As an important metal element in human body, copper can be involved in many important biological processes such as cell metabolism, anti-oxidation, detoxification, iron absorption and so on. Copper in the human body is mainly ingested through diet, combined with transport proteins in the digestive tract into the blood, and then transported to all tissues of the body through carrier proteins. It is strictly regulated by copper ion chaperone protein and carrier protein, and its intake and excretion are in a dynamic balance. Copper plays an important role in tumor cell growth, migration and angiogenesis, so when copper homeostasis is out of balance, it can affect tumor cell growth and lead to apoptosis. Recent studies have found that copper can induce a new type of cell death - Cuprotosis, which is different from the classical cell death forms such as necrosis, pyrodeath, autophagy and necrotic apoptosis, and is closely related to the regulation of copper metabolism. Therefore, the novel cell death mechanism induced by copper has triggered extensive research. In the breast cancer related research, it was found that the genes and proteins related to copper death play an important role in the progression of breast cancer disease, immune cell infiltration, drug resistance, combination therapy and disease prognosis assessment, etc. Therefore, the cuprotosis mechanism should be further studied and applied in clinical anti-tumor therapy. It is expected to provide new treatment options for breast cancer patients.

Lung cancer is one of the most prevalent and the highest mortality rate malignancies, and its treatment landscape has undergone a disruptive transformation with the discovery and clinical application of immune checkpoint inhibitors. However, there still exists a number of patients who acquire resistance or fail to respond to these treatments, posing new challenges for lung cancer therapy. In light of this, there is an urgent need to actively explore and develop novel targets and innovative therapeutic strategies. This article aims to review the cutting-edge advancements in the novel immune checkpoint inhibitors, agonists, bispecific antibodies, adoptive cellular immunotherapy, and combination therapies involving immune checkpoint inhibitors, as well as to revisit existing related clinical trials along with their limitations, with the goal of advancing lung cancer immunotherapy towards a more personalized and precise approach.

Gastric cancer is one of the most common malignant tumors of the digestive system. Most gastric cancer patients are already in advanced stage when initially diagnosed. Advanced gastric cancer has a poor prognosis and has received limited benefit from chemotherapy-based therapies. In the recent years, with the development of biomolecular technologies, more and more researches have set their focus on the search for key molecules that affect the progression of gastric cancer, prognostic indicators, and therapeutic targets. Claudin-18.2 is a promising novel tumor therapeutic target which brings new hope for targeted therapy for gastric cancer. Various types of Claudin-18.2-targeting drugs have been developed, including monoclonal antibody, bispecific antibody (BsAb), antibody-drug conjugate (ADC), chimeric antigen receptor T cell (CAR-T), and so on. At present, several clinical trials have been carried out and the results are encouraging. This review summarizes the progress in clinical trials of Claudin-18.2 targeted therapy, in the hope to provide reference for improving the prognosis of patients with advanced gastric cancer.

Objective: To investigate the expression pattern, clinical significance, and the regulatory role of 2', 5'-oligoadenylate synthetase 1 (OAS1) in the proliferation of pancreatic ductal adenocarcinoma (PDAC) cells.

Methods: Public databases such as Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were used to analyze the expression of OAS1 in pancreatic cancer tissues. Immunohistochemical staining was applied to validate the expression level of OAS1 in PDAC tissue microarrays, and the association between OAS1 expression level and the prognosis of patients was analyzed. Real-time fluorescence quantitative PCR was performed to examine the expression level of OAS1 mRNA in different PDAC cell lines. CCK-8 assay and colony formation assay was used to assess the effect of OAS1 on the proliferation of PDAC cells after OAS1 silencing in Patu-8988 and PDC0034 cells by siRNA treatment. Further, Gene Set enrichment analysis (GSEA) was performed to screen for possible molecular mechanism of the regulatory role of OAS1 in PDAC. Cell viability and cholesterol level was analyzed after treatment with mTOR signaling activator MHY1485 in OAS1-silenced Patu-8988 and PDC0034 cells in order to verify the underlying mechanism of the regulatory role of OAS1 in PDAC cell proliferation.

