American journal of cancer research最新文献

Cancer remains a leading cause of morbidity and mortality worldwide, and the abnormal activation of glycolysis is a hallmark that enables tumor cells to adapt and sustain rapid proliferation. Beyond providing energy and biosynthetic precursors, glycolysis also supports tumor cell survival, invasion, and metastasis through multiple mechanisms. Hexokinase is a key rate-limiting enzyme in glycolysis, catalyzing the phosphorylation of glucose to glucose-6-phosphate. Among its isoforms, hexokinase 2 (HK2) exhibits particularly high enzymatic activity and substrate specificity, and it plays a central role in tumor metabolic reprogramming. Recent studies have shown that HK2 is markedly upregulated in many cancer types, where it promotes tumor initiation and progression by suppressing apoptosis and enhancing proliferation and metastasis. This review summarizes current evidence on the role of HK2 in tumor development and discusses emerging therapeutic strategies targeting HK2. By clarifying the link between HK2 and cancer, we aim to provide new insights and potential clinical applications for metabolism-based therapies.

This study aimed to investigate the long-term clinical outcomes of patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy with residual disease and to identify relevant clinicopathological prognostic factors. A total of 106 patients who underwent nCRT and surgery were identified. The chemotherapy regimen consisted of cisplatin plus 5-fluorouracil every 4 weeks, along with weekly carboplatin combined with paclitaxel, and the prescribed radiotherapy dose was either 41.4 Gy or 50.4 Gy. Most patients experienced tumor stage migration following nCRT and esophagectomy, such as upstaging or downstaging. Patients with ESCC undergoing trimodality therapy were categorized into three groups based on residual tumor status: ypT+N+, ypT+N0, and ypT0N+. In our cohort, the median disease-free survival (DFS) and overall survival (OS) were 8.2 months and 14.0 months, respectively. Pathological T status emerged as an independent prognostic factor associated with DFS and OS in both univariate and multivariate analyses. Patients with upstaging demonstrated inferior DFS and OS compared to those without upstaging, while patients experiencing downstaging showed superior DFS and OS compared to those without downstaging. Furthermore, DFS and OS appeared relatively worse in patients with ypT+N+ compared to those with ypT+N0 and ypT0N+. In conclusion, pathological T status serves as an independent prognostic factor for DFS and OS in ESCC patients with residual disease following nCRT and surgery, and prognosis is significantly correlated with upstaging or downstaging after nCRT. Identifying patients with the poorest prognosis is important, as additional adjuvant treatment may be necessary.

[This corrects the article on p. 1835 in vol. 7, PMID: 28979807.].

Objective: To evaluate the diagnostic value of bone metabolism and immune cell indexes in screening for tumor bone metastasis.

Methods: A retrospective study was conducted on 247 patients with malignant tumors. conducted on 247 patients with malignant tumors. According the presence of tumor bone metastasis, patients were divided into a bone metastasis group (156 cases) and a non-bone metastasis group (91 cases). Bone metabolism markers [calcium ion (Ca²⁺), β-Carbox-terminal telopeptide of type I collagen (β-CTX), type I procollagen N-terminal peptide (P1NP), osteocalcin (OC)] and immune cell indicators (CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, CD4⁺CD25⁺CD127^low Treg cells) were compared between groups. Correlations among these indices were analyzed using Pearson correlation, and interaction effects were evaluated using multiple linear regression with interaction terms. Receiver operating characteristic (ROC) curves were used to evaluate the screening efficacy of each index for tumor bone metastasis.

Results: Compared with the non-bone metastasis group, the bone metastasis group showed significantly higher levels of Ca²⁺, β-CTX, P1NP, CD3⁺CD4⁺ T cells, and CD4⁺CD25⁺CD127^low Treg cells (P<0.05), and lower levels of OC and CD3⁺CD8⁺ T cells (P<0.05). According to the Soloway classification, levels of Ca²⁺, β-CTX, P1NP, CD3⁺CD4⁺ T cells, and CD4⁺CD25⁺CD127^low Treg cells increased progressively from grade I to grade III (P<0.05), whereas OC and CD3⁺CD8⁺ T cells decreased (grade I > grade II > grade III) (P<0.05). Ca²⁺, β-CTX and P1NP were positively correlated with CD3⁺CD4⁺ T cells and CD4⁺CD25⁺CD127^low Treg cells (P<0.05) but negatively correlated with CD3⁺CD8⁺ T cells (P<0.05). In contrast, OC was negatively correlated with CD3⁺CD4⁺ T cells and CD4⁺CD25⁺CD127^low Treg cells (P<0.05) and positively correlated with CD3⁺CD8⁺ T cells (P<0.05). A significant interactive effect was observed between bone metabolism and immune indicators (P<0.05). The AUC the combined model (0.899) was higher than that of individual indicators - Ca²⁺ (0.835), β-CTX (0.843), P1NP (0.817), OC (0.750), CD3⁺CD4⁺ T cells (0.837), CD3⁺CD8⁺ T cells (0.771), CD4⁺CD25⁺CD127^low Treg cells (0.848). Internal validation showed that the accuracy of the combined model in diagnosing tumor bone metastasis was 88.26%.

