Search Results (51,245)

The kidney is an essential organ that has a crucial role in preserving homeostasis within the human body. Kidney cancer is considered a major clinical challenge owing to its resistance to traditional treatments such as chemotherapy, radiotherapy, and immunotherapy. Nanoparticles (NPs) gain great attention in cancer therapy due to their low toxicity, biocompatibility, and targeted drug delivery capability. This review focuses on the current role of green-synthesized NPs in renal cell carcinoma management and their applications in targeted drug delivery and cancer-specific targeting mechanisms with the demonstration of the environmentally friendly green synthesis approaches utilizing biological resources such as plant extracts and microorganisms, highlighting their advantages over conventional synthesis methods in terms of biocompatibility, sustainability, and reduced toxicity. Moreover, the therapeutic potential of nanomaterials is discussed, including magnetic NP-mediated thermal therapy, photothermal therapy, gene delivery systems, and RNA interference-based strategies. We underscore the challenges and limitations of NPs, including in vivo toxicity, biodistribution, clinical translation, large-scale production, batch-to-batch variability, long-term safety, scalability, repeatability, regulation, and reproducibility. There is growing potential to improve the treatment of kidney cancer. Hence, the promising prospects of nanotechnology in kidney cancer treatment provide a foundation for future research and clinical application. This comprehensive article highlights the significant contributions of nanomedicine to oncology and shows an optimistic perspective for more effective and precise treatment strategies for kidney cancer. Full article

The war in Ukraine, beginning in February 2022, disrupted continuous medical care for Ukrainian childhood and adolescent cancer patients (UCC), many of whom were relocated to pediatric cancer centers worldwide, including Switzerland. In this Brief Report, we describe their health-related quality of life (HRQoL) after arrival. In a multicenter, cross-sectional survey across five Swiss pediatric oncology centers, we included patients ≤18 years at diagnosis who arrived after 24 February 2022 and were undergoing active treatment. HRQoL was assessed by the PedsQL™ 4.0 Generic Core Scales (self- and parent-reports). Fourteen of 23 eligible families (61%) participated. HRQoL declined with age, particularly in physical functioning, while psychosocial functioning remained relatively stable but lower among adolescents; parent scores closely matched self-reports. Scores were referenced against a published cohort of healthy Ukrainian children and previously reported pediatric cancer populations. Given the small sample and lack of a matched control group, the findings cannot separate the effects of displacement, cancer, and treatment and are hypothesis-generating. They suggest a potential role for age-tailored supportive care in displaced children with cancer and call for larger, controlled studies. Full article

As of 2020, liver cancer has emerged as the fifth most common cancer and the third leading cause of cancer death worldwide, following lung and colorectal cancers. The most prevalent type is hepatocellular carcinoma (HCC), originating from hepatocytes. Despite advancements, liver cancer treatment outcomes remain poor due to metastasis and recurrence. Existing anticancer drugs often exhibit narrow therapeutic windows and limited selectivity for cancer cells. Manilkara zapota (L.) P. Royen has attracted significant scientific attention because of its diverse bioactive constituents and potential therapeutic properties. Of particular interest in this review, we explored the molecular connectivity of oxidative stress-induced liver cancer. We discussed the underlying mechanisms of Manilkara zapota (L.) P. Royen involved in cancer and inflammation. The phytochemical constituents were also highlighted in this study. The phytochemicals reported from Manilkara zapota (L.) P. Royen included flavonoids, tannins, saponins, and phenolic compounds. These compounds demonstrated potential anticancer activities through mechanisms such as induction of apoptosis, inhibition of cell proliferation, modulation of oxidative stress, and regulation of PI3K/Akt and NF-κB signaling pathways. Further investigations are required to clarify the benefit–risk profile of Manilkara zapota (L.) P. Royen through large-scale clinical trials. Collectively, the current evidence suggests that this plant may offer a promising strategy for cancer management, provided that such interventions are optimized to minimize adverse effects. Full article