Results: Database analysis showed significant upregulation of OAS1 expression in pancreatic cancer tissues (P < 0.05). Immunohistochemical staining results from PDAC tissues microarray showed that OAS1 expression was significantly upregulated in PDAC tissues compared with the paired paracancerous tissues, and high OAS1 expression was associated with poor prognosis (P < 0.05). Real-time fluorescence quantitative PCR and Western blotting analysis show that OAS1 expression was higher in PDAC cells lines compared with normal ductal cells of the pancreas. The proliferative activity of PDAC cells decreased significantly after OAS1 silencing in Patu-8988 and PDC0034 cells (P < 0.001). GSEA results indicated that OAS1 may affect PDAC cell proliferation through mTOR signaling pathway and cholesterol metabolism associated pathway. The mTOR signaling pathway may be inhibited and the total cellular cholesterol decreased after OAS1 silencing. Treatment with mammalian target of rapamycin (mTOR) activator MHY1485 partially reversed the inhibitory effect of OAS1 silencing on the proliferation and cholesterol metabolism of PDAC cells.

Conclusion: OAS1 expression is upregulated in PDAC tumor tissues and cells and is associated with poor prognosis. OAS1 may promote the proliferation of pancreatic cancer cells by enhancing cholesterol metabolism through activation of the mTOR signaling pathway.

Pancreatic cancer is one of the common gastrointestinal malignancies, the incidence of which is increasing year by year and has become one of the most important public health problems worldwide. At present, tumor treatment has entered the era of immunotherapy, but the response of pancreatic cancer patients to immune checkpoint inhibitors is not ideal. In addition, there is a lack of effective and validated biomarkers to stratify patients who may benefit from immunotherapy. This review has summarized the current research advances of immunotherapeutic biomarkers in pancreatic cancer, hoping to help clinicians understand relevant biomarkers systematically and guide the precise treatment of pancreatic cancer.

Tumor immunotherapeutics include immune checkpoint inhibitors, adoptive cellular therapy, tumor vaccines, immunomodulators, which regulate or induce anti-tumor activity by blocking immunosuppressive signals, infusing in vitro-induced anti-tumor effector cells, and enhancing the immunogenicity of tumor cells in the fight against cancer. The effect mechanisms of tumor immunotherapy is different from that of other tumor therapeutic approaches, such as surgery and chemotherapy. Therefore, in the evaluation of anti-tumor efficacy, the use of conventional imaging methods to detect the volume change of tumor lesions shows special response patterns such as “false progression” and “superprogression”, which cannot timely and accurately evaluate the objective efficacy of tumor immunotherapy. This review is an attempt to focus on those challenges in evaluating immunotherapy efficacy and the latest developments of relevant evaluation criteria, and is aimed at providing reference for the scientific evaluation of tumor immunotherapy efficacy and the selection of appropriate immunotherapy strategies for tumor patients.

Methods: The data of GSE7803 and GSE9750 about cervical squamous cancers were downloaded from Gene Expression Omnibus (GEO), and differentially expressed genes were screened by using GEO2R and R software. The Hub genes were further obtained through the analysis from DAVID, STRING, GEPIA and HPA databases. Univariate proportional-hazards and multivariate COX regression analyses were used to identifying prognostic factors from data about cervical squamous cell carcinoma obtained from The Cancer Genome Atlas (TCGA) database. Real-time fluoroscent quantifative PCR was used to detect the expression levels of CXCL8 and MSMO1 mRNA in cervical squamous cancer Siha cells. CCK-8 assay was used to evaluate the effect of MSMO1 gene sliencing on the proliferation of Siha cells.

