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Antibodies and antibody-based immunotherapeutics are the mainstays of cancer immunotherapy. Expanding the repertoire of cancer-specific and cancer-associated epitopes targetable with antibodies represents an important area of research. Phage display is a powerful approach allowing the use of diverse antibody libraries to be screened for binding to a wide range of targets. In this review, we summarize the basics of phage display technology and highlight the advances in anticancer antibody identification and modification via phage display platform. Finally, we describe phage display-derived anticancer monoclonal antibodies that have been approved to date or are in clinical development. • Concise review of principles of phage display technology. • Various approaches for library construction and selection strategies. • Antibody engineering via phage display technology. • Ab formats, guided selection, humanization, affinity maturation, Ab developability. • Current landscape of anticancer antibodies derived from phage display technology. [ABSTRACT FROM AUTHOR]

Spontaneous locomotion is a common feature of most metazoan cells, generally attributed to the properties of actomyosin networks. This force-producing machinery has been studied down to the most minute molecular details, especially in lamellipodium-driven migration. Nevertheless, how actomyosin networks work inside contraction-driven amoeboid cells still lacks unifying principles. Here, using stable motile blebs from HeLa cells as a model amoeboid motile system, we imaged the dynamics of the actin cortex at the single filament level and revealed the co-existence of three distinct rheological phases. We introduce "advected percolation," a process where rigidity percolation and active advection synergize, spatially organizing the actin network's mechanical properties into a minimal and generic locomotion mechanism. Expanding from our observations on simplified systems, we speculate that this model could explain, down to the single actin filament level, how amoeboid cells, such as cancer or immune cells, can propel efficiently through complex 3D environments. [Display omitted] • Actin filament density at the cell front controls bleb protrusion • A solid-like actomyosin cortex in the cell middle sterically enables cell propulsion • The material properties of amoeboid cells organize spatially by advected percolation • Stable blebs in adhesive environments can fragment into cytoplasts García-Arcos et al. propose a universal framework for amoeboid migration: actin filaments and myosin motors spatially self-organize and give rise to different material properties in different parts of the cell. A solid-like state in the actin network found in the middle of the cell enables efficient cell propulsion. [ABSTRACT FROM AUTHOR]

Cancer immunotherapies produce remarkable results in B cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor and normal tissues to identify biologically relevant cell surface immunotherapeutic targets for neuroblastoma, an often-fatal childhood cancer. Proteogenomic analyses reveal sixty high-confidence candidate immunotherapeutic targets, and we prioritize delta-like canonical notch ligand 1 (DLK1) for further study. High expression of DLK1 directly correlates with a super-enhancer. Immunofluorescence, flow cytometry, and immunohistochemistry show robust cell surface expression of DLK1. Short hairpin RNA mediated silencing of DLK1 in neuroblastoma cells results in increased cellular differentiation. ADCT-701, a DLK1-targeting antibody-drug conjugate (ADC), shows potent and specific cytotoxicity in DLK1-expressing neuroblastoma xenograft models. Since high DLK1 expression is found in several adult and pediatric cancers, our study demonstrates the utility of a proteogenomic approach and credentials DLK1 as an immunotherapeutic target. [Display omitted] • Multi-omic data integration prioritizes DLK1 as an immunotherapeutic target • DLK1 expression is driven by a super-enhancer • DLK1 silencing in neuroblastoma cells results in cellular differentiation • DLK1-directed ADC shows potent and specific cytotoxicity in preclinical models Hamilton et al. perform proteogenomic analyses to discover high-confidence candidate immunotherapeutic targets in neuroblastoma. Delta-like canonical notch ligand 1 (DLK1) is prioritized and validated. A DLK1-directed antibody-drug conjugate (ADCT-701) is developed and shows potent and specific in vivo cytotoxicity, supporting a phase 1 first-in-human clinical trial (ClinicalTrials.gov: NCT06041516). [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV), known for its oncogenic properties, is the primary cause of cervical cancer and significantly contributes to mortality rates. It also plays a considerable role in the globally rising incidences of head and neck cancers. These cancers pose a substantial health burden worldwide. Current limitations in diagnostic and treatment strategies, along with inadequate coverage of preventive vaccines in low- and middle-income countries, hinder the progress toward the World Health Organization (WHO) HPV prevention and control targets set for 2030. In response to these challenges, extensive research in structural virology has explored the properties of HPV proteins, yielding crucial insights into the mechanisms of HPV infection that are important for the development of prevention and therapeutic strategies. This review highlights recent advances in understanding the structures of HPV proteins and discusses achievements and future opportunities for HPV vaccine development. [Display omitted] In this review, Han et al. provide a comprehensive overview of HPV-related protein structures. The authors describe their roles within the HPV life cycle and discuss important protein-protein interactions. They emphasize the importance of structural biology for the development of prophylactic vaccines and therapeutics against HPV. [ABSTRACT FROM AUTHOR]

Coronary microvascular dysfunction (CMD) has been implicated as a potential mechanism in the pathophysiology of different clinical presentations, including ischemia and no obstructive coronary artery disease (INOCA), myocardial infarction and nonobstructive coronary arteries (MINOCA), stress cardiomyopathy, heart failure, and myocarditis. There are limited data about the role of CMD in cancer therapy-related cardiovascular toxicities. Four women with a diagnosis of active cancer receiving treatment who developed subsequent MINOCA or INOCA presented for cardiac catheterization. Upon coronary angiography showing no obstructive coronary arteries, coronary function testing was performed to evaluate for CMD. Coronary physiology was assessed measuring non-hyperemic (resting full-cycle ratio [RFR]) and hyperemic (fractional flow reserve [FFR]) indices using a physiologic pressure wire. The wire also measured coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and RFR using thermodilution technology. CMD was confirmed if the CFR was <2.5 and the IMR was >25. Among 4 patients with diagnosis of active cancer presenting with chest pain, there was no evidence of obstructive coronary artery disease, leading to separate diagnoses of INOCA, MINOCA, stress cardiomyopathy, and myocarditis. We found CMD in 2 patients (1 with INOCA and 1 with immune checkpoint inhibitor-related myocarditis). CMD may play a role in cardiovascular toxicities. Further coronary physiology studies are needed to understand the mechanisms of cancer therapy-related cardiovascular toxicity and CMD, as well as optimal preventive and treatment options. • Cancer therapies may increase the risk of coronary microvascular dysfunction (CMD). • Invasive testing with the thermodilution method is effective for diagnosis of CMD. • The association of CMD and cancer therapies requires further study. [ABSTRACT FROM AUTHOR]

We recommend the stratification of high-grade (HG) non–muscle-invasive bladder cancer into HG/G2 and HG/G3, as patients with HG/G3 have worse prognosis than those with HG/G2. A Hybrid grading system (categories: low grade, HG/G2, and HG/G3) outperforms the current World Health Organization 2004/2016 system. Grade is an important determinant of progression in non–muscle-invasive bladder cancer. Although the World Health Organization (WHO) 2004/2016 grading system is recommended, other systems such as WHO1973 and WHO1999 are still widely used. Recently, a hybrid (three-tier) system was proposed, separating WHO2004/2016 high grade (HG) into HG/grade 2 (G2) and HG/G3 while maintaining low grade. We assessed the prognostic performance of HG/G3 and HG/G2. Three independent cohorts with 9712 primary (first diagnosis) Ta-T1 bladder tumors were analyzed. Time to progression was analyzed with cumulative incidence functions and Cox regression models. Harrell's C-index was used to assess discrimination. Time to progression was significantly shorter for HG/G3 than for HG/G2 in multivariable analyses (cohort 1: hazard ratio [HR] = 1.92; cohort 2: HR = 2.51, and cohort 3: HR = 1.69). Corresponding progression risks at 5 yr were 18%, 20%, and 18% for HG/G3 versus 7.3%, 7.5%, and 9.3% for HG/G2, respectively. Cox models using hybrid grade performed better than models with WHO2004/2016 (all cohorts; p < 0.001). For the three cohorts, C-indices for WHO2004/2016 were 0.69, 0.62, and 0.75, while, for hybrid grade, C-indices were 0.74, 0.68, and 0.78, respectively. Subdividing the HG category into HG/G2 and HG/G3 stratifies time to progression and supports the recommendation to adopt the hybrid grading system for Ta/T1 bladder cancers. [ABSTRACT FROM AUTHOR]

Cysteine cathepsins are a fascinating group of proteolytic enzymes that play diverse and crucial roles in numerous biological processes, both in health and disease. Understanding these proteases is essential for uncovering novel insights into the underlying mechanisms of a wide range of disorders, such as cancer. Cysteine cathepsins influence cancer biology by participating in processes such as extracellular matrix degradation, angiogenesis, immune evasion, and apoptosis. In this comprehensive review, we explore foundational research that illuminates the diverse and intricate roles of cysteine cathepsins as diagnostic markers and therapeutic targets for cancer. This review aims to provide valuable insights into the clinical relevance of cysteine cathepsins and explore their capacity to advance personalised and targeted medical interventions in oncology. • Cysteine cathepsins are pivotal in many cancer processes, making them desirable therapeutic targets. • Irregular cysteine cathepsin levels can serve as diagnostic and prognostic biomarkers in various cancers. • Development of molecular probes for cysteine cathepsins enhances diagnostic imaging and image-guided surgery. • Selective inhibitors and novel drug delivery systems targeting cysteine cathepsins hold promise for innovative cancer treatments. • Advances in antibody-drug conjugates utilizing cysteine cathepsins offer major potential in cancer treatment. [ABSTRACT FROM AUTHOR]

