A novel NIR fluorescent probe inhibits melanoma progression through apoptosis and ERK/DRP1-mediated mitochondrial fission.

Melanoma, a highly metastatic malignant tumour, necessitated early detection and intervention. This study focuses on a hemicyanine fluorescent probe activated by near-infrared (NIR) light for bioimaging and targeted mitochondrial action in melanoma cells. IR-418, our newly designed hemicyanine-based NIR fluorescent probe, demonstrated effective targeting of melanoma cell mitochondria for NIR imaging. In vitro and in vivo experiments revealed IR-418's inhibition of melanoma growth through the promotion of mitochondrial apoptosis (Bax/Bcl-2/Cleaved Caspase pathway). Moreover, IR-418 inhibited melanoma metastasis by inhibiting mitochondrial fission through the ERK/DRP1 pathway. Notably, IR-418 mitigated abnormal ATL and ASL elevations caused by tumours without inflicting significant organ damage, indicating its high biocompatibility. In conclusion, IR-418, a novel hemicyanine-based NIR fluorescent probe targeting the mitochondria, exhibits significant fluorescence imaging capability, anti-melanoma proliferation, anti-melanoma lung metastasis activities and high biosafety. Therefore, it has significant potential in the early diagnosis and treatment of melanoma.

Multifunctional Near-Infrared Dye IR-817 Encapsulated in Albumin Nanoparticles for Enhanced Imaging and Photothermal Therapy in Melanoma.

Background: Near-infrared cyanine dyes have high sensitivity and spatial resolution imaging capabilities, but they also have unavoidable drawbacks such as photobleaching, low water solubility, fluorescence quenching, and toxic side effects. As an effective biologic drug carrier, albumin combines with cyanine dyes to form albumin@dye nanoparticles. These nanoparticles can alleviate the aforementioned issues and are widely used in tumor imaging and photothermal therapy. Methods: Herein, a newly synthesized near-infrared dye IR-817 was combined with bovine serum albumin (BSA) to create BSA@IR-817 nanoparticles. Through the detection of fluorescence emission and absorption, the optimal concentration and ratio of BSA and IR-817 were determined. Subsequently, dynamic light scattering (DLS) measurements and scanning electron microscopy (SEM) were used for the physical characterization of the BSA@IR-817 nanoparticles. Finally, in vitro and in vivo experiments were conducted to assess the fluorescence imaging and photothermal therapeutic potential of BSA@IR-817 nanoparticles. Results: IR-817 was adsorbed onto the BSA carrier by covalent conjugation and supramolecular encapsulation, resulting in the formation of dispersed, homogeneous, and stable nanoparticles with a particle size range of 120-220 nm. BSA@IR-817 not only improved the poor water solubility, fluorescence quenching, and toxic side effects of IR-817 but also enhanced the absorption and fluorescence emission peaks in the near-infrared region, as well as the fluorescence in the visible spectrum. In addition, BSA@IR-817 combined with laser 808 irradiation was able to convert light energy into heat energy with temperatures exceeding 50 °C. By creating a mouse model of subcutaneous melanoma, it was discovered that the tumor inhibition rate of BSA@IR-817 was greater than 99% after laser irradiation and that it achieved nearly complete tumor ablation without causing significant toxicity. Conclusion: Our research, therefore, proposes the use of safe and effective photothermal nanoparticles for the imaging, diagnosis, and treatment of melanoma, and offers a promising strategy for future biomedical applications.

A novel multifunctional mitochondrion-targeting NIR fluorophore probe inhibits tumour proliferation and metastasis through the PPARγ/ROS/ß-catenin pathway.

Recent advancements in tumour-targeted therapies and immunotherapy offer hope to patients with various malignancies. However, the uncontrolled growth and metastatic infiltration of malignant tumours remain a huge therapeutic challenge. Therefore, this study aimed to develop an integrated multifunctional diagnostic and treatment reagent IR-251 that can not only be used for tumour imaging but also to inhibit tumour growth and metastasis. Besides, our results showed that IR-251 targeted and damaged the mitochondria in cancer cells via organic anion-transporting polypeptides. Mechanistically, IR-251 induced ROS overproduction by inhibiting PPARγ and then inhibiting the ß-catenin signalling pathway and downstream protein molecules related to the cell cycle and metastasis. Moreover, the excellent anti-tumour proliferation and metastasis ability of IR-251 were verified in vitro/in vivo. And histochemistry staining revealed that IR-251 inhibited tumour proliferation and metastasis, which showed no significant side effect. In conclusion, this novel, multifunctional, mitochondria-targeting near-infrared fluorophore probe IR-251 has great potential in achieving accurate tumour imaging and inhibiting tumour proliferation and metastasis, and the underlying mechanism of action of IR-251 is mainly via the PPARγ/ROS/ß-catenin pathway.

