Oncolytic virus is a unique anti-tumor immunotherapy that can specifically infect and lyse tumor cells, while inducing and activating the body's own anti-tumor immune response to attack tumors. So far, three oncolytic viruses have been approved for marketing. In 2005, China first approved recombinant human adenovirus type 5 (H101/Oncorine) combined with chemotherapy for the treatment of advanced nasopharyngeal cancer patients. In 2015, the US Food and Drug Administration (FDA) approved herpes simplex virus type I (T-VEC) for the treatment of recurrent melanoma after primary surgery, T-VEC was subsequently approved in Europe. In 2021, Japan's Ministry of Health, Labour and Welfare approved third-generation recombinant herpes simplex virus type I (Delytact/G47Δ) for the treatment of malignant glioma. Although the approval of H101 in China marks a breakthrough in the development of oncolytic viruses, compared to T-VEC and Delytact, H101 has not significantly impacted the treatment of patients with advanced nasopharyngeal carcinoma. This may be due to its inability to provide a complete tumor response as a monotherapy, and the fact that most nasopharyngeal carcinoma patients in China undergo radiotherapy, making it difficult for them to benefit from chemotherapy combined with H101. Therefore, this treatment regimen still needs improvement. In recent years, with the maturity of genetic engineering technology, oncolytic viruses have been continuously improved and refined. This review summarizes the clinical research progress of oncolytic viruses and discusses their characteristics and development prospects.

Pancreatic cancer is a malignant tumor with extremely poor prognosis, and its biological behavior is closely related to its genetic characteristics. Traditional preclinical research models struggle to accurately simulate the complex genetic heterogeneity and histological characteristics of pancreatic cancer. In recent years, the development of organoid models and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology has provided new tools for pancreatic cancer research. Organoids can simulate the genetic and histological features of primary tumors, while CRISPR technology enables precise genetic manipulation in organoids. CRISPR Gene-Editing Organoids can model the occurrence and evolution of pancreatic cancer, conduct gene function analysis, and perform drug screening. This review discusses the recent advancements in the application of organoid models combined with CRISPR technology in pancreatic cancer research, which are expanding our understanding of pancreatic cancer.

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.

Osteosarcoma is the most common primary malignant bone tumor, typically treated with a combination of surgery and chemotherapy in clinical practice. However, the increasing prevalence of chemotherapy resistance poses a significant challenge. Chemotherapy resistance can lead to a sharp decline in patients’ survival rates. Traditional Chinese medicine, known for its low cost, wide-ranging efficacy, and diverse varieties, has attracted significant attention from researchers. Their attempts to investigate the sensitizing effect of extracted ingredients on osteosarcoma chemoresistance both in vitro and in vivo have yielded promising results. This review has summarized the studies of single traditional Chinese medicine ingredients on reversing osteosarcoma chemoresistance by the mechanisms of chemoresistance, and found that the current research of the clinical mechanism of traditional Chinese medicine ingredients in reversing osteosarcoma chemoresistance is still lacking, indicating significant potential for future development. Utilizing the theory of herbal medicine properties as the theoretical basis for ingredient development may provide novel strategies for the development of new therapeutic approaches.

In January 2024, professor Shen Baiyong's team at the Pancreas Center-Shanghai Key Laboratory of Translational Research in Pancreatic Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, published a research paper in Nature Medicine titled “Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma”. The team conducted a prospective observational study that included a total of 1 171 pancreatic cancer patients who underwent radical resection. First, paired samples of tumors from 191 pancreatic ductal adenocarcinoma (PDAC) patients were obtained by microdissection and subjected to proteomic analysis, which revealed unique protein modules of pancreatic tumors, particularly those related to chemotherapeutic drug sensitivity. Further, the research team established a prognostic risk model for pancreatic cancer at the proteomic level and validated the validity and reliability of this prognostic model with an external cohort. Using multicenter and large sample data, the study constructed and validated the generalizability of two protein markers in predicting the efficacy of chemotherapy in pancreatic tumors.

Pancreatic cancer has an insidious onset and a high degree of malignancy, and due to the limited efficacy of traditional treatments such as surgery and chemotherapy, this tumor has been one of the malignant tumors with the highest morbidity and mortality rates. In recent years, cell therapy, which utilizes and modifies the patient's own immune cells to target and kill tumor cells, is gradually becoming one of the potential alternatives to traditional treatment of tumors, and has achieved positive results in hematologic tumors. However, cell therapy in solid tumors, such as pancreatic cancer, is still in the research stage, and although it has achieved some efficacy, it is still full of challenges. In this review, the mechanism of chimeric antigen receptor-T cells (CAR-T), T cell receptor-T cells (TCR-T), and tumor infiltrating lymphocytes (TILs) in cell therapy and the efficacy in the treatment of pancreatic cancer were thoroughly discussed. Meanwhile, the main reasons for the poor effect of cell therapy in pancreatic cancer and the current research progress in improving the effect of cell therapy are preliminarily analyzed.

Objective: This study aimed to investigate the correlation between the use of glucose-lowering drugs and the risk of pancreatic cancer through propensity score matching (PSM), which provides a scientific basis for clinical decision-making.

Methods: This study retrospectively analyzed the clinical data of patients diagnosed with type 2 diabetes mellitus (T2DM) and treated with glucose-lowering drugs in Nanjing Drum Tower Hospital between 2000 and 2023. The patients were divided into two groups: those with T2DM alone and those with T2DM combined with pancreatic cancer. PSM was employed to align the baseline characteristics of patients across groups, minimizing the impact of confounding factors. According to the use of glucose-lowering drugs, the correlation between the use of various types of glucose-lowering drugs and the occurrence of pancreatic cancer was explored by logistic regression analysis, and the drug influencing factors that might potentially affect the occurrence of pancreatic cancer were screened out. Additionally, the relationship between the use of glucose-lowering medications, both as monotherapy and in combination, and the occurrence of pancreatic cancer was further analyzed.

