Cancer Cell International最新文献

Background: The aim of this study was to establish a primary mouse gastric carcinoma cell line.

Methods: Gastric adenocarcinoma in the body region was induced in immunocompetent BALB/c mice using N-Methyl-N-nitrosourea and a 2% NaCl solution. Fresh gastric cancer tissue samples were cultured in 1640 medium supplemented with 10% fetal bovine serum for primary culture and subculture. Cellular morphology was assessed via light microscopy, and a cell growth curve was established. Genomic and proteomic analyses were conducted to characterize the molecular features of the cell lines. This cell line demonstrated a 100% success rate in forming subcutaneous tumors in BALB/c mice. By integrating proteomic profiles from clinical gastric cancer patients and the murine subcutaneous tumor model, several molecular targets suitable for preclinical investigation were identified. Trametinib, a MEK inhibitor, was employed as a model compound in our preclinical study.

Results: A novel gastric carcinoma cell line, designated MCC, was established from BALB/c mice. This cell line exhibited a doubling time of approximately 33 h. Genomic and proteomic analyses identified mutations frequently observed in clinical gastric cancer patients, such as Kras, Egfr, and Ccnd3. Additionally, MCC overexpresses proteins, including SLC1A5, MCM6, and ITGA2, which are significantly upregulated in gastric cancer tissues compared to adjacent non-cancerous tissues. The MCC cell line demonstrated stable tumorigenicity in immunocompetent BALB/c mice, forming subcutaneous tumors that closely resemble the proteomic profile of clinical gastric cancer samples. This high concordance facilitated the identification of several potential therapeutic targets for gastric cancer. Preclinical studies with trametinib revealed that treatment effectively inhibited gastric cancer growth, likely mediated through the activation of immune cells, particularly neutrophils and T cells.

Conclusions: The MCC cell line serves as an indispensable model for gastric cancer research, offering a robust platform for investigating tumor development and progression. Its exceptional tumorigenic capacity and strong concordance with clinical proteomic profiles underscore its significance in translational research, facilitating the discovery of novel therapeutic targets and elucidation of molecular pathways critical for developing effective treatment strategies.

Clear cell renal cell carcinoma (ccRCC) is a globally severe cancer with an unfavorable prognosis. PANoptosis, a form of cell death regulated by PANoptosomes, plays a role in numerous cancer types. However, the specific roles of genes associated with PANoptosis in the development and advancement of ccRCC remain unclear. Our study developed a risk model utilizing three PANoptosis-associated genes (Caspase 4 (CASP4), TLR3, and CASP5). This model demonstrated a high degree of precision in predicting the prognosis for patients with ccRCC. ccRCC patients in the high-risk group had the strongest immune cell activity, experiencing immune evasion, and might potentially derive advantages from treatment involving combined immune checkpoint inhibitors. CASP5 was highly expressed in ccRCC tissues by RT-qPCR, western blotting, and immunofluorescence. Stable CASP5 knockdown cell lines were constructed by lentivirus in vitro transfection technique. Reducing CASP5 level suppressed the growth, migration, and invasion of ccRCC cells, while encouraging cell apoptosis. In addition, the results of in vivo tumorigenesis experiments showed that down-regulating CASP5 expression inhibited the tumorigenic ability of 786-O cells. Together, the innovative risk model using PANoptosis-associated genes effectively forecasts the tumor microenvironment and survival rates for ccRCC, offering a novel approach to the early, precise diagnosis of ccRCC and the advancement of personalized treatment strategies.

Super-enhancers (SEs) represent a distinct category of cis-regulatory elements notable for their robust transcriptional activation capabilities. In tumor cells, SEs intricately regulate the expression of oncogenes and pivotal cancer-associated signaling pathways, offering significant potential for cancer treatment. However, few studies have systematically discussed the crucial role of SEs in hepatocellular carcinoma (HCC), which is one of the most common liver cancers with late-stage diagnosis and limited treatment methods for advanced disease. Herein, we first summarize the identification methods and the intricate processes of formation and organization of super-enhancers. Subsequently, we delve into the roles and molecular mechanisms of SEs within the framework of HCC. Finally, we discuss the inhibitors targeting the key SE-components and their potential effects on the treatment of HCC. In conclusion, this review meticulously encapsulates the distinctive characteristics of SEs and underscores their pivotal roles in the context of hepatocellular carcinoma, presenting a novel perspective on the potential of super-enhancers as emerging therapeutic targets for HCC.

