Oncology Research最新文献

Background: Circular RNAs play an important role in regulating lung adenocarcinoma (LUAD). Bioinformatics analysis identified circ_0015278 as differentially expressed in LUAD. However, the biological mechanism of circ_0015278 in LUAD has not been fully clarified, especially in ferroptosis.

Materials and methods: Bioinformatics analysis was employed to explore the downstream mechanisms of Circ_0015278, subsequently confirmed by luciferase reporter assays. The impact of Circ_0015278 on cell proliferation, migration, invasion, and ferroptosis was investigated through a loss-of-function experiment. A xenotransplantation mouse model elucidated the effect of Circ_0015278 on tumour growth.

Results: Circ_0015278 exhibited downregulation in LUAD. It inhibited cell proliferation, migration, and invasion while promoting ferroptosis by interacting with miR-1228 to regulate P53 expression through a competitive endogenous RNA mechanism. Moreover, circ_0015278 suppressed tumour growth in mice.

Conclusions: Circ_0015278 was identified as a novel factor promoting ferroptosis in LUAD. Furthermore, it suppressed the malignant progression of LUAD through the miR-1228/P53 axis.

Background: Clear cell renal carcinoma (ccRCC), the leading histological subtype of RCC, lacks any targeted therapy options. Although some studies have shown that early growth response factor 1 (EGR1) has a significant role in cancer development and progression, its role and underlying mechanisms in ccRCC remain poorly understood.

Methods: The Cancer Genome Atlas (TCGA) database was utilized to examine the expression of EGR1 in ccRCC. The expression of EGR1 in 55 ccRCC tissues was evaluated using immunohistochemistry. The link between EGR1 expression and clinicopathological variables was examined through an analysis. Gain-of-function assays were employed to investigate EGR1's biological functions in ccRCC cells, involving proliferation, colony formation, invasion assays, and tumorigenesis in nude mice. In order to assess the protein expression of mitogen-activated protein kinase 15 (MAPK15), E-cadherin, matrix metalloproteinase-9/-2 (MMP-9 and MMP-2), Western blot technique was applied.

Results: The results revealed a decrease in EGR1 expression in ccRCC tissues. This decrease was strongly linked to TNM stage, lymphatic metastasis, tumor size, histological grade, and unfavorable prognosis in ccRCC patients. It has been demonstrated that overexpressing EGR1 inhibits the growth of xenograft tumors in vivo and inhibits cell colony formation, motility, and invasion in vitro. Furthermore, EGR1 can prevent the development and movement of ccRCC cells by controlling the expression of MMP-2, MMP-9, E-cadherin, and MAPK15.

Conclusions: The EGR1/MAPK15 axis may represent a promising target for drug development, with EGR1 serving as a possible target for ccRCC therapy.

Cancer, a leading cause of global mortality, remains a significant challenge to increasing life expectancy worldwide. Forkhead Box R2 (FOXR2), identified as an oncogene within the FOX gene family, plays a crucial role in developing various endoderm-derived organs. Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases. Dysregulation of FOXR2 has been linked to numerous malignant tumors, spanning the brain, nervous system, thyroid, osteosarcoma, Hodgkin lymphoma, colorectal, liver, pancreatic, lung, breast, ovarian, prostate, female genital tract, endometrial, and uterine cancers. Despite extensive research on FOXR2 dysregulation, its practical applications remain underexplored. This review delves into the mechanisms underlying FOXR2 dysregulation during oncogenesis and its implications for cancer diagnosis, prognosis, and treatment.

Background: To date, there is no effective cure for the highly malignant brain tumor glioblastoma (GBM). GBM is the most common, aggressive central nervous system tumor (CNS). It commonly originates in glial cells such as microglia, oligodendroglia, astrocytes, or subpopulations of cancer stem cells (CSCs). Glucose plays an important role in the, which energy metabolism of normal and cancer cells, but cancer cells exhibit an increased demand for glucose is required for their differentiation and proliferation. The main aim of this study is to explore the anti-cancer efficacy of the ketogenic diet against GBM. Also, this research focuses on the identification of the catalytic action of zinc in epigenetic modulators such as oxyresveratrol and ensures the combinatorial effect in the treatment of GBM.

Method: In this study, we have evaluated various parameters to understand the therapeutic efficacy of the treatment groups through in vivo experiments against aggressive brain tumors. Intracerebroventricular experiments were performed to induce the tumor in the animals and estimate the tumor burden and proliferative index. Followed by the Morris water maze, an open field test, and rota rod was performed to evaluate the memory and motor coordination. To understand the glucose, and ketone level modification before and after treatment, the level of glucose and ketone was analyzed. Moreover, the zinc level is assessed using flame atomic absorption spectroscopy.

