Progression of radio-labeled molecular imaging probes targeting chemokine receptors.

Chemokine receptors are significantly expressed in the surface of most inflammatory cells and tumor cells. Guided by chemokines, inflammatory cells which express the relevant chemokine receptors migrate to inflammatory lesions and participate in the evolution of inflammation diseases. Similarly, driven by chemokines, immune cells infiltrate into tumor lesions not only induces alterations in the tumor microenvironment, disrupting the efficacy of tumor therapies, but also has the potential to selectively target tumoral cells and diminish tumor progression. Chemokine receptors, which are significantly expressed on the surface of tumor cell membranes, are regulated by chemokines and initiate tumor-associated signaling pathways within tumor cells, playing a complex role in tumor progression. Based on the antagonists targeting chemokine receptors, radionuclide-labeled molecular imaging probes have been developed for the emerging application of molecular imaging in diseases such as tumors and inflammation. The value and limitations of molecular probes in disease imaging are worth reviewing.

Prediction of HER2 Expression in Gastric Adenocarcinoma Based On Preoperative Noninvasive Multimodal 18F-FDG PET/CT Imaging.

RATIONALE AND OBJECTIVES: This study aims to investigate the role of a flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) multimodal radiomics model in predicting the status of human epidermal growth factor receptor 2 (HER2) expression preoperatively in cases of gastric adenocarcinoma. MATERIALS AND METHODS: This retrospective study included 133 patients with gastric adenocarcinoma who were classified into training (n = 93) and validation (n = 40) cohorts in a ratio of 7:3. Features were selected using Least Absolute Shrinkage and Selection Operator and Extreme Gradient Boosting (XGBoost) methods; further, prediction models were constructed using logistic regression and XGBoost. These models were evaluated and validated using area under the curve (AUC), decision curves, and calibration curves to select the best-performing model. RESULTS: Six different models were established to predict HER2 expression. Among these, the comprehensive model, which integrates seven clinical features, one CT feature, and five PET features, demonstrated AUC values of 0.95 (95% confidence interval [CI]: 0.89-1.00) and 0.76 (95% CI: 0.52-1.00) in the training and validation cohorts, respectively. Compared with other models, this model exhibited a superior net benefit on the decision curve and demonstrated good alignment agreement with the observed values on the calibration curve. Based on these findings, we constructed a nomogram for visualizing the model, providing a noninvasive preoperative method for predicting HER2 expression. CONCLUSION: The preoperative 18F-FDG PET/CT multimodal radiomics model can effectively predict HER2 expression in patients with gastric adenocarcinoma, thereby guiding clinical decision-making and advancing the field of precision medicine.

Identification and validation of COL6A1 as a novel target for tumor electric field therapy in glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain malignancy. Novel therapeutic modalities like tumor electric field therapy (TEFT) have shown promise, but underlying mechanisms remain unclear. The extracellular matrix (ECM) is implicated in GBM progression, warranting investigation into TEFT-ECM interplay. METHODS: T98G cells were treated with TEFT (200 kHz, 2.2 V/m) for 72 h. Collagen type VI alpha 1 (COL6A1) was identified as hub gene via comprehensive bioinformatic analysis based on RNA sequencing (RNA-seq) and public glioma datasets. TEFT intervention models were established using T98G and Ln229 cell lines. Pre-TEFT and post-TEFT GBM tissues were collected for further validation. Focal adhesion pathway activity was assessed by western blot. Functional partners of COL6A1 were identified and validated by co-localization and survival analysis. RESULTS: TEFT altered ECM-related gene expression in T98G cells, including the hub gene COL6A1. COL6A1 was upregulated in GBM and associated with poor prognosis. Muti-database GBM single-cell analysis revealed high-COL6A1 expression predominantly in malignant cell subpopulations. Differential expression and functional enrichment analyses suggested COL6A1 might be involved in ECM organization and focal adhesion. Western blot (WB), immunofluorescence (IF), and co-immunoprecipitation (Co-IP) experiments revealed that TEFT significantly inhibited expression of COL6A1, hindering its interaction with ITGA5, consequently suppressing the FAK/Paxillin/AKT pathway activity. These results suggested that TEFT might exert its antitumor effects by downregulating COL6A1 and thereby inhibiting the activity of the focal adhesion pathway. CONCLUSION: TEFT could remodel the ECM of GBM cells by downregulating COL6A1 expression and inhibiting focal adhesion pathway. COL6A1 could interact with ITGA5 and activate the focal adhesion pathway, suggesting that it might be a potential therapeutic target mediating the antitumor effects of TEFT.

