Search Results (2,935)

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited therapeutic options due to the lack of estrogen, progesterone, and HER2 receptors. This study investigated the synergistic anticancer effects of recombinant human apurinic/apyrimidinic endonuclease 1/redox factor-1 (rhAPE1/Ref-1) and acetylsalicylic acid (ASA), a combination that has not been previously tested in vivo. Methods: We treated MDA-MB-231 TNBC cells with rhAPE1/Ref-1, ASA, or their combination to assess cell viability and apoptosis in vitro. In vivo, a murine xenograft model was established to evaluate the efficacy of the combination treatment on tumor growth, tumor-specific biomarkers, and key apoptotic proteins. The safety profile of the combination therapy was also assessed by monitoring hematological parameters. Results: While monotherapy with either rhAPE1/Ref-1 or ASA had minimal effects, their combination significantly reduced cell viability and enhanced apoptosis in vitro by increasing DNA fragmentation. These synergistic cytotoxic effects were significantly inhibited by the receptor for advanced glycation end-products (RAGE) siRNA, suggesting that RAGE acts as an important mediator. In the xenograft model, the combination treatment suppressed tumor growth by approximately 70%, an effect comparable to paclitaxel (PTX). This was confirmed by a significant reduction in the plasma levels of TNBC biomarkers (CEA, CA27-29, and CA15-3) and increased tumor apoptosis via the upregulation of p53 and Bax and downregulation of Bcl-2. Notably, ASA, alone or combined with rhAPE1/Ref-1, induced the expression of RAGE in MDA-MB-231 tumors. In contrast to PTX, the combination of rhAPE1/Ref-1 and ASA did not cause hematological toxicity, such as anemia or thrombocytopenia. Conclusions: The combination of rhAPE1/Ref-1 and ASA represents a promising new therapeutic strategy for TNBC by enhancing apoptosis and significantly inhibiting tumor progression in a mouse xenograft model. Full article

Background and Objectives: Low-grade triple-negative breast carcinomas (LG-TNBCs) represent a rare subset of breast cancers that deviate from the aggressive clinical course typically associated with triple-negative tumors. This narrative review aims to consolidate current knowledge on LG-TNBCs, highlighting their diagnostic features, molecular characteristics, and clinical implications to guide appropriate patient management and prevent overtreatment. Materials and Methods: We conducted a comprehensive narrative review using PubMed/MEDLINE, Embase, and Scopus databases up to September 2025. Search terms included combinations of “triple-negative breast carcinoma”, “low-grade”, “adenoid cystic carcinoma”, “secretory carcinoma”, “acinic cell carcinoma”, “tall cell carcinoma with reversed polarity”, “low-grade adenosquamous carcinoma”, and “fibromatosis-like metaplastic carcinoma.” Studies reporting clinicopathologic, immunohistochemical, or molecular data were included. Results: LG-TNBCs include seven distinct entities: adenoid cystic carcinoma, secretory carcinoma, acinic cell carcinoma, tall cell carcinoma with reversed polarity, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, and mucoepidermoid carcinoma. These neoplasms are characterized by distinct morphologic patterns, specific immunohistochemical profiles, and recurrent molecular alterations such as ETV6-NTRK3 fusions and MYB rearrangements. Despite their triple-negative immunoprofile, they demonstrate indolent clinical behavior with excellent prognosis and low metastatic potential, although local recurrence is reported in variants exhibiting infiltrative, locally aggressive behavior. Conclusions: Recognition of LG-TNBCs is essential to prevent overtreatment and guide personalized patient management. Molecular characterization provides diagnostic confirmation and therapeutic opportunities, particularly for NTRK-fusion-positive tumors treatable with targeted inhibitors, highlighting the importance of precision medicine in rare breast tumors. Full article

Oral squamous cell carcinoma (OSCC) is an aggressive epithelial malignancy with high local invasiveness and a tendency for early cervical lymph node metastasis. Conventional prognostic markers often lack precision. This study evaluated the expression of putative cancer stem cell markers—CD44, CD133, and CD166—in OSCC tissues and explored their associations with clinical parameters, including salivary flow rates. Twelve patients with histologically confirmed OSCC (9 males, 3 females; mean age: 65 years) were included. Clinical TNM staging and tumor dimensions were recorded. Depth of invasion was measured histologically. Tumor tissues were enzymatically dissociated to establish primary cell cultures, and flow cytometry was used to quantify putative cancer stem cell markers expression. Unstimulated salivary flow rates were measured using sialometry. CD44 expression was uniformly high (median: 96.4%) and CD166 showed moderate to high expression (median: 85.5%), while CD133 was low (median: 1.5%). Co-expression levels were the highest for CD44+/CD166+ (median: 86.6%). Triple-marker co-expression had a median of 2.0%. Depth of invasion was positively correlated with CD133+ and its co-expression with CD44+ and CD166+ (p ≤ 0.05). Salivary flow rates were negatively correlated with CD166+ and CD44+/CD166+ expression (p ≤ 0.01). These findings suggest putative cancer stem cell markers, particularly CD133, may have prognostic value in OSCC and warrant further investigation. Full article