Exercise is one of the most important activities for every individual due to its proven health beneficials. Several investigations have highlighted the advantageous impacts of aerobic exercise, largely attributed to its capacity to enhance the body's capability to defend against threats against oxidative stress. The information currently accessible suggests that adding regular aerobic exercise to a daily routine greatly decreases the chances of developing serious cancer and passing away. An unevenness in the levels of free radicals and the body's antioxidant defenses, made up of enzyme and non-enzyme antioxidants, results in oxidative pressure. Generally, an imbalance in the levels of oxidative stress triggers the creation of harmful reactive oxygen or nitrogen compounds, causing the development or progression of numerous ailments, including cancer. The equilibrium between pro-oxidant and antioxidant substances is a direct indicator of this imbalance. Green tea and its derivatives are rich sources of bioactive substances such as flavonoids and polyphenols which possess antioxidant abilities. Moreover, modulation of epigenetic targets as well as inflammatory pathways including ERK1/2 and NF-κB are other proposed mechanisms for its antioxidant activity. Recent studies demonstrate the promise of green tea as an antioxidant, showing its ability to decrease the likelihood of developing cancer by impacting actions like cell growth, blood vessel formation, and spread of cancer cells. This summary will concentrate on the complex network of different pathways related to physical activity and consumption of green tea. In particular, the focus of this research will be on examining how oxidative stress contributes to health and investigating the potential antioxidant properties of green tea, and the interconnected relationship between exercise and green tea in the treatment of cancer. Elucidation of these different pathways would help scientists for development of better therapeutic targets and further increase of current anticancer agents efficiency.

Background: Hepatocellular carcinoma (HCC) continues to be a major cause of cancer-related death worldwide, primarily due to delays in diagnosis and resistance to existing treatments. Recent research has identified ATP-dependent chromatin remodeling-related genes (ACRRGs) as promising targets for therapeutic intervention across various types of cancer. This development offers potential new avenues for addressing the challenges in HCC management.

Methods: This study integrated bioinformatics analyses and experimental approaches to explore the role of ACRRGs in HCC. We utilized data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), applying machine learning algorithms to develop a prognostic model based on ACRRGs' expression. Experimental validation was conducted using quantitative real-time Polymerase Chain Reaction (qRT-PCR), Western blotting, and functional assays in HCC cell lines and xenograft models.

Results: Our bioinformatics analysis identified four key ACRRGs-MORF4L1, HDAC1, VPS72, and RUVBL2-that serve as prognostic markers for HCC. The developed risk prediction model effectively distinguished between high-risk and low-risk patients, showing significant differences in survival outcomes and predicting responses to immunotherapy in HCC patients. Experimentally, MORF4L1 was demonstrated to enhance cancer stemness by activating the Hedgehog signaling pathway, as supported by both in vitro and in vivo assays.

Conclusion: ACRRGs, particularly MORF4L1, play crucial roles in modulating HCC progression, offering new insights into the molecular mechanisms driving HCC and potential therapeutic targets. Our findings advocate for the inclusion of chromatin remodeling dynamics in the strategic development of precision therapies for HCC.

Background: Colorectal cancer (CRC) is a globally prevalent malignancy, primarily affecting the colon and rectum, characterized by uncontrolled cellular changes in the intestinal wall lining. Recent evidence underlines the significant role of the CXCL12/CXCR4 axis in the development of CRC, suggesting that inhibiting this pathway could be a promising therapeutic approach. This study focuses on investigating the potential of N, N''-thiocarbonylbis (N'-(3,4-dimethyl phenyl)-2,2,2-trifluoroacetimidamide) (A1), a novel fluorinated CXCR4 inhibitor, through a comprehensive analysis encompassing in silico, in vitro, and in vivo studies.

Methods: The molecular dynamic simulation method was employed to compute A1 binding affinity and energy for the CXCR4 receptor compared to AMD3100. In vitro experiments utilized the CT-26 mouse CRC cell line to compare the inhibitory effects of A1 and AMD3100 on tumor cell proliferation and migration. Following the development of the CRC animal model in BALB/c mice, immune system responses within the tumor microenvironment (TME) were evaluated. Flow cytometry and real-time PCR (RT-PCR) were used to measure the effects of AMD3100 and A1 on regulatory T-cell (Treg) infiltration and the expression of CXCR4, vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF), interleukin-10 (IL-10), and tumor growth factor-beta (TGF-β) genes in tumor tissue. Additionally, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) techniques were employed to assess VEGF, IL-10, and TGF-β tissue levels at the protein level.

Results: Molecular dynamic simulation studies with molecular mechanics Poisson-Boltsman surface area (MM-PBSA) analysis revealed that A1 exhibits significantly lower binding energy for the CXCR4 receptor than AMD3100. A1 effectively inhibited the proliferation of CT-26 cells, significantly reduced tumor cell migration, attenuated Treg infiltration, and suppressed IL-10 and TGF-β expression at both mRNA and protein levels in vivo. Notably, A1 outperformed AMD3100 in reducing tumor size and increasing survival rate in treated animals, with minimal side effects.

