Cancer Biotherapy and Radiopharmaceuticals最新文献

Purpose: Immunohistochemistry (IHC) is the main method to detect human epidermal growth factor receptor 2 (HER2) expression levels. However, IHC is invasive and cannot reflect HER2 expression status in real time. The aim of this study was to construct and verify three types of radiomics models based on ¹⁸F-fuorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) imaging and to evaluate the predictive ability of these radiomics models for the expression status of HER2 in patients with gastric cancer (GC). Patients and Methods: A total of 118 patients with GC were enrolled in this study. ¹⁸F-FDG PET/CT imaging was performed prior to surgery. The LIFEx software package was applied to extract PET and CT radiomics features. The minimum absolute contraction and selection operator (least absolute shrinkage and selection operator [LASSO]) algorithm was used to select the best radiomics features. Three machine learning methods, logistic regression (LR), support vector machine (SVM), and random forest (RF) models, were constructed and verified. The Synthetic Minority Oversampling Technique (SMOTE) was applied to address data imbalance. Results: In the training and test sets, the area under the curve (AUC) values of the LR, SVM, and RF models were 0.809, 0.761, 0.861 and 0.628, 0.993, 0.717, respectively, and the Brier scores were 0.118, 0.214, and 0.143, respectively. Among the three models, the LR and RF models exhibited extremely good prediction performance. The AUC values of the three models significantly improved after SMOTE balanced the data. Conclusions: ¹⁸F-FDG PET/CT-based radiomics models, especially LR and RF models, demonstrate good performance in predicting HER2 expression status in patients with GC and can be used to preselect patients who may benefit from HER2-targeted therapy.

Background: Hsa_circ_0028861, a newly discovered serum exosome circular RNA (circRNA), is greatly reduced in the serum of patients with hepatocellular carcinoma (HCC). However, the exact role of hsa_circ_0028861 in the progression of liver cancer is still unknown. Materials and Methods: Thirty patients with HCC were enrolled in this study. Hsa_circ_0028861 expression was explored via real-time polymerase chain reaction (PCR) assay. The influence of curcumol on HCC cells were tested using CCK-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, cell wound healing assay, and migration assay, respectively. The related mechanism was determined by Western blot. A xenograft tumor model was constructed, and mice were administrated with curcumol. Results: The expression of hsa_circ_0028861 in tumor tissues was elevated of patients with HCC and in HCC cells. Curcumol treatment decreased the expression of hsa_circ_0028861 in HCC cells. Curcumol treatment could largely suppress the viability, proliferation, and migration of HCC cells by reducing hsa_circ_0028861 expression and mediating the epithelial-mesenchymal transition (EMT) process. Curcumol also effectively restrained tumor growth in the HCC mice model. Conclusions: Curcumol exerted an inhibitory role in HCC progression by downregulating hsa_circ_0028861 expression and mediating the EMT process, which provides evidence for screening new therapeutic targets and drug therapies for HCC treatment.

Introduction: Personalizing neoadjuvant therapy for locally advanced rectal cancer (LARC) requires identifying biomarkers that predict treatment response. This study evaluates soluble immune checkpoints (sICPs) as predictive markers for neoadjuvant treatment response in LARC patients located in the middle and lower rectum. Materials and Methods: This prospective study included patients diagnosed with clinical stage T3 or T4 rectal cancer (RC) based on pelvic magnetic resonance imaging, with or without pelvic lymph node involvement. The modified Ryan scoring system was used to assess the response to neoadjuvant chemoradiotherapy (nCRT). Blood samples were collected from all RC patients before initiating nCRT. Various sICPs (sCD25, 4-1BB, B7.2, free active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, galectin-9), along with age, gender, stage, blood cell counts, and biochemical variables, were recorded and compared based on tumor regression grade (TRG). Results: Among 38 participants, lymphocyte count was higher, and platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and platelet count were lower in patients with complete/near-complete response (TRG 0/1). In addition, TRG 0/1 patients had significantly lower levels of soluble galectin-9 than TRG 2/3 patients. Furthermore, platelet count was the only parameter that showed a significant difference among the three groups (TRG 0/1, TRG 2, and TRG 3). PLR demonstrated the highest sensitivity and specificity, with >80% for both measures. Conclusions: Lymphocyte count, PLR, NLR, platelet count, and galectin-9 may help predict favorable neoadjuvant treatment response in LARC patients, although without providing a definitive outcome. Personalized therapy based on these markers could enhance treatment decision making in LARC management.

