Search

The epidermal growth factor receptor 1 (EGFR) plays a crucial role in the progression of various malignant tumors and is considered a potential target for treating triple-negative breast cancer (TNBC). However, the effectiveness of representative tyrosine kinase inhibitors (TKIs) used in EGFR-targeted therapy is limited in TNBC patients. In our study, we observed that the TNBC cell lines MDA-MB-231 and MDA-MB-468 exhibited resistance to Gefitinib. Treatment with Gefitinib caused an upregulation of Fascin-1 (FSCN1) protein expression and a downregulation of miR-221-3p in these cell lines. However, sensitivity to Gefitinib was significantly improved in both cell lines with either inhibition of FSCN1 expression or overexpression of miR-221-3p. Our luciferase reporter assay confirmed that FSCN1 is a target of miR-221-3p. Moreover, Gefitinib treatment resulted in an upregulation of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in MDA-MB-231 cells. Using Stattic, a small-molecule inhibitor of STAT3, we observed a significant enhancement in the inhibitory effect of Gefitinib on the growth, migration, and invasion of MDA-MB-231 cells. Additionally, Stattic treatment upregulated miR-221-3p expression and downregulated FSCN1 mRNA and protein expression. A strong positive correlation was noted between the expression of STAT3 and FSCN1 in breast cancer tissues. Furthermore, patients with high expression levels of both STAT3 and FSCN1 had a worse prognosis. Our findings suggest that elevated FSCN1 expression is linked to primary resistance to EGFR TKIs in TNBC. Moreover, we propose that STAT3 regulates the expression of miR-221-3p/FSCN1 and therefore modulates resistance to EGFR TKI therapy in TNBC. Combining EGFR TKI therapy with inhibition of FSCN1 or STAT3 may offer a promising new therapeutic option for TNBC. [ABSTRACT FROM AUTHOR]

The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane‐coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C–C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single‐mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug‐loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane‐coated nanomaterials offer new opportunities for precise drug delivery and disease‐specific targeting, which represent a versatile platform for targeted therapy in AD. [ABSTRACT FROM AUTHOR]

In the extracorporeal shock wave lithotripsy for infants, we used a medical polymer gel pad to assist ultrasonic positioning, so that the ultrasonic probe could be far away from the shock wave energy field. Although not affecting the ultrasonic positioning and monitoring effect, we discussed the protective effect of this method on the ultrasonic probe. A retrospective analysis was made on 21 infants (0–3 years old) who received ESWL in our hospital from June 2021 to February 2023. After the stones were accurately located by B-ultrasound before surgery, a 4 * 5 * 10 cm medical polymer gel pad was placed between the skin and the ultrasonic probe to keep the ultrasonic probe away from the shock wave energy field. The B-ultrasonic wave source locked the target stone through the gel pad, and the lithotripter Dornier Compact Delta II was used for lithotripsy. The extracorporeal shock wave lithotripsy was completed under the whole process of B-ultrasonic monitoring. All patients completed the surgery under ultrasound monitoring, and there were no abnormalities in the ultrasound probe during the surgery. The average stone size was 0.60 ± 0.21 cm, the surgical time was 39.8 ± 13.8 min, and the total energy of lithotripsy was 7.41 ± 4.35 J. There were no obvious complications in all patients after the surgery. After 2 weeks of ultrasound examination, the success rate of lithotripsy in 21 patients reached 85.7%. We believe that the use of the gel pad increases the distance between the ultrasonic probe and the skin, leaving the probe away from the shock wave energy field, avoiding the damage of the shock wave source to the ultrasonic probe, and does not affect the monitoring effect of ultrasound on stones and the success rate of lithotripsy, which is worthy of further promotion in the field of children's urinary stones. [ABSTRACT FROM AUTHOR]

Breast cancer causes morbidity and mortality among women worldwide, despite much research illuminating the genetic basis of this disease. Anti-angiogenesis therapies have been widely studied, although the association between angiopoietin-2 (ANGPT2) single nucleotide polymorphisms (SNPs) and breast cancer subtypes remains unclear. This case–control study included 464 patients with malignant breast neoplasms and 539 cancer-free females. We explored the effects of ANGPT2 SNPs on the susceptibility for a malignant breast neoplasm in a Chinese Han population. Five ANGPT2 SNPs (rs2442598, rs734701, rs1823375, 11,137,037, and rs12674822) were analyzed using TaqMan SNP genotyping. Carriers of the variant GG allele of rs1823375 were less likely than wild-type carriers to be diagnosed with clinically staged breast cancer, while females with human epidermal growth factor receptor 2 (HER2)-enriched disease carrying the CG or the CG+GG genotype at rs1823375 were significantly less likely than CC genotype carriers to be of lymph node status N1–N3. We also found that the T-T-C-A-T ANGPT2 haplotype significantly increased the risk for developing a malignant breast neoplasm by 1.385-fold (95% CI: 1.025–1.871; p < 0.05). Our study is the first to document a correlation between ANGPT2 polymorphisms and the development and progression of a malignant breast neoplasm in females of Chinese Han ethnicity. [ABSTRACT FROM AUTHOR]

Elevated levels of resistin and epidermal growth factor receptor (EGFR) facilitate the development of breast cancer, although there are no reports of any correlation between these proteins. This study analyzed 392 human breast cancer tissue specimens and 42 samples of adjacent normal tissue. Rates of positive and strongly positive resistin expression were significantly higher in breast cancer tissue than in the adjacent nontumor tissue (83.2% vs. 23.8% and 20.9% vs. 0.0%, respectively; P < 0.001 for both comparisons). Positive resistin expression was significantly associated with tumor size, grade, stage, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and molecular classification; strongly positive resistin expression was associated with tumor grade, ER, PR, HER2 status, and molecular classification. Significantly positive correlations were observed between positive and strongly positive resistin expression and corresponding levels of EGFR expression. Relapse-free and overall survival was worse for patients with high levels of both proteins than for those with high levels of only one protein or normal levels of both proteins. Our evidence suggests that combined high levels of resistin and EGFR expression correlate with survival in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates that resistin and fascin-1 may possess a causal role in the development of several types of cancers. However, the clinical significance of resistin expression in colorectal cancer (CRC) tissues is unclear, and there are no reports of any correlation between resistin and fascin-1. Our analyses explored the expression of resistin in CRC tissue and analyzed the clinical and prognostic significance of the observed positive correlation between resistin and fascin-1. The rate of strongly positive resistin expression (27.5%) was significantly higher in CRC tissues than in normal colorectal tissues (5.2%). Strongly positive resistin expression is related to multiple poor prognostic factors in CRC, including depth of tumor invasion, lymph node metastasis, and tumor stage. In this study, survival was worse in CRC patients with high levels of both resistin and fascin-1 expression than in those with high levels of only one protein or normal levels of both proteins. We suggest that a combined high level of resistin and fascin-1 expression correlates reliably with survival in CRC, so it may serve as a potential therapeutic target. [ABSTRACT FROM AUTHOR]