Search Results (111,620)

The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 10⁹/L; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England, Canada, and Australia. Patients aged 40 years and over with a full blood count were included and stratified by age (in 10-year bands), sex, (male/female), and platelet count group. Cancer incidence within one year of the test date was estimated from linked registry data. In all three countries, there was a clear upwards trend in cancer incidence with increasing platelet count for both sexes and at all age groups. Lung and colorectal were the most common sites. These results have important implications for the international application of this work; analysis of local health datasets will be crucial to determining appropriate thresholds. Appropriate upper thresholds will depend on local populations, healthcare needs, and priorities. Further research is needed to assess the likely impact of new recommendations on the healthcare system, on cancer outcomes, and patient benefit. Full article

Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to bone marrow-derived mesenchymal stem cells (BM-MSCs) for potential clinical applications because of their accessibility and anti-inflammatory capacity. We previously demonstrated that DT-MSCs from dental pulp (DP-MSCs), periodontal ligaments (PDL-MSCs), and gingival tissue (G-MSCs) show immunosuppressive effects similar to those of BM, but to date, the DT-MSC-mediated immunoregulation of T lymphocytes through the purinergic pathway remains unknown. In the present study, we compared DP-MSCs, PDL-MSCs, and G-MSCs in terms of CD26, CD39, and CD73 expression; their ability to generate adenosine (ADO) from ATP and AMP; and whether the concentrations of ADO that they generate induce an immunomodulatory effect on T lymphocytes. BM-MSCs were included as the gold standard. Our results show that DT-MSCs present similar characteristics among the different sources analyzed in terms of the properties evaluated; however, interestingly, they express more CD39 than BM-MSCs; therefore, they generate more ADO from ATP. In contrast to those produced by BM-MSCs, the concentrations of ADO produced by DT-MSCs from ATP inhibited the proliferation of CD3⁺ T cells and promoted the generation of CD4⁺CD25⁺FoxP3⁺CD39⁺CD73⁺ Tregs and Th17⁺CD39⁺ lymphocytes. Our data suggest that DT-MSCs utilize the adenosinergic pathway as an immunomodulatory mechanism and that this mechanism is more efficient than that of BM-MSCs. Full article

Purpose: Conceptual models provide frameworks to illustrate relationships among patient-, provider-, system-, and community-level factors that inform care delivery and research. Existing models of cancer survivorship care focus largely on pediatric or adult populations whose needs differ from adolescents and young adults (AYAs). We developed a patient-centered conceptual model of AYA survivorship care. Methods: We conducted a narrative literature review of current conceptual and theoretical models of care. We engaged AYA cancer survivors (n = 25) in semi-structured one-hour telephone interviews. Most participants were in their 20s and 30s, and the majority (84%) were women. Recruitment was stratified by age and time since cancer diagnosis. We conducted a thematic analysis of interview transcripts to identify themes that exemplified patient-centered care. Results: Most participants identified as white and female. Leukemia and breast cancer were the most common cancer types. Main themes included the need for (1) care coordination, (2) ongoing mental health support, (3) connection to AYA peer support, (4) support during fertility preservation efforts, (5) support with financial burden, (6) support for quality of life, (7) information about and support with side effects and late effects, and (8) attention to the unique needs of young adults. Conclusions: We present a patient-centered conceptual model of AYA survivorship care needs that can inform future cancer care delivery and research. Full article

Elite athletes in speed roller skates perceive skating to be a more demanding exercise for the groin when compared to other cyclic disciplines, increasing their risk of injury. The objective of this study was to monitor the kinematic and electromyographic parameters of roller speed skaters, linearly, on a treadmill, and to compare different skating speeds, one at 20 km/h and one at 32 km/h, at a 1° inclination. The acquisition was carried out by placing an inertial sensor at the level of the first sacral vertebra, and eight surface electromyographic probes on both lower limbs. The kinematic and electromyographic analysis on the treadmill showed that a higher speed requires more muscle activation, in terms of maximum and average values and co-activation, as it not only increases the intrinsic muscle demand in the district, but also the athlete’s ability to coordinate the skating technique. The present study allows us to indicate not only how individual muscle districts are activated during skating on a surface different from the road, but also how different speeds affect the overall district load distributions concerning effective force, which is essential for the physiotherapist and kinesiologist for preventive and conditional purposes, while also considering possible variations in the skating technique in linear advancement. Full article

