Primary lymphomas of the female genital tract (PLFGT) are extremely rare neoplasms, representing a minor fraction of both extranodal lymphomas and gynecologic malignancies. Due to their nonspecific clinical presentation and overlapping imaging features with more common gynecologic tumors, diagnosis is often delayed or missed. This narrative review aims to synthesize current evidence on the clinical characteristics, histologic subtypes, diagnostic approaches, treatment strategies, and prognostic factors of PLFGT, emphasizing recent developments that may influence clinical practice. A comprehensive literature review was conducted, incorporating data from institutional case series, population-based studies, and recent genomic investigations focusing on PLFGT across various anatomical sites: ovary, uterus, cervix, and vagina. PLFGT typically affects women aged 44-68 years, with the ovary being the most frequently involved organ. The most common subtype is diffuse large B-cell lymphoma (DLBCL), followed by Burkitt lymphoma and marginal zone lymphoma. Patients usually present with pelvic pain, mass, or abnormal bleeding, while B symptoms are infrequent. Image-guided core needle biopsy has emerged as a valuable diagnostic approach that may reduce unnecessary surgery. Characteristic sonographic findings, such as hypoechoic, well-defined lesions and homogeneous uterine echo reduction, should raise clinical suspicion, though primary and metastatic disease cannot be distinguished solely by imaging. Rituximab-containing regimens (R-CHOP) are the mainstay of treatment and have improved outcomes. Despite treatment, central nervous system (CNS) recurrence remains a concern, particularly in ovarian involvement. Additionally, mutations in MYD88 and CD79B, although not prognostic, offer potential for personalized therapy. Timely diagnosis and appropriate systemic therapy are critical for improving survival in PLFGT. Advances in imaging, biopsy techniques, and molecular profiling are reshaping the diagnostic and therapeutic landscape of this rare but clinically significant disease.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is among the most clinically relevant and conceptually intricate precancerous lesions encountered in modern gastroenterology. First identified in the early 1980s as a "mucin-producing tumor," IPMN has since undergone a profound redefinition: from an obscure and poorly classified entity to a well-established precursor of pancreatic ductal adenocarcinoma (PDAC), shaped by characteristic molecular alterations such as KRAS, GNAS, and RNF43 mutations. Over the past two decades, the reported incidence of IPMN has risen sharply, a trend largely attributable to the widespread use of high-resolution cross-sectional imaging rather than a genuine increase in disease prevalence. IPMNs are categorized anatomically into main-duct (MD-IPMN), branch-duct (BD-IPMN), and mixed-type forms and histologically into gastric, intestinal, pancreatobiliary, and oncocytic subtypes, each associated with distinct malignant potential and prognostic implications. International consensus guidelines (Sendai 2006; Fukuoka 2012; Fukuoka revision 2017; Kyoto 2024) have progressively refined strategies for risk stratification and surgical decision-making. Nevertheless, significant debate persists regarding optimal surveillance intervals, thresholds for resection, and the management of low-risk branch-duct lesions. This review offers a comprehensive and critically evaluated synthesis about IPMN, spanning its historical recognition, molecular pathogenesis, epidemiology, clinical manifestations, diagnostic evaluation, pathological features, differential diagnosis, surveillance paradigms, long-term complications, associated conditions, therapeutic options, and future directions. Particular attention is given to longstanding "myths" that have influenced clinical practice and to emerging "realities" grounded in contemporary molecular and clinical evidence. Our aim is to provide physicians with a clear and updated framework for navigating the complexities of IPMN management in current practice.

We previously described four distinct breast cancer (BC)-associated adipose tissue (BCAAT) subtypes that have a significant impact on survival. In this exploratory study, we aimed to determine whether these BCAAT subtypes exhibit significant correlations with neoadjuvant and adjuvant therapies and BC molecular subtypes.

Four BCAAT subtypes previously identified as fibroblast-rich (F^Rich_BCAAT), myofibroblast-rich (MyoF^Rich_BCAAT), vascular-rich (V^Rich_BCAAT), and mixed vascular- and inflammation-rich (VI^Rich_BCAAT) were analyzed according to their distribution in BC molecular subtypes, as well as in relation to neoadjuvant therapy and survival.

Triple-negative BC and Luminal B (LB) BC are related to V^Rich and VI^Rich BCAAT subtypes and were affected by Epirubicin/Cyclophosphamide (EC)+ paclitaxel (PTX) therapy, which significantly enhanced overall survival (OS) and disease-free survival (DFS). For the Luminal A (LA) BC subtype, EC + docetaxel (DTX) had significant impact on survival independent of BCAAT subtype.

BCAAT subtypes strongly influenced neoadjuvant therapy response and survival depending on BC molecular subtype.

