Search Results (469)

Celtis africana, a rare plant native to southwestern Saudi Arabia, was explored for the first time as a source for the green synthesis of silver nanoparticles (AgNPs). Catechol-bearing phenolic amides in the aqueous leaf extract acted as both reducing and capping agents, enabling eco-friendly AgNP fabrication. The synthesized AgNPs were characterized using SEM, TEM, XRD, UV-Vis, and FTIR, revealing predominantly spherical nanoparticles with an average size of 9.28 ± 0.11 nm, a face-centered cubic crystalline structure, and a pronounced surface plasmon resonance at 424 nm. HPLC analysis confirmed the presence of caffeoyltryamine in the extract, while UV-Vis and FTIR indicated its attachment to the AgNP surface. The AgNPs exhibited broad-spectrum antimicrobial activity against Gram-positive bacteria (S. aureus, MRSA and E. faecalis) and Gram-negative bacteria (E. coli, K. pneumoniae, S. typhimurium, and P. aeruginosa), as well as pathogenic fungi such as C. albicans, C. glabrata, C. parapsilosis, and C. krusei with performance comparable to or exceeding that of AgNPs from Artemisia vulgaris, Moringa oleifera, and Nigella sativa. The MIC and MBC values for S. aureus, MRSA, E. coli, and S. typhimurium were consistently 6.25 µg/mL and 25 µg/mL, respectively, reflecting strong inhibitory and bactericidal effects at low concentrations. MTT assays demonstrated selective cytotoxicity, showing higher viability in normal human skin fibroblasts (HSF) than in MCF-7 breast cancer cells. The AgNPs also displayed strong antioxidant activity (IC₅₀ = 5.41 µg/mL, DPPH assay) and efficient catalytic reduction of 4-nitrophenol (4-NP) and methylene blue (MB), with rate constants of 0.0165 s⁻¹ and 0.0047 s⁻¹, respectively, exceeding most reported values. These findings identify Celtis africana as a promising source for eco-friendly AgNPs with strong antimicrobial, antioxidant, and catalytic properties for broad biological and environmental applications. Full article

Gynecological cancers remain a major global health burden due to their high incidence, molecular heterogeneity, and frequent resistance to conventional therapies. Beyond well-established genetic alterations and targeted treatments, growing attention has been directed toward the role of cancer stem cells (CSCs), a rare tumor subpopulation with self-renewal, differentiation, and tumor-initiating capacities. CSCs are sustained by a specialized microenvironment, the cancer stem cell niche, where growth factors, cytokines, hypoxia, and stromal interactions converge to promote stemness, chemoresistance, and metastatic potential. In breast cancer, signaling axes such as EGFR, IGF, TGFβ, and HGF/c-Met critically regulate CSC expansion, particularly in aggressive subtypes like triple-negative tumors. In ovarian cancer, factors including HGF, VEGFA, IGF, and stromal-derived BMPs drive CSC plasticity and contribute to relapse after platinum therapy. Endometrial CSCs are supported by pathways involving TGFβ, BMP2, and Netrin-4/c-Myc signaling, while in cervical cancer, VEGF, IGF-1, Gremlin-1, and TGFβ-mediated circuits enhance stem-like phenotypes and drug resistance. Cytokine-driven inflammation, especially via IL-3, IL-6, IL-8, IL-10, and CCL5, further fosters CSC survival and immune evasion across gynecologic malignancies. Preclinical studies demonstrate that targeting growth factors and cytokine signaling, through monoclonal antibodies, receptor inhibitors, small molecules, or cytokine modulation, can reduce CSC frequency, restore chemosensitivity, and enhance immunotherapy efficacy. This review highlights the interplay between CSCs, growth factors, and cytokines as central to tumor progression and relapses, emphasizing their translational potential as therapeutic targets in precision oncology for gynecological cancers. Full article

