Search Results (2,353)

Background/Objectives: Vernodalin (VD) and crude extracts from Gymnanthemum extensum leaves have previously demonstrated anticancer activity; however, their underlying molecular effects remain incompletely understood. This study investigated the anticancer activities of VD and G. extensum extracts and characterized their associated molecular responses in breast (MDA-MB-231) and ovarian (A2780) cancer cells. Methods:G. extensum leaves were extracted with dichloromethane and ethyl acetate to obtain DEGE and EAGE, respectively. VD was isolated from EAGE and characterized by ¹H-NMR and HPLC. Phytochemical profiles of the extracts were analyzed by GC-MS and HPLC. Cytotoxicity, clonogenic survival, cell cycle progression, migration, and protein expression were evaluated using MTT assay, colony formation assay, flow cytometry, wound healing assay, and Western blotting. Results: GC–MS analysis revealed distinct phytochemical compositions between DEGE and EAGE, although both extracts contained high levels of neophytadiene and phytol. VD, DEGE, and EAGE inhibited cell proliferation and migration in both cancer cell lines. VD suppressed proteins associated with cancer progression, including SMYD3, BRAF, MELK, FOXM1, Cyclin B1, MDR1/ABCB1, and MMP-9, with molecular responses differing between MDA-MB-231 and A2780 cells. DEGE and EAGE exhibited molecular regulatory patterns distinct from those of purified VD, suggesting contributions from multiple phytochemical constituents. Conclusions: VD and G. extensum crude extracts exhibit significant in vitro anticancer activity against breast and ovarian cancer cells and induce distinct molecular responses. The differential effects of DEGE and EAGE may be attributable to differences in their phytochemical constituents. Full article

Epithelial ovarian cancer (EOC) remains one of the most aggressive gynecological malignancies, largely due to late-stage diagnosis, therapeutic resistance, and molecular heterogeneity. This study aimed to identify biologically relevant hub genes and evaluate potential dual-target compounds against Cyclin-Dependent Kinase 1 (CDK1) and DNA Topoisomerase II Alpha (TOP2A) through an integrated computational framework. Transcriptomic datasets from GSE28799, GSE54388, and GSE14407 were analyzed to identify overlapping differentially expressed genes, followed by protein–protein interaction analysis, functional enrichment, survival assessment, molecular docking, ADMET profiling, and molecular dynamics simulations. Mechanistically, CDK1 and TOP2A participate in coordinated cell-cycle regulation associated with G2/M progression and chromosomal dynamics in ovarian cancer. Among the identified hub genes, CDK1 and TOP2A demonstrated marked overexpression and central topological importance within the interaction network. Functional enrichment analyses highlighted significant associations with mitotic cell-cycle regulation, DNA replication, and proliferative signaling pathways. Molecular docking analyses identified Naringin as a potential dual-target candidate with favorable binding affinity toward both CDK1 and TOP2A. ADMET profiling suggested acceptable pharmacokinetic and toxicity characteristics, while molecular dynamics simulations supported stable protein–ligand interactions under dynamic conditions. Although survival analyses did not demonstrate statistically significant independent prognostic associations, the findings support the biological relevance of CDK1 and TOP2A in EOC progression. Collectively, this study provides an integrated computational perspective on CDK1/TOP2A-associated oncogenic signaling and prioritizes Naringin as a preliminary candidate for future experimental investigation in epithelial ovarian cancer. Full article