Cathepsins, a family of lysosomal peptidases, play a crucial role in maintaining cellular homeostasis by regulating protein turnover and degradation as well as many specific regulatory actions that are important for proper cell function and human health. Alterations in the activity and expression of cathepsins have been observed in many diseases such as cancer, inflammation, neurodegenerative disorders, bone remodelling-related conditions and others. These changes are not exclusively harmful, but rather appear to be a compensatory response on the lack of one cathepsin in order to maintain tissue integrity. The upregulation of specific cathepsins in response to the inhibition or dysfunction of other cathepsins suggests a fine-tuned system of proteolytic balance and understanding the compensatory role of cathepsins may improve therapeutic potential of cathepsin's inhibitors. Selectively targeting one cathepsin or modulating their activity could offer new treatment strategies for a number of diseases. This review emphasises the need for comprehensive research into cathepsin biology in the context of disease. The identification of the specific cathepsins involved in compensatory responses, the elucidation of the underlying molecular mechanisms and the development of targeted interventions could lead to innovative therapeutic approaches. [Display omitted] [ABSTRACT FROM AUTHOR]

L'actualité en oncologie radiothérapie est marquée par les résultats d'essais stratégiques particulièrement pour les cancers de l'œsophage et du rectum. Pour l'adénocarcinome de l'œsophage, en situation préopératoire, les résultats de l'étude ESOPEC ont montré un bénéfice de survie de la chimiothérapie périopératoire par 5-fluoro-uracile, leucovorine oxaliplatine, taxotère en comparaison à la chimioradiothérapie (irradiation de 41,4 Gy avec une chimiothérapie concomitante par carboplatine/paclitaxel). En situation exclusive, l'étude CONCORDE n'a pas montré de bénéfice de l'escalade de dose et la dose standard reste 50 Gy. Pour le cancer du pancréas opérable, l'étude NRG/RTOG0848 qui comparait la chimiothérapie adjuvante avec ou sans chimioradiothérapie complémentaire a retrouvé une augmentation significative de la probabilité de survie sans maladie à 5 ans dans le sous-groupe de patients sans atteinte ganglionnaire. Pour les cancers du rectum, l'actualisation à 7 ans des résultats de l'étude PRODIGE 23 a confirmé le bénéfice non seulement en termes de survie sans récidive mais également de survie globale d'une chimiothérapie néoadjuvante par 5-fluoro-uracile, acide folinique, irinotécan et oxalipalatine avant la chimioradiothérapie, alors que l'actualisation de l'étude RAPIDO a montré un taux de rechute locale inacceptable dans le bras expérimental. L'actualisation de l'étude OPRA a montré un taux de survie avec conservation d'organe à 5 ans significativement supérieur en faveur du bras chimioradiothérapie suivie de la chimiothérapie en comparaison à la chimiothérapie d'induction première suivie de chimioradiothérapie. Une étude de phase 2 incluant 41 patients atteints d'un cancer du rectum localement avancé avec défaillance du système de réparation de l'ADN, a montré qu'un traitement exclusif par immunothérapie anti-PDL1 (dostarlimab) pendant 6 mois permettait une réponse clinique complète sans recours à un traitement complémentaire (ni radiothérapie, ni chirurgie). Pour le carcinome épidermoïde du canal anal, la survie et les profils de toxicité des patients inclus dans la cohorte anabase traités pour une tumeur de petit stade (T1 ou T2) ont été comparés selon qu'ils aient reçu exclusivement de la radiothérapie ou de la chimioradiothérapie. L'ajout d'une chimiothérapie à la radiothérapie ne montrait pas de bénéfice mais augmentait la toxicité et le risque d'allongement du traitement en raison d'interruption. Current events in radiotherapy oncology are marked by the results of strategic trials, particularly for esophageal and rectal cancers. For resectable esophageal adenocarcinoma, results of the ESOPEC study showed a benefit in overall survival from the perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin and docetaxel compared to chemoradiotherapy (41.4 Gy radiotherapy and carboplatin/paclitaxel chemotherapy). In definitive setting, the CONCORDE study did not show any benefit from dose escalation and the standard dose remains 50 Gy. For resectable pancreatic cancer, the NRG/RTOG0848 study that compared adjuvant chemotherapy with or without chemoradiotherapy found a significant increase of the 5-year disease-free survival rate in the subgroup of node-negative patients. For rectal cancers, the 7-year update of PRODIGE 23 study confirmed the benefit in disease-free- and overall survival of neoadjuvant folinic acid, fluorouracil, irinotecan and oxaliplatin chemotherapy before chemoradiotherapy of T3, T4 or N+ adenocarcinoma, while the update of the RAPIDO study revealed an unacceptable local recurrence rate in the experimental arm. The update of the OPRA study shows a significantly higher 5-year organ preservation rate in favor of the chemoradiotherapy arm followed by consolidation chemotherapy compared to induction chemotherapy followed by CRT. A phase 2 study, including 41 patients with mismatch repair deficient, locally advanced rectal cancer reported that exclusive treatment with anti-PDL1 immunotherapy (dostarlimab) for 6 months resulted in complete clinical response without the need of additional treatment (neither radiotherapy nor surgery). For anal carcinoma, the analysis of survival and toxicity profiles of patients treated for a small stage T1 or T2 tumor were compared depending on whether they received exclusive radiotherapy or chemoradiotherapy. The addition of chemotherapy to radiotherapy did not show any survival benefit but significantly increased toxicity and the risk of radiotherapy disruption. [ABSTRACT FROM AUTHOR]

Nous proposons une sélection non exhaustive des principaux essais cliniques présentés courant 2023–2024 ayant retenu notre attention dans le cadre de l'oncologie-radiothérapie appliquée aux cancers urologiques et incluant la prise en charge du cancer de la prostate (radiothérapie du cancer localisé, radiothérapie après prostatectomie, réirradiation, récidive biochimique après traitement local, radiothérapie du cancer métastatique), du cancer de vessie infiltrant le muscle et du primitif rénal. Herein, we provide a non-exhaustive selection of the main clinical trials presented in 2023–2024 related to radiation-oncology used in the treatment of urological cancers including prostate cancer (radiotherapy of localized prostate cancer, post-prostatectomy irradiation, reirradiation, biochemical recurrence following local treatment, radiotherapy for metastatic cancer), muscle invasive bladder cancer and primary kidney cancer. [ABSTRACT FROM AUTHOR]

In recent years, more substrates and cellular and physiological processes under the control of sentrin-specific proteases (SENPs) have been revealed. SENPs play important roles in gene expression, cell cycle progression, genome stability, cellular metabolism, macromolecular assemblies, and infection and immunity. SENPs have emerged as important players in tumorigenesis and as potential therapeutic targets in cancer. SENPs are frequently overexpressed in cancer and are associated with poor prognosis and resistance against anticancer drugs. Besides cancer, the dysregulation of SENPs has been linked to other diseases, including cardiac, metabolic, muscular, and neurological conditions. Because of their therapeutic potential in cancer and other diseases, increasing effort has been put into the discovery and development of SENP inhibitors. Posttranslational modification by small ubiquitin-like modifiers (SUMOs) is critical in regulating diverse cellular processes including gene expression, cell cycle progression, genome integrity, cellular metabolism, and inflammation and immunity. The covalent attachment of SUMOs to target proteins is highly dynamic and reversible through the concerted action of SUMO conjugating and deconjugating enzymes. In mammalian cells, sentrin-specific proteases (SENPs) are the most abundant family of deconjugating enzymes. This review highlights recent advances in our knowledge of the substrates and cellular and physiological processes controlled by SENPs. Notably, SENPs are emerging as significant players in cancer, as well as in other diseases, making them attractive targets for therapeutic intervention. Consequently, a growing amount of effort in the field is being directed towards the development of SENP inhibitors. [ABSTRACT FROM AUTHOR]