Background: BRCA1/2 mutations are the most recognized causes of hereditary breast cancer (BC), but their penetrance is incomplete. BRCA1-driven tumors are often chromosomally unstable and exhibit increased antigenicity. We hypothesized that inherited variations in immune-related pathways may influence BRCA1 penetrance. Methods: Case–control comparison of BC-affected versus non-affected BRCA1-mutated women is generally complicated because the latter groups are often low in numbers, represented by younger subjects and may contain relatives of the analyzed patients. We utilized a novel approach, i.e., we compared young-onset and late-onset BRCA1-associated BC cases, assuming that the early age at disease manifestation may be an indicator of increased BRCA1 penetrance. Results: NGS for 353 genes implicated in inborn errors of immunity was performed on 42 young-onset (<39 y.o.) and 35 late-onset (>57 y.o.) BC patients carrying BRCA1 pathogenic variants. This effort identified 22 potentially relevant variants, which were further analyzed in an extended cohort (up to 90 patients per group). The PRF1 p.Ala91Val variant, associated with familial hemophagocytic lymphohistiocytosis, was found in 9.6% of young-onset patients and none of the late-onset group (7/73 vs. 0/78, p = 0.005). The significance of this allele was further validated in an additional group of Russian patients (14/164 (8.5%) vs. 8/236 (3.4%), p = 0.042). This trend also retained upon the pooled analysis of Russian and Polish subjects (24/278 (8.6%) vs. 15/337 (4.4%), p = 0.045). Conclusions: Rare variants in immune-related genes, such as PRF1 p.Ala91Val, may influence BRCA1 penetrance. Broader exome-wide analyses comparing affected vs. unaffected BRCA1/2 mutation carriers, or women stratified by age at cancer onset, could help identify additional genetic modifiers of cancer risk. Full article

Background and Clinical Significance: Collagenous colitis is an uncommon form of microscopic colitis characterized by chronic watery diarrhea and thickening of the subepithelial collagen layer. While various medications have been implicated in its pathogenesis, paclitaxel-associated collagenous colitis remains exceptionally rare in the literature. Recognition of this adverse event is crucial for appropriate management, particularly in patients receiving dose-modified chemotherapy regimens. This case highlights the importance of considering drug-induced collagenous colitis in cancer patients presenting with severe diarrhea during chemotherapy. Case Presentation: We report a 71-year-old Japanese male with metastatic breast cancer who developed acute-onset collagenous colitis during paclitaxel treatment. His primary tumor was invasive ductal carcinoma with hormone receptor-positive, HER2-negative disease (ER+, PgR+, HER2-, Ki-67 46%) and progressive metastatic disease. Given pre-existing renal dysfunction, paclitaxel was initiated at 60% dose reduction. Sixteen days after treatment initiation, the patient experienced abrupt onset of profuse watery diarrhea with approximately 10 bowel movements daily, necessitating hospital admission. Colonoscopic evaluation demonstrated increased vascular permeability and superficial mucosal erosions. Histopathological analysis revealed diagnostic features of collagenous colitis with a markedly thickened subepithelial collagen band measuring 23 μm. Following immediate cessation of paclitaxel, the patient experienced complete resolution of diarrheal symptoms without subsequent relapse. Conclusions: This case represents a rare manifestation of paclitaxel-induced collagenous colitis. Clinicians should maintain heightened awareness of this potential complication in patients receiving taxane-based chemotherapy who develop significant diarrhea. Prompt recognition and immediate drug discontinuation are essential for favorable outcomes and symptom resolution. Full article

Breast cancer rarely metastasizes to the parotid gland. Early recognition in patients with a history of malignancy is critical for timely diagnosis and treatment. We report the case of a 60-year-old female who presented with a two-month history of a left periauricular mass, 18 months after completing treatment for breast carcinoma. Despite the patient’s oncologic history, initial evaluation by our maxillofacial surgery service showed no evidence of distant metastasis, and we initially ruled out metastatic disease. Clinical evaluation, contrast-enhanced computed tomography (CT), fine-needle aspiration cytology (FNAC), PET-CT, and histopathological analysis were performed. Given the persistent and progressive nature of the mass, surgical excision was undertaken to obtain a definitive diagnosis and provide local control. Immunohistochemical analysis of the resected mass and adjacent node confirmed metastatic breast carcinoma infiltrating the parotid parenchyma and an intra-parotid lymph node, with strong positivity for progesterone receptor (PR) and carcinoembryonic antigen (CEA). Unfortunately, several months later, the patient developed pulmonary metastases and subsequently died. 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