Results: The logistic regression analyses showed that previous use of sulfonylureas was significantly associated with pancreatic cancer in patients with T2DM, and previous use of dipeptidyl peptidase-4 (DPP-4) inhibitors was weakly associated with pancreatic cancer, and sulfonylureas [odds ratio (OR)=0.631，95% CI: 0.415-0.961，P=0.032] and dipeptidyl peptidase-4 (DPP-4) inhibitors (OR=0.639，95% CI: 0.388-1.052，P=0.078) may be associated with a reduced risk of pancreatic cancer in T2DM patients. Other drugs, including insulin, metformin, α-glucosidase inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors, were not significantly associated with pancreatic cancer development. In a further analysis of glucose-lowering treatment regimens, it was shown that metformin in combination with other oral glucose-lowering agents was associated with pancreatic cancer [adjustment OR (aOR)=0.463， 95% CI：0.224-0.959， P=0.038] and may be a protective factor for pancreatic carcinogenesis.

Conclusion: The use of sulfonylureas and DPP-4 inhibitors in T2DM patients is related to the reduction of pancreatic cancer, and compared with the use of drugs alone, the use of drugs combined with oral hypoglycemic drugs can further reduce the incidence of pancreatic cancer.

The incidence of cachexia in pancreatic cancer is high, which seriously affects the therapeutic effect and survival rate of patients. There is currently no effective intervention for tumor cachexia, so studying its regulatory mechanism has important clinical significance. In 2024, Professor Li Min's team from the Health Science Center of the University of Oklahoma published a research report on Cancer Cell entitled "The crosstalk between macroscopic and cancer cells potentials pancreatic cancer cachexia", which first revealed the relationship between the immune microenvironment (macrophages) of pancreatic cancer and the body's macro environment cachexia (muscle atrophy), opening up a new direction and new intervention ideas for the study of pancreatic cancer cachexia.

Pancreatic cancer is a highly malignant digestive system tumor with poor prognosis. Its incidence is closely related to the level of regional development. Epidemiology shows that with the progress of urbanization, the proportion of obese people in the world is increasing over the years. Meanwhile, obesity has also been found to be one of the risk factors for pancreatic cancer. However, the mechanism of obesity regulating pancreatic cancer is still unclear at present. Researches show that obese people with pancreatic cancers have different tumor pathological mechanisms and higher risk of surgical complications. Therefore, this article will review the potential transformation mechanism between microscopic pathological changes and clinical manifestations of obesity related pancreatic cancer.

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.

Objective: To investigate the role of RASAL2 in vasculogenic mimicry in pancreatic cancer cells and to preliminarily explore the potential molecular mechanisms involved.

Methods: The clinical proteomic tumor analysis consortium (CPTAC) database was used to analyze the expression of RASAL2 in pancreatic cancer, and immunohistochemical method was used to detect the expression of RASAL2, β-catenin and Vimentin in pancreatic cancer and adjacent tissues. In the pancreatic cancer cell line, after lentivirus infection knockdown and overexpression of RASAL2, transcriptome sequencing was performed on pancreatic cancer cells silencing RASAL2 expression, and vasculogenic mimicry experiment was used to detect the effect of RASAL2 on angiogenesis of pancreatic cancer cells; The molecular mechanism of RASAL2 promoting vasculogenic mimicry in pancreatic cancer was studied by real-time fluorescent quantitative PCR and Western blotting detection.

Results: The analysis results of CPTAC database showed that the expression level of RASAL2 protein in pancreatic cancer tissue was significantly higher than that in normal pancreatic tissue. Immunohistochemical test results showed that the expression of RASAL2 in pancreatic cancer tissue was up-regulated, and the expression of β-catenin and Vimentin in pancreatic cancer tissue was also significantly up-regulated. The second-generation transcriptome sequencing results showed that RASAL2 may be involved in the biological behavior of intercellular connections and adhesion. After knocking down RASAL2 expression in pancreatic cancer cell PANC-1, the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins decreased, and the formation of vasculogenic mimicry structure was inhibited; After overexpression of RASAL2 in pancreatic cancer cell BxPC-3, the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins increased, promoting the formation of vasculogenic mimicry.

Conclusion: The effect of RASAL2 on vasculogenic mimicry in pancreatic cancer cells is related to AKT/β-catenin signaling pathway.

Pancreatic fibrosis is an important pathological feature of pancreatic cancer and chronic pancreatitis, and plays an important role in the progression of pancreatic cancer and chronic pancreatitis. Pancreatic fibrosis blocks the chemotherapy drugs from reaching the cancer cells to do their job and also affects the stiffness of the pancreatic tissue. Therefore, it is important to assess the degree of pancreatic fibrosis as an adjunct to surgical and chemotherapeutic treatments for pancreatic cancer and chronic pancreatitis. In recent years, there have been new research advances and technological breakthroughs in non-invasive diagnostic methods for pancreatic fibrosis. The fields of CT, ultrasound elastography and magnetic resonance imaging have extended new imaging techniques, yielded new imaging indices to assess the degree of pancreatic fibrosis. In this paper, we have collected relevant literatures since 2018 to describe the research progress related to non-invasive diagnostic methods for pancreatic fibrosis.

As a real-time, rapid and non-invasive method for monitoring the occurrence and development of various diseases and evaluating the health status of the body, breath detection has attracted wide attention in the application of early lung cancer screening. However, there is significant variability in the reported specific biomarkers of lung cancer, making it difficult to reach a unified consensus. Meanwhile, the pathways for the generation of volatile organic compounds (VOCs) in exhaled breath of lung cancer patients remain unclear, and further research on the detailed metabolic mechanisms is required. Therefore, this review comprehensively summarizes the VOCs detected in the exhaled breath of lung cancer patients from relevant literature in the past five years, deeply analyzes the production mechanism of these VOCs and the internal correlation with the disease, and evaluates the performance of the lung cancer prediction models constructed based on these VOCs, in order to provide reference for clinical and subsequent researches.