Background: Therapeutic resistance following cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) represents a key unmet need in hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (mBC). Treatment paradigms have advanced from non-targeted options, such as fulvestrant monotherapy or everolimus-based combinations, to precision medicine strategies, including inhibitors of the PI3K/AKT pathway, oral selective estrogen receptor degraders (SERDs), and novel ER-modulating agents, often guided by biomarkers and molecular surveillance. Methods: This narrative review synthesizes evidence from randomized clinical trials, real-world studies, and biomarker-driven analyses published from 2010 to 2026, with emphasis on next-generation sequencing (NGS)-guided genomic profiling, targeted pathway therapies, and circulating tumor DNA (ctDNA)-based proactive interventions in the post-CDK4/6i setting. This review was conducted and reported in accordance with the SANRA recommendations for narrative reviews. Results: Early second-line standards, including fulvestrant and alpelisib for PIK3CA-mutated tumors, established the basis for biomarker-guided treatment in hormone receptor–positive, HER2-negative metastatic breast cancer. With the widespread use of CDK4/6 inhibitors in the first-line setting, the optimal post-progression strategy has shifted toward molecularly selected combination approaches rather than single-agent endocrine therapy, as endocrine monotherapy has shown limited efficacy in acquired resistance. Multiple randomized studies have demonstrated that adding targeted agents to endocrine therapy improves progression-free survival compared with hormonal therapy alone, supporting combination regimens as the preferred strategy after CDK4/6 inhibitor progression, except in carefully selected patients with low disease burden, indolent biology, or frailty where tolerability is a major concern. Precision-based trials have further refined this approach. Elacestrant improved progression-free survival in ESR1-mutated disease in the EMERALD trial, capivasertib plus fulvestrant demonstrated significant benefit in tumors harboring AKT/PIK3CA/PTEN pathway alterations in CAPItello-291, and inavolisib plus palbociclib and fulvestrant achieved both progression-free and overall survival improvement in PIK3CA-mutated patients with early relapse in INAVO120. Real-world analyses further support the effectiveness of these biomarker-directed strategies across diverse clinical subgroups. Comprehensive genomic profiling has identified multiple resistance mechanisms, including ESR1 mutations, PI3K/AKT/mTOR pathway activation, RB1 loss, and FGFR alterations, which may co-occur and reduce sensitivity to endocrine monotherapy. While ESR1 and PI3K pathway alterations now guide approved therapies, FGFR alterations remain investigational targets, with ongoing trials evaluating selective FGFR inhibitors. Proactive switching approaches evaluated in SERENA-6 and PADA-1 demonstrate that serial circulating tumor DNA (ctDNA) monitoring can detect emergent ESR1 mutations before radiographic progression, providing a clinically actionable lead time for early therapeutic modification and extending endocrine-based disease control by approximately 5 to 7 months. Conclusions: Post-CDK4/6i management increasingly relies on NGS-guided precision approaches, integrating pathway-specific therapies and ctDNA surveillance to tailor sequencing based on resistance profiles, prior ET response, and tumor heterogeneity. Future investigations into novel ER degraders and multi-targeted combinations hold potential to further optimize algorithms, extend non-chemotherapy options, and enhance survival in HR+/HER2− mBC. Full article

Background: A combination of cyclin-dependent kinase 4/6 inhibitors (CDKi) and radiotherapy (RT) may enhance antitumoral immunity, yet clinical evidence of this interaction in HR+/HER2− metastatic breast cancer (MBC) remains limited. This study evaluates the impact of combined CDKi and stereotactic body radiotherapy (SBRT) on immune biomarkers and treatment response. Methods: We report a case of a 51-year-old woman with oligometastatic HR+/HER2− MBC involving the sacrum. Clinical management included letrozole plus palbociclib and SBRT (30 Gy in 3 fractions). Serial Neutrophil-to-lymphocyte ratio (NLR) measurements, MRI, and PET-CT scans were used to monitor systemic immune modulation and treatment efficacy over a five-year period. Results: Baseline NLR was 1.068. Following four weeks of CDKi, NLR decreased by 44.7% (0.591). Post-SBRT, a further 17.8% reduction was observed (nadir 0.486). Five months post-RT, MRI showed a volumetric increase in sacral lesions despite clinical improvement. Subsequent PET-CT demonstrated a complete metabolic response, confirming the MRI findings as pseudoprogression. As of January 2026, the patient remains in sustained complete metabolic remission. Conclusion: The integration of CDKi and SBRT might induce an immune-mediated antitumoral response, evidenced by dynamic NLR reductions and radiologic pseudoprogression. Multimodal imaging is essential to differentiate immune-mediated swelling from true progression in this setting. Full article