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: Cancer-related cognitive impairment (CRCI) is a frequent and clinically significant consequence of breast cancer (BC) and its treatments. With rapidly evolving therapeutics and a growing body of biomarker research, a BC-specific synthesis is needed. This review aimed to evaluate associations between blood- and saliva-based biomarkers and objective and patient-reported cognitive outcomes in adults with non-metastatic BC, while accounting for treatment modality and assessment timing. Methods: This systematic review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and was pre-registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD420251079969). PubMed, Embase, and Web of Science were searched for articles published up until April 2025. Eligible studies included adults with BC that investigated associations between blood and/or saliva biomarkers and cognitive outcomes. Results: A total of 53 studies met inclusion criteria: 31 examined biochemical biomarkers; 17, genetic; and 5, both. Assessments were predominantly post-treatment. Baseline measures were more infrequent. Chemotherapy (ChT) predominated, while endocrine therapy (ET) and radiotherapy (RT) were variably examined. Targeted therapies and immunotherapies were rarely included. IL-6 and TNF-α were most consistently linked to poorer cognition, although results varied by timing and assessment type. CRP and derived indices showed intermittent associations. Stress-axis markers and BDNF were mainly related to subjective outcomes. Genetic findings implicated DNA repair and oxidative stress pathways, while APOE, COMT, and BDNF results were inconsistent. Conclusions: Evidence for biomarker correlates of CRCI in BC is highly heterogeneous. Longitudinal, harmonized, and treatment-specific studies are needed to establish reproducible biomarker panels for risk stratification and targeted intervention. Full article

Cancer therapy is rapidly evolving from a one-size-fits-all paradigm toward highly personalized approaches. Traditional chemotherapies and radiotherapies, while broadly applied, often yield suboptimal outcomes due to tumor heterogeneity and are limited by significant toxicities. In contrast, precision oncology tailors prevention, diagnosis, and treatment to the individual patient’s genetic and molecular profile. Key advancements underscore this shift: molecularly targeted drugs (e.g., trastuzumab for HER2-positive breast cancer, EGFR and ALK inhibitors for lung cancer) have improved efficacy and reduced toxicity compared to conventional therapy. Pharmacokinetic (PK) and pharmacodynamic (PD) considerations are central to personalizing treatment, explaining variability in drug exposure and response among patients and guiding dose optimization. Modern strategies like therapeutic drug monitoring and model-informed precision dosing seek to maintain drug levels in the therapeutic range, improving outcomes. Immunotherapies, including checkpoint inhibitors and CAR-T cells, have transformed oncology, though patient selection via biomarkers (such as PD-L1 expression or tumor mutational burden) is critical to identify likely responders. Innovative drug delivery systems, notably nanomedicine, address PK challenges by enhancing tumor-specific drug accumulation and enabling novel therapeutics. Furthermore, rational combination regimens (informed by PK/PD and tumor biology) are being designed to achieve synergistic efficacy and overcome resistance. Key barriers include the high cost of biomarker testing, insufficient laboratory infrastructure, and inconsistent reimbursement policies. Operational inefficiencies such as long turnaround times or lack of clinician awareness further limit the use of precision diagnostics. Regulatory processes also remain complex, particularly around the co-development of targeted drugs and companion diagnostics, and the evidentiary requirements for rare subgroups. Addressing these barriers will require harmonized policies, investment in infrastructure, and educational initiatives to ensure that the promise of personalized medicine becomes accessible to all patients. Ensuring that advances are implemented responsibly—guided by pharmacological insights, supported by real-world evidence, and evaluated within ethical and economic frameworks—will be critical to realizing the full potential of personalized cancer medicine. Full article

Trastuzumab deruxtecan (T-DXd) has demonstrated efficacy in HER2-positive and HER2-low breast cancer. Its main safety concern is interstitial lung disease, while clinically relevant hepatotoxicity is rarely reported. In our case report we describe a 49-year-old woman with HER2-positive advanced breast cancer that developed persistent grade 3 transaminase elevations after 2 cycles of T-DXd, refractory to corticosteroid treatment and requiring treatment discontinuation. This case underlines the unpredictable and idiosyncratic nature of T-DXd associated hepatotoxicity and the importance of liver function monitoring. Clinicians should consider DILI in patients with unexplained liver enzyme elevations during therapy. Further studies are needed to clarify mechanisms and risk factors. Full article