• We screened the expression profiles of miRNAs in the late stage of RBC preservation. • We identified miRNAs that changed during different storage times as well as potential target genes. • We predicted the potential regulatory effects of these differential miRNAs through bioinformatics. To detect the differentially expressed regulatory miRNAs in the late stage of red blood cell (RBC) preservation and predict their roles. Suspended RBCs with different storage periods of 35 day, 42 day, and 50 day were collected for routine blood tests, RNA extraction, and preparation of small RNA sequencing libraries. The constructed libraries were sequenced and the biological functions of differential miRNAs in RBCs in the late storage were analyzed by bioinformatics. Routine indicators of RBCs in the late stage were not significantly affected by preservation time. The Pearson correlation analysis performing on RBC miRNAs with different storage days revealed that RBC miRNAs changed with the increase of storage days. RBC miRNAs from day 35 (D35), day 42 (D42) and day 50 (D50) showed significant differences (P < 0.05). Compared RBC miRNAs from D42 with these from D35, there were 690 up-regulated miRNAs and 82 down-regulated miRNAs; compared RBC miRNAs from D50 with these from D35, there were 638 up-regulated miRNAs and 123 down-regulated miRNAs; compared RBC miRNAs from D42 with these from D50, there were 271 up-regulated miRNAs and 515 down-regulated miRNAs. GO enrichment analysis of target genes of differential miRNAs were mainly involved in cell metabolism, biosynthesis, protein modification, gene expression and transcriptional regulation of biological processes. KEGG pathway enrichment analysis of miRNA target genes showed that differential miRNA target genes were closely related to pathways in cancer. MiRNAs were differentially expressed in the late stage of RBC preservation, and may be involved in various biological processes, especially cancer. [ABSTRACT FROM AUTHOR]

The microbiome is a modifiable factor influencing the efficacy of immune checkpoint blockade (ICB) through multiple mechanisms. Clinical trial reports reveal that modulation of the efficacy of ICB through fecal microbiota transplantation (FMT) and probiotics for altering the intestinal microbiome is clinically feasible. The presence and role of a tumor microbiome, in addition to the intestinal microbiome, may be crucial in the regulation of tumorigenesis. Advances in sequencing technology and analytical methods are accelerating microbiome research, enabling more in-depth investigations. Immune checkpoint blockade (ICB) is one of the leading immunotherapies, although a variable extent of resistance has been observed among patients and across cancer types. Among the efforts underway to overcome this challenge, the microbiome has emerged as a factor affecting the responsiveness and efficacy of ICB. Active research, facilitated by advances in sequencing techniques, is assessing the predominant influence of the intestinal microbiome, as well as the effects of the presence of an intratumoral microbiome. In this review, we describe recent findings from clinical trials, observational studies of human patients, and animal studies on the impact of the microbiome on the efficacy of ICB, highlighting the role of the intestinal and tumor microbiomes and the contribution of methodological advances in their study. [ABSTRACT FROM AUTHOR]

Altered immune system activity is one of the common pathomechanisms of depressive disorders and cancer. The aim of this study is to evaluate level of selected elements of the kynurenine pathway in groups of depressed and oncological patients. The study included 156 individuals, aged 19–65 years (M = 43.46, SD = 13.99), divided into three groups, namely depressive disorders (DD), oncology patients (OG), and a comparison group of healthy subjects (CG). A sociodemographic questionnaire and the Hamilton Depression Rating Scale (HDRS) were used in the study to assess the intensity of depressive symptoms. Level of TDO2, L-KYN, HK, AA and QA was significantly higher in patients from OG and DD groups than in the comparison group. TDO2 level in the OG group was positively correlated with the severity of depressive symptoms. When the OG and DD groups were analyzed together, level of TDO2, 3-HKYN, AA, QA correlated positively with the severity of depressive symptoms. Thus, kynurenine pathway might play an integral role in the pathogenesis of depression. [ABSTRACT FROM AUTHOR]

Organic nanocrystals, particularly those composed of conjugated molecules, hold immense potential for various applications. However, their practical utility is often hindered by the challenge of achieving stable aqueous dispersions, which are essential for biological compatibility and effective delivery. This study introduces a novel and versatile strategy for preparing stable aqueous organic nanocrystals using a modified reprecipitation method. We demonstrate the broad applicability of this approach by successfully preparing a diverse library of nanocrystals from 27 conjugated molecules. Our findings reveal a charge-balanced aggregation mechanism for nanocrystal formation, highlighting the crucial role of surface charge in controlling particle size and stability. Based on this mechanism, we establish a comprehensive molecular combination strategy that directly links molecular properties to colloidal behaviour, enabling the straightforward prediction and preparation of stable aqueous dispersions without the need for excipients. This strategy provides a practical workflow for tailoring the functionality of these nanocrystals for a wide range of applications. To illustrate their therapeutic potential, we demonstrate the enhanced efficacy of these nanocrystals in treating acute ulcerative colitis, myocardial ischemia/reperfusion injury, and cancer in mouse models. This work paves the way for developing next-generation nanomaterials with tailored functionalities for diverse biomedical applications. [Display omitted] • Bridging Disciplines: This research bridges crystal engineering and colloid science by achieving aqueous stability of organic nanocrystals. • New Design Rules: Charge-balanced aggregation links molecular properties to colloidal behaviour for stable nanocrystals. • Predictive Strategy: A strategy for identifying suitable molecular combinations for aqueous organic nanocrystals. • Practical Workflow: A practical workflow for preparing diverse aqueous organic nanocrystals. • Functional Control & Applications: Diverse molecular combinations enable control over nanocrystal functionality for bioapplications. [ABSTRACT FROM AUTHOR]

Over the past decade, ultrasound (US) has gathered significant attention and research focus in the realm of medical treatments, particularly within the domain of anti-cancer therapies. This growing interest can be attributed to its non-invasive nature, precision in delivery, availability, and safety. While the conventional objective of US-based treatments to treat breast, prostate, and liver cancer is the ablation of target tissues, the introduction of the concept of immunogenic cell death (ICD) has made clear that inducing cell death can take different non-binary pathways through the activation of the patient's anti-tumor immunity. Here, we investigate high-intensity focused ultrasound (HIFU) to induce ICD by unraveling the underlying physical phenomena and resulting biological effects associated with HIFU therapy using an automated and fully controlled experimental setup. Our in-vitro approach enables the treatment of adherent cancer cells (B16F10 and CT26), analysis for ICD hallmarks and allows to monitor and characterize in real time the US-induced cavitation activity through passive cavitation detection (PCD). We demonstrate HIFU-induced cell death, CRT exposure, HMGB1 secretion and antigen release. This approach holds great promise in advancing our understanding of the therapeutic potential of HIFU for anti-cancer strategies. A dedicated HIFU set-up was developed that allows to monitor and correlate HIFU induced cavitation with the biological outcomes focusing on cancer cell death, antigenicity and adjuvanticity (ICD hallmarks). This set-up allows the successful in vitro treatment of adherent cells with US as well as collection of the samples for analysis without any form of contamination. The inclusion of a broadband backscatter transducer allowed passive cavitation detection during the HIFU treatment in two or three dimensions, depending on the need. [Display omitted] • Ultrasound provides significant beneficial traits in cancer treatments due to its non-invasiveness, precision, and safety. • PCD enables automated, controlled in vitro cancer cell treatment with real-time monitoring of US-induced cavitation. • Key biological effects observed include HIFU-induced cell death, CALR exposure, HMGB1 secretion, and antigen release. • Using HIFU to induce immunogenic cell death and stimulate anti-tumor immunity presents a promising cancer treatment strategy. [ABSTRACT FROM AUTHOR]

More than half of new cancer cases occurred in older adults. Older patients with cancer are particularly at risk of physical, psycho-existential or socio-familial suffering as defined by the concept of Serious Health-related Suffering (SHS). To assess the direct and indirect effects of physical, psycho-existential and socio-familial dimensions of suffering on cancer treatability, supportive care needs and 12-month mortality in older patients with cancer. We included patients with cancer aged 70 years and over from the Elderly Cancer Patients cohort (ELCAPA, Ile-de-France), referred for geriatric assessment between 2007 and 2019 before cancer treatment. Structural equation modelling examined the direct and indirect relationships between SHS dimensions (latent variables), patients' characteristics (age, sex, tumor location and metastatic status, comorbidity, period of care), and outcomes. The analysis included 4,824 patients (mean age: 82.2 ± 4 years; women: 56%; main cancer sites: breast [22.3%], colorectal [15.2%], prostate [8.5%], and lung [6.8%]; metastatic cancer: 46%). Physical suffering had direct pejorative effects on cancer treatability, and mortality (standardized coefficient [SC] = 0.12 [ P < 0.001], SC = 0.27 [ P < 0.001], respectively). Psycho-existential and socio-familial sufferings had indirect pejorative effects on survival through decreased cancer treatability (SC = 0.08 [ P < 0.001], SC = 0.03 [ P < 0.001], respectively). Psycho-existential dimension had the main direct effect size on supportive care needs (SC = 0.35 [ P < 0.001]) and was interrelated with physical suffering. Physical suffering has direct pejorative effect on survival. All dimensions indirectly decrease survival due to poorer cancer treatability. Our findings support concomitant management of physical and psycho-existential suffering. [ABSTRACT FROM AUTHOR]