The incidence and mortality rates of gastrointestinal tumors account for 26% and 35% of global malignant tumors, respectively, and continue to rise annually. Elucidating the molecular mechanisms of occurrence and development of gastrointestinal tumors, as well as establishing precise molecularly targeted intervention strategies, have become critical scientific challenges in oncology research. Doublecortin-like kinase 1 (DCLK1), a type II transmembrane protein harboring serine/threonine kinase domains, is well-recognized as a specific molecular marker for cancer stem cells. DCLK1 has been demonstrated to directly promote tumor progression by enhancing the autonomous malignant phenotype of tumor cells, while also indirectly driving tumorigenesis through modulation of tumor immune microenvironment. In recent years, tissue-resident memory T cells (TRM), characterized by their sustained tissue residency and potent antitumor immune efficacy, have emerged as a novel avenue for cancer immunotherapy. This article systematically reviews the molecular regulatory mechanisms of DCLK1 in gastrointestinal tumors, with a focus on its potential association with TRM cell functional activation, aiming to provide a theoretical foundation for DCLK1-targeted inhibitors or monoclonal antibody-based immunotherapeutic strategies.

Objective: To investigate the effect of copper chlorophyllin sodium salt (CHL) on the sensitivity of human pancreatic cancer cells in response to gemcitabine (GEM) therapy and on the therapeutic effect on pancreatic cancer cells that have developed GEM resistance.

Methods: MIA GR (a pancreatic cancer cell line resistant to GEM) was induced by a low-dose continuous incremental method, and the half inhibitory concentration (IC₅₀) of MIA WT and MIA GR to GEM treatment was detected by the CCK-8 method, and the resistance index was calculated; the difference in IC₅₀ of CHL on the two types of cells was detected by the CCK-8 method after treating MIA WT and MIA GR cells with different concentrations of CHL, CCK-8 method was used to detect the difference in IC₅₀ of CHL on the two types of cells; on the basis of IC₅₀, MIA WT and MIA GR cells were intervened with CHL and (or) GEM with different multiplicity of IC₅₀, respectively, and the growth inhibition curves of MIA WT and MIA GR cells were detected by the CCK-8 method under the intervention of CHL combined with GEM; After the intervention of MIA WT and MIA GR cells with CHL and (or) GEM at IC₅₀, respectively, the effects on the proliferation of the two different cells were detected using the clone formation assay; the effects on cytotoxicity/activity were observed under fluorescence microscopy; and the effects on apoptosis were detected using flow cytometry. Finally, western blotting was used to detect the effects of CHL and (or) GEM interventions on the drug resistance-associated molecules P-glycoprotein (P-gp) and ribonucleotide reductase regulatory subunit M2 (RRM2) in MIA GR cells, the and sensitivity-related molecule deoxycytidine kinase (DCK) on protein expression levels.

Results: MIA GR cells were verified to be well drug resistant, with resistance indices of 549.1 and 667.9 after 48 h and 96 h after GEM intervention compared to homologous wild-type MIA WT cells, respectively; CHL intervention inhibited the proliferation of MIA GR cells more significantly compared to that of MIA WT cells; and CHL in combination with GEM exerted a more significant growth inhibitory effect compared to GEM alone in both MIA WT cells (P<0.001) and MIA GR cells (P<0.01). CHL significantly inhibited the tumor proliferation of MIA GR cells, and the inhibitory effect was more pronounced in both cells when combined with GEM (P < 0.000 1); furthermore, compared to GEM alone, the intervention with CHL could cause more pronounced cytotoxicity (P < 0.000 1) in both MIA WT and MIA GR cells. caused more pronounced cytotoxicity (P < 0.000 1) and induced a higher percentage of apoptosis than GEM alone. The results of the western blotting assay showed that CHL intervention caused a decrease in the expression levels of P-gp and RRM2 proteins, as well as an increase in the protein expression level of DCK in MIA GR cells.

Conclusion: CHL increases the sensitivity of pancreatic cancer cells to GEM and also induces a decrease in the resistance of drug-resistant pancreatic cancer cells to GEM.

Ferroptosis is a form of iron dependent cell death, which is closely related to the progress and prognosis of bladder cancer (BCa). Among them, erroptosis related genes (FRGs) play an important role in the biological effects of BCa, such as participating in regulating the proliferation, migration, metastasis, drug resistance, immune regulation, and therapeutic efficacy of BCa cells. In addition, FRGs are also important biomarkers for predicting the prognosis of tumor patients. However, the specific mechanism of action of FRGs in BCa remains elusive. How to use FRGs to predict the prognosis of BCa and guide the treatment of BCa is still in the exploratory stage. Therefore, exploring the regulatory and predictive role of FRGs in BCa is particularly important for the diagnosis and treatment of BCa. This article aims to systematically elucidate the role of FRGs in the occurrence, development, treatment, and prognosis of BCa. To provide theoretical reference for further exploring the treatment of refractory and drug-resistant BCa patients, and constructing prognostic risk prediction models.

In 2024, Xue Jing's research team from Shanghai Jiao Tong University School of Medicine published a research paper in the journal Cancer Cell titled “Tumor Cell inflammatory dysregulation shapes cancer associated fibroblasts heterogeneity to metabolically support pancreatic cancer”. Studies have found that deletion of the tumor-intrinsic SET domain containing 2 (SETD2) releases bone morphogenetic protein 2 (BMP2) signals through abnormal increases in H3K27Ac, leading to the differentiation of cancer-associated fibroblasts (CAFs) cells toward a lipid-rich phenotype. Lipid-rich CAFs cells provide lipids to tumor cells through the ABCA8a transporter and enhance mitochondrial oxidative phosphorylation metabolism. Taken together, this study links epigenetic dysregulation of CAFs cells to tumor cells and highlights previously unrecognized metabolic crosstalk between CAFs cells and pancreatic tumor cells. In addition, the study also proposed using oxidative phosphorylation as a potential strategy for targeted treatment of patients with SETD2-deficient pancreatic ductal adenocarcinoma, providing new ideas for precise diagnosis and treatment.

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.

