Oncology Research最新文献

[This retracts the article DOI: 10.3727/096504017X15144755633680.].

[This retracts the article DOI: 10.3727/096504018X15166193231711.].

Background: Lung cancer (LC) is one of the most common neoplastic diseases and a leading cause of death in Saudi Arabia. Its incidence in Saudi Arabia has increased by more than 3% within two decades. Our study aimed to describe the epidemiological and genetic landscapes of LC in Al-Madinah city in Saudi Arabia.

Methods: A retrospective analysis was conducted on the medical records of 65 patients diagnosed with lung cancer between 2015 and 2021 at a single medical oncology center in Al-Madinah city of Saudi Arabia.

Results: The mean patients' age was 59.2 years, with 50 (76.9%) males and 15 (23.1%) females; 37 (57%) smokers, and 28 (43%) non-smokers. The number of cases per year has increased gradually over six years from 2015 (n = 3) to 2020 (n = 13). The most prevalent histopathological diagnosis was non-small cell lung cancer (NSCLC) (n = 58, 89%) followed by small cell lung cancer (SCLC) (n = 5, 7.8%). NSCLC was frequently more common in smokers while squamous cell carcinoma was more frequent in non-smokers. Around 89% (n = 58) of the cases were diagnosed in late stage IV and the most common metastatic sites were to pleura and lymph nodes (n = 32, 49.2%). Program Death Legend-1 (PDL-1) was fairly expressed in 7/10 (70%) patients. Epidermal Growth Factor Receptor (EGFR) was mutated in 5/17 (29%) patients. Other mutations detected include Anaplastic Lymphoma Kinase (ALK) and phosphatidylinositol 3-kinase (PIK3C) mutations in two patients.

Conclusions: Our study revealed that lung cancer is a significant burden in Al-Madinah city of Saudi Arabia. If the risk factors are not controlled, the number of cases may increase considerably. Health education about the risk factors and cancer prevention helps in early lung cancer detection.

Background: Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer characterized by a high rate of metastasis, poor prognosis, and lack of efficient therapies. KBU2046, a small molecule inhibitor, can inhibit cell motility in malignant tumors, including breast cancer. However, the specific targets and the corresponding mechanism of its function remain unclear.

Methods: In this study, we employed (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium) (MTS) assay and transwell assay to investigate the impact of KBU2046 on the proliferation and migration of TNBC cells in vitro. RNA-Seq was used to explore the targets of KBU2046 that inhibit the motility of TNBC. Finally, confirmed the predicted important signaling pathways through RT-qPCR and western blotting.

Results: In this study, we found that KBU2046 functioned as a novel transforming growth factor-β (TGF-β1) inhibitor, effectively suppressing tumor cell motility in vitro. Mechanistically, it directly down-regulated leucine-rich repeat-containing 8 family, member E (LRRC8E), latent TGFβ-binding protein 3 (LTBP3), dynein light chain 1 (DNAL1), and MAF family of bZIP transcription factors (MAFF) genes, along with reduced protein expression of the integrin family. Additionally, KBU2046 decreased phosphorylation levels of Raf and ERK. This deactivation of the ERK signaling pathway impeded cancer invasion and metastasis.

Conclusions: In summary, these findings advocate for the utilization of TGF-β1 as a diagnostic and prognostic biomarker and as a therapeutic target in TNBC. Furthermore, our data underscore the potential of KBU2046 as a novel therapeutic strategy for combating cancer metastasis.

EVI2A has emerged as a significant biomarker in various diseases; however, its biological role and mechanism in kidney renal clear cell carcinoma (KIRC) remains unexplored. We used TCGA and GEO databases to analyze EVI2A gene expression comprehensively and performed pan-cancer assessments. Clinical relevance was evaluated through Kaplan-Meier analysis and ROC curves. The gene's immune relevance was explored through analyses of the tumor microenvironment (TME), Tumor Immune Single-cell Hub (TISCH), immune checkpoints, and immunotherapy sensitivity. Our results indicate that EVI2A expression is upregulated in KIRC, showing correlations with tumor grade and T/N/M stage. EVI2A demonstrates high diagnostic accuracy (AUC=0.906) and predicts poor overall and progression-free survival in KIRC patients. Furthermore, EVI2A expression exhibits significant associations with immunity, including TME scores and specific immune cell types such as Tfh cells, CD4 memory T cells, and CD8+ T cells. Elevated EVI2A expression suggests increased sensitivity to PD-1/CTLA-4 and tyrosine kinase inhibitors. In vitro assays confirmed the impact of EVI2A on KIRC behavior, with its knockdown resulting in reduced cell proliferation and migration. In conclusion, our comprehensive analysis identifies EVI2A as a promising biomarker and a novel therapeutic target for intervening in KIRC. These findings hold significant implications for further research and potential clinical applications.

Background: Despite significant advancements in the development of anticancer therapies over the past few decades, the clinical management of colorectal cancer remains a challenging task. This study aims to investigate the inhibitory effects of cancer-targeting liposomes against colorectal cancer.

Materials and methods: Liposomes consisting of 3β-[N-(N', N'-dimethylamino ethane)carbamoyl]-cholesterol (DC-CHOL), cholesterol (CHOL), and dioleoylphosphatidylethanolamine (DOPE) at a molar ratio of 1:1:0.5 were created and used as carriers to deliver an apoptosis-inducing plasmid encoding the tumor necrosis factor-related apoptosis-inducing ligand (pTRAIL) gene, along with the toll-like receptor (TLR7) agonist Rsiquimod (R848). The rationale behind this design is that pTRAIL can trigger cancer cell apoptosis by activating the DR4/5 receptor, while R848 can stimulate the immune microenvironment.

Results: Experimental results demonstrated the synergistic effects of R848 and pTRAIL encapsulated by liposomes (RTL) in suppressing the proliferation of colorectal cancer cells. Moreover, further in vivo investigations revealed the strong anti-tumor efficacy of RTL in xenograft and orthotropic in situ models of colorectal cancer.

Conclusions: These findings collectively highlight the therapeutic potential of R848/pTRAIL-loaded liposomes in the treatment of colorectal cancer.

[This retracts the article DOI: 10.3727/096504018X15213058045841.].

The environment surrounding a tumor, known as the tumor microenvironment (TME), plays a role in how cancer progresses and responds to treatment. It poses both challenges and opportunities for improving cancer therapy. Recent progress in understanding the TME complexity and diversity has led to approaches for treating cancer. This perspective discusses the strategies for targeting the TME, such as adjusting networks using extracellular vesicles to deliver drugs and enhancing immune checkpoint inhibitors (ICIS) through combined treatments. Furthermore, it highlights adoptive cell transfer (ACT) therapies as an option for tumors. By studying how components of the TME interact and utilizing technologies like single-cell RNA sequencing and spatial transcriptomics, we can develop more precise and efficient treatments for cancer. This article emphasizes the need to reshape the TME to boost antitumor immunity and overcome resistance to therapy, providing guidance for research and clinical practices in precision oncology.

[This retracts the article DOI: 10.3727/096504017X15009792179602.].

[This retracts the article DOI: 10.3727/096504017X15000784459799.].