Conclusions: The combine

Transactivation response RNA-binding protein 2 (TRBP) mediates microRNA (miRNA) biogenesis and regulates messenger RNA (mRNA) stability. It is a pivotal regulator of post-transcriptional gene expression, influencing processes including cellular senescence and tumorigenesis. Elevated TRBP expression correlates with poor prognosis in breast cancer, underscoring its potential as a therapeutic target. We identified a 3,4-diamino-substituted coumarin derivative (3ai), a novel small-molecule compound inhibitor of miR-21 biogenesis. Compound 3ai increased the expression of tumor-suppressor proteins targeted by miR-21. Further mechanistic studies revealed that 3ai binds TRBP and disrupts the biogenesis of senescence-associated miRNAs. This interaction induces cell cycle arrest and DNA damage in tumor cells, ultimately promoting cellular senescence in breast cancer cells and suppressing their proliferation and metastasis potential. Our study reveals that 3ai directly engages TRBP to modulate miRNA biogenesis, thereby inducing cellular senescence. These results support TRBP as a therapeutic target in breast cancer and warrant further development of 3ai as a candidate therapeutic for breast cancer.

Exosomes, as important intercellular message transporters, can be secreted by hepatocellular carcinoma (HCC) cells and transported to adjacent cells, thus promoting their migration and invasion in turn. However, whether the exosomes secreted by HCC are affected by physical abnormalities, such as fluid shear stress (FSS), is still largely unknown. Here, we observed that 1.4 dyn/cm² FSS could significantly increase the release of exosomes by up-regulating Rab27a and down-regulating Rab7 in HCC cells. Exosomes from FSS-induced HCC cells were more effective at encouraging recipient cell migration and invasion. Exosomes produced by static or FSS-stimulated cells were thoroughly analyzed using quantitative proteomics, and more than 1000 exosome proteins were found. Based on the differentially expressed proteins, IGF2, a potential migration-related protein, was discovered to be strongly expressed in FSS-stimulated cells, HCC tissues, as well as HCC patient-derived exosomes. Furthermore, we verified that exosomal IGF2 aggravated HCC migration and invasion via activating Ras/Raf/Erk signaling in recipient cells. Collectively, our data demonstrated that exosomes from FSS-stimulated HCC cells promote recipient cell migration through IGF2-Ras/Raf/Erk signaling, which might serve as potential targets for both cancer treatment and cancer prevention.

Circulating amino acid levels differ between patients with cancer and healthy individuals, and plasma histidine levels are lower in patients with periampullary cancer. This study examines histidine-related metabolic signaling in ampullary cancer. In total, 106 cancer specimens and 49 plasma samples from ampullary cancer patients were analyzed using immunohistochemistry, high-performance liquid chromatography for histidine levels, and enzyme-linked immunosorbent assays for histamine levels. Additionally, three ampullary cancer cell lines (TGBC-18 TKB, SNU-478, and SNU-869) were treated with histidine or histamine to assess growth. Plasma histidine levels were lower in patients with ampullary cancer than in healthy controls, whereas plasma histamine levels were similar between these groups. Elevated plasma histidine level was correlated with improved recurrence-free and overall survival in patients with ampullary cancer, as demonstrated by Kaplan-Meier survival analysis and multivariate Cox proportional hazards modeling. Expression of histidine-catabolic enzymes, namely histidine decarboxylase and histidine ammonia-lyase, was synergistic and positively correlated with early-stage cancer. Histidine treatment suppressed cancer cell proliferation, whereas histamine promoted cell proliferation of TGBC-18 TKB ampullary cancer cells. These findings suggest that plasma histidine is a prognostic survival factor, and combined treatment with histidine may offer therapeutic potential in patients with ampullary cancer.

