Browsing by Subject "5-fluorouracil"

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    Knockdown of circ_0004585 enhances the chemosensitivity of colorectal cancer cells to 5-fluorouracil via the miR-874-3p/CCND1 axis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Shijie; Cao, Juan; Pei, Lijuan
    Background. Colorectal cancer (CRC) is a serious threat to human health and is drug-resistant. Circular RNA _0004585 (circ_0004585) has been shown to be expressed in CRC, but whether it plays a role in CRC with chemoresistance remains unknown. Therefore, this study aimed to investigate the potential role of circ_0004585 in CRC with 5-fluorouracil (5-FU) resistance. Methods. The expression of related genes was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expressions of cleaved caspase-3, cleaved caspase-9, and cyclin D1 (CCND1) were detected by western blot. Cell functions were identified using CCK-8, colony formation, flow cytometry, tube formation and transwell assays. The putative relationships between miR-874-3p and circ_0004585 or CCND1 were validated by dualluciferase reporter assays. Animal experiments were conducted to verify the effect of circ_0004585 on 5-FU resistance in vivo. Results. Circ_0004585 was highly expressed in CRC tissues and cells, particularly in 5-FU-resistant CRC tissues and cells. Circ_0004585 knockdown enhanced 5- FU sensitivity to further inhibit CRC cell viability, colony formation, cell migration and invasion, and accelerate cell apoptosis. MiR-874-3p was the target of circ_0004585, and miR-874-3p depletion partially recovered the malignant behaviors of 5-FU-resistant CRC cells that were blocked by silencing of circ_0004585. In addition, CCND1 was the target of miR-874-3p, and overexpression of CCND1 was able to restore the malignant effects of 5-FU-resistant CRC cells that were repressed by miR-874-3p enrichment. Animal experiments confirmed that circ_0004585 knockdown inhibited the growth of CRC tumors and enhanced 5-FU sensitivity in vivo. Conclusion. Circ_0004585 promotes the development of CRC and increases 5-FU resistance in CRC through the miR-874-3p/CCND1 axis. These results suggest that circ_0004585 may be a therapeutic target for 5-FU-ressitant CRC.
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    Palatal shelf reorientation in hamster embryos following treatment with 5-fluorouracil
    (Murcia : F. Hernández, 1989) Shah, Ravindra M.; Chen, Yung Ping; Burdett, David N.
    A study was undertaken to examine the issue of whether achieving a critical mass of cells andor palatal shelf volume during vertical development of shelf is essential for reorientation to occur. In control and 5- fluorouracil (5FU)-treated hamster embryos' palatal shelves, at different times during gestation, the numbers of both epithelial and mesenchymal cells were counted and cross-sectional area was measured. DNA synthesis was measured by 3H-thymidine incorporation and was used as an index of growth by cell proliferation. The control data indicated that, unlike development during initial 24 hours, the later period of vertical palatal development was characterized by a steady level of mesenchymal and epithelial cell numbers and palatal shelf area. Following 5FU treatment all the measurements were reduced, and until they reached the equivalent of control values, the palatal shelves did not reorient. The density of mesenchymal cells in the developing palate did not seem to affect cell number. On the basis of the analysis of results of the present study, along with those reported in the literature, it is suggested that, in hamsters, acquisition and maintenance of both a specified number of mesenchymal cells and shelf area, at least 24 hours prior to reorientation, may be critical for ensuing mesenchymal differentiation to enforce palatal shelf reorientation on schedule. 5FU affected these features to delay reorientation of the palatal shelf.
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    Weekly continuous infusion of 5-fluorouracil with oral leucovorin in metastatic breast cancer patients with primary resistance to doxorubicin
    (Springer, 1998) Nieto, Yago; Martín, Miguel; Alonso-Romero, José Luis; Casado, Antonio; Ayala, Francisco; López-Martín, José Antonio; Rodríguez-Lescure, Alvaro; Díaz-Rubio, Eduardo; Medicina
    Doxorubicin-resistant metastatic breast cancer (MBC) is a very poor prognosis scenario, where only taxanes have shown activity, often at the expense of severe toxicity that compromises palliation. This study was undertaken to test the antitumor activity and tolerability of infusional 5-fluorouracil (5-FU) modulated with low-dose oral leucovorin (LV), in heavily pretreated patients with stringent criteria of primary resistance to doxorubicin, visceral involvement, and suboptimal performance status. Twenty-six patients with measurable MBC and primary resistance to anthracyclines received a weekly outpatient 48-hour infusion of high-dose 5-FU with low dose oral leucovorin. All patients were assessable for response and toxicity. Eight partial responses were seen (30% response rate) in soft tissue and visceral sites, with a median response duration of eight months (5 + to 12). 98% of the cycles were minimally toxic or non-toxic. Toxicities included mucositis, diarrhea, and plantar-palmar-syndrome. Our results suggest that this schedule of LV-modulated infusional 5-FU can produce a substantial number of long-lasting responses and meaningful palliation to this very poor prognosis population.