Background: Racial and socioeconomic differences in prostate cancer outcomes are often described as survival disparities, but observed differences may also reflect healthcare access, treatment delivery, and resource allocation. Methods: NCDB and SEER–Medicare were treated as independent, complementary retrospective data sources without individual-level linkage. The analytic material comprised 111,396 database records from 2010 to 2020 across two independent source files; this is a cross-source record count, not a deduplicated count of unique persons. Harmonized descriptive analyses characterized stage, treatment, and treatment timing, while multivariable Cox proportional hazards modeling evaluated prostate cancer-specific survival (CSS) in outcome-eligible SEER–Medicare records. The CSS model denominator is therefore substantially smaller than the total record count, and the two should not be confused. Results: Records for non-Hispanic Black (NHB) men more often showed stage III–IV disease than records for non-Hispanic White (NHW) men (26.9% vs. 18.7%) and lower receipt of guideline-concordant first-course management initiated within 90 days, particularly in the low-SES subgroup (51.4% vs. 84.3% among high-SES NHW men). In the adjusted CSS model, NHB race was associated with higher mortality (HR = 1.32; 95% CI: 1.24–1.41). Uninsured status (HR = 1.47; 95% CI: 1.33–1.62), low income (HR = 1.28; 95% CI: 1.19–1.37), and rural residence (HR = 1.14; 95% CI: 1.06–1.22) were also associated with higher mortality. Conclusions: The findings support a healthcare-system interpretation of prostate cancer disparities and identify measurable targets for prospective evaluation, including EHR-enabled monitoring, nurse navigation, telehealth-supported follow-up, and facility-level treatment-concordance review. Full article

Chemotherapy-induced cardiotoxicity is a serious consequence of chemotherapy during cancer treatment that can affect any patient. The purpose of this review is to highlight the development of cardiotoxicity associated with the use of anthracyclines or trastuzumab and to examine prevention and treatment methods using polyphenols, biologically active substances that hold significant therapeutic potential. The main mechanisms of this pathology, modern biomarkers for detection, and the classification and biological activity of polyphenols are discussed. Emphasis is placed on polyphenols found in grapes and their antioxidant potential as a protector of the cardiovascular system. Full article

Colorectal cancer (CRC) remains one of the most frequently diagnosed malignancies worldwide and a leading indication for major abdominal surgery, with a rising incidence among younger adults. Because CRC resection is a physiologically demanding procedure performed in a frequently comorbid, often anemic and malnourished population, the preoperative period represents a decisive window in which laboratory and diagnostic testing shapes staging, risk stratification, and optimization. This narrative review is deliberately confined to the preoperative window—from histological diagnosis to the day of elective, curative-intent colon or rectal resection—and synthesizes evidence retrieved from PubMed/MEDLINE, Scopus, and ScienceDirect together with current society guidelines. It is organized around four themes: (i) the core laboratory workup, including the complete blood count and preoperative anemia, iron studies, metabolic and hepatic panels, coagulation testing, and carcinoembryonic antigen (CEA); (ii) the diagnostic and staging workup, encompassing complete colonic evaluation, contrast-enhanced computed tomography, pelvic magnetic resonance imaging for rectal cancer, and the selective role of positron emission tomography; (iii) risk stratification and preoperative optimization, spanning patient blood management, nutritional assessment and albumin, computed-tomography-defined low skeletal muscle mass, frailty, functional capacity, prehabilitation, and glycemic control; and (iv) molecular characterization, distinguishing mismatch-repair/microsatellite-instability (MMR/MSI) testing—an established, widely recommended component of CRC evaluation—from genuinely emerging biomarkers such as circulating tumor DNA (ctDNA) and systemic inflammatory and prognostic nutritional indices. Differences between colon and rectal cancer, elective and emergency presentation, and upfront versus post-neoadjuvant surgery are signposted throughout. We further integrate these elements within contemporary guideline and Enhanced Recovery After Surgery (ERAS) frameworks, including the 2025 ERAS Society recommendations for elective colorectal surgery, and distill them into a practical, evidence-based preoperative checklist specifying thresholds, timing, interventions, and strength of supporting evidence. We emphasize that the prognostic power of postoperative ctDNA does not yet translate into ctDNA-guided treatment decisions outside clinical trials. The central message is that preoperative testing in CRC should be purposeful and stage- and risk-adapted rather than reflexive: each investigation should refine staging, modify perioperative management, or enable measurable optimization. Each risk domain is paired with the intervention it should trigger, the criteria identifying candidates for extended thromboprophylaxis are specified, and the systemic inflammatory indices are framed as a trigger for optimization rather than as prognostic commentary. Full article