Thyroid cancer is the most common malignant tumor in head and neck surgery. In recent years, the incidence rate of thyroid cancer has increased rapidly. The traditional treatment is mainly surgical resection, supplemented by 131I treatment, but for advanced or metastatic thyroid cancer, these methods have limited effect. With the deepening of research on the molecular pathogenesis of thyroid cancer, targeted therapy has become a new research hot spot and important treatment method. In recent years, targeted therapy drugs have emerged one after another, such as sorafenib, anlotinib, serpatinib, pratinib, etc., all of which have shown good efficacy and significantly improved the progression free survival and objective remission rate of patients. However, targeted therapy still faces many problems such as drug resistance, and further research and development of more effective new drugs are needed. This article summarized the research progress of targeted therapy, and aimed to provide reference for the treatment of advanced or iodine refractory thyroid cancer.

Colon cancer is a common malignant tumor in the gastrointestinal tract, with morbidity and mortality rates increasing every year. Currently, the etiology of colon cancer has not been fully elucidated. With the deepening of colon cancer research and treatment, it is especially important to establish corresponding preclinical in vivo models. In the treatment of colon cancer, Chinese medicine follows the principle of diagnosis and treatment, adopts the method of supporting the positive and dispelling the evil, adjusts the body's qi and blood, and the deficiency of internal organs to maintain the balance of the body's yin and yang, so as to achieve the purpose of anti-tumor. Chinese medicine animal models of colon cancer can be broadly divided into five categories: damp-heat accumulation, qi stagnation and blood stasis, qi and blood deficiency, spleen and kidney yang deficiency and liver and kidney yin deficiency. Western animal models of colon cancer are commonly divided into 4 categories: spontaneous, induced, transplanted and genetically engineered. The paper summarizes the construction methods and characteristics of colon cancer animal models currently commonly used in Chinese and western medicine, and summarizes, analyzes and concludes the colon cancer animal models based on three aspects: how to select animal models, comparison of Chinese and western medicine modeling methods and evaluation of modeling success, with a view to finding suitable modeling methods for preclinical experiments, so as to provide guidance for the selection of animal models of colon cancer.

Objective: To evaluate the efficacy of almonertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), as a first-line treatment for patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) in the real-world clinical practise, and to systematically analyze the independent risk factors influencing their prognosis.

Methods: This retrospective cohort study enrolled 73 patients with EGFR-mutated advanced NSCLC who received first-line treatment with aumolertinib from April 1, 2020 to December 31, 2021. Survival curves were generated by using the Kaplan-Meier method, and intergroup comparisons were performed via log-rank test. Univariate and multivariate analyses of prognostic factors were conducted by using the COX proportional hazards regression model, with a focus on identifying prognostic factors in the subgroup of baseline brain metastases.

Results: Among 73 patients, the median progression-free survival (mPFS) was 19.4 months, and the disease control rate (DCR) was 93.2%. Multivariate COX regression analysis revealed that central nervous system (CNS) metastasis status, EGFR mutation subtype, ECOG performance status (PS) score, and gender might be independent risk factors for PFS. Among 33 patients with baseline brain metastases, combined almonertinib with radiotherapy or bevacizumab, maximum diameter of brain metastases(≥3 cm), and ECOG PS score might be independent risk factors of PFS.

Conclusion: This first real-world study confirms that aumolertinib demonstrates favorable efficacy as first-line treatment for EGFR-mutated locally advanced or metastatic NSCLC patients, aligning with findings from phase Ⅲ clinical trials. For patients in subgroup of baseline brain metastases, combining almonertinib with radiotherapy or bevacizumab is recommended to optimize outcomes.

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.

Cervical esophageal cancer (CEC) is a relatively rare pathological subtype of esophageal cancer, accounting for 2%~10% of all esophageal cancer cases, 95% of which are esophageal squamous cell carcinoma. Due to nonspecific clinical symptoms, most CEC patients are diagnosed at advanced or locally advanced stages, resulting in a 5-year overall survival (OS) rate of approximately 30%. Although therapeutic outcomes for CEC patients remain suboptimal, current studies have demonstrated the clinical value of multiple treatment modalities, including endoscopic therapy, photodynamic therapy, selective or salvage surgery, radiotherapy, chemotherapy, concurrent chemoradiotherapy (CCRT), immunotherapy, and targeted therapy. This article systematically reviews recent advances in CEC management, focusing on the aforementioned approaches, and delves into the optimal treatment strategies, aiming to provide a scientific and reliable foundation for clinical practise.

Primary retroperitoneal sarcomas, due to its special anatomical structure and lack of specific clinical manifestations in early stages, often leads to delayed diagnosis. because of the lack of specific clinical manifestations. By the time patients present with noticeable symptoms or palpable masses during clinical examination, the tumors has typically grown significantly in size and exhibits invasive growth patterns, frequently involving adjacent organs. Surgical treatment often necessitates multivisceral en bloc resection, with combined resection and functional reconstruction of gastrointestinal organs becoming critical components of the procedure. The surgical management of primary retroperitoneal sarcoma is characterized by extensive resection scope, technical complexity, and challenges in achieving complete tumor removal with wide clear negative margins. Additionally, the high propensity for local recurrence further increases the complexity of patient management. Current research on surgical treatment strategies for primary retroperitoneal sarcoma, particularly systematic studies focusing on combined gastrointestinal resection and functional reconstruction, remains insufficient. To enhance clinical understanding and optimize surgical approaches, this article systematically reviews domestic and international literature to summarize current research status and recent advancements in combined gastrointestinal resection and functional reconstruction for primary retroperitoneal sarcoma.

