Search Results (1,195)

Despite the development of new drugs, chemoresistance constitutes a major obstacle in cancer treatment. To investigate mechanisms of resistance and potential therapeutic targets, we developed doxorubicin-resistant models of HER2− (D2F2/Dox) and HER2+ (D2F2E2/Dox) breast cancer cells. Compared with parental cells, the D2F2/Dox and D2F2E2/Dox differed in morphology, increased migratory potential, elevated levels of the transcription factor signal transducer and activator of transcription 3 (Stat3), and a lower proliferation rate in D2F2E2/Dox. Moreover, D2F2/Dox and D2F2E2/Dox differed in the expression profiles of genes related to cell stemness, apoptosis, and drug efflux. Stat3 gene silencing in both doxorubicin-resistant cell types reversed the expression profiles of some genes (different in each resistant cell line), and decreased migratory potential was observed only in D2F2 cells. These data indicate that the acquired doxorubicin resistance was associated with Stat3 status; however, HER2− and HER2+ breast cancer cells did not indicate the same mechanism of chemoresistance acquisition. Importantly, Stat3 silencing did not substantially restore doxorubicin sensitivity, suggesting that effective therapy may require simultaneous targeting of multiple pathways. Furthermore, we demonstrated that siStat3 therapeutics could be selectively delivered to HER2+ cancer cells using H2.1MS1:MS2KN silk spheres, indicating their potential for targeted drug delivery in vivo. Full article

Background: Human papillomavirus (HPV) continues to cause an estimated 4000 preventable cancer deaths each year in the United States. Given the prevalence of HPV-related disease and suboptimal vaccination rates, this study explores perceptions of HPV vaccination among HIV-negative females and females living with HIV in Tennessee. Methods: This prospective, observational qualitative study consisted of narrative interviews which were conducted with HIV-negative and HIV-positive participants, focusing on their perceptions of HPV and its vaccine. Interviews were conducted by phone, and the verbatim transcripts were inductively coded by three researchers. The inductive codes were then grouped into categories based on similarities which facilitated the emergence of themes. Results: A total of 40 participants were interviewed between July 2024 and December 2024. Narrative analysis revealed three themes: (1) “I had never heard of it until I saw the flier.” Gaps in Understanding of HPV and Its Health Implications, (2) Navigating Adolescent Health Decisions and Emotional Influence, and (3) Barriers to Uptake—Skepticism, Trust, and the Need for Tailored Information. Two subthemes emerged: Cohort-Specific Skepticism, and Parental Influence and Communication Gaps. Conclusions: This study revealed significant gaps in HPV knowledge and vaccination uptake among HIV-negative women and women living with HIV in Tennessee. Provider communication was key to vaccine decisions, but clear recommendations were often missed in clinical encounters. Full article

Background: India accounts for one-fifth of global cervical cancer deaths, yet Human Papillomavirus (HPV) vaccination coverage remains low despite the World Health Organization (WHO) recommendations to initiate vaccination at age 9. With the national HPV vaccination campaign in 2026 and its approval for integration into India’s Universal Immunization Programme (UIP), strengthening physician knowledge, beliefs, and confidence in recommending the vaccine is critical. Methods: In 2023, the American Cancer Society and Cancer Foundation of India catalyzed two national medical societies, the Federation of Obstetric and Gynaecological Societies of India and the Indian Academy of Pediatrics, to educate physicians on HPV vaccination using a train-the-trainer (ToT) model. A mixed-methods evaluation, using the RE-AIM Framework, included pre- and post-training surveys assessing changes in knowledge, beliefs, confidence, and intent, as well as monthly engagement surveys and project reports analyzed using descriptive and inferential statistics. A fidelity assessment evaluated consistency of training delivery. Twenty in-depth interviews explored physician reactions and implementation of learnings, analyzed using a rapid approach. Results: A total of 18,206 physicians were trained. The post-training respondent group demonstrated higher HPV vaccination knowledge scores and more favorable responses in confidence, beliefs, and intent than the pre-training respondent group. The fidelity assessment demonstrated consistent delivery overall, with some variability in role play facilitation. Interviews highlighted increased physician confidence, peer knowledge sharing, and community engagement following the training. Medical societies reported strong program adoption and plans for continued efforts. Conclusions: A ToT physician training cascaded through medical societies is a feasible strategy to prepare physicians to recommend the HPV vaccine and address parental concerns at scale. Full article