Ultrasound classification-guided minimally invasive rotary cutting in granulomatous lobular mastitis.

BACKGROUND: To summarize the clinical experience of ultrasound-guided minimally invasive surgery for granulomatous lobular mastitis (GLM), and explore the feasibility of this technique for treating GLM. METHODS: This retrospective study reviewed the clinical features and treatment outcome of 30 patients who were diagnosed pathologically as GLM from 2016.3 to 2019.5 in the Department of Breast Surgery, Women's and Children's Hospital, Xiamen University. These patients weretreated with ultrasound-guided Mammotome minimally invasive surgery, and we tried to classified the lesion into four distinct patterns (diffuse abscess mixed type, sheet hypoechoic type, localized abscess type, localized hypoechoic mass type) according to the sonographic findings and clinical symptoms to find out if these patterns correlated with treatment and recurrence rate. RESULTS: After a median follow-up of 12 months on average (4-42 months), 26 cases (86.7%) were cured without acute or chronic complications such as disseminated inflammation and bleeding. Post-operative bleeding occurred in 1 case, and 3 cases (10.00%) relapsed. The ultrasound classification had 0 cases of diffuse abscess mixed type, 17 cases (56.7%) of sheet hypoechoic type, 9 cases (30%) of localized abscess type, and 4 cases (13.3%) of localized hypoechoic mass type. All 3 recurrent cases were sheet hypoechoic type, which were cured after another open surgical resection and showed no recurrence during an average follow-up of 20 months (11-40 months). CONCLUSIONS: In treating GLM patients with minimally invasive rotary cutting, ultrasound classification helps to select suitable patients, especially those with localized abscess and localized hypoechoic mass types with low recurrence rate, which is one of the safe and effective treatment methods.

The Clinicopathological Features and Survival Outcomes of Different Histological Subtypes in Triple-negative Breast Cancer.

Purpose: To determine the clinicopathological features and survival outcomes of triple-negative breast cancer (TNBC) according to different histological subtypes. Methods: Using the Surveillance, Epidemiology, and End Results database, we included TNBC cases in 2010-2013. The effect of histological subtype on breast cancer-specific survival (BCSS) and overall survival (OS) were analyzed using univariate and multivariate analyses. Results: A total of 19,900 patients were identified. Infiltrating ductal carcinoma not otherwise specified accounted for 91.6% of patients, followed by metaplastic carcinoma (2.7%), medullary carcinoma (1.4%), mixed lobular-ductal carcinoma (1.4%), lobular carcinoma (1.3%), apocrine carcinoma (1.0%), and adenoid cystic carcinoma (0.6%). Medullary carcinoma was more frequently poorly/undifferentiated. Significantly more lobular carcinoma, mixed lobular-ductal carcinoma, and metaplastic carcinoma patients had larger tumors. Adenoid cystic carcinoma, metaplastic carcinoma, medullary carcinoma, and apocrine carcinoma were more frequently node-negative. Lobular carcinoma (16.0%) and mixed lobular-ductal carcinoma (10.4%) more frequently had distant stage at initial diagnosis. Histologic subtype was an independent prognostic factor of BCSS and OS. Compared with infiltrating ductal carcinoma, medullary carcinoma and apocrine carcinoma had better BCSS and OS, while mixed lobular-ductal carcinoma and metaplastic carcinoma had worse survival. Adenoid cystic carcinoma survival was not significantly different from that of infiltrating ductal carcinoma. Conclusions: TNBC histological subtypes have different clinicopathological characteristics and survival outcomes. Medullary carcinoma and apocrine adenocarcinoma have excellent prognosis; mixed lobular-ductal carcinoma and metaplastic carcinoma are the most aggressive subtypes.