Despite increasing awareness about cancer, it still remains one of the biggest threats to human life. Breast cancer is among the most commonly diagnosed types of cancer. Pentacyclic triterpenoids are a group of plant compounds commonly known in traditional medicine due to their anti-inflammatory, antibacterial, antidiabetic, cardioprotective and anticancer effects. This review examined the potential of pentacyclic triterpenoid acids in the treatment of breast cancer, focusing on research from the past 15 years. Although the subject literature demonstrates that pentacyclic acids show anticancer activity, it also reveals their limitations such as low bioavailability, aqueous solubility, or high IC₅₀ values. Therefore, to overcome these limitations, structural modifications, mostly at the C3 and C28 positions, were made, and several novel derivatives with oleanane, lupane and ursane skeletal types were synthesized. This review not only identified pentacyclic acids derivatives but also evaluated how structural modifications enhanced their biological activity and potential in breast cancer treatment. The findings revealed that even though the obtained derivatives enhanced anticancer potential against breast cancer, the main issues of bioavailability and solubility remain unsolved, suggesting that future research in synthesis should focus not only on improving cytotoxicity but also on the bioavailability of novel compounds. Full article

Background: Colorectal cancer (CRC) is characterized by pronounced genetic and phenotypic heterogeneity, which substantially influences therapeutic response and limits the efficacy of uniform treatment strategies. Cannabinoid-derived phytochemicals and boron-based compounds have independently been reported to modulate cancer cell proliferation, survival, and redox balance. However, the extent to which these agents interact at the cellular level and whether such interactions are dependent on tumor-specific molecular contexts remains poorly defined. Methods: Sodium pentaborate (NaB) was combined with non-cytotoxic concentrations of cannabidiol (CBD) or cannabigerol (CBG) and evaluated in HCT-116 and HT-29 colorectal cancer cell lines. Cell viability and drug interactions were assessed by MTS and combination index analyses. Apoptotic responses were examined by Annexin V/PI staining, caspase-3/7 activity assays, and transcriptional profiling of apoptosis-related genes. Cell cycle dynamics and proliferation-associated markers were analyzed by flow cytometry and quantitative PCR. In parallel, ferroptosis-associated gene expression patterns were investigated to evaluate alterations in redox and iron metabolism pathways. Results: NaB–cannabinoid combinations produced divergent biological outcomes depending on cellular background. HT-29 cells exhibited dose-dependent antiproliferative responses to NaB + CBD and NaB + CBG, with synergistic interactions observed only at selected dose combinations accompanied by increased early apoptosis. In contrast, HCT-116 cells primarily responded with cell cycle arrest and transcriptional stress signaling rather than enhanced cytotoxicity. Modulation of ferroptosis-related gene expression further indicated differential redox adaptation between the two cell models. Conclusions: NaB–cannabinoid combinations elicit distinct biological outcomes in colorectal cancer cells that are strongly determined by cellular context. While HT-29 cells are selectively sensitized to combination dose level, HCT-116 cells predominantly respond through cell cycle arrest and adaptive stress-response pathway activation. These findings emphasize the necessity of context-aware combination strategies and provide a mechanistic framework for the further development of boron–cannabinoid-based therapeutic approaches in colorectal cancer. Full article