Urologic malignancies (UMs), including prostate cancer (PCa), bladder cancer (BCa), renal cell carcinoma (RCC), and testicular germ cell tumors (TGCT), are governed by interconnected molecular pathways that regulate proliferation, angiogenesis, metabolism, invasion, immune escape, and treatment resistance. Key pathways include PI3K/AKT/mTOR, VEGF/VEGFR, EGFR, FGFR, c-MET, androgen receptor signaling, DNA damage response, inflammatory transcriptional programs, and regulation of the tumor microenvironment. This structured expert review evaluates mechanistic, translational, epidemiological, and clinical evidence on food- and botanical-derived nutraceuticals that may influence cancer-related signaling, redox balance, inflammation, metabolic adaptation, and host–tumor interactions. Nutraceuticals are considered investigational adjunctive exposures rather than anticancer treatments or alternatives to standard care. Relevant literature was identified through a structured, non-systematic search of PubMed/MEDLINE, Scopus, Web of Science Core Collection, and Embase from database inception to 17 June 2026, supplemented by backward and forward citation searches. Eligible evidence comprised preclinical, observational, interventional, pharmacokinetic, formulation, safety, and drug–nutraceutical interaction studies. Evidence was evaluated by cancer type, compound class, molecular context, formulation, exposure, translational maturity, and safety, and was classified into five stages: prevention signal, mechanistic plausibility, bioavailability and exposure feasibility, exposure-linked biomarker activity, and clinical benefit. An exposure–species–compartment framework was used to assess whether parent compounds and relevant metabolites reached systemic, urinary, or target-tissue concentrations compatible with the proposed effects. Findings based solely on supraphysiological concentrations of unconjugated parent compounds were considered hypothesis-generating unless supported by human exposure or tissue-distribution data. Curcumin, green tea catechins, isoflavones, carotenoids, flavonols, stilbenes, and triterpenoids affect several cancer-related pathways, primarily in experimental models. Translation to clinical practice is constrained by inconsistent formulations, limited bioavailability, inadequate target-tissue exposure data, few biomarker-linked studies, and possible interactions with anticancer therapies. PCa and BCa provide the most suitable settings for exposure-verified mechanistic studies. In RCC, safety and treatment interactions should be prioritized, whereas in TGCTs, non-interference with curative cisplatin-based therapy must be demonstrated. Future studies should use chemically defined formulations, verify clinically relevant exposure, incorporate mechanism-matched biological-response endpoints, and confirm compatibility with established treatment. Current evidence does not support nutraceuticals as treatments for urologic malignancies. Full article

High-risk neuroblastoma (HR-NB) remains a major clinical challenge due to the emergence of therapy resistance. In this study, the anticancer effects of seven previously synthesized betulin (BET), betulinic acid (BA) and ursolic acid (UA) derivatives (1–7) and of their natural precursors BET, BA and UA (8–10) were investigated in HTLA NB cells, selected as the experimental model by MTT assay, to find a possible solution to drugs that have lost their effect. Dynamic light scattering (DLS) analysis showed that amphiphilic compounds 1 and 4–7 form nanovesicles (240–448 nm) in water, while all compounds have high positive ζ-potential (ζ-p, +28.5–+83.1 mV), supporting favourable membrane interaction and cellular uptake. Cytotoxic experiment results and related IC₅₀ values were expressed as the mean ± SD of four independent experiments run in triplicate. Most derivatives exhibited a cytotoxic activity higher than that of their natural precursors and outperformed etoposide; they were particularly effective against the multidrug resistant (MDR) HTLA ER cells. Among them, the ursolic acid (UA) derivative 7 emerged as the most active compound, displaying sub-micromolar to low micromolar IC₅₀ values and markedly improving the activity of native UA. Functional studies revealed that it induces complete suppression of clonogenic growth at low micromolar concentrations in both HTLA ER and parental HTLA 230 NB cells. In addition, a concentration-dependent downregulation of Akt, p-Akt, BMI1 and PARP, was observed consistently with a marked suppression of survival pathways and loss of cellular homeostasis. Collectively, our experiments, which need further direct investigation to confirm subsequent assumption, could suggest that compound 7 could kill cancer cells via a non-apoptotic, bioenergetic collapse mechanism. All of these findings suggest compound 7 as a promising mitochondria-targeted lead candidate and support amphiphilic triterpenoid derivatives as attractive platforms for overcoming multidrug resistance in high-risk NB. Full article