Esophageal adenocarcinoma (EAC) is a subtype of esophageal cancer that is difficult to treat, with overall poor survival and frequent recurrence despite curative-intent treatment strategies. There is limited understanding of EAC resistance mechanisms to chemotherapy or radiation. We have found that the AMP-activated protein kinase (AMPK) can serve a pro-survival function in EAC cells in response to cytotoxic treatments. Treatment with the IL-6 inhibitor tocilizumab, which previously has been shown to inhibit EAC organoid growth, resulted in the activation of AMPK in the OE33 EAC cell line, which was accompanied by a decrease in MTORC1 signaling and an increase in oxidative mitochondrial metabolism, both known downstream effects of AMPK activation to promote cell survival under conditions of metabolic stress. This increase in oxidative metabolism was abrogated in cells with a genetic knockdown of AMPK expression. Furthermore, we found that AMPK was activated in OE33 cells following treatment with cisplatin or ionizing radiation. Treatment with the AMPK inhibitor Compound C or genetic knockdown of AMPK expression enhanced cell death in a synergistic manner with chemotherapeutics or ionizing radiation. These findings were recapitulated in human patient-derived EAC organoids, suggesting that AMPK may be a common pro-survival mechanism to confer treatment resistance in EAC and may serve as a novel target to enhance the efficacy of current and future treatment strategies. Full article

Cells constantly face the challenge of managing oxidants. In aerobic organisms, oxygen (O₂) is used for energy production, generating reactive oxygen species (ROS) as byproducts of enzymatic reactions. To protect against oxidative damage, cells possess an intricate system of redox scavengers and antioxidant enzymes, collectively forming the antioxidant defense system. This system maintains the redox equilibrium and enables the generation of localized oxidative signals that regulate essential cellular functions. One key component of this defense is the thioredoxin (Trx) system, which includes Trx, thioredoxin reductase (TrxR), and NADPH. The Trx system reverses oxidation of macromolecules and indirectly neutralizes ROS via peroxiredoxin (Prx). This dual function protects cells from damage accumulation and supports physiological cell signaling. However, the Trx system also shields tumors from oxidative damage, aiding their survival. Due to elevated ROS levels from their metabolism, tumors often rely on the Trx system. In addition, the Trx system regulates critical pathways such as proliferation and neoangiogenesis, which tumors exploit to enhance growth and optimize nutrient and oxygen supply. Consequently, the Trx system is a potential target for cancer therapy. The challenge lies in selectively targeting malignant cells without disrupting the redox equilibrium in healthy cells. The aim of this review article is threefold: first, to elucidate the function of the Trx system; second, to discuss the Trx system as a potential target for cancer therapies; and third, to present the possibilities for inhibiting key components of the Trx system, along with an overview of the latest clinical studies on these inhibitors. Full article

Background/Objectives: Engaging in physical activity (PA) is crucial for children’s physical and mental health, with PA in childhood influencing lifelong activity levels. However, PA during childhood tends to decrease with age. Childhood friendship networks influence various health behaviors, including physical activity. Centralities are objective measures of an individual’s position and role in friendship networks. The relationship between centrality and PA is inconsistent. This study aimed to determine how centrality affects changes in PA in late childhood longitudinally and to investigate the distribution of centrality in the network. Methods: This prospective cohort study recruited fourth- and fifth-grade children (9–11 years old). A total of 143 children participated. We calculated three centralities—in-degree, closeness, and betweenness—based on social network analysis (SNA). PA was assessed using the physical activity questionnaire for older children (PAQ-C). To explore the relationship between centralities and the percentage change in PA, a multivariate logistic regression analysis was performed. Results: Children with higher closeness had a significantly higher rate of decrease in PA after adjusting for confounding factors. There was no significant association between betweenness and percentage change in PA (p = 0.66) or in-degree and percentage change in PA (p = 0.21). Conclusions: This study highlights the importance of considering social network dynamics in PA interventions, particularly for children with high social closeness. Future research should incorporate objective PA measures and explore broader social networks to enhance intervention strategies, especially for Generation Z and Alpha, who experience unique opportunities and motivations for PA due to pervasive digital environments. Full article