Doxorubicin (Dox)-induced cardiotoxicity (DIC) is a major clinical challenge in cancer therapy. Camel milk exosomes (CMEs) have been applied in anti-tumor treatments as they have a variety of effects, including on inflammation, oxidative stress, metastasis, and apoptosis. However, their role in DIC treatment remains incompletely understood. This research was designed to evaluate the protection provided by CMEs against DIC. The DIC mice were treated with Dox intraperitoneally and divided into a model group and groups treated with different doses of CMEs. Dox-induced H9c2 cell injury was also established and divided into a model group and groups treated with different concentrations of CMEs. The evaluation parameters in vitro included H9c2 cell viability, reactive oxygen species (ROS), mitochondria, and apoptotic cells. The apoptosis and autophagy markers, as well as the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, were assessed via Western blotting both in vivo and in vitro. In addition, transcriptome sequencing of cardiac tissue was also applied to investigate the related mechanisms. Our results indicate that CMEs significantly attenuated the cell viability reduction, apoptosis, and ROS production in H9c2 cells caused by Dox. CMEs also regulated autophagy, inhibited apoptosis, and inhibited the NF-κB and MAPK pathways. In conclusion, our findings demonstrate that CMEs exert a cardiac protective effect against DIC by inhibiting apoptosis and regulating autophagy via NF-κB and MAPK signaling pathways. Full article

Background/Objectives: Advanced endometrial cancer (FIGO III–IV) is characterised by poor prognosis and a heterogeneous biological profile, and molecular classification enables treatment personalisation by identifying subtypes with distinct therapeutic targets. We aimed to characterise the molecular and histopathological features of FIGO III–IV cases in a Polish multicentre cohort and to discuss the resulting treatment implications. Methods: This retrospective multicentre study included 915 consecutive patients with endometrial cancer operated on between April 2022 and May 2025 at three oncology centres in south-eastern Poland. Molecular subtyping (POLEmut, p53abn, dMMR/MSI-H, NSMP) was performed using immunohistochemistry (IHC) and next-generation sequencing (NGS). FIGO stage was assigned according to the FIGO 2009 classification. Results: Among 888 patients with a known molecular subtype, FIGO III–IV cases accounted for 15.9% (n = 141). The p53abn subtype predominated (35.5%), followed by dMMR/MSI-H (26.2%), NSMP (24.1%), and POLEmut (5.7%). The proportion of p53abn increased with stage (I–II vs. III–IV, p < 0.001), whereas dMMR/MSI-H remained stable regardless of stage (p = 0.83). POLEmut was absent in FIGO IV (0/16; 95% CI 0.0–19.4%), which should be regarded as an exploratory observation requiring prospective validation. Conclusions: The molecular profile of advanced endometrial cancer may inform treatment strategy; the therapeutic implications presented here are descriptive and hypothesis-generating, as the study did not include survival data. The dMMR/MSI-H subtype identifies patients who may benefit from immunotherapy in accordance with current clinical indications, supporting routine MMR testing regardless of disease stage. Conversely, p53abn tumours point to the need for a more intensive treatment strategy, in line with current guidelines. The absence of POLEmut in FIGO IV is an exploratory observation requiring prospective validation. Treatment de-escalation in POLEmut FIGO IIIC remains subject to further clinical validation and requires individualised assessment after complete staging. Full article

Tumour hypoxia significantly influences disease advancement and treatment resistance in oral squamous cell carcinoma (OSCC). Hypoxia-inducible factor-1α (HIF-1α) is preserved when oxygen is lacking and triggers the expression of hypoxia-responsive genes that have roles in angiogenesis, metabolic adaptability, tumour cell viability, invasion, and metastasis. The elevated levels of vascular endothelial growth factor (VEGF) induced by HIF-1α result in atypical angiogenesis. The dysfunction of cell junction proteins and heightened activity of matrix metalloproteinases caused by hypoxia facilitate cancer invasion and metastasis. Hypoxic stress prompts cellular modifications, including autophagy and the preservation of cancer cell populations with enhanced survival capabilities, hence facilitating tumour recurrence and heterogeneity. Hypoxia diminishes the effectiveness of standard chemotherapy and radiotherapy due to decreased drug transport, hindered cell growth, and diminished oxygen-dependent radiation-induced DNA damage. Thus, treatment strategies for the hypoxic tumour microenvironment encompass the suppression of HIF and VEGF, tumour reoxygenation, hypoxia radiosensitizers, and hypoxia-activated lethal compounds. Nonetheless, the diverse and fluctuating characteristics of tumour hypoxia, along with the initiation of compensatory survival mechanisms, continue to pose significant obstacles. Enhanced comprehension of hypoxia-induced molecular networks and the advancement of multimodal, biomarker-directed treatment strategies could improve outcomes in OSCC. Full article