Background: Enhancing the binding affinity of monoclonal antibodies (mAbs) has the potential to improve their therapeutic efficacy. In this study, we generated a novel mAb, PB-223, through affinity maturation of the parental antibody NEO-102. NEO-102 (Ensituximab) is a chimeric human IgG1 mAb that targets a cancer-specific glycosylated variant of MUC5AC expressed on colorectal and pancreatic cancers while sparing healthy tissues. In a Phase 2 clinical study involving heavily pretreated patients with advanced, refractory colorectal cancer, NEO-102, as a monotherapy, exhibited modest efficacy. Methods: We engineered the VH and VL regions of NEO-102 through affinity maturation to enhance antigen binding while preserving target specificity. The optimized clone, PB-223, was evaluated for improved binding by Biacore T200, flow cytometry, and immunohistochemistry (IHC). The specific PB-223 target antigen was discovered using an O-glycan array. An internalization assay evaluated the ability of PB-223 to be internalized into human cancer cell lines expressing its target antigen. Results: Analysis performed with the Biacore T200 evaluation (version 3.2) software revealed that PB-223 exhibits a 4.55-fold lower equilibrium dissociation constant (KD) compared with NEO-102 towards recombinant human Bovine Submaxillary Mucin (BSM), a protein rich in O-glycans. PB-223 has enhanced binding to human cancer cell lines recognized by NEO-102 using flow cytometry. O-glycan array analysis identified O-glycans terminating with α(2,6) sialic acids, including core 2 O-glycans and sTn glycans, expressed by human cancer cell lines reactive with PB-223 in flow cytometry, as the specific binding epitope of PB-223. IHC analysis of human tumor tissues showed that PB-223 does not bind to healthy tissues tested in this study, and that demonstrates an increase in the number of cancer tissues recognized and in the IHC score compared to NEO-102. PB-223 is internalized into a human cancer cell line expressing its target antigen. Conclusions: PB-223 can potentially be used as a targeting moiety for antibody-based therapeutics, including antibody–drug conjugates (ADCs), bispecific antibodies, immune-engaging constructs, and radiopharmaceuticals, for the treatment of human cancers expressing O-glycans terminating with α(2,6) sialic acids, including core 2 O-glycans and sTn glycans. Full article

Background/Objectives: Psychosocial, neuropsychological, social, and academic difficulties may persist after pediatric cancer treatment. We described parent/caregiver-reported functioning and support needs and explored their associations with clinical, family-related, socio-economic, premorbid, and place-based characteristics in an Italian survivorship setting. Methods: This single-center cross-sectional exploratory study included 93 of 130 families approached between November 2022 and January 2023 (response rate, 71.5%). One parent or caregiver completed a purpose-built questionnaire for each survivor. The cohort included 38 survivors with central nervous system (CNS) tumors and 55 with non-CNS tumors. Outcomes were evaluated relative to retrospectively reported pre-diagnosis functioning. Exact confidence intervals, effect estimates, multivariable Firth logistic regression, and Benjamini–Hochberg false discovery rate correction were used. Results: Worsening internalizing difficulties were reported for 48/90 survivors (53.3%), neuropsychological difficulties for 42/90 (46.7%), academic worsening for 30/85 (35.3%), and social integration difficulties for 27/90 (30.0%). CNS survivors more frequently had social integration difficulties than non-CNS survivors (47.4% versus 17.3%; odds ratio, 4.22; 95% confidence interval, 1.50–12.73; q = 0.015) and underwent cognitive assessment after cancer (50.0% versus 17.0%; odds ratio, 4.80; 95% confidence interval, 1.71–14.44; q = 0.013). Municipality size and geographic area showed no nominal associations with parent-reported outcomes. No candidate-variable association in the exploratory screen remained significant after false discovery rate correction. Conclusions: Parent-reported difficulties and support needs were common, with differences by CNS versus non-CNS tumor site. Family-related, premorbid, and place-based patterns are hypothesis-generating and require prospective evaluation using validated multi-informant measures. Full article