People with noncancer diagnoses have poorer access to palliative care units (PCUs) or hospices compared to those with cancer diagnoses. The COVID-19 pandemic disrupted how specialist palliative care services were delivered and utilized. To determine the association between the start of the COVID-19 pandemic and PCU/hospice utilization in hospitalized individuals with cancer and noncancer diagnoses with specialist palliative care needs. Retrospective cohort study using routinely collected data. Percentages of individuals experiencing each disposition from hospital, including discharge to PCU/hospice, were calculated monthly for the total, cancer, and noncancer cohorts and were analyzed descriptively. Hospitalized individuals with specialist palliative care needs at a single academic hospital in Toronto, Canada from January 1, 2017, to September 31, 2022 (pandemic start was defined as April 1, 2020). The cohort comprised 4349 individuals (median age=78 years; 52.4% female); 3065 (70.5%) and 1284 (29.5%) had cancer and noncancer diagnoses, respectively. Among individuals with noncancer diagnoses, the most significant absolute changes were a 13.0%-decrease in in-hospital deaths (prepandemic=49.6%; postpandemic=36.6%) and a 11.6%-increase in discharges to PCU/hospice (prepandemic=35.6%; postpandemic=47.3%). Among individuals with cancer, the most significant absolute changes were a 12.8%-increase in discharges home with formal care (prepandemic=2.3%; postpandemic=15.1%) and a 7.0%-decrease in in-hospital deaths (prepandemic=29.1%; postpandemic=22.0%). Despite historically poor PCU/hospice access, the COVID-19 pandemic created circumstances that may have enabled unprecedented utilization in individuals with noncancer diagnoses in our cohort. [ABSTRACT FROM AUTHOR]

Malignant Mesothelioma (MM) has a striking impact on the somatopsychic balance of patients and their families, including physical, psychological, and interpersonal problems. The aim of this systematic literature review was to investigate what psychological interventions are offered to patients with MM and their caregivers worldwide. Methods: The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The literature search led to the identification of 12 articles. Results were categorized into five categories. 1. Individual psychological support, 2. Group psychological support, 3. Cognitive-behavioral group psychotherapy, 4. Brief psychoanalytic groups, 5. Multifamily group. Results: The interventions differed in terms of form, duration and resources used. Most of them were group-based and psychoanalytically oriented, although individual and cognitive-behavioral interventions were also described. Despite the differences, the interventions appeared to be fundamental in facilitating the processing of mental pain and anger related to the diagnosis. Conclusion: Our study has shown that there are still few psychological interventions available for MM patients and their caregivers. The somatopsychic consequences of MM in patients and caregivers should encourage institutions and healthcare professionals to develop assessment and intervention models that address the different dimensions of their suffering and promote their residual vitality. [ABSTRACT FROM AUTHOR]

• ECM synthesis poses significant demands for biomass generation with requirements different from cell proliferation. • With its high glycine and proline content, collagen synthesis imposes unique biosynthetic demands. • Pro-fibrotic signaling cascades mediate metabolic rewiring in activated fibroblasts. • Targeting the metabolic pathways supporting collagen synthesis provides opportunities for treating fibrotic conditions. • Nutrient availability influences metabolic pathways regulating collagen synthesis and creates new vulnerabilities. The extracellular matrix (ECM) is present in all tissues and crucial in maintaining normal tissue homeostasis and function. Defects in ECM synthesis and remodeling can lead to various diseases, while overproduction of ECM components can cause severe conditions like organ fibrosis and influence cancer progression and therapy resistance. Collagens are the most abundant core ECM proteins in physiological and pathological conditions and are predominantly synthesized by fibroblasts. Previous efforts to target aberrant collagen synthesis in fibroblasts by inhibiting pro-fibrotic signaling cascades have been ineffective. More recently, metabolic rewiring downstream of pro-fibrotic signaling has emerged as a critical regulator of collagen synthesis in fibroblasts. Here, we propose that targeting the metabolic pathways involved in ECM biomass generation provides a novel avenue for treating conditions characterized by excessive collagen accumulation. This review summarizes the unique metabolic challenges collagen synthesis imposes on fibroblasts and discusses how underlying metabolic networks could be exploited to create therapeutic opportunities in cancer and fibrotic disease. Finally, we provide a perspective on open questions in the field and how conceptual and technical advances will help address them to unlock novel metabolic vulnerabilities of collagen synthesis in fibroblasts and beyond. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) technologies have become an indispensable tool within the research field driving genomic discoveries and furthering our understanding of the genomic changes that lead to human disease. NGS technologies have great potential to provide invaluable genomic data that can be used to improve clinical diagnosis and the delivery of precision medicine. Over the past decade NGS has translated into the clinical setting for both hereditary and somatic indications. Whilst it has great potential in the clinic, the application of this technology for cancer faces a number of challenges, both technical and logistic. Consideration must be given to the role of this technology and how it is best used in the patient pathway. In this review we describe the current technologies routinely used in the clinical laboratory and provide insights into their application in solid tumour testing. [ABSTRACT FROM AUTHOR]

Thoracic back pain is a common site for inflammatory, neoplastic, metabolic, infectious, and degenerative conditions, and may be associated with significant disability and morbidity. Uncomplicated acute thoracic back pain and/or radiculopathy does not typically warrant imaging. Imaging may be considered in those patients who have persistent pain despite 6 weeks of conservative treatment. Early imaging may also be warranted in patients presenting with "red flag" history or symptoms, including those with a known or suspected history of cancer, infection, immunosuppression, or trauma; in myelopathic patients; or in those with a history of prior thoracic spine fusion. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation. [ABSTRACT FROM AUTHOR]

Tumor-infiltrating B cells play a significant role in tumor development, progression, and prognosis, yet a comprehensive classification system is lacking. To address this gap, we present a pan-cancer single-cell RNA sequencing (scRNA-seq) atlas of tumor-infiltrating B and plasma cells across a large sample cohort. We identify key B cell subset signatures, revealing distinct subpopulations and highlighting the heterogeneity and functional diversity of these cells in the tumor microenvironment. We explore associations between B cell subsets and checkpoint inhibitor therapy responses, finding subset-specific effects on overall response. Additionally, we examine B and T cell crosstalk, identifying unique ligand-receptor pairs for specific B cell subsets, spatially validated. This comprehensive dataset serves as a valuable resource, providing a detailed atlas that enhances the understanding of B cell complexity in tumors and opens new avenues for research and therapeutic strategies. [Display omitted] • A scRNA-seq atlas identifies ten clusters of intratumoral B and plasma cells • Specific B cell subsets are associated with checkpoint inhibitor therapy responses • Atlas-derived B cell gene signatures validated in spatial analyses • Publicly available Shiny tool enables users to interactively explore the atlas Fitzsimons et al. present a comprehensive pan-cancer single-cell RNA-seq atlas of intratumoral B cells, identifying ten distinct B and plasma cell clusters. They uncover associations with checkpoint inhibitor therapy response, explore B-T cell crosstalk, validate findings with spatial data, and offer an interactive tool for further research. [ABSTRACT FROM AUTHOR]

From its earliest characterization, it has been recognized that there is a role for regulated (programmed) cell death in cancer. As our understanding of the different types of programmed cell death processes and their molecular control has advanced, so have the technologies that allow us to manipulate these processes to, for example, fight against cancer. In this review, we describe the roles of the different forms of regulated cell death in the development of cancer as well as their potential therapeutic exploitation. In that vein, we explore the development and use of BH3-mimetics, a unique class of drugs that can directly activate the apoptotic cell death machinery to treat cancer. Finally, we address key challenges that face the field to improve the use of these therapeutics and the efforts that are being undertaken to do so. In this review, La Marca et al. delve into the role of cell death in tumorigenesis; particularly apoptosis, but also touching on emerging roles for other cell death variants. The review also discusses the development, limitations, and future of BH3-mimetics, the most clinically advanced class of compounds for direct apoptosis induction. [ABSTRACT FROM AUTHOR]

In head and neck squamous cell carcinoma (HNSCC), early complications of the radiotherapy (RT) are observed from the beginning of the treatment to a few months after its end. During external radiotherapy treatment, several patient-dependent parameters can cause a modification of the dose distribution compared to the planned distribution due to variation in patient positioning, anatomy, or intra-fractional movements for example. To verify these parameters during treatment sessions, one of the most commonly used solutions is the cone-beam computed tomography (CBCT). Nowadays, the use of CBCT may constitutes a significant part of the total dose at the end of treatment (up to 10 cGy per session) and more often the volume irradiated by imaging is larger than the one irradiated by the treatment, leading to unintentional irradiation of nearby organs. In this study, we asked whether the imaging low dose added to a following fraction dose (2 Gy) may affect the biological response in terms of DNA repair. Using an IVInomad dosimeter and scintillating fiber probes specially designed for this exploratory study, we exposed fibroblasts cells from head and neck cancer (HNC) patients to a CBCT dose followed by a radiotherapy fraction dose. DNA double strand breaks and DNA repair were assessed by immunofluorescence using the biomarkers gamma H2AX (γH2AX) and pATM. The median dose of CBCT was measured between 17 to 21 mGy per session. The kinetics of both biomarkers were found to be strongly dependent on the individual factor in radiosensitive patients. For HNC patients, a prior CBCT dose applied few minutes before the 2 Gy dose may have a sublinear effect on the DNA repair mechanisms and potentially on observed health tissue toxicity. The preliminary results obtained highlight the importance of individual and tissue factors for recognizing and repairing DSB during a treatment by radiotherapy using CBCT. [ABSTRACT FROM AUTHOR]