The ataxia telangiectasia mutated (ATM) gene is an important tumor suppressor gene and a key effector gene in regulating the repair of double-strand DNA breaks. It plays an indispensable role in maintaining genetic stability, facilitating cell cycle arrest, and modulating cell apoptosis. When the ATM gene mutates, it fails to effectively induce the phosphorylation of downstream targets, leading to impaired DNA repair mechanisms, genetic instability, and chromosomal structural abnormalities, ultimately promoting abnormal proliferation of tumor cells. Analysis of next-generation sequencing (NGS) datas reveals a relatively high mutation rate of the ATM gene in bladder cancer cells. Relevant studies have shown that ATM gene regulates the proliferation, invasion, and metastasis of bladder cancer cells through the signaling pathways such as nuclear transcription factor-κB (NF-κB) and Interferon-γ (IFNγ). Mutanted ATM gene can enhance patients’ sensitivity to radiotherapy and chemotherapy, and boost the efficacy of immunotherapy, resulting in a generally better prognosis for patients with ATM gene mutation. This finding marks ATM gene as a potential therapeutic target and predictive prognosis biomarker for bladder cancer patients. Therefore, this article will comprehensively review the research on the ATM gene in bladder cancer from 3 aspects: the structural characteristics of the ATM gene and its tumor-suppressing and tumor-promoting functions, the mechanism of action of the ATM gene in the occurrence and development of bladder cancer, and the impact of the ATM gene on the treatment and prognosis of bladder cancer patients. Additionally, the future research directions of the ATM gene was prospected, with the aim of providing new targets for the drug treatment of bladder cancer, and bringing new hope for the treatment of bladder cancer patients.

Objective: For small molecule drug 630120 based on proteolysis-targeting chimeras (PROTAC) that targets nicotinamide phosphoribosyltransferase (NAMPT), to explore its effect on the proliferation ability of colorectal cancer cells with low expression of nicotinate phosphoribosyltransferase (NAPRT).

Methods: This study detected the protein expression levels of NAMPT and Tubby in tumor tissues and adjacent normal tissues from 5 colorectal cancer patients by immunohistochemical staining. Additionally, the Gene Expression Profiling Interactive Analysis (GEPIA) platform was used to analyze the expression level of NAMPT mRNA in colorectal cancer tissues and corresponding adjacent normal tissues from The Cancer Genome Atlas (TCGA) database. Based on previous studies in hematologic malignancies, to detect the degradation of NAMPT protein in colorectal cancer (CRC) cell lines (SW480, HT29, RKO, SW620 and HCT116) treated with the drug PROTAC-630120. Furthermore, to create NAPRT knockdown and knockout colorectal cancer cell lines by using shNAPRT plasmids and CRISPR-Cas9 technology. The impact of different concentrations of PROTAC-630120 on the proliferation of NAPRT knockdown and knockout colorectal cancer cells was validated by Cell Titer-Glo (CTG) luminescence assay and colony formation assay. Finally, Western blotting was also used to detect the effect of PROTAC-630120 on the expression of downstream proteins in the MAPK signaling pathway in colorectal cancer cells.

Results: In colorectal cancer tissues, the expression levels of NAMPT protein and mRNA were significantly upregulated. The drug PROTAC-630120 can effectively degrade NAMPT protein in different colorectal cancer cells. Moreover, it can significantly inhibit the proliferation of NAPRT knockdown and knockout colorectal cancer cells. The IC₅₀ values (half-maximal inhibitory concentration) for different colorectal cancer cell lines treated with PROTAC-630120 were as follows: RKO^shNAPRT～49.03 nmol/L, HCT116^shNAPRT～42.28 nmol/L, SW620^shNAPRT～55.59 nmol/L, HT29^shNAPRT～29.66 nmol/L, SW480^shNAPRT～76.17 nmol/L, and SW480^sgNAPRT～27.01/34.23 nmol/L. Finally, the drug PROTAC-630120 can inhibit the MAPK-ERK signaling pathway in colorectal cancer cells.

Conclusion: The small molecule drug 630120 based on PROTAC that targets NAMPT protein, can inhibit the proliferation of NAPRT knockdown and knockout colorectal cancer cells, so it is expected to become a drug option for adjuvant therapy of cancer patients.

Objective: Assessing the therapeutic efficacy of methotrexate (MTX) -modified magnetic nanoparticles in thermo-chemotherapy for rat breast cancer and its impact on immune function.

Methods: Female Wistar rats were subcutaneously inoculated with breast cancer Walker-256 cells to establish a transplantation tumor model, and injected with polyethyleneimine (PEI)-modified Fe₃O₄ magnetic nanoparticles (47T group, 42T group and multiple 42T group) or MTX-modified Fe₃O₄ magnetic nanoparticles (47TC group, 42TC group and multiple 42TC group) for thermotherapy under the magnetic field at different temperatures (47 ℃ and 42 ℃). The rats injected with MTX-modified magnetic fluid only (MFC group) and the tumor-bearing rats without any treatment (blank control group), with irradiation treatment in an alternating magnetic field only for 30 minutes (M group), with injection of PEI-modified magnetic fluid only (MF group), with treatment of MTX-mono drug (MTX group) and not inoculated with tumor cells (normal group) were used as control groups. X-ray radiography was used to display the distribution of magnetic fluid in the tumor tissue 24 hours, 2 weeks and 2 months after intra-tumor injection. After 24 hours of treatment, three rats were selected from each of the 47T and 47TC groups, and the effect of magnetic fluid on tumor cells was observed under an electron microscope after execution. After 14 days of treatment, the tumor volume of rats was measured and statistically analyzed. At the same time, 4 rats were selected from each of the 47TC, 47T, 42TC, 42T, MFC, MTX, blank control and normal groups, and the levels of IL-2, IFN-γ and IL-4 in peripheral blood were detected by ELISA method. The remaining rats were observed for long-term survival.

Results: The magnetic nanoparticles were evenly distributed in the center of the tumor but unevenly distributed at the tumor’s edge; they primarily localize amomg tumor cells and can penertrate into tumor cells. Tumor growth was inhibited in rats in the 47TC, 47T, multiple 42TC and multiple 42T groups (all P<0.05), and the survival rates of the rats were high. As compared with the blank control group, the levels of IL-2 and IFN-γ were increased while the IL-4 level was decreased in the 47TC and 47T groups (all P<0.05).

Conclusion: Thermo-chemotherapy at 47 ℃ for 30 minutes and multiple sessions at 42 ℃ for 60 minutes can partially inhibit tumor growth and prolong rat survival. This effect maybe related to the thermo-chemotherapy at 47 ℃ for 30 minutes which can activate the body’s immune function.