Lipocalin-2 (LCN2) is a 25 kDa glycoprotein that has been shown to be a multifunctional player in the metastasis of triple-negative breast cancer (TNBC). In physiological contexts, LCN2 exhibits bacteriostatic properties and plays key roles in iron homeostasis and the transport of hydrophobic molecules. However, several studies have shown that aberrant LCN2 expression is associated with poor prognosis in various malignancies, including breast cancer, which is the most common cancer in women worldwide and can be classified into four molecular subtypes. Among these, TNBC represents a disproportionately aggressive subtype characterized by poor prognosis and high metastatic potential. Although LCN2 has been extensively studied in breast cancer overall, its specific role in TNBC progression and metastasis is only beginning to be understood. Recent evidence suggests that LCN2 contributes to several tumor-promoting processes such as angiogenesis, therapy resistance and modulation of the tumor microenvironment. Moreover, LCN2 appears to influence organ-specific metastasis, particularly to the lung and brain, while its role in liver and bone dissemination remains unclear. Collectively, current data identify LCN2 as a critical mediator of TNBC progression and highlight its potential as a prognostic factor and modulator of disease progression. This review aims to summarize insights from both in vitro and in vivo studies, with particular focus on the role of LCN2 in the metastatic cascade, while also addressing existing research gaps and critically evaluating the current findings. Full article

Breast cancer is a significant global health challenge, with rising incidence rates and substantial morbidity and mortality worldwide. Conventional treatments, while effective, often lead to adverse effects and may not fully eradicate cancer cells, resulting in recurrence and progression of tumors. Addressing these challenges requires innovative treatment strategies. Nanotechnology, particularly polysaccharide-based nanoparticles (NPs), offers a promising approach due to their biocompatibility, tunable properties, and targeted drug delivery capabilities. Polysaccharide NPs, including starch, alginate, hyaluronic acid, and chitosan, possess inherent biocompatibility and can be tailored for specific applications. Furthermore, beyond their inherent biocompatibility, polysaccharide-based NPs shown substantial interest due to their natural abundance, ease of processing, and availability from renewable resources, solidifying their role as a sustainable choice for diverse biomedical applications. By functionalizing their surface with ligands, polysaccharide NPs can target breast cancer cells, enhance therapeutic efficacy while minimizing off-target effects. Moreover, these NPs can modulate biological processes relevant to cancer progression, such as angiogenesis and immune response. This review article provides a concise overview of the pathophysiology of breast cancer and the benefits of polysaccharides in drug delivery. Additionally, it emphasizes the significance of several polysaccharide-based NPs in breast cancer therapy, followed by a detailed discussion on the role of various polysaccharide-based NPs in breast cancer treatment. Full article