Colorectal cancer (CRC) remains a leading cause of cancer morbidity worldwide, highlighting the need for improved therapies. Metformin, a widely used antihyperglycemic agent, has gained attention for its potential antitumor properties. In this study, we evaluated the effects of the tumor suppressor genes TP53 and CDKN1A on metformin responsiveness in a KRAS-mutant CRC in vitro model using HCT116 cells harboring a G13D mutation in KRAS. Using parental (p53^+/+, p21^+/+) and isogenic knockout cell lines, we assessed cell-cycle distribution and transcriptomic responses following metformin treatment. In parental wild-type cells, metformin exposure was associated with a dose- and time-dependent reduction in cell viability and an increased proportion of cells in the G0/G1 phase, with significance levels across treatment conditions ranging from p = 0.03 to p < 0.0001. Loss of p53 or p21 was associated with attenuated cellular responses to metformin, with p21-deficient cells responding primarily at higher doses and prolonged exposure (72 h). Transcriptomic profiling revealed extensive differential gene expression in parental cells (1399 DEGs), compared with more limited responses in p53^−/− (270 DEGs) and p21^−/− cells (32 DEGs). Differentially expressed genes associated with MAPK signaling (DUSP5) and inflammatory regulation (TNFAIP3) were observed across genotypes, whereas pathway enrichment of DNA replication and chromatin organization was specific to p53-deficient cells. These findings provide a transcriptomic and phenotypic characterization of genotype-dependent cellular responses to metformin and establish a basis for future mechanistic and functional validation studies. Full article

Background/Objectives: Malnutrition is prevalent among patients in the pediatric intensive care unit (PICU) and has been shown to worsen in some patients during the PICU stay. In critically ill children, malnutrition is associated with longer PICU length of stay and increased mortality. Several tools have been developed and validated to screen for nutritional status in children, but none were specifically designed for critically ill children. Our study aims to fill this gap. The goal of this study was to refine and validate a novel PICU nutrition screening tool in a diverse population of critically ill children from six PICUs across the United States. Methods: Subjects underwent the nutrition screen and a Subjective Global Nutritional Assessment (SGNA). We used chi-square tests and Mann–Whitney tests to compare elements of the nutrition screen to the SGNA to identify those elements most associated with malnutrition. We used stepwise logistic regression to determine the best fitting model for a malnutrition screening tool. We proposed a scoring system using the factors identified in the best fitting model to define a positive screen. Results: We enrolled 732 subjects at six PICUs. Of these, 131 subjects (17.9%) were malnourished per the SGNA. Children with and without malnutrition did not differ with respect to age, sex, or race. The likelihood of malnutrition increased as weight-for-age percentile decreased (p < 0.001). We found that the best fitting model of a malnutrition screening tool for critically ill children included weight-for-age percentile, cancer, feeding less, parent perception of growth as poor, and being significantly underweight. We defined a positive screen that should prompt referral to a dietitian. Conclusions: We have developed a nutrition screening tool for critically ill children. Full article

There are several forms of monoallelic expression, in which the 50:50 ratio in the expression activity of each of the two copies of the gene is disrupted. This review focuses on the phenomenon of random autosomal monoallelic expression (aRME), a process in which only one of the two alleles is transcribed in a single cell, and the allele choice is not determined by the parental origin. One of the central problems in studying this phenomenon is the differentiation of the two forms of aRME: clonal, in which the expression pattern is mitotically inherited, and stochastic, when the allele choice can change over time due to transcriptional bursting. Distinguishing these events is methodologically challenging: divergent experimental approaches and the lack of standardized detection criteria have produced strikingly contradictory estimates of aRME prevalence. Furthermore, single-cell transcriptomic approaches are particularly susceptible to technical artefacts that can generate false-positive monoallelic calls, complicating the distinction between heritable and transient states. In this review, we critically evaluate the evidence for clonal and stochastic aRME, examine the epigenetic mechanisms proposed to maintain monoallelic expression, and discuss its clinical significance, focusing on the role of monoallelic expression in the penetrance of autosomal dominant diseases (including congenital immune disorders and cardiomyopathy), neurodevelopmental disorders, and cancer progression. Full article