Epidermal growth factor receptor (EGFR) gene exon 20 insertion mutation is a common driver gene activation mutation in non-small cell lung cancer (NSCLC). Tumors harboring this gene mutation are characterized by high heterogeneity, high malignancy, low detectability, poor response to conventional therapies, and poor prognosis. In recent years, significant progress has been made in the study of EGFR ex20ins mutation. The wide application of next-generation sequencing has improved the detection rate. The United States has approved the relevant indications of amivantamab in NSCLC patients with EGFR ex20ins mutation. A variety of new drugs have also achieved good results in previous studies. This article will summarize the structural characteristics, detection methods and clinical treatment progress of NSCLC patients with EGFR ex20ins mutations, hoping to provide help for the choice of clinical treatment for such patients.

Objective: To Evaluate the potential causal relationship between the levels of 179 lipids in peripheral blood and the risk of different subtypes of lung cancer by Mendelian randomization analysis.

Methods: A two-sample Mendelian randomization analysis was performed using data from the Genome-Wide Association Study (GWAS), and sensitivity analysis was performed to verify the reliability of the results. Single nucleotide polymorphisms (SNPs) were used as instrumental variables, and GWAS data for different subtypes of lung cancer were used as outcome variables. We analyze potential causal associations between the levels of 179 lipids and the risk of different subtypes of lung cancer.

Results: The causal relationship between phosphatidylcholine and lung adenocarcinoma was established as a protective factor, and Sphingomyelin and Triacylglycerol have been identified as being linked to lung adenocarcinoma and function as risk factors. Phosphatidylcholine were found to have a causal association with lung squamous cell carcinoma serving as a protective factor, and Phosphatidylethanolamine and Sphingomyelin were identified as risk factors for lung squamous cell carcinoma. However, the effects of different subtypes of Phosphatidylcholine on lung adenocarcinoma and lung squamous cell carcinoma were different. The study did not find evidence that lipids can influence small cell lung carcinoma.

Conclusion: This study provides evidence of a causal relationship between lipids level features and different subtypes of lung cancer.

Objective: To explore potential biomarkers of biliary tract carcinoma (BTC) by proteomic techniques based on isobaric tags for relative and absolute quantitation (iTRAQ).

Methods: Bile samples from 4 patients with BTC and 4 patients with benign biliary tract disease (BBD) were randomly selected from sample library of central laboratory, Qingpu branch of Zhongshan Hospital, Fudan University. After mixing samples within each group, iTRAQ labeling technology combined with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) was used for quantitative proteomic analysis. Then, differentially expressed proteins between the BTC and BBD groups were screened and subjected to bioinformatic analysis, including KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis, GO (Gene Ontology) enrichment analysis and protein-protein interaction (PPI) network analysis. The candidate protein with the largest fold change in expression abundance selected from the differentially expressed proteins as a potential diagnostic biomarker for BTC. Enzyme-linked immunosorbent assay (ELISA) validation and receiver operating characteristic (ROC) cure analysis were performed on this candidate protein using bile samples form 50 BTC patients and 50 BBD patients.

Results: A total of 12 differential expressed proteins were screened from the bile samples of 4 BTC patients and 4 BBD patients (FDR<1%). Haptoglobin (Hp) and Complement Factor H (CFH), as hub proteins in the PPI network, were significantly upregulated in the bile of BBD patients. ELISA results showed that Hp and CFH were significantly upregulated in the bile of patients with various subtypes of BTC (P<0.01).ROC curve analysis indicated that Hp and CFH in bile exhibited significant specificity and sensitivity in the diagnosis of BTC, and their diagnostic performance was superior to that of serum protein CA19-9.

Conclusion: In this study, iTRAQ labeling technology combined with 2D-LC-MS/MS was used to systematically analyze the proteomic differences between bile samples from BTC and BBD patients. Hp and CFH were identified as core differentially expressed proteins, and their diagnostic efficiency for BTC was significantly better than that of serum potein CA19-9. They can serve as potential biomarkers for early diagnosis and therapeutic targets of BTC.

Objective: To design protein binders of human epidermal growth factor receptor 2 (HER2, also known as ErbB2) using de novo protein design and to preliminarily evaluate their biological effects on tumor cells.

Methods: Based on de novo protein design strategy, utilizing RosettaDesign and ProteinMPNN algorithms to design the binding proteins targeting ErbB2. Concurrently, AlphaFold was applied to assess structural accuracy of the protein binders and their interactions with ErbB2. Subsequently, yeast surface display (YSD) technology combined with dual-fluorescence high-throughput flow cytometry were performed to screen for protein binders capable of specifically binding ErbB2. Selected binding proteins were expressed and purified in E. coli system. Bio-layer interferometry (BLI) was used to validate the specific binding capability of the purified protein binders to ErbB2. Finally, Western blotting and CCK-8 assays were used to evaluate the effects of the candidate binding proteins on downstream signaling of ErbB2 and cell proliferation capacity in ovarian cancer (SK-OV-3) and pancreatic cancer (BxPC-3) cell lines, respectively.

Results: In This study, the design of protein binders targeting ErbB2 was successfully designed. A corresponding binding protein library was established, and a protein binder that specifically binds to ErbB2 was screened out from it. After BLI verification, this protein binder could effectively bind to ErbB2. Further investigation revealed that this protein binder could effectively inhibited cell proliferation and reduced the phosphorylation level of AKT from ErbB2 downstream signaling pathway in ErbB2-high-expressing SK-OV-3 and BxPC-3 cells.

Conclusion: Based on the strategy of de novo protein design, this study successfully constructed a protein binder that can effectively bind to ErbB2, and this binder can effectively inhibit the activation of the downstream signaling pathway mediated by ErbB2 and the proliferation of tumor cells. This indicates the potential application value of de novo designed protein binders targeting ErbB2 in cancer therapy, and provides a novel research approach for the field of targeted tumor therapy.