Background/Objectives: Breast cancer is the most common malignancy among women worldwide and poses a significant burden on healthcare systems. Despite evidence that treatment type is associated with hospital length of stay (LOS), current Germany-wide data on this topic are lacking. The present study aims to identify clinical and procedural factors associated with prolonged hospitalisation in women hospitalised for breast cancer in Germany. Methods: This multicentre cross-sectional study analysed anonymised inpatient data from 38 German hospitals (IQVIA database), including 16,062 female breast cancer hospitalisation episodes (inpatient cases; patient-level linkage was not possible due to anonymisation, so these may not represent 16,062 distinct women) treated between January 2019 and December 2024. The primary outcome was LOS; prolonged hospitalisation was defined as LOS > 7 days (75th percentile). Comorbidities were assessed using individual comorbidity categories defined according to the Elixhauser classification (retained at ≥1% prevalence). The primary multivariable analysis was restricted to characteristics documented independently of the in-hospital course (age, tumour site, metastatic status, chronic comorbidities). In-hospital complications, procedures, and diagnoses of ambiguous timing were analysed separately as secondary, descriptive associations. LOS was modelled using negative binomial regression (Poisson regression as a sensitivity analysis) and prolonged LOS using logistic regression, both with hospital-clustered robust (sandwich) standard errors. Results: The overall median LOS was 4 days (IQR 3–7); 19.3% of hospitalisation episodes were prolonged. In the primary analysis, longer LOS was associated with age > 70 years (RR 1.14; 95% CI 1.08–1.20), distant metastases (RR 1.76; 95% CI 1.51–2.04), lymph node metastases (RR 1.09; 95% CI 1.05–1.12), congestive heart failure (RR 1.44; 95% CI 1.31–1.59), anaemia (RR 1.41; 95% CI 1.14–1.75) and depression (RR 1.14; 95% CI 1.03–1.26). In the secondary descriptive analysis, in-hospital complications showed the strongest associations with longer LOS, particularly postoperative infection (RR 2.28), wound disruption (RR 1.92) and pneumonia (RR 1.45). Breast-conserving surgery and partial breast resection were associated with shorter LOS, while mastectomy, blood transfusions, and complex intensive care were associated with prolonged stays; the small inpatient radiotherapy subgroup (1.9%) most likely reflects a highly selected, predominantly palliative population rather than an association attributable to radiotherapy itself. Conclusions: Prolonged hospitalisation was associated with older age, documented lymph node and distant metastases, and chronic somatic comorbidities including congestive heart failure, anaemia, chronic kidney disease and depression, and, in secondary descriptive analyses, with perioperative complications and intensive procedures. The strongest correlates of prolonged stay—in-hospital complications and intensive procedures—are documented during rather than before the hospitalisation and therefore cannot themselves support early risk identification; however, the baseline characteristics documented independently of the in-hospital course (age, metastatic disease, chronic comorbidity burden) may usefully inform structured perioperative management and discharge planning in Germany. Full article

