Journal of cancer research and therapeutics最新文献

Objective: This study aimed to evaluate the effect of exosomes derived from gastric cancer cells on the phenotypic transformation of hepatic stellate cells (HSCs) and the effect of HSC activation on the malignant behavior of gastric cancer cells, including its molecular mechanism.

Methods: Exosomes derived from the human gastric adenocarcinoma cell line AGS were extracted and purified by polymer precipitation and ultrafiltration, respectively. The exosomes' morphologic characteristics were observed using transmission electron microscopy, particle size was determined through nanoparticle-tracking analysis, and marker proteins were detected using western blotting. Exosome uptake by LX-2 HSCs was observed through fluorescence-based tracing. Reverse transcription quantitative PCR (RT-qPCR) was used to detect the messenger RNA (mRNA) expression of alpha-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). Using functional assays, the effects of LX-2 HSC activation on the biological behavior of malignant gastric cancer cells were evaluated. The effects of LX-2 HSC activation on the protein expression of epithelial-mesenchymal transition (EMT)-related genes and β-catenin were evaluated via western blotting.

Results: The extracted particles conformed to the definitions of exosomes and were thus considered gastric cancer cell-derived exosomes. Fluorescence-based tracing successfully demonstrated that exosomes were enriched in LX-2 HSCs. RT-qPCR revealed that the mRNA expression of the cancer-associated fibroblast markers α-SMA and FAP was significantly increased. LX-2 HSC activation considerably enhanced gastric cancer cell proliferation, invasion, and migration. Western blotting showed that the expression of the EMT-related epithelial marker E-cadherin was significantly downregulated, whereas the expression of interstitial markers (N-cadherin and vimentin) and β-catenin was remarkably upregulated in gastric cancer cells.

Conclusion: Exosomes derived from gastric cancer cells promoted phenotypic transformation of HSCs and activated HSCs to become tumor-associated fibroblasts. Gastric cancer cell-derived cells significantly enhanced gastric cancer cell proliferation, invasion, and migration after HSC activation, which may promote EMT of gastric cancer cells through the Wnt/β-catenin pathway.

Background: Protein arginine deiminase 3 (PADI3) is involved in various biological processes of human disease. PADI3 has recently received increasing attention due to its role in tumorigenesis. In a previous study, we found that PADI3 plays a tumor suppressor role in colon cancer by inducing cell cycle arrest, but its critical role and mechanism in cancer metastasis remain obscure. In this study, we fully studied the role of PADI3 in colon cancer cell metastasis.

Methods: The expression levels of related proteins were detected by Western blotting, and Transwell and wound healing assays were used to examine the cell migration ability. Flow cytometry was used to measure and exclude cell apoptosis-affected cell migration. Both overexpression and rescue experiments were employed to elucidate the molecular mechanism of CKS1 in colon cancer cells.

Results: The expression levels of PADI3 and CKS1 are negatively related, and PADI3 can promote CKS1 degradation in a ubiquitin-dependent manner. PADI3 can suppress colon cancer cell migration and reduce the wound healing speed by inhibiting CKS1 expression. The molecular mechanism showed that CKS1 can promote EMT by increasing Snail and N-cadherin expression and suppressing E-cadherin expression. PADI3, as a suppressor of CKS1, can block the process of EMT by impairing CKS1-induced Snail upregulation and E-cadherin downregulation; however, the expression of N-cadherin cannot be rescued.

Conclusions: CKS1 promotes EMT in colon cancer by regulating Snail/E-cadherin expression, and this effect can be reversed by PADI3 via the promotion of CKS1 degradation in a ubiquitylation-dependent manner.

Background: We analyzed the prevalence and genotype distribution of multiple- or single-type cervical human papillomavirus (HPV) infections in a population of women in mainland China.

Methods: PubMed, MEDLINE, and Chinese databases (CNKI, VIP, and Wan Fang) were searched for studies on HPV prevalence and the examination of this relationship. All analyses were performed using STATA (version 12.0). Data from selected studies were extracted into tables, and all included studies were weighted and summarized.

Results: Thirty studies were included. The prevalence of single types (10.4%) and multiple types (4.7%) primarily occurred in healthy Chinese women, in which the dominant single-type infection was HPV16 (1.6%), 52 (1.5%), 58 (1.0%), and 18 (0.5%), and the dominant type of multiple infection was HPV16 (0.7%), 52 (0.7%), 58 (0.6%), and 18 (0.3%). The prevalence in North and South China was 14.3%, in which the prevalence of the single type was 10.41% and 8.27%, and the prevalence of multiple types was 4.00% and 6.52%, respectively.

Conclusion: Mainland China exhibits unique type-specific single and multiple HPV infections. Overall single or multiple HPV prevalence varied across regions of China, whereas type-specific HPV differences were relatively small.

