Anticancer research最新文献

Background/aim: The relationship between peripheral eosinophil levels and prognosis or the tumor microenvironment (TME) in patients undergoing esophagectomy for esophageal cancer (EC) remains unclear. This study aimed to investigate the prognostic significance of preoperative peripheral eosinophils and their association with tumor-infiltrating immune cells.

Patients and methods: A total of 243 patients who underwent curative esophagectomy for EC were retrospectively analyzed. Patients were classified into two groups based on a preoperative peripheral eosinophil cut-off value of 1.6%, determined using Youden's index. Survival outcomes were compared between the groups, and prognostic factors were identified using Cox proportional hazards modeling. In a subset of 96 patients with available data, correlations between preoperative eosinophil levels and tumor-infiltrating CD8⁺ and CD163⁺ cells in the TME were evaluated.

Results: Overall survival (OS) and relapse-free survival (RFS) in the preoperative peripheral eosinophil <1.6% group were significantly worse than those in the preoperative peripheral eosinophil ≥1.6% group. Multivariate analysis revealed that peripheral eosinophil <1.6% was an adverse prognostic factor for OS [hazard ratio (HR)=1.65; 95% confidence interval (CI)=1.03-2.64] and RFS (HR=1.63; 95%CI=1.06-2.49). Additionally, preoperative peripheral eosinophil count positively correlated with the number of TI CD8⁺ cells (r=0.26), while peripheral eosinophils% and the number of TI CD163⁺ cells had no correlation (r=-0.03).

Conclusion: Preoperative low peripheral eosinophil count may be a prognostic factor in esophagectomized patients for EC. Additionally, peripheral eosinophil rate and the number of TI CD8⁺ cells had positive correlation.

Background/aim: Anatomical liver resection along the intersegmental plane provides oncological advantages for primary liver malignancies and may reduce complications such as blood loss and postoperative bile leakage. In left lateral sectionectomy (LLS), the falciform ligament and umbilical fissure are conventionally regarded as landmarks; however, tertiary branches from the dorsal and cephalic sides of the portal umbilicus (P4dor) often annulate the left lateral region of the falciform ligament. We propose a novel LLS technique using an extrahepatic Glissonean approach combined with indocyanine green (ICG) fluorescence.

Patients and methods: To preliminarily investigate the P4dor territory, protocol-based dynamic computed tomography images of 128 patients scheduled for hepatobiliary and pancreatic surgery were analyzed. The safety and efficacy of the technique were assessed using robotic, laparoscopic, and open LLS. The Glissonean pedicles of segments 2 and 3 were isolated, P4dor boundaries delineated under ICG guidance, and the parenchyma transected along the demarcation line to preserve the P4dor region.

Results: P4dor was identified in 91.4% of cases, with a mean of 1.4 branches, an annular volume of 21.7 ml (2.1%), and a mean distance of 15.9 mm between the left border of the P4dor territory and the portal umbilicus. In all three surgical cases, the P4dor boundaries were clearly delineated and preserved. No postoperative complications occurred.

Conclusion: This LLS technique is simple, feasible for minimally invasive surgery, and enables reproducible anatomical resection by clarifying the P4dor demarcation. It may also facilitate adequate margins in biliary tumors while preserving functional liver parenchyma.

Background/aim: Immune checkpoint inhibitors (ICIs) have emerged as a first-line treatment for advanced non-small cell lung cancer (NSCLC), offering the potential for long-term survival. However, predictors of sustained clinical benefit in patients without driver gene mutations remain poorly defined. This study aimed to identify clinical and therapeutic factors associated with long-term survival in NSCLC patients treated with ICIs.

Patients and methods: We retrospectively analyzed 97 NSCLC patients treated with ICIs. Patients who survived for >3 years were classified as the long-term survival group, and those who did not were categorized as the non-long-term survival group. Clinical characteristics and treatment-related factors were compared between these two groups.

Results: Of the 97 patients, 22 (22.7%) were classified into the long-term survival group. This group included a higher proportion of younger patients, patients who responded to initial ICI therapy, and patients who discontinued treatment due to immune-related adverse events (irAEs). Multivariate analysis identified younger age and low neutrophil-to-lymphocyte ratio (NLR) as independent predictors of long-term survival. Adenocarcinoma histology and switching administration of ICIs (i.e., changing from a PD-1 to a PD-L1 inhibitor or vice versa) showed clinically suggestive, though marginally significant, associations with prolonged survival.

Conclusion: Younger age and low NLR were associated with long-term survival in NSCLC patients treated with ICIs. Adenocarcinoma and switching administration may have potential clinical relevance. These findings highlight the importance of patient selection and strategic management of ICI therapy. Nevertheless, confirmation in larger prospective cohorts is warranted.

