Oncology Research最新文献

Background: Immune checkpoint inhibitors play an important role in the treatment of solid tumors, but the currently used immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) show limited clinical efficacy in many breast cancers. B7H3 has been widely reported as an immunosuppressive molecule, but its immunological function in breast cancer patients remains unclear.

Methods: We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program (TCGA) and the Gene Expression Omnibus (GEO) databases. MicroRNAs were selected using the TarBase, miRTarBase, and miRBase databases. The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays, which identified the specific action sites of interaction. The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR (qPCR). In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis. Additionally, the regulatory impact of hsa-miR-214-3p on B7H3 was examined. Enzyme-linked immunosorbent assays (ELISA) and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells (PBMCs) on immune cells and associated cytokines.

Results: In breast cancer tissues, the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p, as well as with the regulatory effects on breast cancercell behavior. Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3. Importantly, our research identified, for the first time, two binding sites for hsa-miR-214-3p on the 3' UTR of B7H3, both of which exert similar effects independently. Co-culture experiments revealed that hsa-miR-214-3p obstructs the suppressive function of B7H3 on CD8⁺ T cells and natural killer cells.

Conclusions: This study confirms the existence of two hsa-miR-214-3p binding sites on the 3' UTR of B7H3, reinforcing the role of hsa-miR-214-3p as a regulatory factor for B7H3. In breast cancer, hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3. These findings suggest new potential targets for the clinical treatment of breast cancer.

Nanotechnology in cancer therapy has significantly advanced treatment precision, effectiveness, and safety, improving patient outcomes and personalized care. Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells, precisely sensing the tumor microenvironment (TME) and sparing normal cells. These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation, and they can also overcome therapy resistance and deliver multiple drugs simultaneously. Despite these benefits, challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies. Cell-based drug delivery systems (DDSs) that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells. This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research. It covers approved and experimental nanoparticle therapies, including liposomes, micelles, protein-based and polymeric nanoparticles, as well as cell-based DDSs like macrophages, T-lymphocytes, dendritic cells, viruses, bacterial ghosts, minicells, SimCells, and outer membrane vesicles (OMVs). The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells. By detailing DDSs at different stages of development, from laboratory research to clinical trials and approved treatments, this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.

Background: The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma (DLBCL) has been reported previously. However, the detailed mechanisms of CCR7 in DLBCL, particularly regarding its interaction with lenalidomide treatment, are not fully understood.

Methods: Our study utilized bioinformatics approaches to identify hub genes in SU-DHL-2 cell lines treated with lenalidomide compared to control groups. Immunohistochemical data and clinical information from 122 patients with DLBCL were analyzed to assess the correlation of CCR7 and p-ERK1/2 expression with the prognosis of DLBCL. Furthermore, in vitro and in vivo experiments were conducted to clarify the role of CCR7 in the response of DLBCL to lenalidomide treatment.

Results: Our bioinformatics analysis pinpointed CCR7 as a hub gene in the context of lenalidomide treatment in DLBCL. Notably, 31.14% and 36.0% (44/122) of DLBCL cases showed positive expression for CCR7 and ERK1/2 respectively, establishing them as independent prognostic factors for adverse outcomes in DLBCL via multivariate Cox regression analysis. Additionally, our studies demonstrated that the external application of the protein CCL21 promoted proliferation, migration, invasion, and activation of the ERK1/2 pathway in SU-DHL-2 and OCI-LY3 cell lines with high levels of CCR7 expression. This effect was mitigated by CCR7 silencing through siRNA, application of ERK inhibitors, or lenalidomide treatment. In vivo experiments reinforced the efficacy of lenalidomide, significantly reducing tumor growth rate, tumor mass, serum total LDH levels, and expression of CCR7 and p-ERK1/2 in a SU-DHL-2 xenograft model in nude mice (p < 0.05).

Conclusion: Our study clarifies the potential role of the CCL21/CCR7/ERK1/2 axis in the therapeutic effects of lenalidomide in DLBCL treatment.

Background: Hepatocellular carcinoma (HCC) is the most common cause of cancer-related death in Saudi Arabia. Our study aimed to investigate the patterns of HCC and the effect of TNM staging, Alfa-fetoprotein (AFP), and Child-Turcotte Pugh (CTP) on patients' overall survival (OS).