Cutaneous Radiation Injuries (CRIs) and wounds within an area of radiation exposure (combined injury, CI) are a significant concern for nuclear accidents and radiation combat/terrorist events. CRIs and CI present unique clinical challenges, and effective countermeasures are urgently needed. Here we describe a murine model of CRI and CI in C57BL/6 mice using 16.9 Gy thoracic X-ray irradiation (5.3 Gy/min, 160 kV) ± experimental wound administered immediately. Wound repair and radiation-induced dermatitis were assessed after irradiation. Our previous studies showed that genistein (200 mg/kg, s.c.), administered 24 h prior to irradiation prevented radiation injuries in two murine models. We investigated the effects of genistein in the CI model. Macroscopic and histological analyses showed that radiation significantly delayed wound closure, although wounds did not significantly alter the progression of radiation dermatitis. Genistein improved the early rate of wound closure and significantly reduced dermatitis in mice. Histological analysis showed that genistein improved skin structure and reduced inflammation and fibrosis. Immunohistochemistry showed that genistein attenuated radiation-induced cyclin-dependent kinase inhibitor 1 (p21/waf1) and α-smooth muscle actin and preserved K15 positive skin adult stem cells. These findings suggest that genistein may be an effective prophylactic against CRIs and CI. Full article

Cold stress poses a significant challenge to aquatic organisms, affecting their survival, growth, and metabolic processes. This review explores the molecular mechanisms by which fish, crustaceans, and mollusks respond to cold stress, highlighting the shared and species-specific pathways that facilitate adaptation. Common responses to cold stress include modulation of energy metabolism, regulation of oxidative stress, immune responses, and maintenance of proteostasis. In particular, the activation of the adenosine 5′-monophosphate-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) pathways plays a critical role in regulating energy balance and autophagy in response to low temperatures. Furthermore, we examine the specific adaptive mechanisms employed by different groups of aquatic organisms. Fish utilize pathways such as peroxisome proliferator-activated receptor alpha/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPAR/PGC-1α) and fatty acid oxidation to optimize energy utilization and improve cold tolerance. Crustaceans rely on crustacean hyperglycemic hormone (CHH) signaling and AMPK pathway activation, while mollusks employ metabolic suppression and glycogen storage to survive cold exposure. Moreover, the regulation of autophagy and apoptosis, mediated by p53 and cyclin-dependent kinase 1 (Cdk1), ensures the survival of healthy cells under prolonged cold stress, with autophagy maintaining energy homeostasis and apoptosis eliminating damaged cells. This review also discusses the role of molecular chaperones like heat shock protein 70 (HSP70) and the ubiquitin-proteasome system (UPS) in protein homeostasis, highlighting their importance to protect cells under cold stress. The combined action of these molecular pathways allows aquatic organisms to cope with and adapt to cold environments, ensuring cellular integrity and enhancing survival. Future research should focus on integrating molecular, physiological, and ecological approaches to better understand cold tolerance mechanisms and improve aquaculture practices under climate change scenarios. Full article

