Clinical & Experimental Metastasis最新文献

By conducting colorectal cancer liver metastases (CRLM) clinical trials and analyzing treatment and prognostic targets, to provide clinical trial references for CRLM. We analyzed global and Chinese CRLM clinical trials from the Informa database, focusing on fruquintinib, sintilimab, and dual immunotherapy (CTLA-4 + PD-1). The study evaluated oncogenic biomarkers and therapeutic targets, assessing their safety by integrating data from Genotype-Tissue Expression (GTEx)-RNA, Human Protein Atlas (HPA)-RNA and HPA-Protein. Target specificity and future potential were further investigated using Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets and HPA pathology. CRLM clinical trials numbers have stabilized, focusing mainly on combination therapies, with China and the US leading in trial numbers. Single-agent trials emphasize targeted therapy, while chemo plus targeted therapy dominates combinations, reflecting a treatment model based on chemotherapy with targeted therapy breakthroughs. Chinese independently developed drugs-fruquintinib and sintilimab-and dual immunotherapy (CTLA-4 + PD-1) are still emerging, with fruquintinib used for CRLM resistant to multi-line chemo and anti-VEGF. The relevance of VEGFA and EGFR targets highlights targeted therapy's importance and supports drugs like fruquintinib. Targets analysis shows most have low safety and specificity, but CD34, FLT1, and TP53 exhibit good profiles and potential for CRLM therapy and prognosis. This study, by integrating and analyzing the clinical trial data related to CRLM, aims to conduct an in-depth investigation and evaluate the safety specificity of the treatment targets through reference.

Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and poor prognosis. Coupled with this, TNBC shows a high rate of metastasis which is known to be aided by tumour vasculature. Endothelial cells that form the lining of the tumour vasculature exhibit distinct genotype and phenotype differences compared with normal tissue vasculature. However, little is known about endothelial signatures that drive metastasis from a primary tumour, particularly in the context of immune infiltration. In this study, we utilized GeoMX Digital Spatial Profiling to investigate spatial proteomics differences in endothelial cells between primary and secondary sites of TNBC. By segmenting tissues using epithelial (PanCK), immune (CD45), and endothelial (CD31) markers, we analysed the microvasculature for a panel of 79 target proteins. In paired primary and secondary TNBC tissues, we identified significant downregulation of fibronectin (- log2(Fold-Change) = - 1.7, p < 0.001) in secondary sites. Specifically in epithelial regions, S100B was found to be downregulated in secondary microvasculature when compared to primary tumours. Additionally, metastasis-free primary tissues exhibited upregulated expression of S100B when compared to primary tissues that metastasized. Our study highlights the potential contributions of microvasculature to metastatic progression in TNBC, presenting new opportunities to explore them as potential biomarkers of TNBC metastasis.

The specific role of minimal extrathyroidal extension (mETE)-particularly the differences between anterior mETE (ant-mETE) and posterior mETE (post-mETE)-in relation to Central lymph node metastasis (CLNM) for papillary thyroid carcinoma (PTC) remains uncertain. This study aimed to examine the effects of ant-mETE and post-mETE on CLNM and to construct a preoperative risk-stratification nomogram for CLNM to guide central lymph node dissection (CLND). This retrospective study analyzed 1694 consecutive clinically node-negative (cN0) PTC cases treated between 2017 and 2024. Univariate and multivariate analyses were performed to identify clinicopathological predictors of CLNM. Subsequently, a predictive nomogram incorporating significant variables was developed and internally validated. Among 1694 cN0 PTC cases analyzed, 833 (49.2%) demonstrated pathologic CLNM, and post-mETE was significantly associated with higher CLNM rates compared to ant-mETE (p < 0.001). Multivariable analysis identified seven independent CLNM predictors: age > 55 years (OR 0.466), male gender (OR 2.479), tumor size > 1 cm (OR 3.290), bilateral involvement (OR 1.335), multifocality (OR 1.420), lower pole location (OR 1.710), and mETE presence (ant-mETE OR = 2.47, post-mETE OR = 3.492). The developed nomogram demonstrated excellent discriminative ability (AUC = 0.774) and clinical utility. Both ant-mETE and post-mETE were independently associated with CLNM, with post-mETE demonstrating significantly higher metastatic propensity. The predictive nomogram developed in this study demonstrated moderate discriminative accuracy for CLNM, which could help identify occult metastases, thereby facilitating prophylactic CLND and reducing reoperation rates in patients.

Kinesin family member 14 (KIF14), a microtubule-associated motor protein, plays a crucial role in cytoskeletal dynamics, intracellular transport, and cell division. Oncological studies have consistently reported KIF14 overexpression across various cancers, including breast, ovarian, lung, liver, and brain tumors, associating it with poor clinical outcomes, increased tumor aggressiveness, and resistance to conventional therapies. This review comprehensively analyzed the involvement of KIF14 in cancer progression, particularly its roles in cell cycle regulation, mitotic spindle formation, and oncogenic signaling pathways. Additionally, the molecular mechanisms underlying its tumorigenic effects, its potential as a prognostic biomarker, and its viability as a therapeutic target are explored. The expanding understanding of KIF14's oncogenic functions present promising opportunities for developing novel therapeutic strategies aimed at this key regulator of tumor growth and metastasis, addressing the urgent need for treatments targeting aggressive and therapy-resistant malignancies.

Colorectal cancer mortality is largely driven by metastatic spread, with colorectal liver metastases (CRLM) being the most frequent. Treatment often combines surgery and systemic therapy, including anti-EGFR agents such as cetuximab. This study evaluated the cytoreductive effect of cetuximab on CRLM and its influence on liver function and regeneration in a selective portal vein ligation (PVL) model. Sixty-six male WAG/RijHsd rats were used. Seven days before PVL, twelve tumor-bearing animals received intra-arterial cetuximab, while other six received vehicle (saline). Additional groups included tumor-bearing rats without PVL, rats undergoing PVL alone, and untreated controls (n = 6 each). Seven days after PVL, the future remnant liver volume (%FRL) and hepatocyte replication were quantified. Serum markers for hepatic, renal, and systemic injury were analyzed, and tumor volume was assessed by ultrasound before and after PVL. The regenerative response following PVL was not significantly affected by cetuximab, with %FRL reaching 80-90%. However, hepatocyte nuclei exhibited a smaller mean area compared with non-treated animals (45.35 ± 9.09 vs. 43.54 ± 9.87 μm²; p < 0.001). Liver function remained preserved, although glucose levels decreased after PVL. Cetuximab significantly reduced tumor growth driven by hepatic regeneration (1.12 ± 0.45 vs. 0.53 ± 0.16 mL; p < 0.01). Neoadjuvant intra-arterial cetuximab does not impair liver regeneration after PVL while effectively limiting tumor proliferation linked to regenerative stimuli. These findings support its perioperative safety and potential use to prevent tumor recurrence in patients with CRLM undergoing staged hepatectomy.