Methods: A retrospective analysis was conducted on 43 HCC patients at a single oncology center in Saudi Arabia from 2015 to 2020. All patients had to fulfill one of the following criteria: (a) a liver lesion reported as definitive HCC on dynamic imaging and/or (b) a biopsy-confirmed diagnosis.

Results: The mean patient age of all HCC cases was 66.8 with a male-to-female ratio of 3.3:1. All patients were stratified into two groups: viral HCC (n = 22, 51%) and non-viral HCC (n = 21, 49%). Among viral-HCC patients, 55% were due to HBV and 45% due to HCV. Cirrhosis was diagnosed in 79% of cases. Age and sex did not significantly statistically differ in OS among viral and non-viral HCC patients (p-value > 0.05). About 65% of patients had tumor size >5 cm during the diagnosis, with a significant statistical difference in OS (p-value = 0.027). AFP was >400 ng/ml in 45% of the patients. There was a statistically significant difference in the OS in terms of AFP levels (p-value = 0.021). A statistically significant difference was also observed between the CTP score and OS (p-value = 0.02). CTP class B had the longest survival. BSC was the most common treatment provided to HCC patients followed by sorafenib therapy. There was a significant statistical difference in OS among viral and non-viral HCC patients (p-value = 0.008).

Conclusions: The most common predictors for OS were the underlying cause of HCC, AFP, and tumor size. Being having non-viral etiology, a tumor size >5 cm, an AFP > 400 ng/mL, and a CTP score class C were all negatively associated with OS.

Liposarcoma is one of the most common soft tissue sarcomas, however, its occurrence rate is still rare compared to other cancers. Due to its rarity, in vitro experiments are an essential approach to elucidate liposarcoma pathobiology. Conventional cell culture-based research (2D cell culture) is still playing a pivotal role, while several shortcomings have been recently under discussion. In vivo, mouse models are usually adopted for pre-clinical analyses with expectations to overcome the issues of 2D cell culture. However, they do not fully recapitulate human dedifferentiated liposarcoma (DDLPS) characteristics. Therefore, three-dimensional (3D) culture systems have been the recent research focus in the cell biology field with the expectation to overcome at the same time the disadvantages of 2D cell culture and in vivo animal models and fill in the gap between them. Given the liposarcoma rarity, we believe that 3D cell culture techniques, including 3D cell cultures/co-cultures, and Patient-Derived tumor Organoids (PDOs), represent a promising approach to facilitate liposarcoma investigation and elucidate its molecular mechanisms and effective therapy development. In this review, we first provide a general overview of 3D cell cultures compared to 2D cell cultures. We then focus on one of the recent 3D cell culture applications, Patient-Derived Organoids (PDOs), summarizing and discussing several PDO methodologies. Finally, we discuss the current and future applications of PDOs to sarcoma, particularly in the field of liposarcoma.

Brain metastasis and primary glioblastoma multiforme represent the most common and lethal malignant brain tumors. Its median survival time is typically less than a year after diagnosis. One of the major challenges in treating these cancers is the efficiency of the transport of drugs to the central nervous system. The blood-brain barrier is cooperating with advanced stages of malignancy. The blood-brain barrier poses a significant challenge to delivering systemic medications to brain tumors. Nanodrug delivery systems have emerged as promising tools for effectively crossing this barrier. Additionally, the development of smart nanoparticles brings new hope for cancer diagnosis and treatment. These nanoparticles improve drug delivery efficiency, allowing for the creation of targeted and stimuli-responsive delivery methods. This review highlights recent advancements in nanoparticle and smart nanoparticle technologies for brain cancer treatment, exploring the range of nanoparticles under development, their applications, targeting strategies, and the latest progress in enhancing transport across the blood-brain barrier. It also addresses the ongoing challenges and potential benefits of these innovative approaches.

Background: Long noncoding RNA, LINC01106 exhibits high expression in lung adenocarcinoma (LUAD) tumor tissues, but its functional role and regulatory mechanism in LUAD cells remain unclear.

Methods: LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed. LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth. The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database (TFDB) database and Gene Expression Profiling Interactive Analysis (GEPIA) database. Additionally, the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes (ATGs) in LUAD cells.

