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4-factor prothrombin complex

✓ Approved

Intas Pharmaceuticals · F2 · 细胞治疗

什么是 4-factor prothrombin complex？

4-factor prothrombin complex 是一种细胞治疗，由Intas Pharmaceuticals研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intravenous (IV)。

药物档案

公司Intas Pharmaceuticals
药物类别细胞治疗
分子靶点F2, F7, F9, F10
给药途径Injectable (Others), Intravenous (IV)
状态Approved
来源： ClinicalTrials.gov, Intas Pharmaceuticals

作用机制

分子靶点

4-factor prothrombin complex 作用于 4 个分子靶点：

F2coagulation factor II, thrombin (THPH1, PT)
F7coagulation factor VII (SPCA)
F9coagulation factor IX (P19, F9 p22)
F10coagulation factor X (FXA, FX)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

4-factor prothrombin complex 针对 2 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Vascular disordersExtravasation blood✓ Approved
Vascular disordersHaemorrhage✓ Approved

相关研究文献

PubMedFrontiers in cellular and infection microbiology2026-09-10

Interpretable machine learning identifies immune-inflammatory and immunothrombotic biomarkers for myocardial injury and mortality risk stratification in severe pneumonia with diverse infectious etiologies.

Wang Yicheng Y, Li Feng F, Yan Tianqiang T, Wu Yi Y et al.

Severe pneumonia is frequently associated with dysregulated immune-inflammatory responses and immunothrombotic activation, contributing to myocardial injury and adverse clinical outcomes. Early identification of patients at high risk for myocardial injury and mortality across varied infectious etiologies remains challenging. We aimed to characterize inflammatory and coagulation-related signatures associated with myocardial injury and construct interpretable machine learning models for risk stratification in patients with severe pneumonia. This retrospective cohort study enrolled 287 adult patients with severe pneumonia admitted to the intensive care unit from 2018 to 2024. All patients were stratified into groups with bacterial infection, COVID-19 and bacterial co-infection, and influenza and bacterial co-infection. Clinical variables collected within 48 h after admission were analyzed using multivariable regression, competing-risk models, and interpretable machine learning. SHapley Additive exPlanations (SHAP) were used to identify key predictive features. Myocardial injury was highly prevalent across all infectious subgroups. Patients with bacterial infection exhibited an exacerbated inflammatory and coagulation burden, characterized by elevated leukocyte counts, D-dimer levels, and prolonged prothrombin time. Multivariate analysis confirmed that D-dimer, prothrombin time, and creatinine were independently associated with myocardial injury. Machine learning analyses identified coagulation and inflammatory markers as major contributors to myocardial injury risk. For mortality prediction, the XGBoost model yielded optimal predictive performance with an AUC of 0.85. SHAP analysis revealed that vasopressor administration, prothrombin time, advanced cardiovascular support, age, and hypoxemia were the top prognostic determinants for mortality. Although infectious etiology was not independently associated with mortality, patients with myocardial injury and bacterial infection exhibited the poorest survival outcomes. Inflammatory and immunothrombotic signatures are closely associated with myocardial injury and adverse outcomes in severe pneumonia. Interpretable machine learning models exhibited promising discriminative performance for both myocardial injury and all-cause mortality in our cohort. Although the initial training dataset was derived from a single center with a relatively limited sample size, we performed temporal validation in this study, which preliminarily suggested the potential clinical applicability of these models for the early identification of high-risk patients.

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PubMedFrontiers in oncology2026-09-10

Case Report: Synergistic potential of RANKL and ACLY inhibition in a breast cancer patient with acquired resistance to CDK4/6 inhibitors.

Samusieva Anastasiia A, Gorodetska Ielizaveta I, Socha Oleg O, Lytovchenko Yuliia Y et al.

The development of acquired resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represents a major clinical challenge in the management of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. Overcoming this resistance requires novel therapeutic strategies that target the underlying molecular escape pathways. We report the case of a patient initially diagnosed in 2011 with pT2N0M0, ER+/HER2- invasive ductal carcinoma. Following multimodality treatment, she experienced disease progression with bone metastases after five years, followed by lymph node metastases at the ten-year mark. Subsequent treatment with the CDK4/6i ribociclib in combination with fulvestrant resulted in disease progression approximately one year later, indicating acquired resistance. Due to progressive bone loss, denosumab was initiated for skeletal support, and bempedoic acid was later added for dyslipidemia. This case provides a clinical basis for exploring two innovative therapeutic concepts to overcome resistance. First, we discuss the complex role of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibition. Given that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) functions as a decoy receptor for RANKL, we hypothesize that a patient's LGR4 expression status may dictate the efficacy and safety of denosumab, potentially serving as a predictive biomarker to personalize its use. Second, we propose that bempedoic acid, a supportive care medication, may exert a direct anti-neoplastic effect. Its dual mechanism, inhibiting ATP-citrate lyase (ACLY) to disrupt lipid synthesis and activating AMP-activated protein kinase (AMPK) to suppress mammalian target of rapamycin complex 1 (mTORC1) signaling, positions it as a potential agent to counteract the metabolic reprogramming associated with therapeutic resistance. This case report illustrates the sequential development of acquired therapeutic resistance in the long-term management of metastatic breast cancer. Although a single clinical observation cannot establish definitive efficacy, this scenario generates compelling hypotheses for future studies. It highlights the potential need to explore biomarker-driven approaches-such as evaluating LGR4 expression to guide RANKL inhibition-to personalize treatment. Additionally, it raises the possibility that repurposed supportive care medications, such as bempedoic acid, might offer hypothetical anti-neoplastic benefits, warranting broader clinical validation to overcome complex resistance mechanisms.

