Search Results (112,922)

Cancer in teenagers and young adults (TYAs) coincides with major life transitions and presents unique psychosocial challenges. Understanding the experiences and needs of TYAs is critical. TYAs want to play an active role in improving cancer for TYAs; however, few opportunities exist for TYAs to do so. Using a tri-partite methodology, an international team collaborated with four TYA co-researchers in this pilot study to explore how performative staging strategies help convey TYA experiences with cancer. Using creative video, TYA co-researchers shared cancer experiences and insights in novel, impactful ways. The process provided intrinsic benefits for co-researchers to connect with other TYAs and creatively share their experiences and perspectives. Furthermore, it provided space for dialogue between TYAs and cancer care allies where TYAs could convey the nuances of their cancer experiences and how cancer care could be improved. This tri-partite methodology can support TYAs to actively engage in a process of connection, reflection, creation, and dissemination to improve cancer experiences for TYAs. Full article

Introduction: Obesity is a chronic, relapsing, and progressive disease. The issue of obesity affects 50 to 80% of patients who have been diagnosed with breast cancer. The aim of this study is to assess the scale of the problem of obesity among breast cancer survivors (BCS) older than 60 years, evaluate their physical fitness, and study the relationship between the occurrence of obesity and levels of fitness among breast cancer survivors. The relationship between fitness and sociodemographic factors has also been analyzed. Materials and Methods: This original epidemiological clinical study included a cohort of 88 female breast cancer survivors treated in 2022 in Holycross Cancer Center, Kielce, Poland. A questionnaire involving demographic information and medical data was utilized. The Senior Fitness Test (SFT) battery has been used to assess the physical fitness of the patients. Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were also analyzed. Results: More than 70% of the studied breast cancer survivors were classified as overweight or obese, according to BMI and WC indices. Depending on the SFT trial, the regression coefficients indicated worse results in participants who were older, lived in urban areas, were professionally active, less educated, and had higher obesity indices. The analysis of the relationship between obesity indices and fitness components revealed that all obesity indices were significantly associated with lower body flexibility (BMI p = 0.0118, WC p = 0.0092, WHR p = 0.0364, WHtR p = 0.0095). Upper body flexibility was significantly correlated with BMI indices (p = 0.0091, p = 0.0193) and WHtR (p = 0.0095). Agility and balance were significantly associated with WC (p = 0.0193), WHR (p = 0.098), and WHtR (p = 0.0095). Lower body strength was significantly correlated with the WHR index (p = 0.0487). Significant differences were found in upper body strength depending on the WHtR category. Conclusions: In the studied group of breast cancer survivors, there is a high prevalence of overweight and obesity. With increasing obesity rates, older age, and lower education levels, physical activity measured by the SFT decreases. Living in urban areas and being professionally active also predispose to lower physical activity levels. As obesity indices increase, physical fitness decreases in trials assessing upper and lower body strength, upper and lower body flexibility, as well as agility and dynamic balance. Full article

Background and Objectives: Sarcopenia, a condition characterized by muscle mass loss, is prevalent in up to 68% of rectal cancer patients and has been described as a negative prognostic factor, impacting overall survival and tumor response. While there are extensive data on rectal cancer globally, only a handful of studies have evaluated the role of sarcopenia in locally advanced rectal cancer (LARC). Our study aimed to investigate the relationship between sarcopenia, overall response rate, and toxicity in patients who underwent total neoadjuvant treatment (TNT) for LARC. Materials and Methods: We performed a retrospective study of patients with rectal cancer treated with TNT and surgery with curative intent between 2021 and 2023 at Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj-Napoca. Sarcopenia was assessed on MRI images by measuring the psoas muscle area (PMA) at the level of the L4 vertebra before and after neoadjuvant therapy. The primary endpoints were the overall complete response rate (oCR) and acute toxicity. Results: This study included 50 patients with LARC. The oCR rate was 18% and was significantly associated with post-treatment sarcopenia (OR 0.08, p = 0.043). Patients who did not achieve a clinical or pathologic complete response had, on average, an 8% muscle loss during neoadjuvant therapy (p = 0.022). Cystitis and thrombocytopenia were significantly associated with post-treatment sarcopenia (p = 0.05 and p = 0.049). Conclusions: Sarcopenia and loss of psoas muscle during neoadjuvant therapy were negatively associated with tumor response in locally advanced rectal cancer. Thrombocytopenia and cystitis are more frequent in sarcopenic than non-sarcopenic patients undergoing neoadjuvant chemoradiation for rectal cancer. Full article