Results: Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines. The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD. Additionally, LINC01106 was found to recruit TATA-binding protein-associated factor 15 (TAF15), an RNA-binding protein, thereby enhancing the mRNA stability of TEA domain transcription factor 4 (TEAD4). In turn, TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression. Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes (ATGs). The silencing of LINC01106 in LUAD cells inhibited autophagy, and cell proliferation, and promoted apoptosis, which all were effectively reversed by ATG5 overexpression.

Conclusions: Overall, LINC01106, transcriptionally activated by TEAD4, interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs, promoting malignancy of LUAD cells.

Background: Transmembrane emp24 trafficking protein 3 (TMED3) is associated with the development of several tumors; however, whether TMED3 regulates the progression of prostate cancer remains unclear.

Materials and methods: Short hairpin RNA was performed to repress TMED3 in prostate cancer cells (DU145 cells) and in a prostate cancer mice model to determine its function in prostate cancer in vitro and in vivo.

Results: In the present study, we found that TMED3 was highly expressed in prostate cancer cells. In vitro, shTMED3 treatment suppressed the proliferation, invasion, and migration and promoted the apoptosis of DU145 cells. Additionally, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed a strong correlation between TMED3 and forkhead box O transcription factor (FOXO) pathway. Furthermore, TMED3 inhibition efficiently decreased FOXO1a and FOXO3a phosphorylation. In vivo, TMED3 downregulation suppressed the apoptosis, growth, and metastasis of prostate cancer cells via FOXO1a and FOXO3a.

Conclusion: The present findings show that TMED3 participates in the regulation of prostate cancer progression via FOXO1a and FOXO3a phosphorylation, thereby revealing a novel mechanism underlying prostate cancer development and suggesting that TMED3 inhibition may serve as a novel strategy for prostate cancer treatment.

Objective: Small cell lung cancer (SCLC) is commonly recognized as the most fatal lung cancer type. Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers, their benefits are limited to a minority of patients with SCLC. In the present study, novel indicators for predicting the outcomes and molecular targets for SCLC treatment were elucidated.

Methods: We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in SCLC. The functional role of the key gene identified in SCLC was determined both in vitro and in vivo.

Results: A significant correlation was observed between patient survival and CD56dim natural killer (NK) cell proportion. Furthermore, we noted that the hub gene ubiquitin-specific protease 1 (USP1) is closely correlated with both CD56dim NK cells and overall survival in SCLC. Bioinformatics analysis revealed that USP1 is upregulated in SCLC. In addition, gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune responses. By co-cultivating NK-92 cells with SCLC cells, we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological inhibition. Furthermore, using a nude-mice xenograft tumor model, we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated markers.

Conclusions: Our study findings highlight the importance of NK cells in regulating SCLC. USP1 overexpression can inhibit NK cell-mediated immunity; therefore, USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.

Background: Lung cancer is a life-threatening disease that occurs worldwide, but is especially common in China. The crucial role of the tumour microenvironment (TME) in non-small cell lung cancer (NSCLC) has attracted recent attention. Cancer-associated fibroblasts (CAFs) are the main factors that contribute to the TME function, and CAF exosomes are closely linked to NSCLC.

Methods: The expression levels of miR-3124-5p and Toll-interacting protein (TOLLIP) were analysed by bioinformatics prediction combined with RT-qPCR/Western Blot detection. Fibroblasts were isolated and identified from clinical NSCLC tissues. Transmission electron microscopy and Western Blot were used to identify exosomes from these cells. Changes in proliferation (CCK-8 and clone formation), migration (wound healing), and invasion (transwell) of NSCLC cells were measured. The Luciferase reporter test was applied to clarify the binding of miR-3124-5p to TOLLIP. The TOLLIP/TLR4/MyD88/NF-κB pathway proteins were determined using Western blot analysis.

Results: MiR-3124-5p is overexpressed in clinical tissues and cells of NSCLC. MiR-3124-5p was dramatically enriched in CAF-derived exosomes. Cellular experiments revealed that CAFs delivered miR-3124-5p into NSCLC cells via exosomes, stimulating cancer cell progression. MiR-3124-5p acted as a sponge to negatively regulate TOLLIP expression, which activated the TLR4/MyD88/NF-κB axis to promote the occurrence and development of NSCLC. Functional salvage tests were performed to determine whether CAF-exosome-derived miR-3124-5p plays a pro-cancer role in NSCLC by affecting the TOLLIP signalling pathway.

Conclusions: These results provide an interesting direction for the diagnosis and therapy of NSCLC.