Osteosarcoma is a primary bone tumor originating from mesenchymal tissues, highly aggressive and metastatic, and is one of the causes of orthopedic disorders in children and adolescents. The establishment of an osteosarcoma model is useful for studying the changes in the physiology and pathology of the organism after the occurrence of osteosarcoma. The establishment methods of osteosarcoma models not only differ in terms of difficulty, tumorigenicity, tumor-formation time, tumor survival time, tumor metastasis, and safety, but also in terms of simulating human osteosarcoma biological characteristics and histological features. In addition, the wide application of tissue engineering in tumor modeling is conducive to better study the role of the osteosarcoma microenvironment in osteosarcoma genesis and development. In this paper, we summarize the roles of different osteosarcoma animal models and their tissue engineering models in different experiments, in order to provide help for the study of osteosarcoma pathogenesis and drug intervention mechanism.

Objective: To explore the effect of C1q like protein 4 (C1ql4) on migration and invasion of breast cancer and its mechanism.

Methods: Real-time fluorescence quantitative PCR was used to detect the expression level of C1ql4 mRNA in tumor tissues and paracancerous tissues from 50 cases of breast cancer, as well as the breast cells including T549 and MCF-7 breast cancer cells, and MCF-10A normal breast cells. The siRNA targeting C1ql4 gene (siC1ql4) was synthesized and transfected into BT549 breast cancer cells by liposome transfection, and the silencing efficiency was detected by Western blotting. MTT assay was used to detect the proliferative ability of the cells in each group, the invasive ability of the cells was detected by Transwell assay, and the migratory ability of the cells was detected by scratch healing assay. Western blotting was used to detect the proliferative ability of the cells in each group. The expression levels of Snail, Slug, nuclear factor-κB (NF-κB) and phospho-NF-κB (p-NF-κB) were detected. The immunofluorescence was used to localize the distribution of NF-κB. Real-time fluorescence PCR was used to detect the mRNA expression levels of the NF-κB target genes TNF-α and IL-1β.

Results: The expression level of C1ql4 mRNA in breast cancer tissues was significantly higher than that in paracancerous tissues, and the expression level of C1ql4 mRNA in BT549 and MCF-7 breast cancer cells was significantly higher than that in MCF-10A normal breast cells (P<0.05). After silencing C1ql4 expression, the proliferation, invasion and migration abilities of BT549 cells were significantly decreased (all P<0.001); the mRNA and prorein expression levels of Snail and Slug were significantly down-regulated (both P<0.001), and the mRNA expression levels of TNFα and IL-1β were significantly reduced (both P<0.001). The amount of NF-κB entering the nucleus was reduced, and the ratio of p-NF-κB to NF-κB was reduced (both P<0.05).

Conclusion: The C1ql4 gene may regulate migration and invasion of breast cancer cells and promote breast cancer progression through the NF-κB pathway.

Objective: To explore the diagnosis and treatment strategies of multiple primary malignancies (MPM).

Methods: The medical records and the process of diagnosis and treatment of a patient with heterochronous double primary cancer were retrospectively analyzed, and the treatment strategy was discussed by multi-disciplinary team (MDT).

Results: A female patient with heterochronous double primary cancer was reported. The first primary tumor was gastric cancer and the second primary tumor was lung cancer. The first primary tumor was diagnosed at 67 years of age, and the interval between the first and second primary tumors was 13 months. Pleural metastasis and pelvic metastasis occurred during the follow-up. Pleural metastasis originated from lung cancer, and pelvic metastasis was considered as gastric cancer implantation. Tumor MDT discussion was conducted at each stage of diagnosis and treatment, and the histopathological diagnosis was confirmed by puncture biopsy or surgical resection. The patient received systemic therapy combined with local treatment for metastases of different tumors and had a longer overall survival (67 months). Side effects were tolerable, and the quality of life was satisfactory throughout the treatment period.

Conclusion: For patients with MPM, it is necessary to actively carry out MDT discussion, clarify the histopathological diagnosis, evaluate the clinicopathological and metastatic characteristics, and implement active and effective treatment.

Objective: To investigate the role of endoplasmic reticulum stress (ERS)-related long noncoding RNA (lnc RNA)-Gm9795 in the progression of hepatocellular carcinoma (HCC).

Methods: This retrospective cohort study included 80 HCC patients who underwent routine surgical procedures at our hospital from 2014 to 2020. Collect clinical data from all patients and use real-time fluorescence quantitative PCR to detect the expression level of Gm9795 in 80 patients' cancer and adjacent tissues, as well as in HCC cells (HepG2, Hep3B, HCCLM3, and Huh7). Analyze the correlation between Gm9795 expression and overall survival time and recurrence free survival time of HCC patients. Constructing HCCLM3 cells overexpressing Gm9795 through lentiviral infection, and constructing Huh7 cells silencing Gm9795 expression through liposome transfection. The proliferation ability of cells was evaluated using CCK-8 method and cell clone formation assay, while the migration and invasion ability of cells were detected using Transwell chamber assay. Identification of Gm9795 specific binding protein by mass spectrometry (MS). The effect of overexpressing or silencing Gm9795 expression on the expression of C/EBP homologous protein (CHOP) gene was detected by Western blotting. The CHOP gene was simultaneously transferred into HCCLM3 cells overexpressing Gm9795, and the effects of up-regulating CHOP expression level on the proliferation, migration, and invasion ability of HCCLM3 cells were evaluated using CCK-8 method, cell clone formation assay, and Transwell chamber assay.