Background and Objectives: Idiopathic inflammatory myopathies (IIMs) are rare autoimmune diseases with extra-muscular manifestations. A firm association with malignancy, mainly observed in dermatomyositis (DM) is well established and several predictors of malignancy were previously published. However, given the low prevalence of IIMs, large population-based studies are scarce, hindering a comprehensive understanding of site-specific cancer patterns and risk factors. This study aimed to evaluate malignancy patterns and predictors, in a large, diverse cohort of patients with DM and PM. Materials and Methods: This retrospective cohort study used the Clalit Health Services electronic database, including 1557 DM patients and 528 PM patients diagnosed between 2002 and 2018, along with age-, sex-, and residence-matched controls at a 1:5 ratio. The incidence and risk of malignancies were assessed using Cox proportional hazards models, and predictors of solid and hematologic malignancies within the PM/DM cohort were analyzed using adjusted logistic regression. Results: In our cohort, DM was associated with an increased risk of both solid and hematologic malignancies (HR 1.89, 95%CI 1.47–2.41), whereas in PM the association was less pronounced and limited to solid malignancies (HR 1.50, 95%CI 1.06–2.11). In DM, higher risks were observed for breast cancer (HR 1.86) and chronic leukemia (HR 5.02). Across both subtypes, older age at diagnosis, the presence of specific autoantibodies were associated with increased malignancy risk. Significant markers included antiphospholipid antibodies (OR 2.28), lupus anticoagulant (OR 2.29), anti-Mi2 (OR 2.09), any of the antinuclear antibodies (OR 2.37), and individually anti-RNP/Sm (OR 1.70), anti-Ro/La (OR 1.79), anti-Scl-70 (OR 1.60), and anti-DNA (OR 1.97). Conclusions: Our study demonstrates an increased risk of malignancy in both DM and PM, with the relationship being stronger and broader in DM, involving both solid and hematologic cancers. Older age at diagnosis, and a distinct serological profile, particularly antiphospholipid antibodies and various antinuclear antibodies, identify patients at highest risk, warranting heightened clinical vigilance. Full article

Echocardiography remains a vital part of the initial assessment and monitoring of oncological patients. It allows for proper treatment selection but can also reveal life-threatening complications, including impaired left ventricular function or thromboembolism. It can rarely detect intracardiac masses that require further investigation. In the presented case, a 51-year-old female patient with left-sided breast cancer, who had undergone neoadjuvant chemotherapy, was hospitalised due to a right atrial mass identified via routine transthoracic echocardiography (TTE). Initial anticoagulation therapy showed no clinical improvement. Follow-up TTE revealed a 12 × 19 mm hyperechogenic, mobile mass in the right atrium (RA). Computed tomography angiography (CTA) ruled out pulmonary embolism and revealed that the mass was located close to the tip of the vascular access port. Transoesophageal echocardiography showed that the lesion was not connected to the vascular port. Based on location and mobility, the lesion was most consistent with a cardiac myxoma. After the Heart Team made a decision, endovascular intervention using a vacuum-assisted device was performed without complications. Histopathological examination excluded thrombosis and myxoma, revealing a fibro-inflammatory lesion. A multimodality approach is necessary to assess RA masses. However, even an extensive evaluation could be misleading, so treatment options should always be subject to the Heart Team’s decision. Full article

Background: Biopsy remains the gold standard for characterizing breast cancer, but it is invasive, costly, and may not fully capture tumor heterogeneity. Advances in artificial intelligence (AI) now allow for the extraction of biological and clinical information from medical images, raising the possibility of using imaging as a non-invasive alternative. Methods: A semi-systematic review was conducted to identify AI-based approaches applied to mammography (MM) and breast tomosynthesis (BT) for tumor subtyping, staging, and prognosis. A PubMed search retrieved 1091 articles, of which 81 studies met inclusion criteria (63 MM, 18 BT). Studies were analyzed by clinical target, modality, AI pipeline, number of cases, dataset type, and performance metrics (AUC, accuracy, or C-index). Results: Most studies focused on tumor subtyping, particularly receptor status and molecular classification. Contrast-enhanced spectral mammography (CESM) was frequently used in radiomics pipelines, while end-to-end deep learning (DL) approaches were increasingly applied to MM. Deep models achieved strong performance for ER/PR and HER2 status prediction, especially in large datasets. Fewer studies addressed staging or prognosis, but promising results were obtained for axillary lymph node (ALN) metastasis and pathological complete response (pCR). Multimodal and longitudinal approaches—especially those combining MM or BT with MRI or ultrasound—show improved accuracy but remain rare. Public datasets were used in only a minority of studies, limiting reproducibility. Conclusions: AI models can predict key tumor characteristics directly from MM and BT, showing promise as non-invasive tools to complement or even replace biopsy. However, challenges remain in terms of generalizability, external validation, and clinical integration. Future work should prioritize standardized annotations, larger multicentric datasets, and integration of histological or transcriptomic validation to ensure robustness and real-world applicability. Full article