Background: Trigger transposable element-derived 1 (TIGD1) is a human-specific gene, but no studies have been conducted to determine its mechanism of action. Our aim is to ascertain the function and mode of action of TIGD1 in the development of colon cancer. Materials and Methods: The authors used bioinformatics to analyze the relationship between TIGD1 and the clinical characteristics of colon cancer, as well as its prognosis. A series of cell assays were conducted to assess the function of TIGD1 in the proliferation and migration of colon cancer, and flow cytometry was used to explore its effects on apoptosis and the cell cycle. Results: The authors discovered that the expression of TIGD1 was remarkably elevated in colon cancer. Clinical correlation analysis demonstrated that TIGD1 expression was elevated in the tissues of advanced-stage patients, and it was remarkably elevated in individuals with both lymph node and distant metastasis. Further, the authors found that individuals showing elevated TIGD1 expression levels had a shortened survival time. Univariate and multivariate Cox regression analyses revealed that TIGD1 was an independent prognostic factor. Overexpression of the TIGD1 gene remarkedly enhances the proliferation and metastasis of colon cancer cells and suppresses apoptosis. In addition, the overexpression of TIGD1 can enhance the transition of tumor cells from the G1 toward the S phase. Western blot results suggested that TIGD1 may promote the malignant activity of colon cancer cells via the Wnt/β-catenin signaling pathway, Bcl-2, N-cadherin, BAX, E-cadherin, CDK6, and CyclinD1. Conclusions: TIGD1 may be an independent prognostic factor in the advancement of colon cancer, and therefore function as a therapeutic target.

Background: The predictive value of Lipiodol was evaluated for response evaluation of hepatocellular carcinoma (HCC) treated with conventional transarterial chemoembolization (cTACE) by analysis of the enhancement pattern during angiography and in postinterventional computed tomography (CT). Materials and Methods: This retrospective study included 30 patients (mean age 63 years, range: 36 to 82 years, 22 males) with HCC. Patients received three Lipiodol-based cTACE sessions, each followed by an unenhanced CT within 24-h. Contrast-enhanced magnetic resonance imaging (MRI) was acquired before and after the treatment to determine tumor response. Lipiodol enhancement pattern, tumor vascularization, and density were evaluated by angiography and CT. Initial tumor size and response to cTACE were analyzed by MRI according to modified response evaluation criteria in solid tumors (mRECIST) in a 4-week follow-up. Results: Analysis of HCC lesions (68 lesions in 30 patients) during cTACE revealed clear visibility and hypervascularization in angiography as a potential independent parameter able to predict tumor response. A significant correlation was found for response measurements by volume (p = 0.012), diameter (p = 0.006), and according to mRECIST (p = 0.039). The amount of Lipiodol and enhancement pattern in postinterventional CT did not correlate with therapy response. Measurements of Hounsfield unit values after cTACE do not allow sufficient prediction of the tumor response. Conclusion: Hypervascularized HCC lesions with clear visibility after Lipiodol administration in the angiography respond significantly better to cTACE compared to hypo- or nonvascularized lesions.