Background/Objectives: Cardiovascular diseases (CVDs) and cancer remain major global health challenges and are among the leading causes of mortality worldwide, including in Kuwait. Medicinal plants are important sources of bioactive compounds with therapeutic potential. This study aimed to identify the phytochemical constituents of Curcuma longa L. root extract and evaluate their potential cardioprotective and anticancer activities using integrated computational approaches. Methods: Phytochemical profiling of Curcuma longa root extract was performed using gas chromatography–mass spectrometry (GC–MS). The identified compounds were evaluated through molecular docking against selected cardiovascular- and cancer-related targets, including HMG-CoA reductase, phosphoinositide 3-kinase (PI3K), cyclin-dependent kinase 6 (CDK6), and HER2 kinase receptors. Protein–ligand interactions were analyzed to determine binding stability. Biological activity prediction and pharmacokinetic properties were assessed using PASS prediction and SwissADME tools, while density functional theory (DFT) calculations were conducted to investigate electronic and quantum chemical characteristics associated with ligand reactivity. Results: GC–MS analysis identified seventeen phytochemical constituents with retention times ranging from 7.57 to 32.70 min. The major compounds detected were 2-oxo-cyclooctaneacetic acid (30.88%), curlone (20.99%), and tumerone (13.85%). Molecular docking revealed favorable binding affinities for α-curcumene, caryophyllene, bergamotene, cyclohexene derivatives, tumerone, curlone, and (6R,7R)-bisabolone against the selected targets, with interaction profiles comparable to reference drugs. PASS and SwissADME analyses indicated promising biological activities, acceptable drug-likeness, and favorable pharmacokinetic properties. DFT analysis demonstrated that curlone and tumerone possessed stable electronic configurations and favorable reactivity profiles. Conclusions: The findings suggest that bioactive compounds from Curcuma longa may serve as promising lead candidates for the development of cardioprotective and anticancer agents. However, further experimental validation through in vitro and in vivo studies is required to confirm these computational predictions. Full article

Resistance to 5-fluorouracil (5-FU) and oxaliplatin (OXA) remains an obstacle in colorectal cancer (CRC) therapy, but the upstream mechanisms enabling adaptive survival remain unclear. Angiomotin (AMOT), a Hippo-YAP regulator, is expressed as two major isoforms, p130 and p80, but the contribution of isoform-specific AMOT regulation to chemoresistance is unknown. RNA-seq of OXA-resistant cells identified AMOT as a candidate determinant, and its isoform-specific regulation and functional relevance were then examined in OXA- and 5-FU-resistant CRC sublines. AMOT-p80 was preferentially upregulated, whereas AMOT-p130 remained largely unchanged. Common AMOT pre-mRNA was elevated, whereas p130-specific pre-mRNA was unchanged, consistent with preferential transcriptional activation favoring the p80 isoform. Functionally, AMOT depletion minimally affected basal viability but significantly sensitized resistant cells to 5-FU or OXA, with increased apoptotic responses. AMOT silencing reduced nuclear YAP and lowered c-Myc and Cyclin D1 protein levels, whereas AMOT-p80 re-expression restored nuclear YAP, with recovery of c-Myc/Cyclin D1 levels and drug tolerance. YAP knockdown attenuated these outputs and blunted the additional effect of AMOT depletion. AMOT-p80 overexpression in parental cells increased c-Myc/Cyclin D1 protein levels and enhanced tolerance to 5-FU and OXA. These findings suggest that preferential AMOT-p80 upregulation is linked to YAP-associated chemoresistant phenotypes in CRC cells. Full article

Prostate cancer (PCa) is the second most frequently diagnosed solid malignancy in men and a major cause of cancer-related mortality worldwide. While localized disease is associated with excellent long-term survival, advanced and castration-resistant PCa continues to represent a major therapeutic challenge. Current management ranges from active surveillance for indolent tumors to multimodal systemic approaches for metastatic disease. In this context, natural compounds are attracting increasing interest as adjunctive or novel therapeutic agents. Among these, silymarin, a Silybum marianum-derived flavonolignan complex, has shown promising antineoplastic activity in preclinical PCa models. In vitro, silymarin compounds consistently inhibit PCa cell proliferation by inducing G1 and G2/M cell cycle arrest, upregulating cyclin-dependent kinase inhibitors, and activating caspase-dependent apoptotic pathways. They also modulate key oncogenic signaling pathways involved in cell survival, proliferation, invasion, and metastasis. In vivo xenograft and transgenic models further show reduced tumor growth, angiogenesis, and metastatic spread with limited systemic toxicity. Emerging clinical evidence, including systematic reviews and meta-analyses, suggests translational potential; however, robust randomized trials are needed to define optimal formulations, dosing strategies, and therapeutic efficacy in PCa patients. This review provides a comprehensive overview of the molecular mechanisms, preclinical efficacy, and emerging clinical evidence supporting silymarin as a candidate for future PCa research. Full article