Background/Objectives: Male breast cancer (MBC) is a rare malignancy representing less than 1% of all breast cancer cases, with rising incidence worldwide. Current treatment strategies largely rely on extrapolation from female breast cancer, despite clear biological and clinical distinctions. This review aims to summarize current knowledge on non-metastatic MBC, with a particular focus on genetic predisposition, tumor biology, and recent therapeutic advances. Methods: A systematic literature search was conducted using PubMed and PMC databases to identify clinical trials, observational studies and systematic reviews related to MBC published up to 1st June, 2025. Studies were selected for their relevance to genetic and molecular features, as well as treatment outcomes in non-metastatic disease. Results: Fifty-one studies were included in the review. Findings confirm the predominance of hormone receptor–positive tumors in MBC and underscore the central role of BRCA2 mutations. Germline mutations in BRCA2 and BRCA1 were reported in approximately 1 and 2% of male cases, respectively. Additional germline alterations were identified in PALB2, CHEK2, and other DNA repair genes. Comparative analyses of surgical approaches showed no significant difference in survival between breast-conserving surgery and mastectomy. Postmastectomy radiotherapy improved overall survival compared to surgery alone. Adjuvant tamoxifen therapy was independently associated with significant survival benefits, although adherence remains a challenge. Conclusions: MBC is a biologically distinct and molecularly heterogeneous disease. Breast-conserving surgery appears safe and effective in selected patients. Adjuvant radiotherapy and tamoxifen confer clear survival advantages. The lack of male-specific clinical trials remains a major limitation in optimizing evidence-based care for MBC. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is a heterogeneous entity lacking ER, PR, and HER2, with aggressive biology and high recurrence risk. Neoadjuvant chemotherapy (NACT) is the standard of care, and a pathological complete response (pCR) is a surrogate marker for survival. Within TNBC, apocrine differentiation (TNAC) is a distinct subtype, often androgen receptor (AR)-positive, with lower chemosensitivity but a favorable prognosis. Comparative studies of TNAC versus classical TNBC remain limited. This study aimed to define clinical and biological differences between TNAC and non-apocrine TNBC (NA-TNBC), representing the largest TNAC cohort to date. Methods: This retrospective study included 129 non-metastatic TNBC patients treated with NACT and surgery (2010–2020). Patients were classified as TNAC or NA-TNBC. Demographic, clinicopathological, and immunohistochemical data (including Ki-67 and AR) were collected. Tumor-infiltrating lymphocytes (TILs), delta Ki-67, pathological complete response (pCR), and survival outcomes were evaluated. Results: Of 129 TNBC patients, 45 (34.9%) were TNAC. AR positivity occurred in 64.4% of TNACs. TNAC patients were predominantly postmenopausal. pCR rates were significantly lower in TNAC (6.6% vs. 30.9%, p = 0.002). TNACs exhibited lower baseline Ki-67, delta Ki-67, and TIL positivity (13.3% vs. 30%). Despite this, 5-year overall survival was higher in TNAC (86% vs. 78%). Delta Ki-67 > 20% strongly predicted pCR across the cohort (p < 0.001). Carboplatin was rarely used in TNAC (8.3%), but was associated with a higher pCR rate (50% vs. 2.4%, p = 0.018). Conclusions: TNAC represents a biologically distinct TNBC subtype, characterized by low pCR but favorable survival. Recognition of its unique features may guide treatment de-escalation and exploration of AR-targeted therapies. Prospective studies focusing on TNAC are warranted. Full article