The monarchE study added the CDK4/6 inhibitor abemaciclib to the care of women with oestrogen-positive (ER+) breast cancers. Eligibility required meeting monarchE criteria—either >3 positive axillary nodes, or 1–3 positive sentinel nodes (SNB+) with tumour size >50 mm or grade 3 cancers. Women were advised to proceed to completion axillary node clearance (cANC) if size/grade criteria were not fulfilled for >3 positive nodes to be identified. However, cANC is associated with significant morbidity, conflicting with the potential benefits of abemaciclib. We analysed data of 229 consecutive women (2016-2022) with ER+ breast cancer and SNB+ who proceeded to cANC, keeping with contemporary treatment guidelines. We used this cohort to assess numbers that, under national guidance in place currently, would be advised to undergo cANC solely to check eligibility for abemaciclib treatment. Using monarchE criteria, 90 women (39%) would have accessed abemaciclib based on SNB+ and size/grade, without cANC. In total, 139 women would have been advised to proceed to cANC to check eligibility, with only 15/139 (11%) having >3 positive nodes after sentinel node biopsy and cANC. The remaining 124 (89%) would have undergone cANC but remained ineligible for abemaciclib. Size, age, grade, and Ki67 did not predict >3 nodes at cANC. Following cANC, a large majority of women with ER+, <50 mm, and grade 1–2 tumours remain ineligible for abemaciclib yet are subject to significant morbidity including lifelong lymphoedema risk. The monarchE authors state that 15 women need abemaciclib therapy for 1 to clinically benefit. Thus, in our cohort, 139 women undergoing cANC would lead to one woman benefitting. Full article

Lung cancer treatment and detection can be improved by the identification of new biomarkers. Novel approaches in investigating circular RNAs (circRNAs) as biomarkers have yielded promising results. A circRNA molecule circHIPK3 was found to be widely expressed in non-small-cell lung cancer (NSCLC) cells, where it plays a crucial role in lung cancer tumorigenesis. CircHIPK3 promotes lung cancer progression by sponging oncosuppressive miRNAs such as miR-124, miR-381-3p, miR-149, and miR-107, which results in increased cell proliferation, migration, and resistance to therapies. Inhibiting circHIPK3 has been demonstrated to suppress tumour growth and induce apoptosis, which suggests its potential use in the development of new lung cancer treatment strategies targeting circHIPK3-related pathways. As a biomarker, circHIPK3 shows promise for early detection and monitoring of lung cancer. CircHIPK3 increased expression levels in lung cancer cells, and its potential link to metastasis risk highlights its clinical relevance. Given the promising preliminary findings, more clinical trials are needed to validate circHIPK3 efficacy as a biomarker. Moreover, future research should determine if the mechanisms discovered in NSCLC apply to small cell lung cancer (SCLC) to investigate circHIPK3-targeted therapies for SCLC. Full article

The epithelial–mesenchymal transition (EMT) phenotype, identified as a significant clinical indicator in regard to cancer, manifests as a biological process wherein cells transition from having epithelial to mesenchymal characteristics. Physiologically, EMT plays a crucial role in tissue remodeling, promoting healing, repair, and responses to various types of tissue damage. This study investigated the impact of BNE-RRC on oral cancer cells (KB) and revealed its significant effects on cancer cell growth, migration, invasion, and the EMT. BNE-RRC induces the epithelial-like morphology in KB cells, effectively reversing the EMT to a mesenchymal–epithelial transition (MET). Extraordinarily, sustained culturing of cancer cells with BNE-RRC for 14 days maintains an epithelial status even after treatment withdrawal, suggesting that BNE-RRC is a potential therapeutic agent for cancer. These findings highlight the promise of BNE-RRC as a comprehensive therapeutic agent for cancer treatment that acts by inhibiting cancer cell growth, migration, and invasion while also orchestrating a reversal of the EMT process. In this study, we propose that BNE-RRC could be an effective agent for cancer treatment. Full article

Antibody–drug conjugates (ADCs) consist of an antibody backbone that recognizes and binds to a target antigen expressed on tumor cells and a small molecule chemotherapy payload that is conjugated to the antibody via a linker. ADCs are one of the most promising therapeutic modalities for the treatment of various cancers. However, many patients have developed resistance to this form of therapy. Extensive efforts have been dedicated to identifying an effective combination of ADCs with other types of anticancer therapies to potentially overcome this resistance. A recent clinical study demonstrated that a combination of the ADC enfortumab vedotin (EV) with the immune checkpoint inhibitor (ICI) pembrolizumab can achieve remarkable clinical efficacy as the first-line therapy for the treatment of locally advanced or metastatic urothelial carcinoma (la/mUC)—leading to the first approval of a combination therapy of an ADC with an ICI for the treatment of cancer patients. In this review, we highlight knowledge and understanding gained from the successful development of EV and the combination therapy of EV with ICI for the treatment of la/mUC. Using urothelial carcinoma as an example, we will focus on dissecting the underlying mechanisms necessary for the development of this type of combination therapy for a variety of cancers. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-associated mortality, with a rising global incidence. A paucity of strong predictive risk factors mean screening programmes are difficult to implement. Historically, a lack of identifiable and actionable driver mutations, coupled with a relatively immunosuppressed tumour microenvironment, has led to a reliance on cytotoxic chemotherapy. The NAPOLI-3 trial has reported data supporting consideration of NALIRIFOX as a new first-line standard of care. Kirsten Rat Sarcoma Virus (KRAS) G12D mutations are present in >90% of all PDAC’s; exciting breakthroughs in small molecule inhibitors targeting KRAS G12D may open new modalities of treatment, and therapies targeting multiple KRAS mutations are also in early clinical trials. Although immunotherapy strategies to date have been disappointing, combination with chemotherapy and/or small molecule inhibitors hold promise and warrant further exploration. Full article