Results: 245 up-regulated genes and 334 down-regulated genes were screened by GEO2R. Gene Ontology (GO) enrichment analysis results showed that the differential expression genes are related to cell replication, division and proliferation. The kyoto encyclopedia of genes and genomes (KEGG) pathway analysis shows that the main enrichment was in tumor and cell cycle pathway, etc. Survival analysis results of 10 Hub genes showed that CXCL8 and MSMO1 were all highly expressed in tumor and significantly related to the poor prognosis of patients with cervical squamous carcinoma (both P < 0.05). The univariate COX regression model showed that the expression levels of CXCL8 and MSMO1 were related to the overall survival (OS) of patients with cervical squamous cancer [hazard ratio (HR) = 1.00, 95% confidence interval (CI): 1.00-1.01, P = 0.018; HR = 1.03, 95% CI: 1.1 - 1.05, P = 0.002]. The random forest model showed that there was a significant difference in the prediction scores of patients between the survival group and the death group (P < 0.05). The AUC of the training group model was 1.00, and the AUC of the experimental group was 0.71, indicating that the model had a good predictive ability and could predict the survival and death status of patients to a certain extent. The mRNA levels of CXCL8 and silencing MSMO1 gene expression in Siha cells, derived from cervical squamous cancer, were significantly higher than in normal HUVE-12 cells (P < 0.05). MSMO1 increased the proliferation of Siha cells (P < 0.05).

Advanced gastric cancer (AGC) includes locally unresectable gastric cancer (GC), metastatic GC, and postoperative recurrent GC. Due to delayed diagnosis and lack of effective treatment for AGC, the median survival time of AGC patients is only 6-12 months. At present, the main treatment goal of AGC is to improve symptoms and prolong the survival time of patients receiving sequential chemotherapy. Although the therapeutic effect of systemic therapy on AGC is gradually becoming apparent, the patient's prognosis is far from expected. In addition, targeted therapy and novel immunotherapy have drawbacks such as high incidence of drug resistance, high toxic side effects, and heavy economic burden on patients. Therefore, finding new therapeutic targets and developing anti-tumor drugs is a key issue that urgently needs to be addressed. According to reports, abnormal activation of the hepatocyte growth factor (HGF)/ cellular-mesenchymal epithelial transition factor (c-MET) pathway plays a crucial role in the progression of GC and the occurrence of multi-line resistance and may be a potential therapeutic target for GC. In recent years, some HGF/c-MET-targeting small molecule tyrosine kinase inhibitors (TKIs) have been found to show good clinical effects in the treatment of GC. Meanwhile, new HGF/c-MET inhibitors (such as monoclonal antibodies, bispecific antibodies, antibody drug conjugates, etc.) have shown good anti-tumor activity in preclinical studies, but they are all at different stages of clinical research, and their efficacy and safety still need further confirmation. This review elaborates on the latest research progress of HGF/c-MET inhibitors in the treatment of AGC and discusses the main reasons and strategies for drug resistance, aiming to provide better guidance for the treatment of AGC and provide reference for future research.

The rapid development of the comprehensive intersection of oncology disciplines makes oncology teaching complex and challenging. In recent years, the deep integration of artificial intelligence (AI) and medical education has brought new opportunities for oncology teaching. Therefore, this paper proposes to construct a new teaching model of AI-enabled problem-based learning (PBL) fused with case-based learning (CBL), which fully combines PBL, CBL, virtual simulation technology, intelligent robots, AI models and other teaching methods, and integrates these innovative elements into all aspects of oncology teaching, including theoretical courses, laboratory operations and clinical practice, in order to provide a comprehensive and interactive oncology teaching system. This new teaching mode brings a new perspective and approach to theoretical, experimental, and clinical teaching in oncology, which not only helps to deepen students’ understanding of the basics of oncology, but also significantly improves their clinical thinking and problem-solving abilities. In addition, this new attempt at an integrated teaching method will provide a new teaching strategy for the development of medical oncology education.

Objective: To investigate mechanisms whereby phospholipase D1 (PLD1) promotes pancreatic ductal adenocarcinoma (PDAC) progression.

Methods: Targets were identified by screening the Genomic Spatial Event (GSE) database for genes differentially expressed in metastatic and primary tumors. Xenograft models were constructed by orthotopic injection of KPC cells into the mouse pancreas. Differential PLD1 expression in paired primary tumors and liver metastases derived from C57 mice and PDAC patients was confirmed using immunohistochemical staining. The effect of PLD1 expression on PDAC prognosis was assessed using a PDAC tissue microarray and clinical data. The effect of PLD1 expression on PDAC metastasis was assessed using transwell migration and scratch assays of cell lines ectopically expressing/silencing PLD1. The role of PLD1 in tumor metastasis was investigated using xenograft models constructed by orthotopic injection of PLD1-overexpression cell lines or vector control into the pancreas of C57 mice. Growth of primary tumors and liver metastases was monitored using bioluminescent imaging. The role of PLD1 in tumor progression was assessed using western blotting, transwell migration and scratch assays, and PLD1 enzyme-mutation cell lines. Downstream PLD1 target genes were identified using quantitative real-time PCR (qPCR), transcriptome sequencing, and response blocking. The effect of downstream target FSTL1 on liver metastasis in mice was assessed using bioluminescent imaging.