Polyubiquitination plays a critical role in tumor biology, yet its significance in prostate cancer remains incompletely understood. Here, we investigated the expression and function of SOCS-box E3 ligases in prostate cancer. Analysis of TCGA data revealed WSB1 overexpression, which correlated with advanced pathological stage, high Gleason score, and poor prognosis. Functional assays demonstrated that WSB1 knockdown suppressed prostate cancer cell proliferation, colony formation, and migration in vitro, and inhibited tumor growth and Ki67 expression in vivo. Mechanistically, mass spectrometry and co-immunoprecipitation identified ISOC2 as a key WSB1 interactor. WSB1 stabilized ISOC2 by promoting its interaction with the deubiquitinase OTUD4, thereby preventing ISOC2 degradation via the ubiquitin-proteasome pathway. Silencing either ISOC2 or OTUD4 phenocopied the tumor-suppressive effects of WSB1 ablation. Importantly, disruption of the WSB1/OTUD4/ISOC2 axis upregulated P16INK4a expression, and co-silencing of P16INK4a partially restored tumorigenic properties. Our findings unveil a novel WSB1/OTUD4/ISOC2 signaling network that drives prostate cancer progression by modulating ubiquitin signaling and repressing P16INK4a, positioning WSB1 as a promising therapeutic target.

The incidence of upper tract urothelial carcinoma (UTUC) continues to rise in Southwestern Taiwan, despite a reduction in known environmental carcinogens. This study aimed to characterize the mutational and molecular profiles of UTUC in this high-incidence region and evaluate potential therapeutic targets. We performed next-generation sequencing using the TruSight Oncology 500 panel on 19 formalin-fixed, paraffin-embedded UTUC samples. We analyzed single nucleotide variants (SNVs), insertions/deletions (INDELs), copy number variants (CNVs), microsatellite instability (MSI), and tumor mutational burden (TMB). MSI was stable in all cases, and 42.1% of samples exhibited high TMB (>20 mutations/Mb), often co-occurring with inactivation of TP53, BRCA1, or BRCA2. CNVs were significantly more frequent in advanced-stage UTUC (46.2%) than in early-stage disease (0%). FGFR3 mutations were enriched in early-stage tumors (83.3%), while TP53 mutations predominated in advanced-stage tumors (46.2%). Notably, actionable mutations in PIK3CA, ERBB2, BRCA1, and BRCA2 occurred at higher frequencies than in previously reported Japanese UTUC cohorts. Our findings reveal a distinct molecular signature of UTUC in Southwestern Taiwan, with early- and late-stage tumors showing divergent mutational landscapes. These insights emphasize the importance of molecular stratification in UTUC management and suggest that a broader repertoire of targeted therapies could benefit patients in this high-incidence region.

Objective: To evaluate the utility of real-time three-dimensional echocardiography (RT-3DE) and two-dimensional speckle tracking imaging (2D-STI) for early detection of chemotherapy-induced cardiotoxicity in lymphoma patients, and to identify independent predictors of cardiotoxicity using these imaging parameters.

Methods: We conducted a single-center retrospective cohort study at The First People's Hospital of Changde City, enrolling 110 lymphoma patients who received anthracycline-based chemotherapy between January 2020 and January 2024. Echocardiographic assessments, including RT-3DE and 2D-STI, were performed before chemotherapy and within 72 hours after the 3rd and 6th cycles. Cardiotoxicity was defined as a ≥ 10% reduction in left ventricular ejection fraction (LVEF) or an LVEF < 50%.

Results: Baseline clinical characteristics showed significant differences in gender and hypertension between the cardiotoxic and non-cardiotoxic groups (both P < 0.05). RT-3DE revealed time-dependent changes, with LAEFa higher and LAEFa/LAEFt lower in the cardiotoxic group at 3 and 6 weeks post-chemotherapy, respectively (all P < 0.05). 2D-STI showed significant differences in LASct and LASr at 3 and 6 weeks (all P > 0.05). GEE analysis indicated that changes in LAEFa, LAEFp, LAEFt, LASr, LASct, and LVEF were driven by the time × group interaction effect (all P < 0.05).

Conclusion: RT-3DE and 2D-STI are sensitive for early detection of anthracycline-induced cardiotoxicity in lymphoma patients. LA functional indices (LAEFa, LAEFp, LAEFt) and LA strain indices (LASr, LASct) may detect cardiotoxicity earlier than LVEF, suggesting their potential role in optimizing cardio-oncology monitoring strategies.