This study investigates heavy metal contamination in soils, irrigation water, and agricultural produce (fruits: Vitis vinifera (grape), Cucumis melo var. saccharimus (melon), and Citrullus vulgaris. Schrade (watermelon); vegetables: Lycopersicum esculentum L. (tomato), Cucurbita pepo (zucchini), Daucus carota (carrot), Lactuca sativa (lettuce), Convolvulus Batatas (potato), and Capsicum annuum L. (green pepper)) in the Boumerdes region of Algeria. The concentrations of seven heavy metals (cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), nickel (Ni), lead (Pb), and zinc (Zn)) in soil and food samples were analyzed using atomic absorption spectrometry. Health risks associated with these metals were evaluated through the estimated daily intake (EDI), non-carcinogenic risks (using target hazard quotient (THQ), total target hazard quotient (TTHQ), and hazard index (HI)), and carcinogenic risks (cancer risk factor (CR)). Statistical analyses, including cluster analysis (CA) and Pearson correlation, were conducted to interpret the data. The results revealed the highest metal transfer as follows: Cd was most significantly transferred to tomatoes and watermelons; Cr to carrots; Cu to tomatoes; and Fe, Ni, Pb, and Zn to lettuce. Among fruits, the highest EDI values were for Zn (2.54·10⁻³ mg/day) and Cu (1.17·10⁻³ mg/day), with melons showing the highest Zn levels. For vegetables, the highest EDI values were for Fe (1.68·10⁻² mg/day) and Zn (8.37·10⁻³ mg/day), with potatoes showing the highest Fe levels. Although all heavy metal concentrations were within the World Health Organization’s permissible limits, the HI and TTHQ values indicated potential health risks, particularly from vegetable consumption. These findings suggest the need for ongoing monitoring to ensure food safety and mitigate health risks associated with heavy metal contamination. Full article

Immunotherapy represents a transformative shift in cancer treatment. Among myriad immune-based approaches, chimeric antigen receptor (CAR) T-cell therapy has shown promising results in treating hematological malignancies. Despite aggressive treatment options, the prognosis for patients with malignant brain tumors remains poor. Research leveraging CAR T-cell therapy for brain tumors has surged in recent years. Pre-clinical models are crucial in evaluating the safety and efficacy of these therapies before they advance to clinical trials. However, current models recapitulate the human tumor environment to varying degrees. Novel in vitro and in vivo techniques offer the opportunity to validate CAR T-cell therapies but also have limitations. By evaluating the strengths and weaknesses of various pre-clinical glioma models, this review aims to provide a roadmap for the development and pre-clinical testing of CAR T-cell therapies for brain tumors. Full article

Background: We designed a multi-institutional retrospective study to investigate the previously unreported failure pattern, survivals, and prognostic factors after postoperative radiotherapy (PORT) in triple negative breast cancer (TNBC) patients in South Korea. Materials and Methods: We retrospectively reviewed 699 patients with TNBC who underwent PORT at six institutions between 2008 and 2010. The median follow-up period was 94 months (range: 7–192 months). There were 216, 380, and 100 patients in stages I, II, and III, respectively. Results: After 94 months post-treatment, all patients with pathologic complete remission after neoadjuvant chemotherapy were alive without any failure. Distant metastasis was the main cause of failure. The 5-year overall survival rate was 91.4%, 5-year loco-regional relapse-free survival rate (LRRFS) was 92.3%, 5-year distant metastasis-free survival rate (DMFS) was 89.4%, and 5-year disease-free survival rate (DFS) was 85.2%. On multivariate (Cox) analysis, T and N stages were significant prognostic factors for survival, and lympho-vascular invasion (LVI) was a significant factor for LRRFS and DMFS. Ki-67 expression was significantly associated with LRRFS and DFS. Conclusion: We verified that T and N stages, LVI, and Ki-67 expression were significantly associated with survival outcomes after PORT in TNBC. Full article