Results: PLD1 expression was significantly higher in metastases than in primary tumors in KPC mice and patients.In the tissue microarray analysis, PLD1 expression was associated with diminished survival in PDAC patients; PLD1 overexpression in MIA PaCa-2 cells or knockdown in SW1990 cells could significantly affect the ability of invasion and migration.Xenograft models were established via orthotopic injections of the KPC cell line into the pancreas.Bioluminescent imaging demonstrated that PLD1 overexpression significantly increased signal intensity in the mouse liver (P<0.01);Treating the SW1990 cell line with PA and choline (PLD1 pathway products) did not restore loss of PDAC cell migration and invasion ability. Transwell and scratch assays in KRM, a PLD1 catalytic-mutation cell line, suggested that PLD1 activity is not required for PDAC metastasis;Transcriptome sequencing identified FSTL1 as a downstream molecule of PLD1. qPCR confirmed the consistency of mRNA levels between PLD1 and FSTL1. A blocking-rescue experiment suggested that FSTL1 is a downstream target of PLD1. A splenectomy metastasis model was constructed by injecting nude mice with tumor cells overexpressing FSTL1 and the results confirmed that overexpression of FSTL1 could induce liver metastases in PDAC cell due to tumor progression.

Conclusion: PLD1 upregulates FSTL1 expression, promotes epithelial-mesenchymal transition of tumor cells, and enhances PDAC metastasis. Thus, PLD1 blockade could inhibit PDAC progression.

The immune related adverse events (irAE) caused by tumor immune checkpoint inhibitors (ICI) have attracted increasing attention of clinical experts. Immune-mediated liver injury caused by ICIs (ILICI) is not uncommon in clinical practice, but specific diagnostic method of ILICI is lacking. Biopsy of liver tissue can help improve the diagnosis and management of ILICI. In the treatment of ILICI, the immediate use of corticosteroid therapy is not ecessarily. A balance between efficacy, toxicity, and specific treatment need to be achieved, and further refined through multidisciplinary team (MDT) cooperation. Appropriate dosaging and identification of novel predictive targets should be considered in order to reduce the incidence and severity of ILICI in the future. Meanwhile, further basic research is required to elucidate the potential pathophysiological mechanisms and risk factors of ILICI. With the refinement of evidence in clinical evidence-based medicine and deepening of basic research, the diagnosis and treatment level of ILICI will also be further improved.

Objective: This study aims to construct a human peripheral blood mononuclear cell (PBMC)-NPSG-PDX (patient-derived xenograft) model, by transferring PBMCs into NPSG (NOD-Prkdc^scidIl2rg^null/Shjh) mice and transplanting human tumor tissues. This model mimics the human tumor microenvironment to investigate the interactions between tumors and the immune system.

Methods: PBMCs from healthy donors were transferred to NPSG mice to generate hPBMC-NPSG model. Patient-derived xenografts (PDX) were established in nude (BALB/c-nu) mice. Third-generation PDX tumors were then transplanted into hPBMC-NPSG mice to establish the hPBMC-NPSG-PDX model. Mouse body weight was monitored, and flow cytometry was used to analyze immune reconstitution and T cell function. Tumor growth was evaluated, and immunohistochemistry was performed to analyze tumor morphology and immune cell infiltration.