Volatile organic compounds (VOCs) reflect cellular metabolic activities and may serve as non-invasive biomarkers in oncology. This study investigated whether acquired oxaliplatin resistance in colorectal cancer is associated with distinct volatilomic alterations. The human colorectal cancer cell line HCT116 and its oxaliplatin-resistant derivative (OXrHCT116) were analyzed under basal conditions and following oxaliplatin exposure. Chemoresistance was confirmed using dose–response, cell viability, and colony formation assays. VOCs were analyzed by headspace needle trap extraction coupled with gas chromatography–mass spectrometry (HS-NTE-GC-MS). OXrHCT116 cells exhibited markedly reduced oxaliplatin sensitivity, increased IC₅₀ values, and reduced proliferative and clonogenic capacity. Volatilomic profiling identified 55 significantly altered VOCs. Parental HCT116 cells displayed broader VOC diversity and higher turnover than OXrHCT116 cells. Hydrocarbons associated with lipid peroxidation and oxidative stress were more abundant in HCT116 cells, whereas resistant cells showed markedly reduced emission of these compounds. Additional alterations in aldehydes, alcohols, and aromatic compounds suggested reduced metabolic flux in resistant cells. Oxaliplatin exposure induced pronounced volatilomic changes in HCT116 cells but only minimal modulation in OXrHCT116 cells. These findings suggest that oxaliplatin resistance may be associated with distinct metabolic reprogramming and support VOC profiling as a promising approach for monitoring chemoresistance. Full article

Background/Objectives: Chemotherapy-related fatigue (CRF) affects 50–80% of children receiving chemotherapy and significantly impairs quality of life. Despite the family-centered care framework guiding pediatric oncology practice, evidence on parent-delivered, home-based non-pharmacological interventions for CRF remains limited. This study aimed to evaluate the effect of a parent-delivered warm-water foot bath on CRF in children aged 7–12 years undergoing chemotherapy. Methods: A two-arm parallel randomized controlled trial (NCT06529484; October 2024–May 2025) was conducted at a university hospital pediatric hematology–oncology outpatient clinic. Sixty-one children with stage 3–4 Non-Hodgkin Lymphoma (intervention, n = 29; control, n = 32) were randomized using computer-generated allocation and sequentially numbered, opaque, sealed envelopes. Following structured family education, parents delivered nightly foot baths (38–40 °C, 20 min) at home for 7 consecutive days after chemotherapy administration. Adherence and fidelity were monitored via a daily WhatsApp communication protocol. Fatigue was assessed daily using the Oncology Nursing Society Visual Fatigue Scale (ONS-VFS; primary outcome) and pre/post analysis using the Pediatric Oncology Fatigue Assessment Scale (child and parent forms). Reporting followed CONSORT 2025. Results: Median ONS-VFS scores declined significantly over the 7 days in both groups (Friedman p < 0.001 for each), from 5 (Day 1) to 2 (Day 7); between-group comparisons showed no statistically significant differences on any day (all p > 0.05). On the Pediatric Oncology Fatigue Assessment Scale, no between-group differences favored the intervention; a single child-report subscale difference favored the control group and is most plausibly attributable to multiple comparisons. Adherence was complete (100%), no adverse events occurred, and all 61 participants completed the protocol. Conclusions: A parent-delivered foot bath is a safe, feasible, and well-accepted family-centered nursing intervention, with complete adherence and no adverse events. This trial was not powered to detect between-group differences and did not demonstrate superiority over standard care; adequately powered trials are needed to determine efficacy. Full article