Assess rates of true pseudoprogression in unconfirmed progressive disease (iUPD) in a pool of immunotherapy clinical trials for different cancers, analyze tumor characteristics that drive iUPD classification, and investigate potentials predictors of pseudoprogression. Retrospective interpretation of prospectively acquired data. Patients from 18 immunotherapy clinical trials with two arms (RECIST 1.1, iRECIST), of 10 cancer types were selected. Pooled rate of true pseudoprogression among iUPD was estimated using a common effect meta-analysis. Target, Non-target, and new lesions as the trigger of confirmed-vs pseudo-progression were compared using Chi-Square and Fisher exact tests. Conditional logistic regression was used to investigate the association between age, sex, tumor burden at baseline, and number of follow ups and pseudoprogression. 60/287 (21%) patients (17 women) were classified as iUPD with at least one subsequent confirmatory timepoint. The overall pooled estimate of pseudoprogression was 15% (95%CI: 8%–-26%). Nontarget lesions were significantly more frequent the cause of iUPD than change in Target lesions size (p < 0.001). Most observations of true pseudoprogression occurred in the first follow-up (77%), whereas confirmed progression occurred in later time points during the trial. Pseudoprogression was not significantly associated with age, sex, tumor burden at baseline, or number of timepoints. In a pool of immunotherapy trials, the rate of true pseudoprogression was 15%, most often in the first timepoint after baseline than later in treatment. iUPD categorization was mostly driven by changes in NT lesions rather than objective changes in measurements of target lesions. • Considering trials size and proportions, the pooled estimate of true pseudoprogression was 15% (95%CI: 8%–26%). • Confirmed progression and pseudoprogression were mainly driven by change in Non-target lesions than size of target lesions. • Pseudoprogression occurred most often in the first follow-up after baseline than true progression. [ABSTRACT FROM AUTHOR]

[Display omitted] • We elaborate on the role of gut microbiota and microbial metabolites in the efficacy and adverse effects of chemotherapeutics. • We further summarize the clinical potential of various ways to harness gut microbiota for cancer chemotherapy. • The potential of gut microbiota severing as predictive markers for chemotherapy efficacy is discussed. • Finally, we discuss current limitations and suggest potential approaches to facilitate utilization of gut microbiota in chemotherapy. The microbiota inhabits the epithelial surfaces of hosts, which influences physiological functions from helping digest food and acquiring nutrition to regulate metabolism and shaping host immunity. With the deep insight into the microbiota, an increasing amount of research reveals that it is also involved in the initiation and progression of cancer. Intriguingly, gut microbiota can mediate the biotransformation of drugs, thereby altering their bioavailability, bioactivity, or toxicity. The review aims to elaborate on the role of gut microbiota and microbial metabolites in the efficacy and adverse effects of chemotherapeutics. Furthermore, we discuss the clinical potential of various ways to harness gut microbiota for cancer chemotherapy. Recent evidence shows that gut microbiota modulates the efficacy and toxicity of chemotherapy agents, leading to diverse host responses to chemotherapy. Thereinto, targeting the microbiota to improve efficacy and diminish the toxicity of chemotherapeutic drugs may be a promising strategy in tumor treatment. [ABSTRACT FROM AUTHOR]

mRNA-based vaccines symbolize a new paradigm shift in personalized medicine for the treatment of infectious and non-infectious diseases. However, the reactogenicity associated with the currently approved formulations limits their applicability in autoinflammatory disorders, such as tumour therapeutics. In this study, we present a delivery system showing controlled immunogenicity and minimal non-specific inflammation, allowing for selective delivery of mRNA to antigen presenting cells (APCs) within the medullary region of the lymph nodes. Our platform offers precise control over the trafficking of nanoparticles within the lymph nodes by optimizing stealth and targeting properties, as well as the subsequent opsonization process. By targeting specific cells, we observed a potent adaptive and humoral immune response, which holds promise for preventive and therapeutic anti-tumoral vaccines. Through spatial programming of nanoparticle distribution, we can promote robust immunization, thus improving and expanding the utilization of mRNA vaccines. This innovative approach signifies a remarkable step forward in the field of targeted nanomedicine. [Display omitted] [ABSTRACT FROM AUTHOR]

According to the International Agency for Research on Cancer, leukemia ranks 14th in incidence and 11th in mortality and has a 5-year prevalence of approximately 1300,000 cases. Acute lymphoblastic leukemia is the most common hematopoietic syndrome in children during the first 5 years of life and represents approximately 75 % of all neoplasms among the pediatric population. The development of leukemia is strongly governed by DNA alterations that accelerate the growth of bone marrow cells. Currently, the most examined factor in pediatric leukemia is exposure to multiple compounds, such as hydrocarbons. Benzene, an aromatic hydrocarbon, can cause health challenges and is categorized as a carcinogen. Benzene toxicity has been widely associated with occupational exposure. Importantly, studies are underway to generate evidence that can provide clues regarding the risk of environmental benzene exposure and hematological problems in children. In this review, we summarize the existing evidence regarding the effects of benzene on pediatric leukemia, the associations between the effect of benzene on carcinogenesis, and the presence of certain molecular signatures in benzene-associated pediatric leukemia. Although there is sufficient evidence regarding the effects of benzene on carcinogenesis and leukemia, epidemiological research has primarily focused on occupational risk. Moreover, most benzene-induced molecular and cytogenetic alterations have been widely described in adults but not in the pediatric population. Thus, epidemiological efforts are crucial in the pediatric population in terms of epidemiological, clinical, and biomedical research. [Display omitted] • Pediatric leukemia incidence, mortality, and long-term prevalence represents a global health concern. • Acute lymphoblastic leukemia is the most frequent hematopoietic neoplasia in children. • Benzene, a carcinogenic aromatic hydrocarbon, represents a risk factor in hematopoietic tumors. • Evidence regarding the effects of benzene on pediatric leukemia is increasing, but still limited. • Future epidemiological efforts may provide insight into the mechanisms of benzene on pediatric leukemia. [ABSTRACT FROM AUTHOR]

The management and treatment of cancer and related disorders is still a challenging goal for the scientists. The current global scenario of cancer mortality is demanding to discover and develop new, safe, cost effective and potent anticancer medications. The anticancer drugs vinblastine and vincristine are solely produced by medicinal herb Catharanthus roseus. These drugs are second most widely consumed anticancer drugs after Taxol in the world; however, the plant is well recognised to produce very modest levels of these important compounds (0.0002–0.0005 %). To address this issue, the review delves into the promising alternative of using endophytic fungi which reside within the healthy plant tissues and have ability to produce host-specific bioactive compounds including vinblastine and vincristine. An endophytic fungus Talaromyces radicus is reported to produce vincristine up to 670 µg/L while Curvularia verruculosa is able to secret vinblastine at a concentration of 182 µg/L in liquid cultures respectively. Some other fungal species reported to produce either vincristine or vinblastine includes Fusarium, Alternaria, Chaetomium, Nigrospora and Eutypella. The review begins by discussing the therapeutic importance of vinblastine and vincristine, highlighting their mechanisms of action and their critical roles in chemotherapy regimens for various types of cancer. Next, the review also provides an in-depth analysis of various endophytic fungi producing vinblastine and vincristine detailing their identification, characterization, biosynthetic ability and strain improvement processes. It aims to contribute to the ongoing efforts to develop more effective and sustainable strategies for producing these critical anticancer agents, ultimately enhancing cancer treatment options and outcomes. [Display omitted] • Vinblastine and vincristine are among the major anticancer compounds used worldwide for treatment of various cancers. • Natural production of these anticancer drugs is limited because of the very low yield in Catharanthus plant. • The endophytic fungi isolated from Catharanthus roseus are reported to produce vinblastine and vincristine in sufficient quantities. • The challenge in fungal production of these drugs is related with optimization and sustainable yield at commercial level. [ABSTRACT FROM AUTHOR]

Access to health services has received increasing attention, and the International Agency for Research on Cancer (IARC) includes 'availability' as one of the indicators to evaluate cancer screening. Evaluating, monitoring, and decision-making on cancer screening depends on systematic quantitative evidence on access to cancer screening, but indicators are currently inconsistently, if they are reported at all. This can be improved by developing systematic indicators for evaluating and reporting access to cancer screening. This requires a thorough understanding of current indicators of access to cancer screening. Scoping review. We completed a scoping review of studies on access to cancer screening services from 2013 to 2022. The relevant indicators were extracted, quantified, and then matched to two widely used frameworks: a universal five-dimensional conceptual framework for access to healthcare ('U5D') and a cancer-specific framework/list on the availability/use of screening indicators endorsed by the IARC. A total of 331 studies on access to cancer screening services were included. Based on the U5D framework, publications from supply side reported approachability (number of publications = 16), acceptability (6), availability and accommodation (44), affordability (30), and appropriateness (11); among this process, 17 sub-indicators were identified. Correspondingly, publications from demand side reported ability to perceive (170), ability to seek (85), ability to reach (58), ability to pay (59), and ability to engage (2); 26 sub-indicators were identified. More macroscopically, the publications of the IARC-endorsed indicators reported availability of policies and guidelines for screening (13), type of screening provided (3), extent of population coverage and participation rates (76), and demographic/behavioural related considerations (167). By integrating the universal and cancer-specific frameworks, a new adapted framework was proposed. This study identified and collated indicators for evaluating access to cancer screening services, and determined the gaps in the current application of various indicators. The findings are anticipated to facilitate further development of an evaluation indicator system for access to cancer screening services. [Display omitted] [ABSTRACT FROM AUTHOR]