Background: Artificial intelligence-derived parameters hold substantial promise as indicators for tumor prognosis prediction and treatment guidance. However, existing studies have not sufficiently addressed the application of these parameters across different cancer types. Methods: We employed a deep learning algorithm to conduct a multi-cancer analysis for disease-free survival (MC-DFS) prediction using 8856 cases with associated whole-slide images and clinical data. The training cohort consisted of 7392 cases from the TCGA set (24 cancer types), and the independent external validation cohort comprised 1464 cases from the CPTAC and General Hospital sets (9 cancer types). A nomogram prediction signature for disease-free survival (NOMO) was developed by integrating the MC-DFS, tumor stage, and patient age. The prognostic model’s performance was validated in an independent cohort. Results: In the training and validation cohorts, the MC-DFS model achieved area under the curve (AUC) values of 0.750 and 0.682, respectively. It effectively differentiated patients with poorer disease-free survival, with hazard ratios of 4.823 (95% CI: 4.343–5.356, p < 0.0001) in the training cohort and 2.092 (95% CI: 1.472–2.971, p < 0.0001) in the validation cohort. Each cancer subtype’s analysis confirmed the model’s robust performance. Additionally, using nomogram analysis, we developed a multi-model prediction signature for disease-free survival across multiple cancer types based on MC-DFS and the clinicopathologic features in the training cohort. This enhanced model offers more precise risk stratification for stage I malignancies and complements the existing tumor staging systems by identifying high-risk patients. Conclusions: The newly developed MC-DFS shows marked improvements in prognostic predictions across multiple cancer types. With further validations across multiple centers, this nomogram prediction system could become a valuable practical tool for managing various cancers. Full article

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a leading cause of cancer-related mortality worldwide. Despite advances in diagnosis and therapy, the prognosis for advanced HCC remains poor due to late-stage diagnosis, high recurrence rates, therapeutic resistance, and pronounced molecular heterogeneity. HCC development is driven by complex somatic gene alterations, epigenetic reprogramming, dysregulated signaling pathways, metabolic changes, and an immunosuppressive tumor microenvironment. Molecular profiling studies have identified key oncogenic pathways involved in HCC progression, including MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase), Wnt/β-catenin, PI3K/AKT/mTOR (Phosphoinositide 3-kinase/Protein Kinase B/mechanistic Target of Rapamycin), Hippo-YAP/TAZ, (Yes-associated protein/transcriptional co-activator with PDZ-binding motif) cell cycle regulators, and p53-mediated tumor suppression. These pathways coordinate critical cellular processes such as proliferation, survival, metabolism, invasion, and genomic stability. Emerging mechanisms, including cancer stem cell plasticity, immune evasion, epigenetic dysregulation, and steroid receptor coactivator (SRC)-dependent transcriptional regulation, further contribute to tumor progression and therapeutic resistance. Additionally, recent bioinformatic analyses suggest a potential role for progesterone-mediated oocyte maturation pathways in HCC, although their functional relevance remains unclear. A thorough understanding of these interconnected mechanisms could lead to novel therapeutic targets and the development of more effective, personalized treatment strategies for HCC. This review discusses key signaling pathways and emerging mechanisms in HCC and their roles in disease development and treatment. Full article

Neoadjuvant therapy for breast cancer is planned by subtype: pathologic complete response (pCR) differs in frequency, meaning, and surrogate validity across HR+/HER2−, HER2+, and triple-negative breast cancer (TNBC). This review examines whether current evidence supports using artificial intelligence (AI) to move beyond predicting response under a fixed regimen to guiding systemic treatment tailoring. Here, tailoring means model-guided drug omission, switching, escalation, or de-escalation for an individual patient. We appraised 102 full-text studies of AI-based response prediction (2020–2026), organized by subtype and clinical decision, and graded each on an author-defined five-level clinical-readiness ladder (L1–L5) measuring validation and translational maturity rather than accuracy. Risk of bias was assessed with PROBAST and reporting against TRIPOD+AI. Readiness clustered low: 43 studies reached internal validation only (L1), 53 temporal or geographic external validation (L2), and 6 prospective observational validation (L3); none reached workflow integration (L4) or interventional evidence (L5). Most carried high overall risk of bias (89/102); external validation appeared in 52 (51%), fully reported decision-curve analysis in 44 (43%), and calibration in 19 (19%). Strategy comparison and individualized-treatment-effect analyses were essentially absent. Subtype-specific AI currently predicts response under fixed regimens with moderate-to-good discrimination; the evidence does not yet support changing an individual patient’s systemic treatment. Full article