Background: Sorafenib is a multikinase inhibitor that has been approved for the treatment of patients with advanced iodine (I) refractory differentiated thyroid cancer (DTC). However, the progression-free survival of patients with advanced I refractory DTC is short, and most DTC patients eventually acquire resistance to sorafenib. Therefore, new therapeutic strategies need to be developed.
Materials And Methods: The thyroid cancer cell lines 8505C and FTC133 were treated with sorafenib in the presence or absence of BEZ235 or small interfering RNA (siRNA) directed against AKT. A CCK8 kit was used to evaluate cell viability. Protein expression levels of relevant genes were determined by Western blotting analysis, whereas messenger RNA expression levels were determined by real-time PCR analysis. Flow cytometry was performed to assess the number of apoptotic cells.
Results: The results indicate that sorafenib simultaneously inhibited the activities of the MAPK and PI3K/AKT/mTOR pathways in thyroid cancer cells. Treatment of 8505C and FTC133 cells with NVP-BEZ235, siRNA against AKT, or sorafenib induced tumor cell apoptosis and led to reduced tumor cell proliferation. Sorafenib in combination with PI3K/AKT/mTOR inhibition by NVP-BEZ235 or AKT siRNA enhanced apoptosis and proliferation suppression.
Conclusions: The evidence of this study suggests that a combinatorial approach that inhibits both the MAPK and PI3K/AKT/mTOR pathways exerts a greater antitumor effect than sorafenib alone in thyroid cancer cell lines.
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http://dx.doi.org/10.1089/cbr.2017.2187 | DOI Listing |
Int J Gen Med
December 2024
Department of Thyroid and Breast Surgery, Quzhou People's Hospital, Quzhou, 324000, People's Republic of China.
Objective: This study aims to demonstrate the impact of sarcopenia on the prognosis of early breast cancer and its role in early multimodal intervention.
Methods: The clinical data of patients (n=285) subjected to chemotherapy for early-stage breast cancer diagnosed pathologically between January 1, 2016, and December 31, 2020, in our hospital were retrospectively analyzed. Accordingly, the recruited subjects were divided into sarcopenia (n=85) and non-sarcopenia (n=200) groups according to CT diagnosis correlating with single-factor and multifactorial logistic regression analyses.
J Clin Transl Endocrinol
December 2024
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy.
Thanks to the identification of crucial molecular pathways, the therapeutic landscape for advanced differentiated thyroid tumors (DTCs) has significantly improved during the last ten years. The therapeutic scenario has been greatly impacted by the discovery of mutually exclusive gene changes in the MAPK and PI3K/AKT pathways, such as or fusions and pathogenic mutations of the and genes. Indeed, multi-kinase inhibitors and selective inhibitors have demonstrated outstanding efficacy for radioactive iodine-refractory (RAI-R) drug treatment, with overall response rates reaching up to 86%.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Introduction: The relationship between immune-related thyroid dysfunction (irTD) and survival rates in cancer patients remains unclear. Furthermore, the impact of variations in immunotherapy line numbers and pathological types among lung cancer patients on this relationship has not been fully elucidated. This study aims to evaluate the potential of irTD as a prognostic marker for immunotherapy in Chinese patients with lung cancer.
View Article and Find Full Text PDFSmall
January 2025
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044, China.
Direct electrochemical detection of miRNA biomarkers in tumor tissue interstitial fluid (TIF) holds great promise for adjuvant therapy for tumors in the perioperative period, yet is limited by background interference and weak signal. Herein, a wash-free and separation-free miRNA biosensor based on photoexcited electro-driven reactive oxygen channeling analysis (LEOCA) is developed to solve the high-fidelity detection in physiological samples. In the presence of miRNA, nanoacceptors (ultrasmall-size polydopamine, uPDA) are responsively assembled on the surface of nanodonors (zirconium metal-organic framework, ZrMOF) to form core-satellite aggregates.
View Article and Find Full Text PDFCell Commun Signal
January 2025
School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Tribbles homolog 2 (TRIB2), a pseudoserine/threonine kinase, is a member of the TRIB family. TRIB2 primarily regulates cell proliferation through its scaffold or adaptor effect on promoting the degradation of target proteins by E3 ligase-dependent ubiquitination and regulating mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) signaling pathways. TRIB2 is not only involved in the physiological proliferation of cells (granulosa cells, myoblasts, naive T cells, and thymocytes) during normal development but also in the pathological proliferation of vascular smooth muscle cells and a variety of cancer cells (lung cancer cells, liver cancer cells, leukemia cells, pancreatic cancer cells, gastric cancer cells, prostate cancer cells, thyroid cancer cells, cervical cancer cells, melanoma cells, colorectal cancer cells, ovarian cancer cells and osteosarcoma cells) under disease conditions.
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