Background/aim: Immune checkpoint inhibitors have recently been applied as anticancer agents for various thoracic malignancies. However, the mechanisms underlying their efficacy remain insufficiently understood. We therefore conducted a study to investigate the role of programmed cell death protein 1 (PD1) molecules expressed on the surface of cancer cell lines.

Materials and methods: We assessed PD1 expression on the surface of nine cell lines using flow cytometry. To explore the involvement of the PD1/programmed cell death ligand 1 (PD-L1) axis in cell proliferation, we inhibited PD1 function by adding nivolumab to PD1-positive tumor cell lines. We then analyzed changes in cell proliferation signaling pathways of a small-cell lung cancer cell line, SBC-3, and changes in PD-L1 expression and associated signaling pathways by adding cobalt chloride and interferon-γ, known to influence PD-L1 expression in vivo.

Results: Among the nine cell-lines, SBC-3 showed strong PD1 expression, whereas the other eight cell lines exhibited minimal or no expression. Significant increases in cell proliferation were observed following treatment of SBC-3 cells with nivolumab at concentrations of 4 and 40 μg/ml. Immunoblotting analysis revealed enhanced phosphorylation of AKT serine/threonine kinase 1 and extracellular-regulated kinase, along with a concentration-dependent decrease in COP9 signalosome subunit 5 (CSN5) expression. Although cobalt chloride treatment increased expression of hypoxia-inducible factor 1α, it did not affect PD-L1 expression. In contrast, treatment with interferon-γ resulted in marked inhibition of cell proliferation and a clear decrease in PD-L1 expression.

Conclusion: Co-expression of PD1 and PD-L1 may play a role in regulating proliferation of tumor cells, particularly in cases with strong PD1 expression on tumor cells.

Background/aim: Accurate staging is critical for optimizing treatment in advanced-stage cervical cancer (FIGO stage IB3 and above). This study evaluated the added value of ^18F-fluorodeoxyglucose positron emission tomography (FDG-PET) compared to magnetic resonance imaging (MRI) and computed tomography (CT) in improving staging accuracy and guiding management decisions.

Patients and methods: A retrospective review was conducted of patients with advanced cervical cancer treated at Derby Gynaecological Cancer Centre (2016-2023) who underwent MRI, CT, and FDG-PET. Differences in staging and management before and after FDG-PET were analyzed using McNemar's test with Yates' correction.

Results: DG-PET led to a change in FIGO stage in 13 of 45 cases (29%; p=0.00087). It upstaged 11 cases (24%) - primarily due to previously undetected nodal metastases - and downstaged 2 cases (4%) due to false-positive findings on CT/MRI. Occult nodal disease was identified in 20% of patients. FDG-PET altered management in five cases (11%; p=0.044), most commonly through para-aortic nodal radiotherapy boost adjustments.

Conclusion: FDG-PET appears to enhance staging accuracy and impact treatment planning in advanced cervical cancer, particularly by detecting occult nodal metastasis. However, its utility may be limited in cases where nodal involvement is already evident on MRI/CT.

Background/aim: α-Santalol, a major component of sandalwood oil, has been shown to have chemopreventive and antitumor effects in different pre-clinical cancer models. The present study was undertaken to determine the in vitro efficacy of α-santalol on SK-MEL2 human melanoma cells and an immortalized human keratinocyte cell line (HaCaT).

Materials and methods: In this study, we employed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Trypan blue, wound-healing, and annexin V apoptosis assays, as well as confocal microscopy for imaging F-actin rhodamine phalloidin/4',6-diamidino-2-phenylindole-stained cells to investigate the cytotoxicity, cell viability, migratory potential and apoptotic cell death, respectively, of cells treated with different concentrations of α-santalol or dimethyl sulfoxide for different time periods.

Results: Results showed that α-santalol treatment significantly reduced SK-MEL2 cell viability and wound-healing ability, while only affecting HaCaT cells at higher concentrations. α-Santalol treatment also disrupted cytoskeletal structure and F-actin in SK-MEL2 cells, whereas HaCaT cells were more resistant to this effect.

Conclusion: The selective growth-inhibitory and anti-migratory effects of α-santalol on human melanoma cells warrants future studies to systemically explore the mechanistic details involved.

Background/aim: This study evaluated the impact of the 2018 S3 guideline for endometrial cancer on clinical management using cancer registry data from Hamburg.

Patients and methods: This retrospective cohort study included 2,249 patients with primary endometrial cancer (2014-2022), divided into a pre-guideline group (2014-2017) and a post-guideline (2019-2022) group. Quality indicators included parametrial resection rates, lymphadenectomy utilization, and radiation therapy application. Poisson regression models assessed changes with adjustment for age, treatment center, and tumor grading.

