An increasing number of reports have shown that diverse microRNAs are involved in tumorigenesis and tumor progression. We performed this study to identify novel miRNAs that may be involved in lung cancer and study on their functions. We tested the expression of 450 miRNAs in lung tumor tissues and adjacent non-cancerous tissues. We found that miRNA-545 was less abundant in cancerous lung tissues than in adjacent non-cancerous tissues. Our further studies showed that miR-545 suppressed cell proliferation in vitro and in vivo. We also found that miR-545 caused cell cycle arrest at the G0/G1 phase and induced cell apoptosis in lung cancer cells by targeting cyclin D1 and CDK4 genes. The effects of cyclin D1 and CDK4 down-regulated by miR-545 were similar to those caused by siRNAs of cyclin D1 and CDK4, and overexpression of cyclin D1 and CDK4 could abolish the miR-545-induced inhibition of cell proliferation. In conclusion, miR-545 suppressed cell proliferation by inhibiting the expression of cyclin D1 and CDK4. Our findings provide new knowledge regarding the role of miR-545 in the development of lung cancer and indicate the potential application of miR-545 in cancer therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914893 | PMC |
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ESMO Open
January 2025
UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, USA.
Background: Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line (1L) treatment of patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). Several real-world studies compared CDK4/6i effectiveness, with inconsistent findings. This study compared overall survival (OS) of patients with HR+/HER2- mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination with an aromatase inhibitor (AI), in US clinical practice.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong SAR 999077, China.
CDK4/6 inhibitors are effective in treating HR/HER2 breast cancer but face limitations due to therapeutic resistance and hematological toxicity, particularly from strong CDK6 inhibition. To address these challenges, designing selective inhibitors targeting specific cyclin-dependent kinases (CDK) members could offer clinical advantages and broaden CDK inhibitor indications. However, the highly conserved binding pockets of CDKs complicate selective targeting.
View Article and Find Full Text PDFJ Manag Care Spec Pharm
January 2025
The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, Department of Pharmacy, University of Washington, Seattle.
Background: The introduction of cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6is) has transformed the treatment landscape for patients with hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC). To our knowledge, no studies have quantified health care resource utilization (HRU) or economic burden following CDK4/6i initiation in the Medicare population.
Objective: To describe HRU and quantify health care costs among Medicare-enrolled patients with HR+ HER2- MBC treated with CDK4/6is in the first-line setting.
Breast J
January 2025
Department of Chemotherapy Jiangsu Cancer Hospital Jiangsu Institute of Cancer Research The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
Purpose: Endocrine therapy combined with cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) is the preferred treatment for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). However, there are currently no recommendations for therapeutic strategies after progression on CDK4/6i-based treatment. This study aimed to examine the efficacy and safety of anlotinib plus chemotherapy in HR+/HER2- MBC after progression on CDK4/6 inhibitors.
View Article and Find Full Text PDFBMC Cancer
December 2024
Ankara Bilkent City Hospital, Department Of Medical Oncology, Ankara Yildirim Beyazit University, Ankara, 06800, Turkey.
Highly selective inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6is) have emerged as a standart of care for first- and second-line therapies in combination with endocrine therapy (ET) for HR+/HER2- metastatic breast cancer (MBC) patients. It has been reported that combination therapy is more effective than ET alone and is safe in elderly patients as well as young patients. Nevertheless, elderly and very old patients with HR+/HER2-MBC treated with CDK4/6 inhibitor (CDK4/6i) combinations are relatively underrepresented in randomized controlled trials.
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