Cancer cell mitochondria are functionally different from those in normal cells and could be targeted to develop novel anticancer agents. The aryl-ureido fatty acid CTU (16({[4-chloro-3-(trifluoromethyl)phenyl]-carbamoyl}amino)hexadecanoic acid) is the prototype of a new class of targeted agents that enhance the production of reactive oxygen species (ROS) that disrupt the outer mitochondrial membrane (OMM) and kill cancer cells. However, the mechanism by which CTU disrupts the inner mitochondrial membrane (IMM) and activates apoptosis is not clear. Here, we show that CTU-mediated ROS selectively dysregulated the OMA1/OPA1 fusion regulatory system located in the IMM. The essential role of ROS was confirmed in experiments with the lipid peroxyl scavenger α-tocopherol, which prevented the dysregulation of OMA1/OPA1 and CTU-mediated MDA-MB-231 cell killing. The disruption of OMA1/OPA1 and IMM fusion by CTU-mediated ROS accounted for the release of cytochrome c from the mitochondria and the activation of apoptosis. Taken together, these findings demonstrate that CTU depolarises the mitochondrial membrane, activates ROS production, and disrupts both the IMM and OMM, which releases cytochrome c and activates apoptosis. Mitochondrial-targeting agents like CTU offer a novel approach to the development of new therapeutics with anticancer activity. Full article

Positron Emission Tomography/Computed Tomography (PET/CT) using Fluorodeoxyglucose (FDG) is an important imaging modality for assessing treatment outcomes in patients with pulmonary malignant neoplasms undergoing radiation therapy. However, distinguishing between benign post-radiation changes and residual or recurrent malignancies on PET/CT images is challenging. Leveraging the potential of artificial intelligence (AI), we aimed to develop a hybrid fusion model integrating radiomics and Convolutional Neural Network (CNN) architectures to improve differentiation between benign post-radiation changes and residual or recurrent malignancies on PET/CT images. We retrospectively collected post-radiation PET/CTs with identified labels for benign changes or residual/recurrent malignant lesions from 95 lung cancer patients who received radiation therapy. Firstly, we developed separate radiomics and CNN models using handcrafted and self-learning features, respectively. Then, to build a more reliable model, we fused the probabilities from the two models through an evidential reasoning approach to derive the final prediction probability. Five-folder cross-validation was performed to evaluate the proposed radiomics, CNN, and fusion models. Overall, the hybrid fusion model outperformed the other two models in terms of sensitivity, specificity, accuracy, and the area under the curve (AUC) with values of 0.67, 0.72, 0.69, and 0.72, respectively. Evaluation results on the three AI models we developed suggest that handcrafted features and learned features may provide complementary information for residual or recurrent malignancy identification in PET/CT. Full article

The Washington National Primate Research Center (WaNPRC) maintains the largest domestic breeding colony of pigtail macaques (Macaca nemestrina) in the United States, with animals housed in small to medium-sized social groups. As part of the animal care plan, a programmatic framework is utilized, which integrates clinical care with socialization considerations for nonhuman primates (NHPs). This framework encompasses the following areas: (1) socialization in the clinical setting; (2) positive reinforcement training (PRT); (3) measures to ensure proper identification and medication distribution; and (4) in-group treatments. The success of this framework is demonstrated by the high socialization rate for hospitalized animals (99.5% social pairing success), with the majority of clinical cases (95%) being treated in social groups. Ultimately, this framework seeks to buffer stressors when animals require clinical care or husbandry manipulations. Taken together, the above components foster an environment that provides a comprehensive approach to NHP medical and behavioral management. Full article