Most cancer-associated pain is experienced in low- and middle-income countries (LMICs) due to inequitable access to opioids. To determine opioid access as estimated by both patients and providers and to understand patient and facility-level factors influencing access among patients with advanced cancer in LMICs in Asia using the Behavioral Model of Health Services Use. The APPROACH cross-sectional study was conducted in seven LMICs in Asia, involving in-depth surveys with providers and advanced cancer patients. A hierarchical logistic regression model was used to assess predisposing (i.e. individual factors), enabling (i.e. health care system and facility-level resources) and need (i.e. pain severity) factors predicting opioid access. Among patient participants (n=1,933), approximately 40% reported opioid use. Meanwhile 80% of facilities, as reported by providers, indicated at least half of their advanced cancer patients receive oral morphine prescriptions. Predisposing characteristics factored in the least in the model, with patient education positively associated with access (Odds ratio (OR): 1.01; 95% CI=1.00, 1.03). Facility-level enabling resources, factoring the most, included oral morphine prescription duration >14 days (OR: 1.27; 95% CI=1.05, 1.53) and the extent of physician palliative care training (extensive (>160 hours) OR: 3.95; CI=3.19, 4.88; basic (up to 40 hours) OR: 1.03; CI=1.03, 1.04). Patient need as indicated by greater pain severity predicted access (OR: 1.55; CI=1.47, 1.64). Study findings emphasize the importance of palliative care training—even a minimal amount—in supporting access to opioids for advanced cancer patients. This study also highlights pragmatic site-level policies, such as extended morphine prescription durations, enabling access. [ABSTRACT FROM AUTHOR]

Little is known about Veterans who die during a short terminal admission, which renders them ineligible for the Department of Veterans Affairs (VA) Bereaved Family Survey. We sought to describe this population and identify opportunities to improve end-of-life (EOL) care quality. Retrospective, cohort analysis of Veteran decedents who died in a VA inpatient setting between October 2018-September 2019. Veterans were dichotomized by short (<24 hours) and long (≥24 hours) terminal admissions; sociodemographics, clinical characteristics, VA and non-VA healthcare use, and EOL care quality indicators were compared. Among 17,033 inpatient decedents, 723 (4%) had short terminal admissions. Patients with short compared to long terminal admissions were less likely to have a VA hospitalization (38% vs. 54%) in the last 90 days of life and were more likely to die in an intensive care (49% vs 21%) or acute care (27% vs 18%) unit. Patients with a short compared to long admission were about half as likely to receive hospice (33% vs 64%) or palliative care (33% vs 69%). Most patients with short admissions (76%) had a life-limiting condition (e.g., cancer, chronic obstructive pulmonary disease) and those with cancer were more likely to receive palliative care compared to those with non-cancer conditions. Veterans with short terminal admissions are less likely to receive hospice or palliative care compared to patients with long terminal admissions. Many patients with short terminal admissions, such as those with life-limiting conditions (especially cancer), receive aspects of high-quality EOL care, however, opportunities for improvement exist. [ABSTRACT FROM AUTHOR]

Gram-positive bacteria are frequently resistant to empirical beta‐lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer. Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia. Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130–14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366–11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059–0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218–0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia. Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer. [ABSTRACT FROM AUTHOR]

Multiple myeloma is a complex disease and supportive care is important for improving quality of life. Management of disease treatment symptoms, bone disease, renal dysfunction, infection, anemia, pain, and coagulation disorder are specific issues. Spirituality, or spiritual well-being, is one of the most fundamental and essential concepts for coping with the difficulties and stress caused by cancer. This study explores whether spiritual well-being, pain, and other demographic factors predict the physical and mental components of quality of life in MM subjects. This cross-sectional descriptive study was conducted with 92 multiple myeloma patients registered with the Cancer Warriors Association in Turkey. The data were collected using the Personal Information Form, The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale-12, the Numeric Rating Scale for Pain, and the Short Form-12 Health-Related Quality of Life Scale. The mean age of the patients was 54.4 ± 10.7 years. It was found that the mean total pain score in the previous week was 3.9 ± 2.6, while the mean total The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale-12 score was 28.1 ± 9.8. Their mean Short Form-12 total physical component score was 39.1 ± 25.4; whereas the Short Form-12 total mental component score was 45.5 ± 24.8. According to this model, 56.7% of the physical component score was explained by vertebroplasty, The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale-12 total score and subscale of peace and the pain intensity experienced in the previous week. According to multiple linear regression analysis, bone-sparing therapy and FACIT-Sp-12-Total and subscale peace significantly predicted the Mental component score (p <.05). Cancer pain remains undertreated, and patients with myeloma are no exception. Pain and spiritual well-being scores were significant predictors of physical and mental component scores of quality of life in this group of patients. According to this result, pain-reducing practices should be implemented to improve the quality of life in MM patients and the spiritual needs of the patients should be met. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the technical and clinical success of middle meningeal artery (MMA) embolization performed for symptomatic subacute subdural hematoma (SDH) in patients with cancer. This study retrospectively included 23 consecutive patients (12 men, 11 women; median age 61 years, interquartile range: 55.5–75.5) who underwent 34 MMA angiograms for symptomatic SDH in 2022 and 2023. Median SDH thickness was 10.5 mm (7−12). Median platelet count was 117 K/mcL (54.5–218). 10 patients (43.5%, 10/23) had hematologic malignancies, seven patients (30.4%, 7/23) had surgery. Fluoroscopy time (FT), reference dose (RD), and kerma area product (Kap) were analyzed. Adverse events and outcomes were recorded. The median imaging and clinical follow-up were 65 days (36.5–190.5) and 163 days (86–274), respectively. The technical success rate was 91.2% (31/34) as three MMA were not identified in two patients. Median procedure duration was 61 min (55.5–75.5). Median FT was 21.6 min (15.5–31.8); median RD was 158 mGy (96–256); and median Kap was 32.9 Gy.cm2 (20.4–45.1). No further intervention was needed. For 16 patients, SDH resolved after in median 59.5 days (50–90). For seven patients, SDH remained visible on the last imaging follow-up performed at 24 days in median (6.5–36.5). No predictive factor of failure was identified. The adverse event rate was 1/23 (4.3%). Eight patients (34.8%, 8/23) died during follow-up from progression of cancer. MMA embolization of symptomatic SDH in patients with cancer appears safe and is associated with improvement in clinical symptoms. [ABSTRACT FROM AUTHOR]

• The high incidence of depression in cancer patients and its impact on their quality of life. • Summarizes the potential mechanisms of comorbidity between cancer and depression. • Provides discussion and analysis of potential treatments for depression. Cancer and depression are closely interrelated, particularly in patients with advanced cancer, who often present with comorbid anxiety and depression for various reasons. Recently, there has been a growing interest in the study of depression in cancer patients, with the aim of assessing the possible triggers, predictors, adverse events, and possible treatment options for depression in several common cancers. The objective of this narrative review is to synthesize the extant literature on the relationship between the occurrence and progression of depression in several common patient categories. The authors conducted a comprehensive review of 75 articles published in PubMed over the past five years. This review was further evaluated in the present paper. Ultimately, it was determined that depression is a prevalent and detrimental phenomenon among cancer patients, particularly those with advanced disease. Consequently, there is a pressing need to prioritize research and interventions aimed at improving the quality of life and psychosocial well-being of cancer patients, including those with advanced disease. The relationship between cancer and depression has been evolving dynamically in recent times. The current research findings indicate a strong association between cancer and depression. However, the direction of causality remains unclear. Focusing on depression in cancer patients may, therefore, be beneficial for these patients. [ABSTRACT FROM AUTHOR]