Yeast protein (YP) offers nutritional and sustainable benefits; however, its poor gelation properties limit its use in soft material formulations. This study investigates the rheological behavior and the formation of crosslinked networks using YP–polysaccharide mixtures for extrusion-based 3D printing. Binary bioink blends with alginate (Alg) or xanthan gum (XG) showed enhanced viscosity and exhibited shear-thinning properties. However, a high concentration of Alg negatively affected the material’s thixotropic recovery. On the other hand, YP–XG bioink displayed more pronounced elastic behavior and demonstrated thixotropic recovery, though they lacked the capacity for ionic crosslinking. A triple bioink formulation consisting of 8% (w/v) YP, 2% (w/v) Alg, and 0.5% (w/v) XG effectively combined the advantages of both polysaccharides. Alg provided structural stability through calcium crosslinking, while XG offered rheological flexibility. These bioinks were successfully printed using embedded 3D printing and maintained their shape fidelity after printing. The crosslinked triple hydrogel exhibited good mechanical strength, volume retention after crosslinking, structural integrity under compression of up to 70%, and recovery after deformation that indicates high structural stability. This research presents an effective strategy to enhance the application of yeast-derived proteins in sustainable, animal-free 3D printed food products and other soft biomaterials. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is among the most aggressive subtypes, lacking estrogen, progesterone, and HER2 receptors, which limits the efficacy of targeted therapies. Standard treatments often fail due to rapid drug resistance and poor long-term outcomes. Repurposing approved drugs with anticancer potential offers a promising alternative. Disulfiram (DSF), an FDA-approved alcohol-aversion drug, forms a copper complex [Cu(DDC)₂] with potent anticancer activity, but its clinical translation is hindered by poor solubility, limited stability, and inefficient delivery. Methods: Here, we present an amphiphilic dendrimer-stabilized [Cu(DDC)₂] nanoparticle (NP) platform synthesized via the stabilized metal ion ligand complex (SMILE) method. Results: The optimized nanocarrier achieved high encapsulation efficiency, enhanced serum stability, and potent cytotoxicity against TNBC cells. It induced immunogenic cell death (ICD) characterized by calreticulin exposure and ATP release, while modulating the tumor microenvironment by downregulating MMP-3, MMP-9, VEGF, and vimentin, and restoring epithelial markers. In a 4T1 TNBC mouse model, systemic [Cu(DDC)₂] NP treatment significantly inhibited tumor growth without combinational chemo- or radiotherapy. Conclusions: This DSF-based metal–organic NP integrates drug repurposing, immune activation, and tumor microenvironment remodeling into a single platform, offering strong translational potential for treating aggressive breast cancers. Full article

Background/Objectives: To evaluate changes in background parenchymal enhancement (BPE) in the contralateral breast on MRI before and after neoadjuvant chemotherapy (NAC), stratified by molecular subtype in patients with unilateral breast cancer. Methods: This study retrospectively analyzed 116 individuals diagnosed with unilateral breast cancer by biopsy, all of whom underwent breast MRI examinations before and after neoadjuvant chemotherapy. Contralateral breast BPE was graded into four levels (BPEC: 1 = minimal, 2 = mild, 3 = moderate, 4 = marked) by two readers in consensus. Histopathological features and BPE reduction were compared according to molecular subtype. Results: BPE showed a reduction across all molecular subtypes after NAC. In ER-positive cancers, BPEC shifted from 26/16/28/30% to 68/28/4/0%; in HER2-positive cancers, from 37.8/26.7/22.2/13.3% to 73.3/20.0/6.7/0%; and in triple-negative breast cancers, from 47.6/14.3/23.8/14.3% to 76.2/14.3/9.5/0%. Compared to the ER-positive cancer, the reduction in BPE over time was significantly greater in the HER2-positive cancer group (Estimate = 0.48, p = 0.0168) and TNBC (Estimate = 0.55, p = 0.0321), suggesting that the extent of BPE decrease varied by subtype. Conclusions: The extent of BPE reduction on breast MRI following NAC varies significantly across different molecular subtypes of breast cancer. Full article

Deep neural network-based deep clustering has achieved remarkable success by unifying representation learning and clustering. However, conventional representation modules are typically not tailored for clustering, resulting in conflicting objectives that hinder the model’s ability to capture semantic structures with high intra-cluster cohesion and low inter-cluster separation. To overcome this limitation, we propose a novel framework called Triple-stream Contrastive Deep Embedding Clustering via Semantic Structure (TCSS). TCSS is composed of representation and clustering modules, with its innovation rooted in several key designs that ensure their synergistic interaction for modeling semantic structures. First, TCSS introduces a triple-stream input framework that processes the raw instance along with its limited and aggressive augmented views. This design enables a new triple-stream self-training clustering loss, which uncovers implicit cluster structures by contrasting the three input streams. Second, within this loss, a dynamic clustering structure factor is developed to represent the evolving semantic structure in the representation space, thereby constraining the clustering-prediction distribution. Third, TCSS integrates semantic structure-aware techniques, including a clustering-oriented negative sampling strategy and a triple-stream alignment scheme based on k-nearest neighbors and centroids, to refine semantic structures both locally and globally. Extensive experiments on five benchmark datasets demonstrate that TCSS outperforms state-of-the-art methods. Full article