Results: The results suggested that the ketogenic diet has an anti-cancer efficacy against C6-induced GBM cell lines. Also, it exerts a synergistic effect with the epigenetic modulator, oxyresveratrol, and zinc against GBM cell lines. Moreover, the treatment groups improved memory and motor coordination and modified the glucose and ketone levels to reduce the tumor burden and Ki-67 proliferative index.

Conclusion: This study revealed the therapeutic effect of the ketogenic diet along with its combination such as oxyresveratrol and zinc against the C6-induced GBM in the Wistar rats. Also, it improved memory and motor coordination and reduced tumor growth. It also modified the glucose and ketone levels in the tumor-induced animal and supported to diminish the tumor burden.

Objectives: Mitochondrial Ca²⁺ uniporter (MCU) provides a Ca²⁺ influx pathway from the cytosol into the mitochondrial matrix and a moderate mitochondrial Ca²⁺ rise stimulates ATP production and cell growth. MCU is highly expressed in various cancer cells including breast cancer cells, thereby increasing the capacity of mitochondrial Ca²⁺ uptake, ATP production, and cancer cell proliferation. The objective of this study was to examine MCU inhibition as an anti-cancer mechanism.

Methods: The effects of MCU-i4, a newly developed MCU inhibitor, on cell viability, apoptosis, cytosolic Ca²⁺, mitochondrial Ca²⁺ and potential, glycolytic rate, generation of ATP, and reactive oxygen species, were examined in breast cancer BT474 cells.

Results: MCU-i4 caused apoptotic cell death, and it decreased and increased, respectively, mitochondrial and cytosolic Ca²⁺ concentration. Inhibition of MCU by MCU-i4 revealed that cytosolic Ca²⁺ elevation resulted from endoplasmic reticulum (ER) Ca²⁺ release via inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors (RYR). Unexpectedly, MCU-i4 enhanced glycolysis and ATP production; it also triggered a large production of reactive oxygen species (ROS) and mitochondrial membrane potential collapse.

Conclusion: Cytotoxic mechanisms of MCU-i4 in cancer cells involved enhanced glycolysis and heightened formation of ATP and ROS. It is conventionally believed that cancer cell death could be caused by inhibition of glycolysis. Our observations suggest cancer cell death could also be induced by increased glycolytic metabolism.

Background: Gastric Cancer (GC) is the 5th most prevalent and 4th most deadly neoplasm globally. Immunotherapy has emerged as a promising treatment approach in GC, potentially improving positive clinical outcomes while addressing the limitations of conventional therapies. GC immunotherapy modalities consist of adoptive cell therapy (ACT), cancer vaccines, and immune checkpoint inhibitors (ICI).

Objectives: This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC, highlighting the potential of this therapy as a strategy for GC treatment.

Methods: Key studies investigating several immunotherapeutic agents and combination therapies were searched in PUBMED and included in this study. Specific cancer outcomes related to disease progression or survival were analyzed.

Results: After screening 236 studies, the results revealed that immunotherapy, particularly the ICI pembrolizumab, demonstrated promising efficacy in the treatment of GC, as several studies reported improved OS, PFS, and objective response rate with the use of pembrolizumab alone or in combination with other treatment modalities.

Conclusion: Safety analysis showed that immunotherapy was mostly well-tolerated, with manageable adverse events and relatively good safety profiles. Nonetheless, further research is required to understand the mechanisms of tumor resistance better and identify predictive biomarkers that can direct treatment optimization.

Angiogenesis, the expansion of pre-existing vascular networks, is crucial for normal organ growth and tissue repair, but is also involved in various pathologies, including inflammation, ischemia, diabetes, and cancer. In solid tumors, angiogenesis supports growth, nutrient delivery, waste removal, and metastasis. Tumors can induce angiogenesis through proangiogenic factors including VEGF, FGF-2, PDGF, angiopoietins, HGF, TNF, IL-6, SCF, tryptase, and chymase. This balance is disrupted in tumors, and extracellular vesicles (EVs) contribute to this by transferring proangiogenic factors and increasing their expression in endothelial cells (ECs). Malignant melanoma, a particular type of skin cancer, accounts for only 1% of skin cancer cases but more than 75% of deaths. Its incidence has risen significantly, with a 40% increase between 2012 and 2022, especially in fair-skinned populations. Advanced metastatic stages have a high mortality due to delayed diagnosis. This review examines the molecular basis of angiogenesis in melanoma, focusing on melanoma-derived EVs and their possible use in new antiangiogenic therapies.