Background/Objectives: Conventional anticancer therapies often lack specificity, targeting both cancerous and normal cells, which reduces efficacy and leads to undesired off-target effects. An additional challenge is the presence of hypoxic regions in tumors, where the Hypoxia Inducible Factor (HIF) transcriptional system drives the expression of pro-survival and drug resistance genes, leading to radio- and chemo-resistance. This study aims to explore the efficacy of targeted nanoparticle (NP)-based small interfering RNA (siRNA) therapies in downregulating these genes to enhance treatment outcomes in pancreatic cancer, a tumor type characterized by high CD44 expression and hypoxia. Methods: We utilized hyaluronic acid (HA)-displaying nanoparticles composed of positively charged chitosan (CS) complexed with siRNA to target and knock down HIF-1α in pancreatic cancer cells. Two NP formulations were prepared using either low molecular weight (LMW) or high molecular weight (HMW) CS. These formulations were evaluated for their internalization by cells and their effectiveness in gene silencing, both in vitro and in vivo. Results: The study found that the molecular weight (MW) of CS influenced the interaction between HA and CD44, as well as the release of siRNA upon internalization. The LMW CS formulation shows faster uptake kinetics, while HMW CS is more effective in gene knockdown across different cell lines in vitro. In vivo, both were able to significantly knockdown HIF-1α and some of its downstream genes. Conclusions: The results suggest that HMW and LMW CS-based NPs exhibit distinct characteristics, showing that both MWs have potential for targeted pancreatic cancer therapy by influencing different aspects of delivery and gene silencing, particularly in the hypoxic tumor microenvironment. Full article

Background: Comprehensive genomic profiling (CGP) is frequently adopted to direct the clinical care of myeloid neoplasms and solid tumors, but its utility in the care of lymphoid and histiocytic cancers is less well defined. Methods: In this study, we aimed to evaluate the frequency at which mutations identified by CGP altered management in non-myeloid hematologic malignancies. We retrospectively examined the CGP results of 105 samples from 101 patients with non-myeloid hematologic malignancies treated at an academic medical center who had CGP testing between 2014 and 2021. Results: CGP revealed one or more pathogenic or likely pathogenic variant in 92 (88%) of samples and 73 (72%) of tested patients had one or more mutations with diagnostic, prognostic, or therapeutic significance. The identification of a resistance variant resulted in the suspension of the active treatment or affected subsequent treatment choice in 9 (69%) out of 13 patients. However, the presence of a therapy sensitizing variant only led to consideration of a biomarker-directed therapy in 6 (10%) out of 61 patients. Conclusions: Overall, CGP of non-myeloid hematologic malignancies identified clinically significant variants in 72% of patients and resulted in a change in management in 22% of patients. Full article

Glioblastoma (GBL) is one of the more malignant primary brain tumors; it is currently treated by a multimodality strategy including surgery, and radio- and chemotherapy, mainly consisting of temozolomide (TMZ)-based chemotherapy. Tumor relapse often occurs due to the establishment of TMZ resistance, with a patient median survival time of <2 years. The identification of natural molecules with strong anti-tumor activity led to the combination of these compounds with conventional chemotherapeutic agents, developing protocols for integrated anticancer therapies. Curcumin (CUR), resveratrol (RES), and its glucoside polydatin (PLD) are widely employed in the pharmaceutical and nutraceutical fields, and several studies have demonstrated that the combination of these natural products was more cytotoxic than the individual compounds alone against different cancers. Some of us recently demonstrated the synergistic efficacy of the sublingual administration of a new nutraceutical formulation of CUR+PLD in reducing tumor size and improving GBL patient survival. To provide some experimental evidence to reinforce these clinical results, we investigated if pretreatment with a combination of CUR+PLD can improve TMZ cytotoxicity on GBL cells by analyzing the effects on cell cycle, viability, morphology, expression of proteins related to cell proliferation, differentiation, apoptosis or autophagy, and the actin network. Cell viability was assessed using the MTT assay or a CytoSmart cell counter. CalcuSyn software was used to study the CUR+PLD synergism. The morphology was evaluated by optical and scanning electron microscopy, and protein expression was analyzed by Western blot. Flow cytometry was used for the cell cycle, autophagic flux, and apoptosis analyses. The results provide evidence that CUR and PLD, acting in synergy with each other, strongly improve the efficacy of alkylating anti-tumor agents such as TMZ on drug-resistant GBL cells through their ability to affect survival, differentiation, and tumor invasiveness. Full article