Background/Objectives: This study aimed to improve the biological profile of oleanolic acid (OA) through structural modification at the C-17 carboxyl group and the C-3 hydroxyl group, with a focus on the design of short-chain alkyl esters and 3-O-furoyl hybrids. Methods: Two series of OA derivatives were synthesized and characterized using spectroscopic methods, including ¹H NMR, ¹³C NMR and MS. In silico structure–activity relationship (SAR) analysis, ADMETox profiling, and molecular docking to the epidermal growth factor receptor (EGFR) tyrosine kinase domain were performed as predictive and hypothesis-generating tools. Anticancer activity was evaluated in vitro using the MTT assay against human cancer cell lines, including HeLa, MCF-7, A-549, SKBR-3, PC-3 and SKOV-3, as well as non-malignant human dermal fibroblasts (HDFs). Antioxidant properties were assessed using cell-free CUPRAC and DPPH assays. Results: The C-17 esterification markedly enhanced cytotoxic potency compared to the parent OA, while the introduction of the 3-O-furoyl moiety further improved antiproliferative activity in several derivatives. Selected compounds showed low-micromolar IC₅₀ values and moderate selectivity toward cancer cells. Molecular docking suggested favorable accommodation of selected derivatives within the EGFR ATP-binding pocket, mainly through hydrophobic and π-related interactions; however, these results do not confirm direct EGFR binding and require experimental validation. The CUPRAC and DPPH assays provided preliminary insight into chemical redox behavior but should not be directly extrapolated to intracellular antioxidant or pro-oxidant activity. Predicted ADMETox profiles indicated moderate permeability and relatively low predicted risk for selected toxicity endpoints, while also highlighting high lipophilicity, poor aqueous solubility and potential metabolic liabilities. Conclusions: Overall, the results identify several OA derivatives as promising anticancer lead compounds for further optimization and mechanistic investigation. Full article

Background/objectives: To describe and compare Korean AYAs’ and parental perspectives on the family environment in terms of agreement and significant differences and examine which variables were associated with AYAs’ symptom distress. Sample and setting: Self-report data were collected from a total sample of 113 AYAs, recruited from a pediatric-oncology outpatient clinic at a university-affiliated hospital and community group in South Korea. Because each study aim required different data sources, different analytic samples were used. Specifically, 54 AYA–parent dyads were included for Aim 1, whereas self-report data from 111 AYAs with complete data were used for Aim 2. Methods and variables: This subgroup analysis used a quantitative–descriptive, cross-sectional design. AYAs’ and parent perceptions of the family environment (family cohesion and adaptability, family strength, and social support from family) and AYAs’ symptom distress were collected using reliable and validated self-report questionnaires and analyzed using descriptive and inferential statistics. Results: AYAs and their parents showed low (family support) to moderate agreement (family strength, family cohesion, and adaptability) on perceptions of family environment (ICC = 0.374–0.612). AYAs reported significantly lower perceptions of family support than their parents, with a small to moderate effect (p < 0.001, d = 0.48). All family environment variables were correlated with AYAs’ symptom distress (p < 0.05). Among these variables, AYAs’ perceived family strength emerged as the only family environment variable significantly associated with their symptom distress (F = 14.309, p < 0.001, R² = 0.359, R²adj = 0.334), which was stronger during treatment. Conclusions: AYAs’ perceived family strength should be routinely assessed, especially during cancer treatment. Additional nursing interventions focusing on enhancing AYAs’ families as a support group are needed. Full article

Opisthorchis viverrini (OV) is a liver fluke endemic to the Lower Mekong Basin. Infections often begin in childhood and are causally linked to cholangiocarcinoma, an often-fatal bile duct cancer. Anthelmintic treatment is the primary control strategy, but infection can recur. Therefore, additional strategies are needed. This study assessed the impact of “The Magic Glasses Opisthorchiasis” (MGO), a cartoon-based intervention, on schoolchildren’s OV-related knowledge, attitudes and practices (KAP). A cluster (school)-randomised controlled trial was conducted in Cambodia, Laos and Thailand. Clusters were randomised into either school health education only or with MGO. OV KAP was measured using a standardised questionnaire. FGDs and interviews were also conducted in intervention schools with schoolchildren, parents, and teachers. Cambodia intervention knowledge and attitude scores improved by 19.2 (p < 0.001) and 25.3 (p < 0.001) percentage points, respectively, relative to the control. Laos intervention knowledge and attitude scores improved by 19.0 (p < 0.001) and 14.2 (p < 0.001) percentage points. However, Thailand’s intervention knowledge and attitude scores declined by 23.3 (p < 0.001) and 15.8 percentage points (p < 0.001). There were no improvements in behaviour scores in any country, but parents and schoolchildren in Cambodia and Laos reported improved fish preparation practices, suggesting positive spillover effects from MGO. The findings support MGO as an effective tool for school-based health education. Full article