The B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) protein of the polycomb complex is an essential mediator of the epigenetic transcriptional silencing by the chromatin structure. It has been reported to be crucial for homeostasis of the stem cells and tumorigenesis. Though years of investigation have clarified Bmi-1's transcriptional regulation, post-translational modifications, and functions in controlling cellular bioenergetics, pathologies, and DNA damage response, the full potential of this protein with so many diverse roles are still unfulfilled. Bmi-1 is overexpressed in many human malignancies. Unraveling the Bmi-1's precise functional role in head and neck cancers can be attractive for mechanisms-based developmental therapeutics. This review attempts to synthesize the current knowledge on Bmi-1 with an emphasis on the role that Bmi-1 plays in oral cancer progression and evaluates how this can be used in advancing clinical treatment strategies for head and neck cancer. Bmi-1 is a promising target for therapy because it has been linked to a stemness and oncogenesis signature. However, to use Bmi-1 as a prognostic marker and a therapeutic target in the long run, new methods are imperative for further characterization of the physiological roles of Bmi-1. Current biological insights of Bmi-1 as a master regulator of stem cell self-renewal have emerged as a prominent player in cancer stem cell (CSC) biology. Bmi-1+ cells mediate chemoresistance and metastasis. On the other hand, inhibiting Bmi-1 rescinds CSC function and re-sensitizes cancer cells to chemotherapy. Therefore, elucidating therapeutic approaches targeting Bmi-1 can be leveraged to further research analysis to advance clinical treatment strategies for head and neck cancer.

Background: Hepatocellular carcinoma (HCC) is a health problem due to multi-drug resistance (MDR). Codelivery of multiple oncotherapy in one cargo as chimeric cancer therapy (CCT) is suggested as a solution for MDR. This study aims to engineer chitosan-coated nanostructure lipid carriers (NLCs) loaded with gefitinib (GF) and simvastatin (SV) as CCT for HCC.

Methods: Both GF and SV-loaded nanostructure lipids carriers (GFSVNLC) and chitosan-capped GF and SV-loaded nanostructure lipids carriers (CGFSVNLC) formulations were assembled by top-down techniques. Moreover, particle size (PS), zeta potential (ZP), and polydispersity index (PDI) were measured by Zetasizer. The biosafety of GFSVNLC preparations was investigated by using erythrocytes as a biological model. The cytotoxic, and apoptotic effects of the prepared GFSVNLCs were investigated using HepG2 cell lines as a substitute model for HCC. The effect of GF, SV, and NLC composition on JNK3, HDAC6, and telomerase was studied using molecular docking simulation (MDS).

Results: The present results revealed that the obtained GFSVNLC and CGFSVNLC have nanosized and consistent, CS coating shifts anionic ZP of GFSVNLC into CGFSVNLC with cationic ZP. Moreover, both formulations are biocompatible as indicated by their gentle effect on erythrocyte hemolysis. The treatment of HepG2 cells with GFSVNLC, and CGFSVNLC induced marked cell death compared to other groups with a decrease of IC50. Equally, the percentage of the apoptotic HepG2 cells was increased upon treatment of the cells with GFSV, GFSVNLC, and CGFSVNLC compared to the control group. Additionally, GF, SV, stearic acid (SA), and oleic acid (OA) modulate the activity of JNK3, HDAC6, and telomerase.

Conclusions: This study suggests CGFSVNLC achieves codelivery, selective targeting, and enhancing the synergistic effect of GF and SV for inducing HepG2 cell death. Mechanistically, CGFSVNLC inhibits key cascades implicated in MDR and HepG2 cell survival. CGFSVNLC is promising for overcoming drug resistance mechanisms and improving therapeutic outcomes against HepG2 cells.

Background: Circular RNAs (circRNAs) play a pivotal role in the development and advancement of various cancer types. However, the involvement of circ-PAN3 in hepatocellular carcinoma (HCC) is not well understood. To shed light on this, we conducted a comprehensive study through biochemistry, cell biology, molecular biology, and bioinformatics techniques to investigate the role of circ-PAN3 and its associated pathway in the progression of HCC.

Methods: Cell Counting Kit-8 (CCK-8) assay and colony formation assay were utilized to evaluate cell proliferation; Quantitative real-time PCR (RT-qPCR) and Western blot were adopted for assessing mRNA and protein expression; Annexin V/propidium iodide (PI) staining was applied to detect cellular apoptosis; CircInteractome and Targetscan databases were searched to predict potential targets of circRNA and miRNA; Luciferase reporter assay and RNA pull-down assay were performed to examine the interaction of RNA molecules.

Conclusions: Our findings revealed a significant increase in circ-PAN3 expression in HCC clinical specimens, which correlated with a poor survival rate in HCC patients. Knockdown of circ-PAN3 resulted in impaired cell proliferation, reduced cell survival, and inhibited tumorigenesis of HCC in vivo. Further analysis demonstrated that circ-PAN3 could serve as a sponge for miR-153, leading to a decrease in its expression level. This in turn upregulated cyclin D1 and ultimately promoted the proliferation of HCC cells. Additionally, overexpression of cyclin D1 mitigated the inhibitory effect on HCC proliferation induced by circ-PAN3 knockdown. Our study highlights the presence of a novel circ-PAN3/miR-153/cyclin D1 regulatory axis that plays a crucial role in the progression of HCC.