Oncology Research最新文献

Objectives: EGFR tyrosine kinase inhibitor (EGFR-TKI) therapies such as erlotinib and gefitinib are approved for the treatment of non-small cell lung cancer (NSCLC). However, the high incidence of acquired resistance to these EGFR-TKIs may preclude their effectiveness. Piperlongumine (PPL), an extract from the long pepper fruit (Piper longum), has been shown to possess anticancer properties. The purpose of the study was to investigate piperlongumine as an anticancer agent and to study a combination treatment approach with EGFR-TKIs against lung cancer cells.

Methods: Anticancer efficacy of PPL, erlotinib (ERL), gefitinib (GEF), and cisplatin (CIS) were investigated in H1299 and H1975 cell lines. Cells were treated with PPL, ERL, GEF, and CIS alone, and in combination, cell viability was determined after 72 h. The mechanism of PPL-induced cytotoxicity was investigated via reactive oxygen species (ROS) induction, and apoptosis induction using acridine orange/ethidium bromide staining and flow cytometry. The effect of treatment on EGFR-mediated oncogenic signaling was investigated by immunoblotting for mitogenic and apoptotic markers.

Results: PPL exhibited a potent cytotoxic effect in H1299 and H1975 cells compared to ERL, GEF, and CIS. Combination treatments of PPL with GEF and ERL showed significant reductions in cancer cells compared to control in both cell lines, which were associated with apoptotic induction, but without significant ROS induction. Compared to control, PPL with GEF significantly increased apoptotic cell death in H1975as confirmed with flow cytometry. Treatment with PPL alone and in combination induced anti-mitogenic and apoptotic responses at the molecular level.

Conclusion: PPL sensitized lung cancer cells to EGFR-TKI and induced potent cytotoxic effects at low concentrations.

Background: Osteosarcoma (OS), recognized as the predominant malignant tumor originating from bones, necessitates an in-depth comprehension of its intrinsic mechanisms to pinpoint novel therapeutic targets and enhance treatment methodologies. The role of fat mass and obesity-associated (FTO) in OS, particularly its correlation with malignant traits, and the fundamental mechanism, remains to be elucidated.

Materials and methods: 1. The FTO expression and survival rate in tumors were analyzed. 2. FTO in OS cell lines was quantified utilizing western blot and PCR. 3. FTO was upregulated and downregulated separately in MG63. 4. The impact of FTO on the proliferation and migration of OS cells was evaluated using CCK-8, colony formation, wound healing, and Transwell assays. 5. The expression of miR-150-5p in OS cells-derived exosomes was identified. 6. The binding of miR-150-5p to FTO was predicted by TargetScan and confirmed by luciferase reporter assay. 7. The impact of exosome miR-150-5p on the proliferation and migration of OS cells was investigated.

Results: The expression of FTO was higher in OS tissues compared to normal tissues correlating with a worse survival rate. Furthermore, the downregulation of FTO significantly impeded the growth and metastasis of OS cells. Additionally, miR-150-5p, which was downregulated in both OS cells and their derived exosomes, was found to bind to the 3'-UTR of FTO through dual luciferase experiments. Exosomal miR-150-5p was found to decrease the expression of FTO and inhibit cell viability.

Conclusions: We identified elevated levels of FTO in OS, which may be attributed to insufficient miR-150-5p levels in both the cells and exosomes. It suggests that the dysregulation of miR-150-5p and its interaction with FTO could potentially promote the development of OS.

[This retracts the article DOI: 10.3727/096504018X15149775533331.].

Background: Papillary thyroid cancer (PTC) is the most prevalent histological type of differentiated thyroid malignancy. Circular RNAs (circRNAs) have been implicated in the pathogenesis and progression of various cancers. circTIAM1 (hsa_circ_0061406) is a novel circRNA with aberrant expression in PTC. However, its functional roles in PTC progression remain to be investigated.

Methods: The expression levels of circTIAM1 in the PTC and the matched para-cancerous tissues were detected by quantitative real-time reverse-transcription PCR (qRT-PCR). The subcellular localization of circTIAM1 was examined by fluorescence in-situ hybridization (FISH). Kaplan-Meier plot was used to analyze the association of clinicopathological features with circTIAM1 expression. Bioinformatics databases were utilized to predict the target miRNAs of circTIAM1 and the downstream target mRNAs. RNA pull-down, RIP assay, and dual-luciferase reporter assay were used to confirm the interactions. Functional experiments, such as CCK-8, EDU staining, and apoptosis assays, as well as in vivo xenograft model were employed to explore the impacts of circTIAM1, miR-338-3p, and LIM/SH3 protein 1 (LASP1) on the malignant phenotype of the PTC cells.

Results: CircTIAM1 was highly expressed in PTC cells. Moreover, circTIAM1 silencing suppressed the proliferation and invasion of PTC cells in vitro and impaired tumorigenesis in vivo. Furthermore, miR-338-3p was verified as a miRNA target of circTIAM1. LASP1 was also identified as a downstream target of miR-338-3p. The anti-tumorigenic effect of miR-338-3p overexpression and the pro-tumorigenic effect of LASP1 was further explored by functional assays, which demonstrated that circTIAM1 modulated the PTC progression through targeting miR-338-3p/LASP1 axis.