Results: Fourteen days after constructing the hPBMC-NPSG mouse model, the proportion of human hu-CD45⁺CD3⁺ T cells reached 97%. The proportions of human CD8⁺ T, CD4⁺ T, CD56⁺ natural killer (NK), and CD19⁺ B cells were 64%, 24%, 4.6%, and 1.0%, respectively. Human CD4⁺ and CD8⁺ cells secreted various cytokines (IL-2, IFN-γ, and TNF-α) and expressed cytotoxic molecules (FasL, granzyme B, and perforin) 28 days post reconstitution. Tumor growth in hPBMC-NPSG-PDX mice was rapid initially but then stabilized. Immunohistochemistry staining revealed typical tumor morphology, and tumor cell apoptosis was observed in areas with immune cell infiltration.

Conclusion: This study successfully constructed a hPBMC-NPSG-PDX model that effectively simulates the human tumor microenvironment, providing an ideal platform for tumor immunology research.

Objective: To construct a scientific and objective competency index system for clinical research nurse, providing a reference for establishing a systematic and specialized training system.

Methods: A preliminary framework and corresponding indicators for the competency of clinical research nurse were developed through literature analysis with the guidance of the iceberg model. The expert meeting method was utilized to determine the framework, and the Delphi method and Analytic Hierarchy Process were employed to screen indicators and calculate weights. Finally, the competency index system for clinical research nurses was established.

Results: In this research, 9 experts participated in the expert meeting, confirming that this competency framework consists of two dimensions: knowledge skills and self-concept. The knowledge and skills dimension encompasses five roles of clinical research nurses, and based on this, four levels were further divided. In addition, the self-concept dimension is divided into three aspects. A panel of 17 experts was selected to evaluate these indicators through two Delphi rounds. The effective response rates were 100% and 88.2%, respectively. The expert authority coefficients were 0.968 and 0.963, respectively, while the Kendall’s coefficient of concordance were 0.244 and 0.403, respectively (P<0.001). In the end, 87 indicators for clinical research nurse competency were developed.

Conclusion: Under the guidance of the iceberg model, the competency index system for clinical research nurse constructed in this study is scientific and reliable, closely aligned with clinical practice, and possesses specialized characteristics. It can be used to evaluate the competencies of clinical research nurses and provides a basis for conducting relevant training and improving position management.

Rolling circle amplification (RCA) is an efficient isothermal enzymatic reaction using a circular DNA single strand as a template and catalyzed by DNA polymerases. It is simple, fast, and efficient, and can rapidly produce ultra-long single-stranded DNA with a large number of tandem repeats in a short time. Due to the codability of DNA, template DNA sequences can be designed according to needs to result in a wide range of functional products, displaying a unique advantage in the fields of biological detection and drug delivery. This review has summarized the basic principle and classification of RCA technology, focused on the applications of RCA technology in tumor detection and drug delivery in recent years, and finally discussed the application prospects and potential challenges of this technology.

Lung cancer is the second most common and the deadliest malignant tumor worldwide. With the popularization and improved accuracy of computed tomography (CT) screening technology, more and more patients with lung cancer are detected at an early stage. Concurrently, the rapid development of gene sequencing technology has gradually evolved the treatment model for lung cancer patients into a precision treatment model that integrates pathological classification, staging, and molecular identification. Against this backdrop, targeted drugs such as osimertinib and icotinib have been formally approved for adjuvant therapy after radical resection surgery for resectable non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor(EGFR) mutations, marking the advent of a new era in adjuvant targeted therapy for lung cancer. Despite this significant progress, the optimal perioperative treatment strategies for resectable NSCLC patients with oncogenic driver mutations (including EGFR mutations) are still unclear. To address this issue, multiple clinical trials are currently ongoing. There is increasing attention on neoadjuvant and adjuvant treatment strategies based on targeted therapy (alone or combined with other treatment). These strategies are expected to provide more precise and effective perioperative treatment options for resectable NSCLC patients with EGFR mutations, thereby further improving their prognosis and quality of life.

The incidence and mortality of colorectal cancer (CRC) have been increasing year by year, and liver metastasis is the main cause of death for CRC patients. Approximately 49% of CRC patients died of liver metastasis, and about 25% of them developed liver metastasis after radical resection. The interaction between various cytokines (such as chemokines, exosomes) and immune cells in the tumor microenvironment (TME) is essential for tumor metastasis. So far, the mechanism of colorectal liver metastases (CRLM) has not been fully elucidated, but some studies have shown that CRLM does not only occur in the late stage of CRC, but also in the early stage of some patients. In this paper, we summarized the current understanding of CRLM pathogenesis from genomics, pathology, and TME perspectives. And we also reviewed the latest molecular regulatory mechanisms of CRLM, as well as the mechanisms of immune cells and cytokines related to TME. Finally, the latest research findings of CRLM immunotherapy are summarized, in order to provide new insights into the comprehensive treatment for CRLM patients.