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Psychometric properties of a Greek translation of the intuitive eating Scale-3 (IES-3) in adults from Greece.

Argyrides Marios M, Maïano Christophe C, Tylka Tracy L TL, Reppa Glygeria G et al.

The Intuitive Eating Scale-3 (IES-3) is a new, 12-item measure of intuitive eating, which is recognised as a protective factor of disordered eating. Given its recency, there has been limited evaluation of the psychometric properties of the IES-3 in diverse national and linguistic contexts. Therefore, we report on the translation and psychometric evaluation of a novel Greek version of the IES-3 in Greek adults. A total of 1,138 women and 712 men completed the Greek IES-3 alongside additional measures selected to assess validity. Exploratory factor analysis with a first split-half subsample showed that the original 4-factor model fit the data well. In a second split-half subsample, a bifactor-exploratory structural equation model (B-ESEM) with a G-factor and four S-factors fit the data and demonstrated superior fit compared to alternative models. Across subsamples, the 4-factor and B-ESEM models demonstrated gender invariance and did not show measurement bias in terms of age and body mass index. Validity analyses revealed that intuitive eating was associated with higher positive body image and psychological well-being and lower disordered eating and psychological distress. These results indicate that the Greek IES-3 has robust psychometric properties.

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PubMedAnnals of translational medicine2026-09-10

Tumor microenvironment and signaling pathways in melanoma brain metastasis.

Rosell Rafael R, González-Cao María M, Olmo-González Daniel D, Hold Emilia E et al.

Melanoma has one of the highest propensities to metastasize to the brain, and despite major advances with immune checkpoint inhibitors, brain metastases remain a leading cause of morbidity and mortality. The biological mechanisms governing brain colonization, immune evasion, and resistance to therapy are incompletely understood. This review summarizes recent advances in the understanding of the tumor microenvironment and signaling pathways involved in melanoma brain metastasis, with emphasis on mechanisms that may provide novel therapeutic opportunities. We performed a review of preclinical and clinical studies investigating molecular pathways, immune-cell interactions, and metabolic programs associated with melanoma brain metastasis and response to immunotherapy. Emerging evidence identifies enhancer of zeste homolog 2 (EZH2) phosphorylation by Src kinase as a key driver of brain metastasis through granulocyte colony-stimulating factor (G-CSF) production and recruitment of immunosuppressive neutrophils. Microglia and tumor-associated macrophages constitute major components of the brain metastatic microenvironment and actively support tumor progression. Spleen tyrosine kinase (Syk) signaling contributes to microglial activation and immune-related neurotoxicity during anti-programmed death 1 (PD-1) therapy. Mitochondrial dysfunction, including alterations in mitochondrial contact site and cristae organizing system (MICOS) complex components such as Mic19 and Mic60, promotes innate immune signaling through cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) and TANK-binding kinase 1 (TBK1). TBK1 emerges as a central regulator linking neuroinflammation, microglial activation, metastatic progression, and therapeutic resistance. In addition, metabolic reprogramming mediated by tectonic family member 1 (TCTN1) and carnitine palmitoyltransferase 1A (CPT1A) enhances fatty acid oxidation and promotes melanoma metastasis. These pathways may represent actionable targets that complement immune checkpoint blockade. Melanoma brain metastasis is driven by complex interactions between tumor cells, neutrophils, microglia, and mitochondrial signaling networks. Src-EZH2, TBK1-dependent inflammatory pathways, and TCTN1/CPT1A-mediated metabolic reprogramming are emerging biomarkers and therapeutic targets. Integrating these approaches with anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapies may improve disease control, overcome resistance, and reduce immune-related adverse events in patients with melanoma brain metastases.

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PubMedCancer communications (London, England)2026-09-10

The PROM1+SMAD5+ Tumor-Initiating Subpopulation Shapes Premetastatic Niches through Spatial Multi-Omics Landscapes in HER2-Positive Breast Cancer.

Yin Huijing H, Wang Wei W, Ge Jing J, Fan Guangjian G et al.