[An epidemiological survey of malignant tumors among fluoride-exposed workers in aluminum industry].

OBJECTIVE: To investigate the incidence of malignant tumors among fluoride-exposed workers in aluminum industry. METHODS: Sampling points were set in the working positions at different radii around an workshop for treating the waste gas from aluminum electrolysis, and the concentrations of fluoride ions, aluminum, and benzo[a]pyrene (B[a]P) in air were measured by electrode method, atomic absorption spectrophotometry, and high performance liquid chromatography, respectively. The incidence of tumors among the workers in the aluminum plant from 1995 to 2009 was investigated by questionnaires and medical records and then statistically analyzed. RESULTS: There was a negative correlation between the concentrations of fluoride and aluminum and the radius around the fluoride source at each sampling point. B[a]P was not detected at each sampling point. The crude incidence rate of tumors among factory workers was 117.95/100 000 (standardized rate = 58.81/100 000); the standardized incidence rate of tumors was higher in female workers than in male workers (male-to-female ratio = 1:2.64). The peak age of onset of tumors was 40 ∼ 49 years. The most and second most common tumors were liver cancer and lung cancer in male workers and breast cancer and lung cancer in female workers. Compared with the unexposed population in the city where the aluminum plant was located, the female fluoride-exposed workers had an increased tumor incidence, 2.14 times that of the city's average level, and the fluoride-exposed workers had a younger age of onset of tumors and approximately the same types of tumors. CONCLUSION: Fluoride exposure may lead to an increasing trend in tumor incidence among female workers in aluminum industry.

Long-term exposure to low level of fluoride induces apoptosis via p53 pathway in lymphocytes of aluminum smelter workers.

Long-term occupational exposure to low level of fluoride can induce oxidative stress and apoptosis in many cells, including lymphocyte. However, the underlying mechanism remains unclear. Hence, this study was designed to explore the potential oxidative stress and apoptosis of long-term occupational exposure to low level of fluoride in aluminum smelter workers. A total of 120 aluminum smelter workers were recruited in control, low-, middle-, and high-fluoride exposure groups with 30 workers for each group. The peripheral blood samples were collected, centrifuged, and isolated to obtain serum and lymphocyte suspensions. The air and serum fluoride concentrations were detected by fluoride ion-selective electrode method. The lymphocytic apoptosis rate, DNA damage, oxidative stress, and mRNA levels of p53, Bcl-2, and Bax were assessed by Annexin V/PI staining, comet assay, attenuated total reflectance Fourier transform infrared spectroscopy and real-time polymerase chain reaction, respectively. Results showed that the air and serum fluoride concentrations of fluoride-exposed groups were higher than those of the control group (p < 0.05). Fluoride exposure might induce apoptosis, DNA damage and oxidative stress in a dose-dependent manner in lymphocytes (p < 0.05). The expression levels of p53 and Bax were increased with fluoride exposure in lymphocytes (p < 0.05), whereas the Bcl-2 expression was decreased but not significantly. Taken together, these observations indicate that long-term occupational exposure to low level of fluoride may lead to oxidative stress and induce apoptosis through the p53-dependent pathway in peripheral blood lymphocytes of aluminum smelter workers. Serum fluoride level may be the potential biomarker of fluoride exposure.