Introduction: Hepatocellular carcinoma is a prevalent contributor to global mortality rates. The main palliative treatments are trans-arterial chemoembolization and selective intra-arterial radionuclide therapy. Methods: A novel freeze-dried nonradioactive microsphere kit formulation has been developed, and the behavior and therapeutic potential of ¹⁸⁸Re microspheres have been assessed. The microspheres were labeled with fluorescein isothiocyanate (FITC) and ¹⁸⁸ReO₄^-. The uptake of FITC microspheres by HepG2 cells was examined at various time intervals. The impact of ¹⁸⁸Re microspheres on cell viability and the mode of cell death were investigated with HepG2 cells using MTT and Annexin FITC-V/propidium iodide (PI) apoptosis assay. Results: The labeling efficiency of microspheres was more than 99% with FITC and ¹⁸⁸ReO₄^-. The maximum uptake of FITC microspheres by HepG2 cells was achieved at 6 h. The exposure to ¹⁸⁸Re microspheres has shown a decrease in cellular viability from 77.81% ± 0.015% to 42.03% ± 0.148% at 192 h of incubation (∼11 half-lives). The cellular uptake of ¹⁸⁸Re microspheres was 0.255-0.901 MBq. These values were concordant with Annexin FITC-V/PI apoptosis assay. At 192 h, 53.28% ± 0.01% of cells entered the apoptotic phase after treatment with ¹⁸⁸Re microspheres, and only 39.34% ± 0.02% of cells remained viable. However, in the cells treated with ¹⁸⁸ReO₄^- alone, 74.86% ± 0.005% of cells were viable, and only 24.75% ± 0.577% of cells were in the early apoptotic phase at 192 h. Conclusion: The data revealed that ¹⁸⁸Re microspheres treatment led to significant growth inhibition in HepG2 cells compared with ¹⁸⁸ReO₄^-.

Purpose: This study aims to evaluate the short-term outcomes and prognosis and the cardiac safety of pegylated liposomal doxorubicin (PLD)-based neoadjuvant chemotherapy (NAC) compared with epirubicin-based therapy in breast cancer treatment. Methods: In total, 304 patients diagnosed with stages II and III breast cancer were enrolled that included 97 cases treated with PLD and 207 controls treated with epirubicin in NAC. The effectiveness of the antibreast cancer treatment was evaluated using overall survival (OS) and disease-free survival (DFS) metrics, whereas cardiac toxicity was measured through the left ventricular ejection fraction (LVEF) and electrocardiogram (ECG) assessments. Results: The 5-year DFS and OS rates in the PLD group were 84.5% and 88.7% (with 15 recurrences and 11 deaths), respectively, whereas in the control group, these rates were 72.9% and 79.2% (with 56 recurrences and 43 deaths). Regarding cardiac toxicity, there was no significant difference in ECG abnormalities or LVEF decline between the two groups. Conclusions: The study suggests that PLD-based NAC may provide substantial benefits in terms of DFS and OS, along with a safe cardiac toxicity profile, in patients with stage II-III breast cancer.

Background: Sevoflurane (Sev), a volatile anesthetic agent, is widely used in neurosurgery for anesthesia maintenance, accompanied with antitumor activity postanesthesia in multiple human cancers, including glioma. However, the molecular mechanism of Sev in glioma is largely unclear, including associated informative noncoding RNAs, such as long noncoding RNAs (lncRNA) and microRNAs (miRNAs). Methods: Expression of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), miRNA (miR)-146b-5p, and stanniocalcin-1 (STC1) was measured by real-time quantitative polymerase chain reaction and Western blotting. Cell proliferation, apoptosis, migration, and invasion in vitro were examined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, fluorescence-activated cell sorting method, and transwell assays, respectively. Tumor growth in vivo was determined by xenograft models. The direct interaction between genes was confirmed by dual-luciferase reporter assay. Results: Sev enhanced apoptotic rate, but inhibited cell viability, migration, and invasion abilities of human glioma A172 and U251 cells in vitro, as well as tumor growth inhibition in vivo. The tumor-suppressive role of Sev in glioma was accompanied with downregulated KCNQ1OT1 and STC1, and upregulated miR-146b-5p. Overexpression of KCNQ1OT1 through transfection reversed, while KCNQ1OT1 silencing aggravated the antitumor role of Sev in A172 and U251 cells. Moreover, KCNQ1OT1-mediated tumor-promoting activity in A172 and U251 cells under Sev treatment was abrogated by miR-146b-5p restoration or STC1 deletion. Essentially, KCNQ1OT1 could positively regulate STC1 by acting as miR-146b-5p decoy. Conclusion: KCNQ1OT1 knockdown mediated the role of Sev in glioma cell proliferation, apoptosis, migration, and invasion both in vitro and in vivo through miR-146b-5p/STC1 pathway.