Background: Studying causality relationships between different brain regions using the fMRI method has attracted great attention. To investigate causality relationships between different brain regions, we need to identify both the brain network structure and the influence magnitude. Most current methods concentrate on magnitude estimation, but not on identifying the connection or structure of the network. To address this problem, we proposed a nonlinear system identification method, in which a polynomial kernel was adopted to approximate the relation between the system inputs and outputs. However, this method has an overfitting problem for modelling the input–output relation if we apply the method to model the brain network directly. Methods: To overcome this limitation, this study applied the least absolute shrinkage and selection operator (LASSO) model selection method to identify both brain region networks and the connection strength (system coefficients). From these coefficients, the causality influence is derived from the identified structure. The method was verified based on the human visual cortex with phase-encoded designs. The functional data were pre-processed with motion correction. The visual cortex brain regions were defined based on a retinotopic mapping method. An eight-connection visual system network was adopted to validate the method. The proposed method was able to identify both the connected visual networks and associated coefficients from the LASSO model selection. Results: The result showed that this method can be applied to identify both network structures and associated causalities between different brain regions. Conclusions: System identification with LASSO model selection algorithm is a powerful approach for fMRI effective connectivity study. Full article

The World Health Organization has emphasized the importance of consuming small fruits for the prevention of chronic health problems, including diabetes, cardiovascular diseases, cancer, and obesity, which are named chronic non-communicable diseases (NCDs). Azara serrata Ruiz & Pav., commonly called “aroma de Castilla”, is a shrub endemic to Chile from the Salicaceae family that produces an underutilized blue-grey berry that grows wild in southern Chile. The species is widely used as a medicinal plant by the Andean communities of southern Chile. In this work, a high-resolution mass spectrometric analysis of the methanolic extract revealed several phenolic compounds for the first time in the edible berry of this endemic species. Furthermore, several glycosylated anthocyanins were detected and quantified using UHPLC coupled with UV/Vis detection and trapped ion mobility mass spectrometry (UHPLC-DAD-TIMS-TOF) for the anthocyanin-rich extract, which was prepared using an optimized anthocyanin extraction protocol. The extract proved to be active in the inhibition of several enzymes linked to NCDs, such as acetylcholinesterase, tyrosinase, amylase, lipase, and glucosidase (IC₅₀ = 3.92 ± 0.23, 12.24 ± 0.03, 11.12 ± 0.10, 32.43 ± 0.0, and 371.6 ± 0.0 μg/mL, respectively). Furthermore, the extract concentrated in anthocyanins showed good antioxidant activity evidenced by the bleaching of the radicals DPPH and ABTS, ferric-reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC). The results show that these neglected endemic small berries can be a source of healthy phytochemicals. These Chilean berries can be used as functional food and their extracts are candidates for use as functional ingredients in naturally healthy products. Full article

Aggressive B-cell lymphoma encompasses Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and, as per the 2016 WHO classification, high-grade B-cell lymphoma (HGBL) not otherwise specified (NOS) and HGBL double/triple hit (DH/TH). However, the diagnostic distinction of HGBL from BL and DLBCL is difficult by means of histology/immunostaining in a substantial number of patients. This study aimed to improve subtyping by the identification of molecular features of aggressive B-cell lymphomas, with a specific focus on HGBL. To this end, we performed a comprehensive gene expression and mutational pattern analysis as well as the detection of B-cell clonality of 34 cases diagnosed with BL (n = 4), DLBCL (n = 16), HGBL DH (n = 8), and HGBL NOS (n = 6). Three distinct molecular subgroups were identified based on gene expression, primarily influenced by MYC expression/translocation and cell proliferation. In HGBL, compared to BL, there was an upregulation of PRKAR2B and TERT. HGBL DH exhibited elevated expression of GAMT and SMIM14, while HGBL NOS showed increased expression of MIR155HG and LZTS1. Our gene mutation analysis revealed MYC, ARID1A, BCL2, KMT2D, and PIM1 as the most affected genes in B-cell lymphoma, with BCL2 and CREBBP predominant in HGBL DH, and MYC and PIM1 in HGBL NOS. Clonality analysis of immunoglobulin heavy and light chain rearrangements did not show distinguishable V- or J-usage between the diagnostic subgroups. Full article