Results: Compared with the corresponding non tumor tissues, the expression level of Gm9795 was significantly up-regulated in HCC tissues (P<0.001). All HCC cells exhibited significantly higher levels of Gm9795 expression than LO2 cells (all P<0.05). Higher expression levels of Gm9795 are associated with invasive clinical pathological features, including tumor size, multiple tumors, Barcelona Clinic Liver Cancer (BCLC) staging, and portal vein thrombosis (all P<0.05). The results of multivariate analysis showed that Gm9795 expression was an independent risk factor for overall survival and recurrence free survival in HCC patients (both P<0.05). The higher expression of Gm9795 was significantly correlated with shorter overall survival and recurrence free survival in the cohort (both P<0.01). Compared with the Vector group, the Gm9795 group showed a significant increase in cell viability, clone number, migration, and invasion of HCCLM3 cells (all P<0.01); Compared with the siNC group, the cell viability, clone number, migration, and invasion of Huh7 cells were significantly reduced in the siGm9795-1 and siGm9795-2 groups (all P<0.01). CHOP was identified as a Gm9795 specific binding protein by MS. Compared with the Gm9795+Vector group, the CHOP+Gm9795 group showed significant reductions in cell viability, clone number, migration, and invasive cell numbers (all P<0.01).

Conclusions: Gm9795 is up-regulated in HCC tissues, and the high expression of Gm9795 is an independent risk factor for the overall survival of HCC patients. Gm9795 promotes the proliferation and invasion of HCC cells, and its mechanism may be related to the inhibition of ERS mediated by CHOP signaling pathway.

Gasdermin family proteins play critical roles in cell pyroptosis. Previous studies mainly focused on the function of Gasdermin D and Gasdermin E, less attention has been paid to Gasdermin C. Recently, accumulating studies revealed some distinctive characters of Gasdermin C different from other Gasdermin proteins and the impact of Gasdermin C on the prognosis of different types of tumor. This review summarized the recent study progresses in terms of molecular structure of Gasdermin C, the Gasdermin C mediated pyroptotic pathway as well as the prognostic significance of Gasdermin C in tumors, by which to provide informative references for corresponding researchers.

With the progression of global population aging, the incidence and mortality of prostate cancer (PCa) have been increasing year by year, drawing widespread attention from all sectors of society. Based on the synthetic lethality strategy, the U.S. Food and Drug Administration (FDA) has successively approved multiple poly ADP-ribose polymerase (PARP) inhibitors for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years. This advancement has greatly stimulated the interest of researchers in novel synthetic lethal combination: the ataxia telangiectasia-mutated (ATM) gene and the ataxia telangiectasia and Rad3-related protein (ATR). In the DNA damage repair pathway, the ATM kinase primarily participates in the repair of DNA double-strand breaks, while ATR plays a crucial role in the repair of DNA single-strand breaks and exerts a positive regulatory function. ATR inhibitors are considered one of the most promising synthetic lethal targeted agents following PARP inhibitors, offering potential as a novel therapeutic option for patients with ATM gene mutations. However, current clinical research data on ATR inhibitors in the treatment of prostate cancer remain insufficient. Therefore, a deeper understanding of the synthetic lethality mechanism involving the ATM/ATR kinase combination is of crucial importance for advancing precision therapy of prostate cancer.

Objective: To compare the efficacy differences between the combination therapy of Callicarpa nudiflora and dexamethasone versus dexamethasone monotherapy via retention enema in the treatment of acute radiation proctitis.

Methods: A total of 100 patients with pelvic malignancies who developed acute radiation proctitis during radiotherapy at Jiangxi Provincial People's Hospital from November 2021 to June 2023 were enrolled, and randomly divided into two groups: a control group (50 cases) vs a treatment group (50 cases). Based on the acute radiation injury scoring criteria established by the Radiation Therapy Oncology Group (RTOG), patients with injury severity scores ≤1 were excluded. Subsequently, the remaining patients received the following interventions: the control group (45 cases) underwent single-agent dexamethasone retention enema, while the treatment group (47 cases) received a combined regimen of Callicarpa nudiflora combined with dexamethasone retention enema. Clinical symptoms, defecation frequency, and routine fecal parameters (leukocyte and erythrocyte counts) were recorded before and at 2 weeks of retention enema, to compare the efficacy differences between the two regimens.

Results: A statistically significant difference in therapeutic efficacy was observed between the treatment and control groups (χ² =11.37, P=0.003, P<0.05), with the regimen of Callicarpa nudiflora combined with dexamethasone retention enema in the treatment group demonstrating a markedly higher efficacy rate compared to the regimen of single-agent dexamethasone retention enema in the control group (82.2% vs 62.2%).

Conclusion: Callicarpa nudiflora combined with dexamethasone retention enema in the treatment of acute radiation proctitis, can significantly alleviates clinical symptoms and improves life quality of patients with acute radiation proctitis. This approach provides novel insights for optimizing clinical treatment strategies for acute radiation proctitis.

p21-activated kinase 5 (PAK5), a critical member of the PAK family, plays a significant regulatory role in cellular signaling transduction and cytoskeleton rearrangement. Accumulating researches have revealed that PAK5 is aberrantly expressed in various human malignancies, and its expression level is significantly correlated with tumor metastasis, invasiveness, and clinical prognosis of patients. At the molecular level, PAK5 promotes tumor cells migration and invasion by activating key signaling pathways (such as Wnt/β- catenin and MAPK) to induce epithelial-mesenchymal transition (EMT), modulating tumor-associated microRNA (miRNA) networks, and remodeling actin cytoskeleton to enhance cellular motility. This review systematically dissects the molecular structural features and phosphorylation-dependent activation mechanisms of PAK5, delves into molecular mechanisms of PAK5 in tumor cells migration and invasion, and evaluates the potential of PAK5 as a therapeutic target. This work aims to provide a new perspective for developing PAK5-targeted precision therapeutic strategies in malignant tumors.

Gastric cancer is one of the malignant tumors with strong invasion and heterogeneity. Individualized treatment of gastric cancer based on precise classification guidance is currently a research hotspot. Microsatellite instability-high (MSI-H) gastric cancer has specific clinical features, tumor microenvironment, and pathological characteristics, which have been used as tumor markers to evaluate the prognosis of gastric cancer patients. In recent years, immunotherapy has brought new hope for the treatment of gastric cancer patients, among whom MSI-H patients are considered the advantageous population for immunotherapy. This paper reports a case of MSI-H metastatic gastric cancer receiving immunotherapy combined with chemotherapy, and provides reference for clinical practice based on literature review.