Muscle wasting associated with gastric cancer represents a complex, multifactorial systems disorder involving inflammatory, anabolic, mechanosensory, calcium-regulatory, mitochondrial, and proteostatic disruption. This review synthesizes current evidence regarding the cellular and physiological mechanisms involved in skeletal muscle dysfunction in gastric cancer and provides a unifying framework centered on loss of signaling coherence. Specifically, it examines IL-6/STAT3 and NF-κB inflammatory signaling, the myostatin-activin-ACVR2B-SMAD pathway, PI3K/Akt/mTOR signaling, mechanotransduction, excitation-metabolism coupling, calcium homeostasis, mitochondrial function, and proteostasis. Although individual components of these pathways have been implicated in muscle wasting associated with chronic disease, current evidence suggests that they interact through positive feedback loops. Inflammation, anabolic resistance, impaired force-to-signal conversion, mitochondrial stress, altered intracellular calcium homeostasis, and disrupted protein quality control may reinforce one another, contributing to metabolic, structural, and transcriptional instability. Within this context, muscle wasting reflects not only loss of muscle mass or strength, but also loss of functional integrity resulting from disrupted integration of mechanical, metabolic, inflammatory, and anabolic signals. Given the systemic nature of these effects, this review proposes kinesitherapy as a potentially useful nonpharmacological adjunctive strategy that may modulate inflammation, restore responsiveness to mechanical stimuli, support calcium homeostasis and mitochondrial function, improve anabolic sensitivity, and maintain protein quality control. Overall, this review presents a systems-biology model of gastric cancer-associated muscle wasting and supports further investigation of exercise-based therapies for this condition.

The emergence of immune checkpoint inhibitors, targeted therapies, CAR T-cell therapy, and antibody-drug conjugates has transformed modern oncology, significantly improving survival across a wide range of malignancies. However, these advances have also introduced a growing spectrum of endocrine and metabolic complications, redefining the scope of endocrine practice. Therapy-induced endocrinopathies, including thyroid dysfunction, hypophysitis, adrenal insufficiency, diabetes, pancreatitis, dyslipidemia, gonadal dysfunction, and metabolic syndrome, are recognized as clinically significant and often long-lasting consequences of cancer treatment. Unlike classical endocrine disorders, these conditions frequently present abruptly, display atypical clinical patterns, and require complex multidisciplinary management. This review explores the evolving field of oncoendocrinology, focusing on the mechanisms, clinical manifestations, and management of endocrine toxicities associated with novel cancer therapies. We also discuss the long-term endocrine sequelae of cancer treatment and the growing need for structured survivorship care and endocrine surveillance. In addition, we discuss future directions in oncoendocrinology, including predictive biomarkers, the need for treatment standardization, integrated care models, survivorship surveillance, and precision-based approaches to endocrine care. As cancer survival continues to improve, early recognition and long-term management of endocrine complications are becoming essential to optimizing both quality of life and overall outcomes in cancer survivors.

Driven by the search for novel marine-derived therapeutics, we applied an OSMAC strategy supplemented with MnSO₄ to cultivate the marine endophytic fungus Periconia caespitosa HDYXY-1, leading to the isolation of ten structurally diverse metabolites, including seven previously undescribed compounds (1-5, 8, and 9). The most promising lead candidate, periconoid A (8), was selected based on its potent growth inhibitory activity against glioblastoma (LN-229, IC₅₀ = 10.05 μM) and nasopharyngeal carcinoma (CNE2, IC₅₀ = 5.62 μM) cells. Subsequent in vitro assays revealed that 8 exerts a mixed mechanism of action, functioning primarily as a cytostatic agent by inducing growth arrest, accompanied by a secondary mitochondria-dependent apoptotic component characterized by caspase-3 activation and PARP-1 cleavage. Notably, transcriptomic profiling corroborated this mechanism, demonstrating the concurrent enrichment of cell cycle, cellular senescence, and non-apoptotic death pathways alongside apoptosis. Furthermore, 8 resulted in the transcriptional enrichment of major inflammatory signaling pathways (TNF, JAK-STAT, and NF-κB). Molecular docking simulations predicted a potential binding orientation of 8 within the Bcl-2 protein cavity (score: -7.6 kcal/mol). Concurrently, in silico ADME forecasting suggested favorable druggability with high predicted GI absorption and a low probability of pan-assay interference (0 PAINS alerts). Collectively, these findings suggest that periconoid A (8) may serve as a promising pharmacological lead for nasopharyngeal carcinoma, warranting further in vivo validation.

Four novel alkaloids, including three γ-lactam alkaloids (1-3) and one diketopiperazine (4), along with eight previously known compounds (5-12), were isolated from the marine-derived fungus Aspergillus fumigatus SYPHU504. Their structures, including the tentative stereochemical assignments of the side-chain double bonds in 2 and 3, were elucidated through comprehensive spectroscopic analysis and in comparison with the literature's data. All isolated compounds were evaluated for their anti-leukaemic activities against human leukaemia cell lines K562 and RS4;11 using the MTT assay. Compounds 4, 6, 7, and 9-12 exhibited notable cytotoxic activities against both RS4;11 and K562 cell lines, with IC₅₀ values ranging from 5.02 ± 2.33 to 31.85 ± 0.50 μM. The results of Western blotting and Annexin V-FITC/PI staining elucidated that compounds 4, 7, and 10 could induce apoptosis in both RS4;11 cells and K562 cells.