Background/Objectives: The prognostic significance of the uric acid-to-albumin ratio (UAR) in patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has not been adequately investigated. This study aimed to investigate the association between baseline UAR and survival outcomes in this patient population. Methods: This retrospective study included HR-positive/HER2-negative metastatic breast cancer patients treated with ribociclib or palbociclib at Necmettin Erbakan University between May 2020 and April 2025. UAR was calculated by dividing the serum uric acid level (mg/dL) by the serum albumin level (g/dL). Based on receiver operating characteristic (ROC) analysis, the optimal cut-off value for UAR was identified as 1.0 (AUC = 0.67; sensitivity 68%; specificity 58%). Patients were subsequently classified into two groups as UAR < 1 and UAR ≥ 1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared with the log-rank test. Independent prognostic factors were evaluated using Cox regression analyses. Results: A total of 118 eligible patients were included in the analysis, including 34 (28.8%) in the UAR < 1 group and 84 (71.2%) in the UAR ≥ 1 group. The proportion of postmenopausal patients was significantly higher in the UAR ≥ 1 group (p = 0.01). Kaplan–Meier analysis showed that median PFS was not reached in the UAR < 1 group, whereas it was 33.05 months in the UAR ≥ 1 group (log-rank p = 0.06). Median OS was not reached in the UAR < 1 group and was 50.7 months in the UAR ≥ 1 group (p = 0.017). Multivariate Cox regression analysis demonstrated that UAR < 1 was associated with improved PFS (HR = 0.65; 95% CI: 0.34–0.89; p = 0.04). Postmenopausal status emerged as an independent adverse prognostic factor for PFS (HR = 1.92; 95% CI: 1.10–4.05; p = 0.04). In addition, UAR < 1 was associated with a reduced risk of mortality in the OS analysis (HR = 0.61; 95% CI: 0.26–0.87; p = 0.01). Conclusions: Lower baseline UAR was associated with more favorable survival outcomes in HR-positive/HER2-negative metastatic breast cancer patients treated with CDK4/6 inhibitors. As an inexpensive and easily accessible biomarker derived from routine laboratory parameters, UAR may provide additional prognostic information for clinical risk stratification. Full article

Introduction: In the treatment of hormone receptor-positive (HR+), HER2-negative (HER2−) metastatic breast cancer (MBC), the current guidelines recommend endocrine therapy combined with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors as the preferred first-line treatment to preserve quality of life. Ribociclib is a CDK4/6 inhibitor that has been used in combination with aromatase inhibitors or fulvestrant in patients with HR+, HER2− metastatic breast cancer. Various adverse drug reactions associated with ribociclib have been reported, including cutaneous reactions, hepatotoxicity, and hematologic toxicity. In this study, we aimed to evaluate the clinical manifestations and risk factors of dermatologic toxicities in patients with metastatic breast cancer treated with ribociclib. Methods: This retrospective study included patients with metastatic/recurrent breast cancer who were prescribed ribociclib from April 2021 to December 2024 at a single institution. We retrospectively reviewed the medical records of these patients to identify the frequency of cutaneous adverse events, the time of onset, and the clinical characteristics of skin reactions. Logistic regression analysis was performed on several clinical factors, including body surface area (BSA) and concomitant medications, to identify risk factors associated with the occurrence of cutaneous adverse events. Results: A total of 110 patients with MBC were enrolled during the study period. The median age was 53 years (range, 28–82); all 110 patients (100.0%) were female; the median BSA was 1.56 m² (range, 1.29–2.07); and 32 patients (29.1%) were premenopausal. Ribociclib plus letrozole was administered in 48 patients (43.6%) and ribociclib plus fulvestrant in 29 patients (26.4%). An additional 33 patients (30.0%) received ribociclib plus letrozole with a gonadotropin-releasing hormone (GnRH) agonist. Cutaneous adverse events occurred in 29 patients (26.4%), and the median time to onset was 84 days (range, 3–498). The cutaneous adverse event patterns included pruritus, erythematous macular rash, eczematous rash/contact dermatitis, vitiligo, urticarial reactions, polymorphous light eruption, toxic epidermal necrolysis (TEN), and desquamation. Grade 1 or 2 cutaneous adverse events occurred in 93.1% of patients; Grade 3 toxicity occurred in one patient; and Grade 4 toxicity, namely toxic epidermal necrolysis (TEN), was reported in one patient. Dose reduction was required in three patients (10.3%), and permanent discontinuation of ribociclib occurred in one patient. Clinical improvement was achieved in the majority of patients (86.2%) with cutaneous adverse events following supportive care. Logistic regression analysis revealed that age, Eastern Cooperative Oncology Group (ECOG) performance status, body surface area (BSA), treatment regimen, and use of cholesterol-lowering medications were not independently associated with the development of cutaneous adverse events. Conclusion: CDK4/6 inhibitors represent one of the most important treatment options for HR+/HER2− metastatic breast cancer. Regardless of their clinical efficacy, cutaneous adverse events remain a common source of patient discomfort. Therefore, careful clinical attention and appropriate supportive care are essential to improve patients' quality of life. Full article

