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  • 1
    In: Cells, MDPI AG, Vol. 11, No. 3 ( 2022-02-01), p. 511-
    Abstract: Colorectal cancer is the second most common cancer in women, the third in men, and an important cause of cancer-related mortality. Recurrence and the development of chemotherapy resistance are major hindrances for patients’ treatment. The presence of cancer stem cells with chemotherapy resistance able to generate proliferating tumor cells contributes to tumor recurrence and resistance. In addition, tumor cells can develop chemoresistance through adaptation mechanisms. In this article, cancer stem cells were isolated from HT29 and SW620 colorectal cancer cell lines. Oxaliplatin resistance was induced by a single drug treatment simulating the usual guidelines of patient treatment. A comparison of these two populations showed similarities since cancer stem cells presented increased oxaliplatin resistance, and resistant cells contained an increased number of cancer stem cells. Cancer stem cells isolated from resistant cells showed increased oxaliplatin resistance. Cell invasion capacity and epithelial-mesenchymal transition were increased both in cancer stem cells and oxaliplatin-resistant cells. mRNA expression analysis showed that both cell types shared a significant proportion of commonly regulated genes. In summary, the data presented indicate that colorectal cancer stem cells and oxaliplatin-resistant cells are highly related cell populations that might have interesting implications in the development of tumor recurrence and resistance to chemotherapy.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
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  • 2
    In: Cells, MDPI AG, Vol. 11, No. 3 ( 2022-02-05), p. 561-
    Abstract: Head and neck squamous cell carcinomas (HNSCCs) are the eighth most common cancers worldwide. While promising new therapies are emerging, cisplatin-based chemotherapy remains the gold standard for advanced HNSCCs, although most of the patients relapse due to the development of resistance. This review aims to condense the different mechanisms involved in the development of cisplatin resistance in HNSCCs and highlight future perspectives intended to overcome its related complications. Classical resistance mechanisms include drug import and export, DNA repair and oxidative stress control. Emerging research identified the prevalence of these mechanisms in populations of cancer stem cells (CSC), which are the cells mainly contributing to cisplatin resistance. The use of old and new CSC markers has enabled the identification of the characteristics within HNSCC CSCs predisposing them to treatment resistance, such as cell quiescence, increased self-renewal capacity, low reactive oxygen species levels or the acquisition of epithelial to mesenchymal transcriptional programs. In the present review, we will discuss how cell intrinsic and extrinsic cues alter the phenotype of CSCs and how they influence resistance to cisplatin treatment. In addition, we will assess how the stromal composition and the tumor microenvironment affect drug resistance and the acquisition of CSCs’ characteristics through a complex interplay between extracellular matrix content as well as immune and non-immune cell characteristics. Finally, we will describe how alterations in epigenetic modifiers or other signaling pathways can alter tumor behavior and cell plasticity to induce chemotherapy resistance. The data generated in recent years open up a wide range of promising strategies to optimize cisplatin therapy, with the potential to personalize HNSCC patient treatment strategies.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
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  • 3
    In: Cancers, MDPI AG, Vol. 13, No. 15 ( 2021-08-02), p. 3888-
    Abstract: As some evidence suggests that hypoxia might be an inducer of nuclear paraspeckle formation, we explore whether intermittent hypoxia (IH)-mediated paraspeckle protein-1 (PSPC1) overexpression might contribute to the activation of tumor growth factor (TGF)β-SMAD pathway in patients with obstructive sleep apnea (OSA). This activation would promote changes in intracellular signaling that would explain the increased cancer aggressiveness reported in these patients. Here, we show that patients with OSA exhibit elevated PSPC1 levels both in plasma and in monocytes. Our data suggest that PSPC1 is ultimately delivered to the plasma through its cleavage from OSA monocytes by matrix metalloproteinase-2 (MMP2). In addition, IH promotes PSPC1, TGFβ, and MMP2 expression in monocytes through the hypoxia-inducible factor. Lastly, both PSPC1 and TGFβ induce increased expression of genes that drive the epithelial-to-mesenchymal transition. Our study details the mechanism by which hypoxemia upmodulates the extracellular release of PSPC1 by means of MMP2, such that plasma PSPC1 together with TGFβ activation signaling further promotes tumor metastasis and supports cancer aggressiveness in patients with OSA.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 4
    In: Cancers, MDPI AG, Vol. 12, No. 4 ( 2020-03-26), p. 786-
    Abstract: Despite often leading to platinum resistance, platinum-based chemotherapy continues to be the standard treatment for many epithelial tumors. In this study we analyzed and validated the cytogenetic alterations that arise after treatment in four lung and ovarian paired cisplatin-sensitive/resistant cell lines by 1-million microarray-based comparative genomic hybridization (array-CGH) and qRT-PCR methodologies. RNA-sequencing, functional transfection assays, and gene-pathway activity analysis were used to identify genes with a potential role in the development of this malignancy. The results were further explored in 55 lung and ovarian primary tumors and control samples, and in two extensive in silico databases. Long-term cell exposure to platinum induces the frequent deletion of ITF2 gene. Its expression re-sensitized tumor cells to platinum and recovered the levels of Wnt/β-catenin transcriptional activity. ITF2 expression was also frequently downregulated in epithelial tumors, predicting a worse overall survival. We also identified an inverse correlation between ITF2 and HOXD9 expression, revealing that Non-small cell lung cancer (NSCLC) patients with lower expression of HOXD9 had a better overall survival rate. We defined the implication of ITF2 as a molecular mechanism behind the development of cisplatin resistance probably through the activation of the Wnt-signaling pathway. This data highlights the possible role of ITF2 and HOXD9 as novel therapeutic targets for platinum resistant tumors.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 5
    In: Biomedicines, MDPI AG, Vol. 10, No. 3 ( 2022-03-19), p. 710-
    Abstract: Objectives: To evaluate the relationship of the immune-checkpoint PD-1/PD-L1 with the clinical evolution of OSCC; to assess survival in OSCC based on the characteristics of TME and histologic risk score; to evaluate the clinical and histopathological relationship of OSCC with immunological TME. Material and Methods: A retrospective study was carried out on 65 samples from patients with OSCC on the floor of the mouth or tongue. Clinicopathological variables and the expression of the biomarkers PD-1, PD-L1, FoxP3, CD4, CD8, CSF1R, and p16 were recorded. The relationship of the clinical and histological variables with the expression of the biomarkers and survival was studied. Results: The univariate and multivariate analysis indicated that positive PD-1 expression was an independent protective factor for survival (overall, disease-free, disease-specific survival) and that high PD-L1 also improved survival. Poorly differentiated histological grades and metastasis were associated with a worse prognosis. Conclusions: PD-1 is a protective survival factor that is maintained independently of PD-L1 expression. High values of PD-L1 expression also improve survival. Higher expression of PD-1 is observed in smaller tumors, and higher expression of PD-L1 is more likely in women. No relationship between the tumor microenvironment and histologic risk score was found to influence the survival patterns studied in the OSCC. There is no evidence of a relationship between the histopathological features and the studied markers, although the positive PD-1 and PD-L1 cases have a lower risk of a high WPOI score, and positive PD-1 expression was associated with a lower DOI.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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