Abstract: This expert consensus reviews current literature and provides clinical practice guidelines for the diagnosis and treatment of multiple ground glass nodule-like lung cancer. The main contents of this review include the following: ① follow-up strategies, ② differential diagnosis, ③ diagnosis and staging, ④ treatment methods, and ⑤ post-treatment follow-up.

Background: We found that the occurrence of hepatocellular carcinoma (HCC) has increased significantly in non-cirrhotic individuals, with HCC being frequently overlooked or misdiagnosed. Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is known to have a high diagnostic quality in high-risk HCC patients. Therefore, we aimed to compare the detection accuracy of CEUS LI-RADS for HCC between low- and high-risk individuals, to confirm its value in low-risk patients at increased risk of HCC, but not yet included in the high-risk groups of LI-RADS. In addition, since CEUS LR-4 and LR-M categories contain a relatively high proportion of HCC, and serum alpha-fetoprotein (AFP) is the most commonly used biomarker for HCC, and the clinically valid, we attempted to further improve the early diagnostic capability of CEUS LI-RADS for HCC in the low-risk and high-risk patients by combining CEUS LR-4 and LR-M categories with AFP.

Methods: We defined high-risk groups (HR)-included in the high-risk patients of LI-RADS, low-risk groups (LR)-not included in the high-risk patients of LI-RADS and enrolled 189 HCC patients with LR and HR settings in a retrospective study. All lesions were confirmed histopathologically. The CEUS LI-RADS accuracy for detecting HCC in these two patients was compared. In addition, the diagnostic algorithm in our study was proposed (for CEUS LR-4 and LR-M patients with AFP>20 ng/ml). we analyzed the ability of CEUS LI-RADS as a valid method of establishing the early diagnosis of HCC in LR and HR patients by combining LR-4 and LR-M categories with AFP.

Results: Through comparative analysis, the specificity of the CEUS LR-5 category for HCC in the HR group was 78.4%, whereas in the LR group, it was 94.2%. Meanwhile, the sensitivity (63.2% vs. 63.0%) and positive predictive value (PPV) (75.0% vs. 88.7%) did not differ between the LR and HR groups ( P = 0.990, P = 0.299). It is noteworthy that there were the high proportion of HCC in CEUS LR-4 and LR-M categories in our cases and when we combined CEUS LR-4 and LR-M categories with AFP significantly improved the sensitivity by 21.0% (84.2%) in the LR group, and by 16.0% (79.0%) in the HR group, with statistically difference in sensitivity after combination in the HR group ( P = 0.014).

Conclusions: The CEUS LR-5 category has real meaningful utility in the diagnosis of HCC in both LR and HR patients. The early detection power of the CEUS LI-RADS category for HCC patients was further increased when the CEUS LR-4 and LR-M categories were combined with elevated AFP.

Purpose: Malignant and aggressive, small cell lung cancer (SCLC) constitutes about 15% of all diagnosed lung cancer cases. With primary therapeutic options such as chemotherapy accompanied by debilitating side effects, interest has been soaring in the therapeutic competencies of herbs. The pharmacological driving force behind the beneficial properties of Nigella sativa is the quinone, thymoquinone (TQ). The anti-cancer effects of TQ on different cancers have been extensively studied. Nonetheless, only one paper in the entire National Center for Biotechnology Information (NCBI) database describes its effects on SCLC. A more detailed investigation is required.

Methods: The current study examined the impact of TQ in vitro on five SCLC cell lines and in vivo in a nude mouse xenograft model. The following in vitro effects of TQ on SCLC were evaluated: (a) cell viability; (b) apoptosis; (c) cell cycle arrest; (d) intracellular reactive oxygen species (ROS) levels, and (e) protein expression in concomitant signaling pathways. For the in vivo effects of TQ on SCLC, (a) tumor volume was measured, and (b) selected protein expression in selected concomitant signaling pathways was determined by Western blotting.

Result: In general, TQ reduced cell viability, induced apoptosis and cell cycle arrest, depleted ROS, and altered protein expression in associated signaling pathways. Furthermore, TQ exhibited a tumor-suppressive effect in an H446 SCLC xenograft model.

Conclusion: The cytotoxic impact of TQ arising from anti-cancer mechanisms was elucidated. The positive results obtained in this study warrant further investigation.

Objective: To establish a prediction model of lung cancer classification by computed tomography (CT) radiomics with the serum tumor markers (STM) of lung cancer.

Materials and methods: Two-hundred NSCLC patients were enrolled in our study. Clinical data including age, sex, and STM (squamous cell carcinoma [SCC], neuron-specific enolase [NSE], carcinoembryonic antigen [CEA], pro-gastrin-releasing peptide [PRO-GRP], and cytokeratin 19 fragment [cYFRA21-1]) were collected. A radiomics signature was generated from the training set using the least absolute shrinkage and selection operator (LASSO) algorithm. The risk factors were identified using multivariate logistic regression analysis, and a radiomics nomogram based on the radiomics signature and clinical features was constructed. The capability of the nomogram was evaluated using the training set and validated using the validation set. A correction curve and the Hosmer-Lemeshow test were used to evaluate the predictive performance of the radiomics model for the training and test sets.

