Discover. Oncology最新文献

Background: Although pentatricopeptide repeat domain 1 (PTCD1) has been found to modulate mitochondrial metabolic and oxidative phosphorylation, its contribution in the growth of clear cell renal cell carcinoma (ccRCC) remains unknown.

Methods: The Cancer Genome Atlas (TCGA) dataset was utilized to examine the transcriptional alterations, patient characteristics, clinical outcomes, as well as pathway activation of PTCD1. The Weighted Gene Co-expression Network Analysis (WGCNA) was performed to investigate potential genes that associated with PTCD1. The researchers estimated the relationship between PTCD1, tumor immunology, and epithelial mesenchymal transition (EMT). Researchers studied how PTCD1 affects the functional behavior of tumor cells in vitro.

Results: PTCD1 expression was greater in ccRCC samples than in normal samples, and expression increased gradually as the stage increased. In TCGA cohorts, higher PTCD1 expression was substantially associated with a poorer clinical stage, histological grading, T stage, N stage, M stage, and survival outcomes. The results of multivariate analysis showed that PTCD1 was an independent variable affecting the survival outcomes of ccRCC patients (p < 0.001). PTCD1 regulated ccRCC progression via various cancer mechanisms including PI3K-Akt signaling, focal adhesion, PD-L1 expression, and PD-1 checkpoints in cancer. WGCNA discovered a significant relationship between PTCD1 and IARS2, LRPPRC, MT-ND2, MT-CO1, MT-CO2, MT-CYB, MT-ATP6, and MT-ND4. Furthermore, PTCD1 expression levels was closely associated with immune infiltrating, immunological checkpoint, EMT, immunotherapy responsiveness, and anti-tumor medication sensitivities. Upregulation of PTCD1 in ccRCC cells resulted in considerably increased cellular invasion and migration. Mechanistically, the upregulation of PTCD1 increased the phosphorylation of AKT at Ser473 and GSK-3β at Ser9, as well as enhanced activation of Wnt/β-catenin pathway.

Conclusion: Elevated expression of PTCD1 was associated with malignant biological behaviors and poor outcomes of ccRCC patients, and PTCD1 may accelerate tumor cells proliferation and invasion via the Akt/GSK3β/β-catenin pathway. Our findings indicated that PTCD1 had the potential to become a new target for predicting prognosis and targeted therapy.

Vanillic Acid (VA) is an aromatic acid extracted from traditional Chinese medicine such as Angelica sinensis and Panax ginseng, which has demonstrated potent anti-cancer activity, inhibiting the onset and progression of various malignant tumors. This review highlights the principal mechanism by which VA exerts its anticancer activity, including apoptosis induction, specifically promoting the generation of intracellular reactive oxygen species (ROS), which in turn triggers mitochondrial apoptosis. Furthermore, VA disrupts the cancer cell cycle, arresting most cancer cells at the G1 phase, curtails cell migration, invasion, angiogenesis, and potentiates the therapeutic efficacy of chemotherapeutic drugs, all while minimizing adverse reactions. This paper offers a comprehensive review of VA's anti-tumor effects and underlying mechanisms, aiming to provide some references for scientists and clinical physicians in the research of anti-tumor therapeutic strategies.

Colon cancer remains a significant health burden globally, necessitating deeper investigation. Identification and targeting of prognostic markers can significantly improve the current therapeutic approaches for colon cancer. The differential nuclear transport (import and export) of cellular proteins, plays an important role in tumor progression. Exportins, critical mediators of nuclear export, have emerged as potential players in cancer pathogenesis. However, their precise roles and prognostic significance in colon adenocarcinoma remain elusive. This study was designed to comprehensively analyse the expression and prognostic significance of all seven exportins in Colon Adenocarcinoma (COAD) using the online public database. We used public databases UALCAN, C-Bio portal, Human Protein Atlas (HPA), and DAVID, to investigate exportins in COAD patients. Kaplan-Meier plotter, Gene ontology (GO), TIMER, STRING, and KEGG were used to analyse data and draw conclusions. Our observations showed a significant correlation of exportins expression with clinical parameters, used to predict a patient's prognosis in general, such as advancing tumor stage, overall/relapse-free survival, and immune cell infiltrations. Mutation analysis showed the presence of amplifications, missense mutations in XPO2 and XPO4, and deep deletions in XPO7 genes contributing to disease progression and patients survival. This study highlights the potential use of exportins as novel prognostic biomarkers and therapeutic targets for colon adenocarcinoma progression and management.

Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men in the United States. While PCa initially responds to androgen deprivation therapy, a significant portion progresses to castration-resistant PCa. Approximately 20-25% of these cases acquire aggressive neuroendocrine (NE) features, ultimately leading to neuroendocrine prostate cancer (NEPC). In this study, we investigated the expression of stathmin 1 (STMN1) across PCa subtypes using bioinformatics, western blotting, and immunohistochemical staining analyses in human and murine models. We found that elevated STMN1 expression correlated with high Gleason Scores, increased cell proliferation, and poor clinical outcomes in PCa patients. Notably, STMN1 expression was significantly higher in NEPC compared to prostate adenocarcinoma, suggesting its role in NEPC progression. Findings from TRAMP tumors, a murine NEPC model, further supported these results. In conclusion, STMN1 expression is elevated in advanced PCa, particularly in NEPC, suggesting its involvement in the progression of aggressive forms of PCa. While STMN1 shows potential as a diagnostic and prognostic marker for aggressive PCa, further studies are necessary to establish its clinical utility.

Objective: Ovarian cancer significantly impacts women's reproductive health and remains challenging to diagnose and treat. Despite advancements in understanding DNA repair mechanisms and identifying novel therapeutic targets, additional strategies are still needed. Recently, a novel form of cell death called disulfidptosis, which is triggered by glucose deprivation, has been linked to treatment resistance and changes in the tumor microenvironment (TME). However, its role in ovarian cancer is not well understood.

Methods: Bioinformatics analysis was performed on RNA-seq data from TCGA and GEO databases to identify disulfidptosis-related genes in ovarian cancer. Differential expression analysis and pathway enrichment were conducted, followed by the development of a prognostic model using LASSO Cox regression, validated with GEO datasets (GSE13876, GSE26712). Clinical samples were analyzed using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) to validate gene expression.

Results: This study identified disulfidptosis-related gene subtypes in ovarian cancer and demonstrated their influence on the tumor microenvironment (TME), immunotherapy responses, and patient prognosis. Six genes (IFNB1, IGF2, CD40LG, IL1B, IL21, CD38) associated with disulfidptosis were identified and incorporated into a prognostic model. This model predicted patient outcomes and was validated externally. Clinical validation showed its accuracy in predicting progression-free survival and resistance to platinum-based chemotherapy.

Conclusion: Our findings highlight the significant impact of disulfidptosis-related genes on the ovarian cancer tumor microenvironment, providing insights that could support the development of clinical evaluations and personalized treatment strategies.

MYC is one of the most deregulated oncogenic transcription factors in human cancers. MYC amplification/or overexpression is most common in Group 3 medulloblastoma and is positively associated with poor prognosis. MYC is known to regulate the transcription of major components of protein synthesis (translation) machinery, leading to promoted rates of protein synthesis and tumorigenesis. MTOR signaling-driven deregulated protein synthesis is widespread in various cancers, including medulloblastoma, which can promote the stabilization of MYC. Indeed, our previous studies demonstrate that the key components of protein synthesis machinery, including mTOR signaling and MYC targets, are overexpressed and activated in MYC-amplified medulloblastoma, confirming MYC-dependent addiction of enhanced protein synthesis in medulloblastoma. Further, targeting this enhanced protein synthesis pathway with combined inhibition of MYC transcription and mTOR translation by small-molecule inhibitors, demonstrates preclinical synergistic anti-tumor potential against MYC-driven medulloblastoma in vitro and in vivo. Thus, inhibiting enhanced protein synthesis by targeting the MYC indirectly and mTOR pathways together may present a highly appropriate strategy for treating MYC-driven medulloblastoma and other MYC-addicted cancers. Evidence strongly proposes that MYC/mTOR-driven tumorigenic signaling can predominantly control the translational machinery to elicit cooperative effects on increased cell proliferation, cell cycle progression, and genome dysregulation as a mechanism of cancer initiation. Several small molecule inhibitors of targeting MYC indirectly and mTOR signaling have been developed and used clinically with immunosuppressants and chemotherapy in multiple cancers. Only a few of them have been investigated as treatments for medulloblastoma and other pediatric tumors. This review explores concurrent targeting of MYC and mTOR signaling against MYC-driven medulloblastoma. Based on existing evidence, targeting of MYC and mTOR pathways together produces functional synergy that could be the basis for effective therapies against medulloblastoma.

