Breast cancer is a common malignant tumor in women. Ferroptosis, a programmed cell death pathway, is closely associated with breast cancer and its resistance. The transferrin receptor (TFRC) is a key factor in ferroptosis, playing a crucial role in intracellular iron accumulation and the occurrence of ferroptosis. This study investigates the influence and significance of TFRC and its upstream transcription factor hypoxia‐inducible factor‐1α (HIF1α) on the efficacy of neoadjuvant therapy in breast cancer. The differential gene obtained from clinical samples through genetic sequencing is TFRC. Bioinformatics analysis revealed that TFRC expression in breast cancer was significantly greater in breast cancer tissues than in normal tissues, but significantly downregulated in Adriamycin (ADR)‐resistant tissues. Iron‐responsive element‐binding protein 2 (IREB2) interacts with TFRC and participates in ferroptosis. HIF1α, an upstream transcription factor, positively regulates TFRC. Experimental results indicated higher levels of ferroptosis markers in breast cancer tissue than in normal tissue. In the TAC neoadjuvant regimen‐sensitive group, iron ion (Fe 2+ ) and malondialdehyde (MDA) levels were greater than those in the resistant group (all p < .05). Expression levels of TFRC, IREB2, FTH1, and HIF1α were higher in breast cancer tissue compared to normal tissue. Additionally, the expression of the TFRC protein in the TAC neoadjuvant regimen‐sensitive group was significantly higher than that in the resistant group (all p < .05), while the difference in the level of expression of IREB2 and FTH1 between the sensitive and resistant groups was not significant ( p > .05). The dual‐luciferase assay revealed that HIF1α acts as an upstream transcription factor of TFRC ( p < .05). Overexpression of HIF1α in ADR‐resistant breast cancer cells increased TFRC, Fe 2+ , and MDA content. After ADR treatment, the cell survival rate decreased significantly, and ferroptosis could be reversed by the combined application of Fer‐1 (all p < .05). In conclusion, ferroptosis and chemotherapy resistance are correlated in breast cancer. TFRC is a key regulatory factor influenced by HIF1α and is associated with chemotherapy resistance. Upregulating HIF1α in resistant cells may reverse resistance by activating ferroptosis through TFRC overexpression.
The incidence of papillary thyroid microcarcinoma (PTMC) has exponentially increased in the past three decades. The 2014 World Cancer Report stated that, among the new cases of thyroid carcinoma, >50% are PTMC. The incidence of thyroid cancer was growing by 20.1% annually in China. Most of PTMC have low risk and excellent prognoses. It must be realized that the problem of overdiagnosis of thyroid cancer is quite serious. In this article, we summarized the phenomenon and the cause of “overdiagnosis” of PTMC, the progress of clinical management, and the countermeasures.
In the past 30 years, the incidence of differentiated thyroid cancer (DTC) has been increasing rapidly and has become one of the most common malignant tumors in females. Currently, the main surgical treatment for DTC is standard open thyroidectomy (SOT) via a traditional Kocher mid-cervical incision, but postoperative neck scarring was associated with significantly worse health-related quality of life (HRQOL) scores. To offer better cosmesis, robotic/endoscopic thyroidectomy via cervical, axillary, anterior chest, breast, postauricular, or transoral approaches have been developed over the past 20 years. In general, gasless transaxillary endoscopic thyroidectomy (GTET) has advantages in terms of convenience, clarity of vision, and aesthetic incision. The current work aims to provide a step-by-step description of GTET, supported by a high-quality, pictorial guide.
25 October 2024 in World Journal of Surgical Oncology
Thyroid cancer (TC) represents one of the most prevalent endocrine malignancies, with a rising incidence worldwide. Epigenetic alterations, which modify gene expression without altering the underlying DNA sequence, have garnered significant attention in recent years. Increasing evidence underscores the pivotal role of epigenetic modifications, including DNA methylation, RNA methylation, and histone methylation, in the pathogenesis of TC. This review provides a comprehensive overview of these reversible and environmentally influenced epigenetic modifications, highlighting their molecular mechanisms and functional roles in TC. Additionally, the clinical implications, challenges associated with studying these epigenetic modifications, and potential future research directions are explored.
21 October 2023 in Clinical and Translational Oncology
Preoperative staging of suspicious axillary lymph nodes (ALNs) allows patients to be triaged to ALN dissection or to sentinel lymph node biopsy (SLNB). Ultrasound-guided fine needle aspiration (FNA) and cytology of ALN is moderately sensitive but its clinical utility relies heavily on the cytologist’s experience. We proposed that the 5-h automated GeneXpert system-based prototype breast cancer detection assay (BCDA) that quantitatively measures DNA methylation in ten tumor-specific gene markers could provide a facile, accurate test for detecting cancer in FNA of enlarged lymph nodes. We validated the assay in ALN-FNA samples from a prospective study of patients (N = 230) undergoing SLNB. In a blinded analysis of 218 evaluable LN-FNAs from 108 malignant and 110 benign LNs by histology, BCDA displayed a sensitivity of 90.7% and specificity of 99.1%, achieving an area under the ROC curve, AUC of 0.958 (95% CI: 0.928–0.989; P < 0.0001). Next, we conducted a study of archival FNAs of ipsilateral palpable LNs (malignant, N = 72, benign, N = 53 by cytology) collected in the outpatient setting prior to neoadjuvant chemotherapy (NAC). Using the ROC-threshold determined in the prospective study, compared to cytology, BCDA achieved a sensitivity of 94.4% and a specificity of 92.5% with a ROC-AUC = 0.977 (95% CI: 0.953–1.000; P < 0.0001). Our study shows that the automated assay detects cancer in suspicious lymph nodes with a high level of accuracy within 5 h. This cancer detection assay, scalable for analysis to scores of LN FNAs, could assist in determining eligibility of patients to different treatment regimens.