Results: Twenty-nine of 1234 radiomics parameters were screened as important factors for establishing the radiomics model. The training (area under the curve [AUC] = 0.925; 95% confidence interval [CI]: 0.885-0.966) and validation sets (AUC = 0.921; 95% CI: 0.854-0.989) showed that the CT radiomics signature, combined with STM, accurately predicted lung squamous cell carcinoma and lung adenocarcinoma. Moreover, the logistic regression model showed good performance based on the Hosmer-Lemeshow test in the training (P = 0.954) and test sets (P = 0.340). Good calibration curve consistency also indicated the good performance of the nomogram.

Conclusion: The combination of the CT radiomics signature and lung cancer STM performed well for the pathological classification of NSCLC. Compared with the radiomics signature method, the nomogram based on the radiomics signature and clinical factors had better performance for the differential diagnosis of NSCLC.

Objectives: This study aimed to evaluate the accuracy of percutaneous computed tomography (CT)-guided puncture based on machine vision and augmented reality in a phantom.

Materials and methods: The surgical space coordinate system was established, and accurate registration was ensured using the hierarchical optimization framework. Machine vision tracking and augmented reality display technologies were used for puncture navigation. CT was performed on a phantom, and puncture paths with three different lengths were planned from the surface of the phantom to the metal ball. Puncture accuracy was evaluated by measuring the target positioning error (TPE), lateral error (LE), angular error (AE), and first success rate (FSR) based on the obtained CT images.

Results: A highly qualified attending interventional physician performed a total of 30 punctures using puncture navigation. For the short distance (4.5-5.5 cm), the TPE, LE, AE, and FSR were 1.90 ± 0.62 mm, 1.23 ± 0.70 mm, 1.39 ± 0.86°, and 60%, respectively. For the medium distance (9.5-10.5 cm), the TPE, LE, AE, and FSR were 2.35 ± 0.95 mm, 2.00 ± 1.07 mm, 1.20 ± 0.62°, and 40%, respectively. For the long distance (14.5-15.5 cm), the TPE, LE, AE, and FSR were 2.81 ± 1.17 mm, 2.33 ± 1.34 mm, 0.99 ± 0.55°, and 30%, respectively.

Conclusion: The augmented reality and machine vision-based CT-guided puncture navigation system allows for precise punctures in a phantom. Further studies are needed to explore its clinical applicability.

Abstract: Intestinal microecology (IM) is the largest and most important microecological system of the human body. Furthermore, it is the key factor for activating and maintaining the physiological functions of the intestine. Numerous studies have investigated the effects of the gut microbiota on the different tissues and organs of the human body as well as their association with various diseases, and the findings are gradually being translated into clinical practice. The gut microbiota affects the occurrence, progression, treatment response, and toxic side effects of tumors. The deepening of research related to IM and tumors has opened a new chapter in IM research driven by methods and technologies such as second-generation sequencing and bioinformatics. The IM maintains the function of the host immune system and plays a pivotal role in tumor-control drug therapy. Increasing evidence has proven that the efficacy of tumor-control drugs largely depends on the IM balance, and strategies based on the IM technology show promising application prospects in the diagnosis and treatment of tumor. The Tumor and Microecology Professional Committee of the Chinese Anti-cancer Association gathered relevant experts to discuss and propose the "Chinese guidelines for integrated diagnosis and treatment of IM technologies in tumor application (2024 Edition)," which was established based on the research progress of the application of the IM technology in tumor to provide a basis for the standardization of the diagnosis and treatment of the IM technology in the tumor.

Purpose: This study evaluates the clinical efficacy and safety of irreversible electroporation (IRE) therapy combined with chemotherapy in patients with stage IV pancreatic cancer.

Methods: Between September 2021 and November 2023, we enrolled 38 patients with stage IV pancreatic cancer, with 20 receiving IRE plus chemotherapy and 18 receiving only chemotherapy. We recorded the general information of the patients and regularly followed up postoperative IRE-related adverse reactions. Progression-free survival (PFS) and overall survival (OS) were evaluated during follow-up.

Results: Median OS was longer in the IRE group than in the chemotherapy group. Median PFS was slightly extended with IRE compared to chemotherapy alone. The mean hospital stay for the IRE group was 5.90 ± 0.75 days. Four serious adverse events occurred after IRE. Postoperative pain scores were significantly lower than preoperative scores.

Conclusion: IRE combined with chemotherapy showed clinical effectiveness in stage IV pancreatic cancer treatment, offering potential pain reduction benefits with fewer adverse effects and shorter hospital stays.