Background: Glioma is a devastating disease with the worst prognosis among human malignant tumors. Although temozolomide (TMZ) improves the overall survival of glioma patients, there are still many glioma patients who are resistant to TMZ. In this study, we focused on the effect of apigenin (API) and TMZ on glioma cells in vitro and in vivo, and we studied the underlying molecular mechanisms. Materials and Methods: To investigate the effect of API on glioblastoma cell proliferation, cell viability was assessed after glioma cells were incubated with various concentrations of API with or without TMZ using MTT assays. Then, we explored the synergistic effect of API and TMZ on glioma cell cycle, apoptosis, and migration. To investigate the molecular mechanism behind the synergism of API and TMZ, we examined the related genes of the major signaling pathways involved in glioma pathogenesis by Western blotting. Results: In this study, we found that API significantly suppressed the proliferation of glioma cells in a dose- and time-dependent manner. Combining API and TMZ significantly induced glioma cells arrest at the G2 phase and inhibited glioma cells proliferation compared with API or TMZ alone. In addition, API promoted the ability of TMZ to induce glioma cells apoptosis and inhibit glioma cells invasion. Furthermore, compared with treatment with individual agents, the combination of API and TMZ significantly inhibited the growth of subcutaneous tumors in mice. These results implied that API could synergistically suppress the growth of glioma cells when combined with TMZ. Combining API and TMZ significantly inhibited the protein expression of p-AKT, cyclin D1, Bcl-2, Matrix Metallopeptidase 2, and Matrix Metallopeptidase 9. Conclusion: API and TMZ synergistically inhibited glioma growth through the PI3K/AKT pathway.

Background: MicroRNA (miR)-519d-3p suppresses tumor development, however, its role in oral squamous cell carcinoma (OSCC) has yet to be determined. Materials and Methods: OSCC and adjacent tissues were collected (n = 45 for adjacent; n = 21 for Stage I-II OSCC; n = 24 for Stage III-IV OSCC). The cell viability, proliferation, and cell cycle of OSCC were, respectively, assessed by the Cell Counting Kit-8 (CCK-8), colony formation assay, and flow cytometry. Relative expressions of cell cycle-regulated proteins (Cyclin D1 [CCND1], CDK4, and CDK6) and miR-519d-3p were measured with Western blot and quantitative real-time polymerase chain reaction as needed. Dual-luciferase reporter assay was performed to verify the prediction of TargetScan that miR-519d-3p and CCND1 shared potential binding sites. Correlation analysis between miR-519d-3p and CCND1 was performed with Pearson's correlation test. Results: In OSCC tissues, downregulating miR-519d-3p expression correlated with a higher tumor grade. Upregulating miR-519d-3p expression inhibited OSCC cell viability and proliferation, increased cells in G0/G1 phase and reduced those in S/G2 phase, and downregulated the expressions of cell cycle-related protein (CDK4, CDK6). CCND1 was the target gene of miR-519d-3p, and overexpressed CCND1 reversed the effects of upregulation of miR-519d-3p on suppressing the viability, proliferation, and cell cycle of OSCC cells. Conclusions: miR-519d-3p upregulation suppressed the cell viability, proliferation, and G1/S cell cycle transition of OSCC through targeting CCND1. The current findings provide a possible clinical option for OSCC treatment.