Recent research has focused on immunotherapy with no side effects as an innovative medical treatment for cancer. However, typical drugs for immunotherapy are very expensive. Here, we propose the use of immunoceramics that activate immune cells by contact with their surface. Previous studies demonstrated that polymers, including the phenylboronic acid group, could activate lymphocytes. This activation may be due to the interaction between the sugar chains in cells and the OH group in B(OH)₃ formed via the dissociation of the BO₂ group. We have clarified that boron-containing apatite (BAp) activated lymphocytes in vitro. In this study, we fabricated the ceramic surfaces using the CaO-P₂O₅-SiO₂-B₂O₃ system (CPSB ceramics) containing BAp as a main crystalline phase. The results of the in vitro evaluation indicated that killer T cells in splenocytes cocultured with the CPSB ceramics were more numerous than in splenocytes cocultured on a control surface. The results of the in vivo evaluation indicated that the CPSB ceramics significantly inhibited tumor growth when CD8-positive T cells were cultured on individual ceramics and subsequently injected into tumor-bearing mice. The present CPSB ceramics are expected to be a valuable biomaterial for immunotherapy. Full article

This study of the features of the biochemical composition of biological fluids in patients with breast cancer, including saliva, allows us to identify some indicators as metabolic predictors of the presence of the disease. Objectives: to study the influence of the menopause factor and body mass index (BMI) on the biochemical composition of saliva and to evaluate the applicability of metabolic markers of saliva for the diagnosis of breast cancer. Methods: The case–control study involved 1438 people (breast cancer, n = 543; fibroadenomas, n = 597; control, n = 298). A comprehensive study of the biochemical composition of saliva was carried out using 36 parameters. Results: When comparing the salivary biochemical composition in breast cancer, fibroadenomas, and controls, it is necessary to take into account the menopausal status, as well as BMI (less than 25 or more) for the group of patients with preserved menstrual function. A complex of biochemical parameters has been identified that change in saliva during breast cancer, regardless of menopause and BMI (total protein, urea, uric acid, NO, α-amino acids, GGT), as well as specific parameters that must be taken into account when analyzing individual subgroups (imidazole compounds, LDH, catalase, α-amylase). During the study of a separate group of patients with leaf-shaped (phyllodes) tumors, we found similarities with breast cancer in the changes in some biochemical parameters that can be attributed to metabolites of malignant growth (protein, α-amino acids, calcium, NO, pyruvate, peroxidase, α-amylase). Conclusions: We demonstrated changes in a wide range of salivary biochemical parameters depending on the presence of fibroadenomas and breast cancer. From the point of view of clinical practice, this may be useful information for monitoring the condition of patients with fibroadenomas, which are difficult to unambiguously classify based on instrumental diagnostics alone. Full article

Background and objective: Colorectal cancer (CRC) is the leading cause of mortality in Spain, with screening programs, such as the faecal occult blood test and colonoscopy, having shown effectiveness in reducing CRC incidence and mortality. Despite these advancements, CRC screening uptake remains low in Spain, highlighting the need for studies comparing outcomes between screening-diagnosed and symptom-diagnosed patients to better understand the impact on overall survival and to quantify the clinical benefit in prognosis at diagnosis and at the end of follow-up. Methods: We conducted a retrospective cohort study with the following objectives: to compare stage at diagnosis, all-cause mortality, and disease-specific mortality among people diagnosed with CRC based on screening and based on symptoms; to identify the risk factors associated with mortality in this population; and to evaluate the effectiveness of screening on survival and early detection. Our study included people diagnosed with CRC in the public hospital of Elda (Spain) from 2014 to 2018; follow-up was until 2023 or death. Our primary outcome was all-cause mortality, which we analysed using Kaplan–Meier curves. We also investigated CRC-specific mortality and other-cause mortality. Results: Our sample included 315 people (186 with symptom-based diagnoses, 129 with screening-based diagnoses). The mean length of follow-up was 62.8 months. The screening group had a higher prevalence of a family history of CRC (p = 0.008), a distal tumour location (p = 0.002), and a cancer stage of 0 or I (p < 0.001). The symptoms group had a higher prevalence of a proximal CRC (p = 0.002), other chronic diseases (p < 0.001), and stages II, III, and IV (p < 0.001). Two variables were associated with mortality: stage IV at diagnosis and previous cancers. People with a symptom-based diagnosis had a higher prevalence of stage IV at diagnosis and a higher cumulative incidence of CRC mortality and all-cause mortality at the end of follow-up (p < 0.05). The Kaplan–Meier curves also showed a higher rate of all-cause mortality in the symptoms group throughout the follow-up. Conclusion: CRC screening enables an earlier diagnosis and improves survival. These findings support public health policies that promote accessible and effective screening. Full article