Objective: The aim of this study was to comparatively analyze the therapeutic effects of uterine artery embolization (UAE) and laparoscopic myomectomy (LM) on uterine fibroids to determine which treatment method is more beneficial for patients.

Materials and methods: A retrospective study was conducted on 396 patients who underwent UAE (n = 153) or LM (n = 243) treatment from April 2010 to September 2019. After 1:1 propensity score matching (PSM), a comparative analysis was conducted on surgical trauma magnitude, postoperative recovery time, improvement in associated symptoms and quality of life, surgical adverse events, recurrence rates, and further interventions.

Results: In PSM, 66 pairs (132 patients) were successfully matched. Both treatments significantly alleviated symptoms and enhanced quality of life. Compared to the LM group, the UAE group had less intraoperative bleeding (P < 0.001), a lower rate of hemoglobin decrease (P < 0.001), shorter operation, postoperative, and overall hospital stays (P < 0.001), and a lower postoperative recurrence rate (P < 0.05), all statistically significant. Moreover, the UAE group showed notable advantages in postoperative activities (P < 0.05). However, UAE patients faced higher hospitalization costs (P < 0.001). Adverse event rates (7.6% vs. 9.1%) and postoperative reintervention rates (7.6% vs. 7.6%) were relatively low and not significantly different between groups (P > 0.05).

Conclusion: Both UAE and LM can significantly improve patient symptoms and enhance their quality of life, and both treatment methods have low rates of adverse events and reinterventions. Compared to LM, UAE treatment for uterine fibroids presents advantages such as less trauma, faster recovery, and lower recurrence rate, but has higher treatment costs.

Rhabdomyoma is a rare benign tumor of striated muscle, which can be either cardiac or extracardiac. Extracardiac rhabdomyomas can occur throughout the body, though the fetal and adult subtypes are most commonly found in the head and neck region.We present three pediatric cases of extracardiac rhabdomyoma, fetal subtype, detailing their clinical presentations, computed tomography imaging, and tissue biopsy findings. Given the very rare occurrence of extracardiac rhabdomyoma and its relatively benign nature, histological diagnosis is crucial. In all three cases reported here, a diagnosis of extracardiac rhabdomyoma was confirmed, and treatment with local excision resulted in favorable outcomes.

Vitamin A is a crucial nutrient renowned for its role in visual health and cellular regulation. Its derivatives influence cell differentiation, proliferation, and tissue homeostasis, making them significant in cancer research due to their effects on both normal and tumour cells. This review explores the intricate relationship between vitamin A metabolism and the extracellular matrix (ECM) in cancer. The ECM profoundly affects tumour behaviour, including proliferation, invasion, and metastasis. Alterations in the ECM can facilitate tumour progression, and vitamin A derivatives have shown potential in modulating these changes. Through transcriptional regulation, vitamin A impacts ECM components and matrix metalloproteinases, influencing tumour dynamics. The review highlights the potential of vitamin A and its derivatives as adjunctive agents in cancer therapy. Despite promising laboratory findings, their clinical application remains limited due to challenges in translating these effects into therapeutic outcomes. Future research should focus on the modulation of retinol metabolism within tumours and the development of targeted therapies to enhance treatment efficacy and improve patient prognosis.

Hepatocellular carcinoma (HCC) remains a global health challenge owing to its widespread incidence and high mortality. HCC has a specific immune tolerance function because of its unique physiological structure, which limits the efficacy of chemotherapy, radiotherapy, and molecular targeting. In recent years, new immune approaches, including adoptive cell therapy, tumor vaccines, and oncolytic virus therapy, have shown great potential. As the efficacy of immunotherapy mainly depends on the spatial heterogeneity of the tumor immune microenvironment, it is necessary to elucidate the crosstalk between the composition of the liver cancer immune environment, from which potential therapeutic targets can be selected to provide more appropriate individualized treatment programs. The role of spatial heterogeneity of immune cells in the microenvironment of HCC in the progression and influence of immunotherapy on improving the treatment and prognosis of HCC were comprehensively analyzed, providing new inspiration for the subsequent clinical treatment of liver cancer.