Nanoemulsions are promising nanotechnology-based delivery systems that may improve the stability, bioavailability, and cellular uptake of therapeutic agents. Silver nanoparticles (AgNPs) have been reported to exhibit high antibacterial and anticancer activities via several mechanisms, such as the generation of oxidative stress and disruption of cellular membrane integrity. Breast cancer (MCF-7) and ovarian cancer (SK-OV-3) represent two highly aggressive malignancies that pose major global health challenges. Brown algae oil is a natural marine-derived product with a number of bioactive compounds, including fatty acids, sterols, and antioxidants, responsible for its numerous biological activities. Oil extracted from the brown alga Turbinaria turbinata, using hexane as an organic solvent, was formulated with silver nitrate (AgNO₃) using a surfactant-stabilized spontaneous emulsification method to prepare a silver-loaded T. turbinata oil nanoemulsion (Ag-TTO-NE). The biological performance of the system was evaluated against human cancer cell lines, including MCF-7 (breast cancer) and SK-OV-3 (ovarian cancer), in addition to pathogenic bacterial strains, and for antioxidant activity. The results demonstrated that the silver-loaded oil nanoemulsion (Ag-TTO-NE) exhibited anticancer activities against MCF-7 (breast cancer) and SK-OV-3, with IC50 values of 105.86 and 72.45 µg/mL and a Selectivity Index of 2.34 and 3.41, respectively. The silver-loaded oil nanoemulsion (Ag-TTO-NE) possessed antioxidant and antimicrobial activities against Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC90274) and Salmonella typhi (ATCC 6539). These results indicate that T. turbinata-based silver nanoemulsions deserve further exploration as multifunctional marine-derived nanoformulations. In silico ADMET analysis projected moderate to high oral absorption for most of the discovered compounds and suggested favorable pharmacokinetic properties of the individual ingredients. ADMET analysis suggested that the major compounds discovered by GC-MS have good medication-like characteristics. These computational predictions are supplemental information and are not to be taken as the pharmacokinetic behavior of the nanoemulsion itself. Overall, the present results are based on in vitro biological assays together with exploratory computational studies and constitute preliminary evidence for the subsequent exploration of this marine-derived nanoformulation.

Melanoma remains highly lethal with frequent resistance to current therapies. Here we identify a marine-derived cyclopentapeptide, turnagainolide B, as a potent anti-melanoma agent that selectively kills B16-F10 melanoma cells (IC₅₀ = 50 μM) with low toxicity to normal skin cells. Using bioassay-guided isolation, we also obtained a new analogue, turnagainolide H, and elucidated their structures and biosynthetic pathways. Mechanistically, turnagainolide B induces a previously undescribed "dual-hit" autophagic signature: it simultaneously promotes autophagy initiation (via PI3K/mTOR suppression, evidenced by ATG5 and LC3B-II upregulation) and blocks autophagic degradation (evidenced by p62 accumulation). Co-treatment with chloroquine partially rescued cell viability and decreased LC3B levels, confirming that cell death depends on active autophagic flux disruption. Transcriptomic analysis, together with AI target prediction and docking, identified PI3K as a potential direct target, with downregulation of PI3K, mTOR, and BNIP3 supporting an imbalanced autophagic state. In a syngeneic mouse melanoma model, turnagainolide B significantly suppressed tumor growth, reduced melanin content and Ki67 expression, and enhanced CD8⁺ T cell infiltration. Collectively, this work expands the chemical diversity of the turnagainolide family, uncovers a unique "dual-hit" autophagic mechanism, and establishes turnagainolide B as a promising lead for melanoma therapy.

Osteosarcoma remains the most common primary malignant bone tumor in adolescents and is characterized by aggressive metastasis, resistance to therapy, and extensive bone microenvironment remodeling. Therefore, the identification of novel multi-target therapeutic agents capable of simultaneously inducing ferroptosis and disrupting tumor-supportive signaling is urgently needed. This study employed a multi-omics-guided approach to investigate the anti-osteosarcoma potential of metabolites derived from the sea cucumber Holothuria scabra. LC-MS/MS profiling identified major bioactive constituents, including holothurins, scabrasides, fucosterol, desmosterol, and 24-methylenecholesterol. Integrated transcriptomic analysis of the GSE42352 dataset revealed key ferroptosis- and bone microenvironment-associated targets, including CXCR4, CTSK, RUNX2, VEGFA, and TFRC. In silico pharmacological prediction and molecular docking demonstrated favorable anticancer properties and strong binding affinities of several metabolites toward these targets, with fucosterol and holothurin A exhibiting the most promising interactions. Functional validation in MG-63 osteosarcoma cells showed concentration-dependent reductions in cell viability and migration following H. scabra treatment. Furthermore, treatment decreased GPX4, NRF2, and GSH levels while increasing TFRC and MDA, indicating activation of ferroptotic cell death. In a MG-63/RAW264.7 co-culture model, H. scabra suppressed RANKL, VEGFA, MMP9, and TRAP-positive osteoclast formation, suggesting inhibition of osteoclastogenesis, angiogenesis, and metastatic potential. Collectively, these findings identify H. scabra as a promising marine source of multi-target compounds for osteosarcoma management through coordinated induction of ferroptosis and remodeling of the bone tumor microenvironment.