Background and Objectives: Vitamins A and D have been reported to improve cancer outcomes. In this work, we reviewed recent meta-analyses, preclinical, and transcriptomics data for these vitamins and combinations for breast and colon cancers. Methods: Searches for meta-analyses, preclinical, and transcriptomic data for vitamins A and D in breast and colorectal cancers were conducted using electronic databases from June 2012 to May 2025. Studies describing the effects of vitamin A and D levels (through diet, supplementation, and serum concentrations) on the risk, prognosis, metastasis, and survival rates of breast and colon cancer patients, and the doses needed to achieve these endpoints, were included. Preclinical and transcriptomics studies investigating combinations of vitamins A and D were also reviewed. Results: The reviewed studies showed an inverse correlation between vitamin A intake and the risk and survival rates of breast cancers. Sufficient vitamin D3 levels were associated with improved survival outcomes, lower tumor grades, and less ER- or triple-negative breast cancers. For colorectal cancers, meta-analyses showed conflicting results for vitamin A, but clear evidence that vitamin D reduced both risk and mortality. Preclinical and transcriptomics studies provide compelling evidence that vitamins A and D combinations may be more effective for the prevention and treatment of breast and colon cancers, due to their significant synergistic effects and the larger number of cancer-signaling pathways impacted. Conclusions: Vitamins A and D reduce breast and colorectal cancer incidence, risk and mortality through multiple mechanisms of action, and offer significant potential as therapeutic and chemopreventative agents. Full article

Background/Objective: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) lacking targeted therapies and characterized by high tumor heterogeneity. In this study, we evaluated the anticancer activity and mechanistic profile of Simalikalactone D (SKD), a quassinoid compound derived from the endemic Puerto Rican tree Simarouba tulae, in three TNBC cell lines, MDA-MB-468, MDA-MB-231, and SUM-149. Methods: MDA-MB-468, MDA-MB-231 and SUM-149 TNBC cells were evaluated for cell viability, proliferation and migration following SKD treatment. Phospho-antibody array, proteomics, and Western blot analyses were used to explore the SKD mechanism of action in MDA-MB-468 and MDA-MB-231 cell lines. Molecular docking was performed to assess SKD’s interaction with potential intracellular targets. Results: SKD exerted a concentration-dependent effect on the three cell lines. However, MDA-MB-468 cells exhibited an IC₅₀ of 67 nM, while the IC₅₀ values for MDA-MB-231 and SUM-149 were 422 nM and 598 nM, respectively. In MDA-MB-468 cells, 100 nM of SKD induced apoptosis, evidenced by the activated caspase-3 activity, PARP-1 cleavage and decrease in Bcl-2 and survivin protein levels. Sublethal SKD (25 nM) impaired migration in MDA-MB-231 cells and reduced proliferation and motility in SUM149 cells. A 6 h SKD treatment markedly reduced phosphorylation of apoptosis-related proteins (p53, BAD, DAXX, AKT1, JUN) and Jak/STAT pathway components, indicating early disruption of intracellular signaling prior to phenotypic changes. Proteomic profiling showed distinct pathway alterations in both MDA-MB-468 and MDA-MB-231 cells, with reduced Integrin β1 (ITGB1) levels emerging as a shared effector. This suggests that SKD broadly disrupts cell adhesion and migration independently of apoptosis-driven cell death. Western blot validation confirmed reduced ITGB1 protein levels across all three TNBC cell lines examined. In silico docking confirmed favorable binding affinities of SKD to both EGFR (ΔG = −6.718 kcal/mol) and STAT4 (ΔG = −8.481 kcal/mol). Conclusions: Overall, our findings suggest that SKD is a potent anticancer agent in a subgroup of TNBC cells. Full article

The analysis of perceived impacts of sporting events and sport tourism is a growing research field. The Sierra Morena Rally, held in Córdoba, Spain, and included for the first time in the European Rally Championship (ERC) in 2025, provides an opportunity to examine residents’ perceptions of both positive and negative effects. This study aims to identify profiles of perception and support towards the event. The theoretical framework integrates the Triple Bottom Line (TBL), Social Exchange Theory (SET), and Social Representations Theory (SRT). Based on 479 valid surveys collected during the rally, an Exploratory Factor Analysis (EFA) identified five factors of perceived impact: positive economic–social, positive environmental, negative economic, negative social, and negative environmental. A non-hierarchical k-means cluster analysis revealed four distinct groups: Critics, who emphasize negative impacts; Enthusiasts, focused on economic–social benefits; Pragmatic Supporters, showing balanced but conditional support; and Supporters Environmentally Concerned, combining favorable views with ecological awareness. The results confirm the heterogeneity of residents’ perceptions and align with previous findings in the literature of motorsport events. Overall, the study contributes to understanding the social sustainability of rally events and highlights the importance of incorporating perceptual diversity into their management. Full article