The human microbiome is a diverse ecosystem of microorganisms that reside in the body and influence various aspects of health and well-being. Recent advances in sequencing technology have brought to light microbial communities in organs and tissues that were previously considered sterile. The gut microbiota plays an important role in host physiology, including metabolic functions and immune modulation. Disruptions in the balance of the microbiome, known as dysbiosis, have been linked to diseases such as cancer, inflammatory bowel disease and metabolic disorders. In addition, the administration of antibiotics can lead to dysbiosis by disrupting the structure and function of the gut microbial community. Targeting strategies are the key to rebalancing the microbiome and fighting disease, including cancer, through interventions such as probiotics, fecal microbiota transplantation (FMT), and bacteria-based therapies. Future research must focus on understanding the complex interactions between diet, the microbiome and cancer in order to optimize personalized interventions. Multidisciplinary collaborations are essential if we are going to translate microbiome research into clinical practice. This will revolutionize approaches to cancer prevention and treatment. ● Gut microbiome influences cancer treatment efficacy and outcomes. ● Dysbiosis is associated with inflammatory diseases and metabolic disorders. ● Antibiotic-induced dysbiosis challenges human health and microbiome resilience. ● Novel interventions such as probiotics and FMT hold promise for disease management. ● A comprehensive review synthesizes multidisciplinary research on microbiome dynamics. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) is a synthetic receptor that induces T cell-mediated lysis of abnormal cells. As cancer driver proteins are present at low levels on the cell surface, they can cause weak CAR reactivity, resulting in antigen sensitivity defects and consequently limited therapeutic efficacy. Although affinity maturation enhances the efficacy of CAR-T cell therapy, it causes off-target cross-reactions resulting in adverse effects. Preferentially expressed antigen in melanoma (PRAME) is an intracellular oncoprotein that is overexpressed in various tumors and restricted in normal tissues, except the testis. Therefore, PRAME could be an ideal target for cancer immunotherapy. In this study, we developed an experimental CAR system comprising six single-chain variable fragments that specifically recognizes the PRAMEp301/HLA-A∗24:02 complex. Cell-mediated cytotoxicity was demonstrated using a panel of CARs with a wide range of affinities (KD = 10−10–10−7 M) and affinity modulation. CAR-T cells with fast on-rates enhance antigen sensitivity by accelerating the killing rates of these cells. Alanine scanning data demonstrated the potential of genetically engineered CARs to reduce the risk of cross-reactivity, even among CARs with high affinities. Given the correlation between on-rates and dwell time that occurs in rebinding and cell-mediated cytotoxicity, it is proposed that CAR-binding characteristics, including on-rate, play a pivotal role in the lytic capacity of peptide-major histocompatibility complex-targeting CAR-T cells, thus facilitating the development of strategies whereby genetically engineered CARs target intracellular antigens in cancer cells to lyse the cells. [ABSTRACT FROM AUTHOR]

Caregiving burden is set to increase with the rising incidence of cancer globally. The meta-analysis seeks to investigate the prevalence of suicide, suicidal ideation and self-harm among the caregivers of patients with cancer (CPCs). This PRISMA-adherent systematic review involved a systematic search of PubMed, Embase, Cochrane and PsycINFO for all studies that evaluated the prevalence of suicide, suicidal ideation and self-harm in CPCs. Random effects meta-analyses were used for primary analysis. Eleven studies were included. Meta-analyses indicated that the prevalence of suicidal ideation in CPCs was 11% (95%CI:6–18), suicide prevalence was 6% (95%CI:3–12), and self-harm prevalence was 15% (95%CI:8–26). Subgroup analyses revealed that CPCs above the age of 50 experienced a greater prevalence of suicidal ideation (17%, 95%CI:10–28) as compared to CPCs below 50 (6%, 95%CI:3–12). Family caregivers particularly spouses were also found to have a higher prevalence of suicidal ideation (17%, 95%CI:13–23), as compared to children (5%, 95%CI:2–10) or mothers (3%, 95%CI:1–8). Systematic review found that having a pre-existing mental health condition and lower socioeconomic status increased likelihood of suicidality. We highlight the need for more support of CPCs at risk of suicidality. Additional research is warranted to identify other risk and protective factors. • Statistically high prevalence of suicide ideation, suicide and self-harm in caregivers of cancer patients. • Cancer caregivers above 50 years old compared to those below 50 experienced greater suicide ideation. • Family caregivers particularly spouses compared to children or mothers experienced greater suicide ideation. • Pre-existing mental health condition and lower socioeconomic status increased the likelihood of suicidality. [ABSTRACT FROM AUTHOR]

Aggregation-induced emission (AIE) is a unique phenomenon observed in various materials such as organic luminophores, carbon dots (CDs), organic-inorganic nanocomposites, fluorescent dye molecules, and nanoparticles (NPs). These AIE-active materials, or AIEgens, are ideal for balancing multifunctional phototheranostics and energy dissipation. AIE properties can manifest in organic fluorescent probes, rendering them effective for cancer treatment due to their ability to penetrate deeply and provide high therapeutic efficacy. This efficacy is attributed to their high photobleaching thresholds, ability to induce Stokes shifts, and capacity to activate fluorophores. Therefore, the development of innovative AIE-based materials for disease diagnosis and treatment, particularly for cancer, is both important and promising. Recent years have seen successful demonstrations of nanoparticles with AIE properties being used for photodynamic therapy (PDT) and multimodal imaging of tumor cells. These fluorophores have been shown to impact mitochondria and lysosomes, generate reactive oxygen species (ROS), activate the immune system, load and release drugs, and ultimately induce apoptosis in tumor cells. In this review, we examine previous studies on the manufacturing methods and effects of AIEgens on cancer cells, with a theranostic strategy of simultaneous treatment and imaging. We also investigate the factors affecting drug delivery on different cancer cells, including internal stimuli such as pH, ROS, enzymes, and external stimuli like near-infrared (NIR) light and ultrasound waves. [Display omitted] [ABSTRACT FROM AUTHOR]

The Kirsten Rat Sarcoma Virus (KRAS) oncoprotein, one of the most prevalent mutations in cancer, has been deemed undruggable for decades. The hypothesis of this work was that delivering anti-KRAS monoclonal antibody (mAb) at the intracellular level could effectively target the KRAS oncoprotein. To reach this goal, we designed and developed tLyP1-targeted palmitoyl hyaluronate (HAC16)-based nanoassemblies (HANAs) adapted for the association of bevacizumab as a model mAb. Selected candidates with adequate physicochemical properties (below 150 nm, neutral surface charge), and high drug loading capacity (>10%, w /w) were adapted to entrap the antiKRASG12V mAb. The resulting antiKRASG12V-loaded HANAs exhibited a bilayer composed of HAC16 polymer and phosphatidylcholine (PC) enclosing a hydrophilic core, as evidenced by cryogenic-transmission electron microscopy (cryo-TEM) and X-ray photoelectron spectroscopy (XPS). Selected prototypes were found to efficiently engage the target KRASG12V and, inhibit proliferation and colony formation in KRASG12V-mutated lung cancer cell lines. In vivo , a selected formulation exhibited a tumor growth reduction in a pancreatic tumor-bearing mouse model. In brief, this study offers evidence of the potential to use nanotechnology for developing anti-KRAS precision therapy and provides a rational framework for advancing mAb intracellular delivery against intracellular targets. [Display omitted] • The HANAs technology represents a new strategy for the intracellular delivery of mAbs and, notably, antiKRASG12V mAb. • The HANAs' surface can be functionalized with the tumor-penetrating peptide tLyP1. • The antiKRASG12V mAb-HANAs technology was able to engage the KRASG12V oncoprotein and exhibit a significant reduction in tumor growth in vivo. [ABSTRACT FROM AUTHOR]

Multiple oxaliplatin-resistance mechanisms have been proposed such as increase of anti-inflammatory M2 macrophages and lack of cytotoxic T-cells. Thereby oxaliplatin chemotherapy promotes an immunosuppressive tumor microenvironment and inhibits anti-tumor efficacy. It has been shown that toll-like receptor (TLR) agonists are capable of triggering broad inflammatory responses, which may potentially reduce oxaliplatin-resistance and improve the efficacy of chemotherapy. In this study, we established colorectal tumor-bearing zebrafish and mice, and investigated the effects of TLR agonists and oxaliplatin in macrophage function and anti-tumor T cell immunity as well as tumor growth control in vivo. To increase the potential of this strategy as well minimize side effects, neutral liposomes carrying oxaliplatin and cationic liposomes co -loaded with TLR agonists Poly I:C and R848 were employed for maximum immune activation. Both of two liposomal systems exhibited good physicochemical properties and excellent biological activities in vitro. The combination strategy delivered by liposomes showed more pronounced tumor regression and correlated with decreased M2 macrophage numbers in both zebrafish and mice. Increasing numbers of dendritic cells, DC maturation and T cell infiltration mediated via immunogenic cell death were observed in treated mice. Our study offers valuable insights into the potential of liposomal combination therapy to improve cancer treatment by reprogramming the tumor microenvironment and enhancing immune responses. [Display omitted] [ABSTRACT FROM AUTHOR]

In recent decades, there has been a burgeoning interest in cell membrane coating strategies as innovative approach for targeted delivery systems in biomedical applications. Platelet membrane-coated nanoparticles (PNPs), in particular, are gaining interest as a new route for targeted therapy due to their advantages over conventional drug therapies. Their stepwise approach blends the capabilities of the natural platelet membrane (PM) with the adaptable nature of manufactured nanomaterials, resulting in a synergistic combination that enhances drug delivery and enables the development of innovative therapeutics. In this context, we present an overview of the latest advancements in designing PNPs with various structures tailored for precise drug delivery. Initially, we describe the types, preparation methods, delivery mechanisms, and specific advantages of PNPs. Next, we focus on three critical applications of PNPs in diseases: vascular disease therapy, cancer treatment, and management of infectious diseases. This review presents our knowledge of PNPs, summarizes their advancements in targeted therapies and discusses the promising potential for clinical translation of PNPs. [Display omitted] • Platelet membrane-coated nanoparticles (PNPs) combines platelet functions with nanomaterials for targeted drug delivery. • PNPs effectively manage vascular, cancer, and infectious diseases through precise targeting mechanisms. • Challenges such as optimizing safety and managing immune responses are critical for advancing PNPs to clinical use. [ABSTRACT FROM AUTHOR]