Background: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer exhibits high metastatic potential, linked not only to intrinsic cancer cell traits but also to critical crosstalk with the tumor microenvironment. However, the coevolutionary mechanisms between cancer cells and multiple stromal subpopulations in driving distant metastasis remain poorly understood. Therefore, this study aimed to explore the microenvironmental regulatory mechanisms of breast tumor-initiating cells and their roles in HER2-positive breast cancer metastasis. Methods: Integrated multi-omics analyses (spatial transcriptomics, metabolomics, spatial in situ analysis, and proteomics) were used to identify novel cell subpopulations and their interactions. High-throughput sequencing of exosomal microRNAs (miRNAs) and single-nucleus RNA from the same tissue was performed to explore the molecular mechanisms underlying cell crosstalk. In vitro experiments were conducted to verify the interaction between stromal cells and prominin 1 (PROM1)+ SMAD family member 5 (SMAD5)+ cells. In vivo murine breast cancer models were established to confirm the role of stromal subpopulations in pulmonary metastasis, and parabiosis assays were carried out to compare key cell subpopulations between tumor-bearing mice and normal mice. Clinical samples were analyzed to correlate key cell subpopulations with clinicopathological features and prognosis. Results: A breast tumor-initiating subpopulation, PROM1+ SMAD5+ cells, and its interactions with stromal cells, specifically adiponectin (ADIPOQ)+ notch receptor 4 (NOTCH4)+ adipocytes and decorin (DCN)+ transmembrane 4 L six family member 1 (TM4SF1)+ fibroblasts, were identified by integrated multi-omics analyses. Mechanistically, these 2 stromal subpopulations delivered functional miRNAs and mediated coatomer protein complex subunit alpha (COPA)-dependent epidermal growth factor receptor (EGFR) activation in PROM1+SMAD5+ cells, thereby triggering the EGFR-SMAD5-cytochrome P450 family 3 subfamily A member 4 (CYP3A4) axis to induce partial epithelial-mesenchymal transition (pEMT) and metastasis. Additionally, stroma-secreted exosomal miR-671-3p down-regulated Claudin1 in PROM1+SMAD5+ cells, promoting their evolution into PROM1+SMAD5+Claudin1- subpopulations with enhanced stemness and metastatic potential. In vivo experiments confirmed that the 2 stromal subpopulations markedly promoted pulmonary metastasis, and the 3 identified subpopulations preferentially accumulated in the primary tumors, lymph nodes, and pulmonary metastatic lesions of tumor-bearing mice. Clinically, these 3 subpopulations form a "trinity niche", whose aggregation associated with HER2 positivity, high malignancy, and lymph node/pulmonary metastasis, and predicted poor prognosis. Conclusion: This study clarified the microenvironmental regulation of breast tumor-initiating cells and provided new insights into precision therapy.

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PubMedJournal of cancer survivorship : research and practice2026-09-10

Buffering the burden: health behaviors, mental distress, and sex disparities in U.S. cancer caregivers.

Mevawalla Areesh A, Sarfraz Azza A, Alizai Qaidar Q, Angez Meher M et al.

Cancer caregivers experience heightened psychological distress, yet the cumulative impact of modifiable health behaviors on mental distress remains understudied. We evaluated the association between individual and cumulative protective factors and frequent mental distress (FMD) among U.S. cancer and non-cancer caregivers. A cross-sectional analysis was conducted using data from the 2022 BRFSS data. Adult caregivers were identified and classified according to whether the individual provided care to an individual with cancer. FMD was defined as ≥ 14 days of poor mental health in the past 30 days. Protective factors included sufficient sleep, regular physical activity, non-smoking status, and adequate emotional support. A Cumulative Protective Factor Score (range, 0-4) was constructed. Among 10,923 caregivers, 1,483 (13.6%) were cancer caregivers. FMD was more prevalent in cancer caregivers than non-cancer caregivers (314 [21.6%] vs 1,227 [13.0%], p < 0.001), who also reported fewer protective factors. Each individual protective factor was associated with lower odds of FMD (all p < 0.001), although these associations were attenuated among cancer caregivers for sleep, physical activity, and emotional support. Predicted probabilities of FMD declined progressively with increasing cumulative protective factor scores in both cohorts. At the highest score (4), predicted FMD was similar in cancer and non-cancer caregivers (10% vs 7%, p = 0.12). Among cancer caregivers, females exhibited higher predicted FMD than males across all cumulative protective factor levels. Cancer caregivers experience disproportionately high mental distress, particularly when protective resources are limited. However, the co-occurrence of multiple health-promoting behaviors and emotional support may offset this burden. Sex-based disparities persisted, underscoring the need for tailored, caregiver-centered support strategies. Supporting caregivers of cancer survivors through interventions that promote healthy behaviors and emotional support may reduce mental distress and improve survivorship care outcomes.

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