Results: Patients without parametrial resection increased from 88% to 93% [adjusted effect estimate: 1.06, 95% confidence interval (CI)=0.94-1.19]. Patients without lymphadenectomy increased from 76% to 88% [adjusted effect estimate: 1.13, 95%CI=0.93-1.37]. Radiation therapy use increased from 95% to 100%. Changes aligned with guideline recommendations but were not statistically significant. Poorly differentiated tumors showed significantly different treatment patterns.

Conclusion: Practice patterns in Hamburg moved closer to S3 Guideline on the Management of Primary Endometrial Cancer after 2018, although statistical significance was not achieved. Improved registry documentation likely contributed to observed trends. Larger studies with longer follow-up are required to clarify the clinical impact of guideline implementation.

Background/aim: Tamoxifen remains a first-line treatment for estrogen receptor-positive breast cancer. Emerging evidence indicates that aberrant 5-methylcytosine (m⁵C) modification of RNAs contributes to chemotherapeutic resistance in various types of cancer, however their role in determining tamoxifen resistance in breast cancer remains elusive.

Materials and methods: We measured global m⁵C RNA methylation and expression of its regulating enzymes in tamoxifen-sensitive (MCF-7) versus tamoxifen-resistant cells (MCF-7 Tam1). Expression of the most significantly dysregulated enzyme NOP2/Sun RNA methyltransferase family member 7 (NSUN7), the key m⁵C writer methyltransferase, was depleted using siRNA-mediated knockdown. Functional assays were performed to measure sensitivity to tamoxifen, cell migration, and colony-forming potential. RNA sequencing followed by enrichment and network analysis identified NSUN7-regulated pathways and hub genes. Finally, the prognostic relevance of hub genes was assessed using the Gene Expression Profiling Interactive Analysis platform.

Results: Tamoxifen-resistant cells exhibited a significant elevation in global m⁵C levels and expression of NSUN7. siRNA-mediated reduction of NSUN7 significantly restored sensitivity to tamoxifen, reducing the half-maximal inhibitory concentration by ~50%, and significantly inhibited cell migration and colony-forming potential. Transcriptomic profiling and enrichment analysis identified that NSUN7 targets were enriched in crucial pathways, including mitogen-activated protein kinase pathway, phosphatidylinositol signaling, cell cycle, and focal adhesion. Notably, NSUN7 depletion caused dysregulation in the expression of genes implicated in tamoxifen resistance, such as brain acid-soluble protein 1 (BASP1), tissue inhibitor of metalloproteinase 3 (TIMP3), ajuba LIM protein (AJUBA), S-phase kinase-associated protein 2 (SKP2) and yes-associated protein 1 (YAP1). Network analysis further identified NSUN7-regulated hub genes significantly associated with disease prognosis.

Conclusion: Our study identified that NSUN7 regulates key oncogenic pathways associated with tamoxifen resistance and metastasis. Its suppression enhanced tamoxifen sensitivity and reduced metastatic potential, collectively highlighting NSUN7 as a novel driver of tamoxifen resistance and a potent therapeutic target in estrogen receptor-positive breast cancer.

Background/aim: Ramucirumab (RAM) is administered either alone or in combination with paclitaxel (PTX) to treat advanced or recurrent gastric cancer. Patients receiving RAM may develop venous thromboembolism (VTE) and require close monitoring. We aimed to identify a practical D-dimer threshold for determining when to perform lower-extremity ultrasonography in patients with advanced or recurrent gastric cancer receiving chemotherapy, including RAM.

Patients and methods: This retrospective study included 112 of 162 patients with advanced or recurrent gastric cancer who received RAM at Ogaki Municipal Hospital (Ogaki, Japan) between July 2015 and February 2024. Patient characteristics, D-dimer trends, ultrasonography use, and the number of VTE events were assessed. The D-dimer cutoff was estimated using receiver operating characteristic (ROC) analysis in a subset of patients who underwent ultrasonography for suspected VTE.

Results: Of the treatment regimens, 106 patients received RAM plus PTX, and six received RAM alone. VTE occurred in three patients (2.6%) during the treatment period. A total of 53 lower-extremity ultrasonography examinations were performed to evaluate suspected deep vein thrombosis (DVT). The ROC-derived candidate D-dimer cutoff for predicting VTE was 4.4 μg/ml [area under the curve (AUC)=0.853; 95% confidence interval (CI)=0.479-1.000].

Conclusion: This exploratory study suggests that a D-dimer level ≥4.4 μg/ml may serve as a candidate indicator for determining the need for lower-extremity ultrasonography in RAM-treated patients with gastric cancer. However, the small number of VTE events and the selective nature of the ROC cohort limit the generalizability. Validation in larger studies is needed.