Cyclin-dependent kinase 1 (CDK1) is frequently upregulated in multiple cancers and plays a central role in cell cycle progression and tumorigenesis. However, whether CDK1 directly regulates the histone acetyltransferase KAT8 (also known as MOF) in non-small cell lung cancer (NSCLC) remains unclear. Here, we identify CDK1 as a kinase that directly interacts with and phosphorylates KAT8 at serine 348 (S348) and threonine 418 (T418). Mechanistically, CDK1-mediated phosphorylation, particularly at S348, enhances the interaction between KAT8 and MSL1, thereby stabilizing the MSL complex and promoting KAT8-dependent acetylation of histone H4 at lysine 16 (H4K16). Functionally, the phosphorylation-deficient mutant KAT8-S348A exhibits impaired MSL complex assembly, reduced H4K16 acetylation, and decreased NSCLC cell proliferation both in vitro and in vivo. Pharmacological inhibition of CDK1 using RO-3306 suppresses KAT8 phosphorylation and H4K16 acetylation, leading to significant tumor growth inhibition. Notably, this effect is partially rescued by re-expression of wild-type KAT8 but not by the S348A mutant, supporting a phosphorylation-dependent mechanism. Collectively, these findings define a CDK1–KAT8 signaling axis that promotes NSCLC proliferation through epigenetic regulation and suggest that targeting CDK1-dependent KAT8 phosphorylation may represent a potential therapeutic strategy for lung cancer. Full article

Background: Leukemic non-nodal variant mantle cell lymphoma (nnMCL) is an uncommon subtype of mantle cell lymphoma that lacks lymphadenopathy and generally follows an indolent clinical course. Adverse genetic alterations such as TP53 inactivation and del(13q) may have prognostic significance. Clinical findings such as splenomegaly may serve as a clue to the diagnosis and should prompt further evaluation. Case Presentation: We describe a 91-year-old woman who presented with a one-month history of anemia (hemoglobin 12.3 g/dL), mild thrombocytopenia (platelets 136 × 10⁹/L), isolated splenomegaly and no palpable lymphadenopathy. Despite a normal total white blood cell count, intermittent relative lymphocytosis with atypical lymphocytes (4%) and smudge cells was detected on the complete blood count. Peripheral blood flow cytometry demonstrated a monoclonal kappa-restricted B-cell population negative for CD5 and CD10, comprising approximately 20% of lymphocytes. Conventional karyotyping and fluorescent in situ hybridization (FISH) analysis identified del(13q), del(17p)/TP53, and IGH-CCND1 rearrangement in 8–19.5% of peripheral blood leukocytes. A month after the initial assessment, the patient presented following a fall. CT imaging of the abdomen revealed marked splenomegaly, a large subcapsular/perisplenic hematoma, and moderate-to-large hemoperitoneum. Emergent laparotomy showed an enlarged spleen (1490 g, 23 × 16 × 7.5 cm) with laceration. Histologic evaluation showed atypical lymphoid cells positive for CD20 and cyclin D1, with strong p53 expression, negative for CD5 and SOX11, and a low Ki-67 index. Similar involvement was identified in the small bowel and appendix. Targeted sequencing of splenic tissue, performed as part of a retrospective molecular characterization, identified a pathogenic TP53 variant (p.His179Gln). Conclusions: This case provides a rare opportunity to evaluate splenic and small intestinal involvement by nnMCL at both the gross and histologic levels. It highlights the importance of integrating clinical findings with flow cytometry, imaging, cytogenetic, and molecular data in establishing the diagnosis. Even when peripheral blood findings suggest a low disease burden, imaging may better define the extent of disease and support appropriate clinical assessment, particularly in elderly patients at risk for complications related to splenomegaly. Full article