Methodological limitations in studying the association between the use of fertility drugs and cancer include the inherent increased risk of cancer in women who never conceive, the increased risk of cancer because of factors (endometriosis and unopposed estrogen) associated with infertility, the low incidence of most of these cancers, and that the diagnosis of cancer is typically several years after fertility drug use. On the basis of available data, there does not appear to be an association between fertility drugs and breast, colon, or cervical cancer. There is no conclusive evidence that fertility drugs increase the risk of uterine cancer, although women with infertility are at higher risk of uterine cancer. There are insufficient data to comment on the risk of melanoma and non-Hodgkin lymphoma associated with fertility drug use. Women should be informed that there may be an increased risk of invasive and borderline ovarian cancers and thyroid cancer associated with fertility treatment. It is difficult to determine whether this risk is related to underlying endometriosis, female infertility, or nulliparity. [ABSTRACT FROM AUTHOR]

Chromosomal abnormalities that involve the MYCN gene are rare; however, it is one of the most commonly mutated genes in retinoblastoma (RB) after the RB1 gene. MYCN is amplified in approximately 1–9 % of all RB tumors. It plays a role in RB oncogenesis via many mechanisms, including synergism with RB1 deletion, positive feedback with MDM2, upregulation of cell cycle regulating genes, upregulation of miRNA, and upregulation of glucose metabolism. MYCN amplifications are not mutually exclusive and can occur even in the presence of RB1 gene mutations. Clinically, RB1+/+MYCNA tumors present as sporadic, unilateral, advanced tumors in very young children and tend to follow an aggressive course. Magnetic resonance imaging features include peripheral tumor location, placoid configuration, retinal folding, tumor-associated hemorrhage, and anterior chamber enhancement. Genetic testing for MYCNA is especially recommended in patients with unilateral RB where genetic blood testing and tumor tissue show a lack of RB1 mutation. MYCN-targeted therapies are evolving and hold promise for the future. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma (LUAD), significantly influences cancer-related mortality and is frequently considered by poor therapeutic responses due to genetic alterations. Cancer cells possess an inclination to develop resistance to individual treatment modalities, thus it is necessary to investigate several pathways simultaneously to obtain insights that will aid in the establishment of improved therapeutic approaches. Exploring regulated cell death (RCD) mechanisms offers promising avenues to augment immunotherapy by reshaping the tumor microenvironment (TME). Here, we investigated the prospective of microwave plasma-infused nitric oxide water (NOW) to initiate immunogenic cell death (ICD) while concurrently modulating autophagy and ferroptosis signaling in LUAD-associated A549 cells. Plasma treatment results in stable NO species nitrite/nitrate (NO 2 −/NO 3 −) in the water, altering its physicochemical properties. Analysis of ICD markers reveals increased expression of damage-associated molecular patterns (DAMPs) at both protein and mRNA levels post-NOW exposure. Intracellular reactive oxygen and nitrogen species (RONS) accumulation suggests NO-mediated mitochondrial dysfunction, triggering autophagy induction. Flow cytometry and western blotting confirm alterations in autophagy regulators Beclin 1 and SQSTM1. Furthermore, NOW treatment induces lipid peroxidation and upregulates ferroptosis-associated genes, as determined by qRT-PCR. Transmission electron microscopy (TEM) imaging reveals autophagosome formation and loss of cristae structures, corroborating the occurrence of autophagy and ferroptosis. Our findings propose that NOW may considered as inducer of ICD and the stimulation of other RCD-related proteins may enhance the anti-tumor immunogenicity. [Display omitted] • Nitric Oxide enriched water (NOW) mediates immunogenic lung cancer cells death. • Mitochondria membrane potential and activity is suppressed via NOW in cancer cells. • NOW-exposure upregulated autophagy mediating protein and gene expressions. • Ferroptosis regulating genes are sensitized after NOW exposure to cancer cells. • NOW suppressed the immunosuppressive receptor proteins; CD47 and PD-L1. [ABSTRACT FROM AUTHOR]

• We compare Meaning Centered Psychotherapy (MCP) to Cognitive Behavioral Therapy (CBT) • This is a randomized controlled trial in a natural setting with cancer survivors. • MCP was more effective than CBT in increasing meaning in life. • MCP and CBT were similarly effective in improving depression. • MCP and CBT were similarly effective in developing posttraumatic growth. Meaning-centered psychotherapy (MCP) has been found to be effective in improving meaning in life and increasing fulfillment in participants with cancer. However, to date, no previous studies have compared MCP with evidence-based treatments such as cognitive behavioral therapy (CBT). The aim of this study was to analyze the differential efficacy of MCP, compared to CBT, in participants with cancer. The study is a randomized controlled trial with 76 participants, n = 41 (MCP) and n = 35 (CBT). At posttreatment, the MCP intervention for cancer survivors was more effective than CBT in increasing the presence of meaning in life, purpose and meaning in life, and life goals. Moreover, our results showed that, at posttreatment and the 6-month follow-up, MCP and CBT were similarly effective in improving depression and developing posttraumatic growth. This study suggests that MCP could be more effective than CBT in improving meaning in life, purpose, and life goals, and equally effective as CBT in improving depression and posttraumatic growth, in cancer survivors. [ABSTRACT FROM AUTHOR]

Chemotherapy-associated side effects significantly contribute to the challenges of cancer treatment, impacting the well-being of patients and complicating existing conditions. Chemotherapy-induced oedema, characterized by abnormal fluid accumulation and swelling, worsens cancer-related issues, such as impaired wound healing. This oedema may result from drug-induced vascular changes and electrolyte imbalances. Addressing such side effects is crucial for improving prognostic outcomes of cancer patients. The rat paw oedema model is a valuable tool for studying inflammatory oedema, testing novel therapies, and understanding their mechanisms. Conventional treatments for cancer chemotherapy-induced oedema have limitations, highlighting the need for alternative or complementary approaches, such as exploring natural products like Syzygium aromaticum (clove), known for its anti-inflammatory properties and potential to alleviate edema. This study examined the effects of Syzygium aromaticum ethanol extract on inflammatory oedema in rats, identified the responsible active compound (s), and explored the possible mechanism involved through computational modeling. Ethanol extract of Syzygium aromaticum (SAEE) was prepared. In vivo anti-inflammatory activities of the extract were evaluated at a specific controlled timeframe in formalin-induced paw oedema in Wistar rats. The binding affinities and interactions of the initially identified chemical constituents of the extract were modeled, through Glide standard precision and quantum polarized ligand docking, against cyclooxygenase-2 for their potential for their possible inhibitory mechanism. SAEE displayed significant time- and dose-dependent amelioration of inflammatory oedema and dose-dependent inhibition of key proinflammatory cytokines in the rat models. In silico modeling of identified SAEE compounds revealed delphinidin, rhamnetin, and quercetin as responsible for the observed in vivo protective effects of SAEE in rat paw oedema models. This study found that Syzygium aromaticum ethanol extract effectively reduced inflammation-induced paw swelling and modulated key inflammatory markers in the rats, with the inhibitory activities of constituting delphinidin, quercetin, and rhamnetin against cyclooxygenase 2 being possibly responsible for the observed in vivo effects. Further experimental validation and dynamic simulations are needed to confirm their potential potency in more advanced preclinical and clinical models, as well as explore the mechanistic pathways involved. [Display omitted] [ABSTRACT FROM AUTHOR]

The use of natural substances in cancer treatment is gaining popularity due to their potentially lower side effects compared to radiation or chemotherapy. The development of these substances for the treatment of cancer has been successful. New technologies now incorporate nanoformulations for nanomedicines that are intended to increase the anticancer potential of drugs synthesized from phytocompounds. Essential oil from Catharanthus roseus plant was extracted and incorporated into IA-NE and assess anticancer activity of synthesized formulation against breast cancer. The 9, 10-dimethylbenz[a] anthracene (DMBA) induced rat mammary tumor model was used to evaluate anticancer properties of biosynthesized nanoemulsion Nanoemulsions was examined for in vitro cytotoxicity activity, anti-cancer effects, and physicochemical characteristics. Study findings demonstrated that incensole acetate mediated nanoemulsion may successfully improve tumor parameters, oxidative stress enzyme levels and over expressed WWP1 level in DMBA induced rats. The present investigations indicate the effect of nanoemulsion to reduce expression level of WWP1 gene significantly in breast cancer induced model. Therefore, this nanoformulation is considered a key therapeutic agent for future cancer treatment, pending extensive molecular studies. [Display omitted] • Formulation and characterization of nanoformulation was performed by interpreting its UV, SEM, Zeta size and PDI. • Investigate the effects of synthesized nanoemulsion on DMBA tumor parameters. • Analysis of oxidative stress markers in cancer induced animals as treated with nanoemulsion. • Optimized nanoemulsions had a significant cytotoxicity against MBA-MB-231 cancer cell lines. • Investigation of WWP1 gene expression in cancer induced animals as treated with nanoemulsion. [ABSTRACT FROM AUTHOR]