Currently, common primary malignant bone tumors in clinical practice include osteosarcoma, chondrosarcoma, Ewing's sarcoma, chordoma, and multiple myeloma. Malignant bone tumors often metastasize to the lungs through the bloodstream, but lymph node metastasis can also occur. Once lymph node metastasis occurs, the prognosis for patients is worse than with lung metastasis, making the study of lymph node metastasis in malignant bone tumors a growing research focus in recent years. According to current research, primary malignant bone tumors mainly metastasize to lymph nodes through two pathways: firstly, bone tumor cells break through the periosteum into the surrounding lymphatic tissue; secondly, they regulate the expression of VEGF-C by secreting factors like WISP-3, CCL5, BDNF, thus inducing the neogenesis of lymphatic vessels in malignant bone tumors. Past research on lymph node metastasis of primary malignant bone tumors has mostly focused on clinical studies of a single type of malignant bone tumor, lacking systematic basic research and reviews, and the mechanisms of metastasis are not yet fully elucidated. Moreover, different types of malignant bone tumors vary in their rates and sites of lymph node metastasis. Therefore, this article mainly reviews the rates, sites, diagnostic methods, potential mechanisms, and treatment methods of lymph node metastasis in these five common types of malignant bone tumors, aiming to deepen understanding of lymph node metastasis in primary malignant bone tumors and to provide new ideas for clinical treatment and drug development.

Objective: To investigate the regulatory mechanism of myoepithelial cells on glandular epithelial cells during the invasive process of ductal carcinoma in situ of breast.

Methods: A total of 157 patients with ductal carcinoma in situ of breast, treated at the Tianjin Medical University Cancer Hospital from May 2008 to July 2010, were randomly selected (including 63 high nuclear grade patients, 51 middle nuclear grade patients, and 43 low nuclear grade patients). Immunohistochemical staining for epithelial-mesenchymal transition (EMT)-related markers (Snail and ZEB1) was performed on tumor tissue specimens from these patients to explore the correlation between tumor cell nuclear grade, EMT process,and expression status of myoepithelial cells. To further investigate the regulatory role of myoepithelial cells on glandular epithelial cells during the invasive process of ductal carcinoma in situ of breast, a co-culture model of human myoepithelial cell line Hs578Bst and adenomatous epithelial cell line MCF-7 was established using Transwell chambers. Experimental, blank control, positive control, and negative control groups were designed by combining co-cultured Hs578Bst and MCF-7 cells with exogenous TGFβ1 and TGFβ1 inhibitors. After 72 hours of culture, morphological changes, migration and proliferation capabilities of MCF-7, as well as the changes in protein and mRNA expression levels of EMT-related genes (Snail and ZEB1), were observed in each group.

Results: Immunohistochemical staining results demonstrated a positive correlation between tumor nuclear atypia, EMT activation, and myoepithelial cell expression in ductal carcinoma in situ tissues. The model of ductal carcinoma in situ of breast demonstrated that myoepithelial cells Hs578Bst promoted morphological changes in glandular epithelial cells MCF-7 by stimulating TGFβ1 expression. Wound healing and cell proliferation assays revealed that myoepithelial cells Hs578Bst can enhance migration and proliferation of glandular epithelial cells MCF-7 via TGFβ1 activation. Western blot and real-time quantitative PCR confirmed that myoepithelial cells Hs578Bst can upregulate the protein and mRNA expression levels of EMT-related genes (Snail and ZEB1) in glandular epithelial cells MCF-7 by through TGFβ1 stimulation.

Conclusion: Breast myoepithelial cells promote EMT in glandular epithelial cells by secreting/stimulating TGFβ1, thereby contributing to the occurrence of invasion in ductal carcinoma in situ of the breast.