Oligometastatic breast cancer represents an intermediate state between localized and disseminated disease with reasonable potential for clinical cure. Advancements in surgery, radiotherapy, and systemic therapy have improved prognosis. Due to the high prevalence of bone metastases, an increasing number of studies are evaluating new treatment strategies for oligometastatic bone disease. The decision to perform skeletal surgery is complex and depends on optimal patient selection. Major criteria include impending or pathologic long bone fractures, severe neurologic compromise, and an expected survival of over 3 months. Factors associated with improved survival include solitary bone metastases, preserved performance status, adequate surgical margins, absence of pathologic fracture, metachronous metastases, and ER-positivity status. Radiotherapy, especially SBRT, offers effective local control and palliation. Interventional radiology techniques such as percutaneous thermal ablation have also been described as potential treatment alternatives, particularly for fragile patients. Systemic treatment varies according to the tumor subtype. For HR+ and HER2 subtypes, a combination of endocrine therapy with CDK4/6 inhibitors may be considered. HER2+ patients are often treated with HER2-targeted therapies combined with chemotherapy. For triple-negative breast cancer, chemotherapy is the primary treatment. Bone-modifying agents are also recommended to maintain bone strength, prevent skeletal-related events, and reduce the need for additional interventions. Skeletal muscle metastases in breast cancer patients are rare and typically indicate advanced disease with poor prognosis. Treatment options include chemotherapy, radiotherapy, and surgical excision, but should be tailored to the patient’s clinical condition and prognosis. Full article

Background/Objectives: Older adults with breast cancer may suffer from over- and undertreatment if intensity of therapy does not align with their physiologic age. We sought to evaluate the association between physiologic age, chronologic age, and treatment patterns in women ≥ 70 years with non-metastatic breast cancer. Methods: Patients ≥ 70 diagnosed with non-metastatic breast cancer 10/2021–3/2024 who had received surgical therapy and frailty (Geriatric-8) and life expectancy (Schonberg index) screening at our institution were identified from our institutional database. Descriptive analyses were run using chi-square tests of proportion. In the largest subgroup (patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2)-disease), multivariate logistic regression adjusting for patient- and disease-level characteristics was used to assess the relationship between life expectancy < 10 years and the omission of sentinel lymph node biopsy (SLNB) and radiation therapy (RT). Results: Of 272 patients, 104 (38.2%) screened positive for frailty and 64 (23.5%) had a life expectancy of <10 years. On bivariate analysis, a higher proportion of frail patients (44 (42.3%) had a life expectancy < 10 years, while 20 (11.9%) robust patients had a life expectancy < 10 years (p < 0.001). Most patients (226, 83.1%) had HR+/HER-2 negative disease; 10 (3.7%) had HER2+ disease; and 33 (12.1%) had triple-negative breast cancer (TNBC) (p < 0.001). Life expectancy was not significantly associated with omission of SLNB (life expectancy < 10 years: reference; life expectancy ≥ 10 years: OR 0.81 95% CI [0.20–3.28]) or RT (life expectancy < 10 years: reference; life expectancy ≥ 10 years: OR 1.14, 95% CI 0.44–2.93]) in patients with stage I–II HR+/HER-2− disease on adjusted analysis. Conclusions: While patients at risk for frailty and limited life expectancy are relatively common in our population, these measures may not significantly influence patient and clinician treatment decision making. Future efforts to tailor therapy by measures of physiologic age are needed. Full article

Breast cancer is a heterogeneous malignancy with distinct molecular subtypes that complicate the development of effective therapies. Traditional drug discovery methods are often constrained by high cost and long development timelines, underscoring the need for more efficient, subtype-aware approaches. Computer-aided drug design (CADD) has emerged as a valuable strategy to accelerate therapeutic discovery and improve lead optimization. This review synthesizes advances from a subtype-centric perspective and outlines the application of CADD techniques, including molecular docking, virtual screening (VS), pharmacophore modeling, and molecular dynamics (MD) simulations, to identify potential targets and inhibitors in receptor-positive (Luminal), HER2-positive (HER2⁺), and triple-negative breast cancer (TNBC). In addition to traditional pipelines, we highlight artificial intelligence (AI)-enabled methods and a hybrid workflow in which learning-based models rapidly triage chemical space while physics-based simulations provide mechanistic validation. These approaches have facilitated the discovery of subtype-specific compounds and enabled the refinement of candidate drugs to enhance efficacy and reduce toxicity. Despite these advances, critical challenges remain, particularly tumor heterogeneity, drug resistance, and the need to rigorously validate computational predictions through experimental studies. Future progress is expected to be driven by the integration of AI, machine learning (ML), multi-omics data, and digital pathology, which may enable the design of more precise, subtype-informed, and personalized therapeutic strategies for breast cancer. Full article