Objective: This study aimed to evaluate the prognostic significance of positron emission tomography/computed tomography (PET/CT)-derived sarcopenia in patients with hormone receptor-positive, HER2-negative metastatic breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Methods: This retrospective single-center study included 77 patients treated between January 2018 and March 2025. Sarcopenia was assessed using skeletal muscle index (SMI) at the L3 level on fluorodeoxyglucose (FDG) PET/CT. Patients were classified as sarcopenic or non-sarcopenic. Clinical, nutritional parameters including body mass index (BMI) and prognostic nutritional index (PNI), and inflammatory parameters including pan-immune inflammation value (PIV) were analyzed. The primary endpoint was progression-free survival (PFS). Results: Sarcopenia was present in 35.1% of patients. After a median follow-up of 38 months, sarcopenic patients had significantly shorter PFS compared with non-sarcopenic patients (18 vs. 38 months; HR: 2.37, 95% CI 1.12–4.99, p = 0.02, multivariable analysis). In multivariable analysis, sarcopenia, recurrent disease, brain metastasis, and liver metastasis were independent predictors of PFS. No significant association was observed between sarcopenia and overall survival. BMI, PNI, and PIV were not associated with survival outcomes. Toxicity profiles were comparable between groups. Conclusions: PET/CT-derived sarcopenia may be a prognostic factor for PFS in patients receiving CDK4/6 inhibitors, whereas conventional nutritional and inflammatory markers are not. These findings support the clinical utility of imaging-based body composition assessment. Prospective studies incorporating functional measures of sarcopenia are warranted. Full article

The oncogenic Marek’s disease virus (MDV) triggers Marek’s disease (MD), which is a substantial threat to poultry as it transforms infected T cells into tumors. Our research identified that long non-coding RNA 9802 (lncRNA-9802) exhibits increased expression in the chicken spleen following MDV infection, with its expression being strongly associated with the expression of tumor p53-binding protein 1 (TP53BP1). The function of lncRNA-9802 in T cells transformed by MDV remains unclear. Consequently, the expression levels of lncRNA-9802 were either over-expressed or knocked down in MDV-transformed T cells, MDCC-MSB1, through lentivirus-mediated over-expression and knock down experiments. Our findings demonstrate that lncRNA-9802 induces proliferation disturbances in MDCC-MSB1 cells by causing arrest in the S phase, which is accompanied by increased expression levels of TP53BP1, p53, and p21. Activation of the p53 pathway results in elevated levels of Cyclin E and Cyclin-dependent kinase 2 (CDK2), thereby facilitating the entry of MDCC-MSB1 cells into the S phase. Concurrently, the reduced levels of Cyclin A inhibit the exit of MDCC-MSB1 cells from the S phase. By modulating the TP53BP1/p53/p21 pathway, lncRNA-9802 induces S phase arrest in MDCC-MSB1 cells, characterized by upregulation of Cyclin E and CDK2 and downregulation of Cyclin A. This research enhances the understanding of the pathogenic mechanisms of MDV and provides a foundation for identifying potential targets for antiviral drug development. Full article