Conclusion: These findings emphasize the potential of A1 as a favorable anti-tumor small molecule in CRC. Further validation through rigorous preclinical and clinical studies may position A1 as a promising alternative to AMD3100 in human cancers.

Breast cancer will overtake all other cancers in terms of diagnoses in 2024. Breast cancer counts highest among women in terms of cancer incidence and death rates. Innovative treatment approaches are desperately needed because treatment resistance brought on by current clinical drugs impedes therapeutic efficacy. The T cell-based immunotherapy known as chimeric antigen receptor (CAR) T cell treatment, which uses the patient's immune cells to fight cancer, has demonstrated remarkable efficacy in treating hematologic malignancies; nevertheless, the treatment effects in solid tumors, like breast cancer, have not lived up to expectations. We discuss in detail the role of tumor-associated antigens in breast cancer, current clinical trials, barriers to the intended therapeutic effects of CAR-T cell therapy, and potential ways to increase treatment efficacy. Finally, our review aims to stimulate readers' curiosity by summarizing the most recent advancements in CAR-T cell therapy for breast cancer.

Background: Specific molecular mechanisms by which AURKA promoted LSCC metastasis were still unknown.

Methods: Bioinformatic analysis was performed the relationship between TRIM28 and LSCC. Immunohistochemistry, Co-IP assay, Rt-PCR and Western Blot were used to examine the expression of related molecular. Flow cytometry was used to examine cell numbers of G0/G1 phase. Plate colony formation, wound healing, migration, invasion and tail vein injection in nude mice assays were applied to examine the proliferation, movement, migration, invasion and metastasis of LSCC.

Results: TRIM28 was significantly correlated with LSCC. TRIM28 highly expressed in LSCC and the high TRIM28 expression was related to TNM stage and poor clinical prognosis. Furthermore, AURKA could regulate TRIM28. In addition, deprivation TRIM28 expression induced LSCC cells into dormant state and inhibited LSCC metastasis. Akt signaling pathway played an essential role in promoting the tumor-promoting effects induced by TRIM28.

Conclusion: AURKA mediated TRIM28 to revive dormant LSCC cells via Akt signaling pathway to promote LSCC metastasis, targeting TRIM28 might provide a potential treatment strategy for LSCC.

Background: Tumor microenvironment (TME) plays a crucial role in tumor growth and metastasis. Exploring biomarkers that are significantly associated with TME can help guide individualized treatment of patients.

Methods: We analyzed the expression and survival of P4HB in pan-cancer through the TCGA database, and verified the protein level of P4HB by the HPA database. In addition, we used the Metascape database to construct protein-protein interaction networks and the single-cell Sequencing database for functional analysis. An immune cell infiltration analysis was performed to explore the potential role of P4HB in TME. We further analyze the relationship between P4HB and immune checkpoint molecules to explore the role of P4HB in immune checkpoint blockade therapy. Finally, the oncogenic role of P4HB in RCC cells was validated using colony formation and wound healing assays.

Results: RNA and protein levels of P4HB were extensively up-regulated in pan-cancer. However, high P4HB expression was associated with poor survival in KIRC. The clinical relevance analyses of P4HB suggested that high P4HB expression was associated with advanced clinical TNM stage. Moreover, multivariate cox regression analysis indicated that P4HB (HR = 1.372, 95% CI 1.047-1.681, P = 0.019) was an independent risk factor for OS in KIRC. Functional analysis revealed that P4HB is involved in hypoxia, TME and immune system processes. Our study also found that high P4HB expression was significantly correlated with elevated infiltration levels in CD8 + T cells and M2 macrophages. The results of colony formation and wound healing assays showed that knockdown of P4HB inhibited the RCC growth and migration.

Conclusions: P4HB is a specific biomarker for KIRC prognosis and is significantly associated with clinical characteristics. In addition, P4HB may play an influential role in TME and is a biomarker for ICB therapy.

Tumor organoids have emerged as powerful tools for in vitro cancer research due to their ability to retain the structural and genetic characteristics of tumors. Nevertheless, the absence of a complete tumor microenvironment (TME) limits the broader application of organoid models in immunological studies. Given the critical role of immune cells in tumor initiation and progression, the co-culture model of organoids and peripheral blood mononuclear cells (PBMCs) may provide an effective platform for simulating the interactions between immune and tumor cells in vitro. This model stands as a robust instrument for dissecting the TME, elucidating the molecular interactions, and exploring the therapeutic applications of chimeric antigen receptor (CAR)-engineered lymphocytes, as well as other cancer treatment modalities. This review systematically evaluates the advantages and disadvantages of the co-culture model, identifies its technical bottlenecks, and proposes corresponding optimization strategies. By summarizing the latest research advancements in this co-culture model, our goal is to provide valuable insights for further model optimization and clinical application, thereby promoting immunological research and bridging the gap between experimental outcomes and clinical practice.