses to identify therapeutic targets, refine diagnoses, and optimize treatment strategies for challenging pediatric and young adult malignancies and underscores the need for broad implementation of precision oncology in clinical settings.
- MeSH
- dítě MeSH
- genomika * metody MeSH
- individualizovaná medicína * metody MeSH
- kohortové studie MeSH
- kojenec MeSH
- lékařská onkologie metody MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory * genetika terapie MeSH
- předškolní dítě MeSH
- stanovení celkové genové exprese MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Progress in cytokine engineering is driving therapeutic translation by overcoming these proteins' limitations as drugs. The IL-2 cytokine is a promising immune stimulant for cancer treatment but is limited by its concurrent activation of both pro-inflammatory immune effector cells and antiinflammatory regulatory T cells, toxicity at high doses, and short serum half-life. One approach to improve the selectivity, safety, and longevity of IL-2 is complexing with anti-IL-2 antibodies that bias the cytokine toward immune effector cell activation. Although this strategy shows potential in preclinical models, clinical translation of a cytokine/antibody complex is complicated by challenges in formulating a multiprotein drug and concerns regarding complex stability. Here, we introduced a versatile approach to designing intramolecularly assembled single-agent fusion proteins (immunocytokines, ICs) comprising IL-2 and a biasing anti-IL-2 antibody that directs the cytokine toward immune effector cells. We optimized IC construction and engineered the cytokine/antibody affinity to improve immune bias. We demonstrated that our IC preferentially activates and expands immune effector cells, leading to superior antitumor activity compared with natural IL-2, both alone and combined with immune checkpoint inhibitors. Moreover, therapeutic efficacy was observed without inducing toxicity. This work presents a roadmap for the design and translation of cytokine/antibody fusion proteins.
- MeSH
- cytokiny metabolismus MeSH
- interleukin-2 * imunologie MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory imunologie terapie farmakoterapie MeSH
- proteinové inženýrství metody MeSH
- regulační T-lymfocyty imunologie účinky léků MeSH
- rekombinantní fúzní proteiny * farmakologie imunologie aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Artificial intelligence (AI) has made a tremendous impact in the space of healthcare, and proton therapy is not an exception. Proton therapy has witnessed growing popularity in oncology over recent decades, and researchers are increasingly looking to develop AI and machine learning tools to aid in various steps of the treatment planning and delivery processes. This review delves into the emergent role of AI in proton therapy, evaluating its development, advantages, intended clinical contexts, and areas of application. Through the analysis of 76 studies, we aim to underscore the importance of AI applications in advancing proton therapy and to highlight their prospective influence on clinical practices.
- MeSH
- lidé MeSH
- nádory * radioterapie terapie MeSH
- plánování radioterapie pomocí počítače metody MeSH
- protonová terapie * metody MeSH
- strojové učení MeSH
- umělá inteligence * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