Conclusion: The overexpression of circTIAM1 is associated with the malignant progression of PTC. A high level of circTIAM1 promotes the malignancy of PTC cells via the miR-338-3p/LASP1 axis.

[This retracts the article DOI: 10.3727/096504018X15152072098476.].

[This retracts the article DOI: 10.3727/096504017X14878518291077.].

Oral squamous cell carcinoma (OSCC) is one of the most prevalent forms of head and neck squamous cell carcinomas (HNSCC) with a poor overall survival rate (about 50%), particularly in cases of metastasis. RNA-based cancer biomarkers are a relatively advanced concept, and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies. This review underlines the function of long non-coding RNAs (lncRNAs) in the OSCC and its subsequent clinical implications. LncRNAs, a class of non-coding RNAs, are larger than 200 nucleotides and resemble mRNA in numerous ways. However, unlike mRNA, lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA, RNA, proteins, or microRNAs depending on concentration and localization in cells. Upregulation of oncogenic lncRNAs and down-regulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers. Targeted inhibition of candidate oncogenic lncRNAs or over-expression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models. The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity. This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival, proliferation, invasion, migration, metastasis, angiogenesis, metabolism, epigenetic modification, tumor immune microenvironment, and drug resistance. Subsequently, we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems, providing details on ongoing research and outlining potential future directions for advancements in this field. In essence, this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.

[This retracts the article DOI: 10.3727/096504017X14878536973557.].

Glutamine is one of the most abundant non-essential amino acids in human plasma and plays a crucial role in many biological processes of the human body. Tumor cells take up a large amount of glutamine to meet their rapid proliferation requirements, which is supported by the upregulation of glutamine transporters. Targeted inhibition of glutamine transporters effectively inhibits cell growth and proliferation in tumors. Among all cancers, digestive system malignant tumors (DSMTs) have the highest incidence and mortality rates, and the current therapeutic strategies for DSMTs are mainly surgical resection and chemotherapy. Due to the relatively low survival rate and severe side effects associated with DSMTs treatment, new treatment strategies are urgently required. This article summarizes the glutamine transporters involved in DSMTs and describes their role in DSMTs. Additionally, glutamine transporter-target drugs are discussed, providing theoretical guidance for the further development of drugs DSMTs treatment.

Objectives: The Brazilian Unified Health System (Sistema Único de Saúde-SUS) is the universal public healthcare system of Brazil that maintains a nationwide database of its patients. Our primary objective was to analyze regional and temporal trends, while our secondary goal was to establish correlations between states' health economy status and their prostate cancer (PCa) epidemiology.

Methods: We analyzed Brazil's nationwide data on prostate cancer (PCa) incidence, mortality, and care gathered between 2013 and 2021 by the Information Technology Department of SUS (DATA-SUS), updated monthly using the International Classification of Diseases (ICD-10) code.

Results: In the period, 273,933 new cases of PCa and 135,336 PCa deaths were reported in men aged 50 years or over in Brazil. The median annual PCa-specific incidence rate (PCSIR) ranged from 14.7 in the Southeast to 6.9 in the North region and the median annual PCa-specific mortality rate (PCSMR) ranged from 7.7 in the Northeast to 6.0 in the South region (per 10,000 men >50). The median annual mortality to incidence ratio (MIR) was highest in the North (0.88) and lowest in the Southeast region (0.44). There were significant regional differences in PCa treatment rates (per new cases); the Midwest region had the highest median annual surgery rate (0.63) while the North region had the highest median annual systemic therapy rate (0.75) and the lowest radiation therapy rate (0.06). Temporal analysis of the data showed significant change in annual rate trends after the year 2018 for PCSIR (coefficient [β] = +3.66, p < 0.001), any treatment (β = -0.06, p = 0.016), surgery ([SR] β = +0.05, p = 0.017) radiation therapy ([RTR] β = -0.06, p = 0.005) and systemic therapy ([STR] β = -0.10, p = 0.002). After the 2020 pandemic, annual PCSIR decreased (β = -2.15, p = 0.002) but annual PCSMR, MIR, and treatment rates remained stable. Correlation studies showed that the PCSIR was strongly negatively correlated with STR (p < 0.001) and positively correlated with RTR (p = 0.004). MIR was positively correlated with STR (p < 0.001) and negatively correlated with the number of robotic surgical systems per million population (p = 0.003).

Conclusion: Our data shows that PCa care is dependent on the region and is likely influenced by access to treatment options. Furthermore, changes after the year 2018 underscore the influence of international guidelines on Brazilian clinicians' decision-making especially concerning population screening which in turn affected incidence and treatment rates. Limitation of our study includes limited patient-related information and data on private practices as well as an unknown impact of traveling patients.