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Abstract Background Vasculogenic mimicry (VM) was increasingly recognized as a form of aggressive melanoma acquiring blood supply. Genistein had attracted much attention as a potential anticancer agent. Therefore, we examined the effect of Genistein on VM in human uveal melanoma cells. Methods VM structure was detected by periodic acid-Schiff (PAS) staining for uveal melanoma C918 cells cultured on the three-dimensional type I collagen gels after exposed to Genistein. We used reverse transcription polymerase chain reaction (RT-PCR) and Western Blot analysis to examine the effect of Genistein on vascular endothelial cadherin (VE-cadherin) mRNA and protein expression. The nude mice models of human uveal melanoma C918 cells were established to assess the number of VM using immunohistochemical and PAS double-staining. Results Genistein inhibited the survival of C918 cells in vitro. The ectopic model study showed that VM in tumor tissue sections were significantly reduced by Genistein in vivo. In vitro, the VM structure was found in control, 25 and 50 μM Genistein-treatment groups but not in 100 and 200 μM. RT-PCR and Western Blot showed that 100 and 200 μM concentration of Genistein could significantly decrease VE-cadherin mRNA and protein expression of C918 cells compared with control (P < 0.05). However, the 25 and 50 μM Genistein slightly decreased the VE-cadherin level in vitro (P > 0.05). Conclusion Genistein inhibits VM formation of uveal melanoma cells in vivo and in vitro. One possible underlying molecular mechanism by which Genistein could inhibit VM formation of uveal melanoma is related to down-regulation of VE-cadherin.

Background: Anoikis, a unique form of cell death, serves as a vital part of the organism's defense by preventing shedding cells from re-attaching to the incorrect positions, and plays pivotal role in cancer metastasis. Nonetheless, the specific mechanisms among anoikis, the clinical prognosis and tumor microenvironment (TME) of bladder cancer (BLCA) are insufficiently understood. Method: BLCA patients were classified into different anoikis subtypes based on the expression of candidate anoikis-related genes (ARGs), and differences in the clinicopathological features, TME, immune cell infiltration, and immune checkpoints between two anoikis subtypes were analyzed. Next, patients in the TCGA cohort were randomized into the train and test groups in a 1:1 ratio. Subsequently, the anoikis-related model was constructed to predict the prognosis via utilizing the univariate Cox, LASSO and multivariate Cox analyses, and validated internally and externally. Moreover, the relationships between the risk score and clinicopathologic features, immune cell infiltration, immunotherapy response, and antitumor drug sensitivity were also analyzed. In addition, representative genes were evaluated using immunohistochemistry in clinical specimens, and in BLCA cell lines, functional experiments were performed to determine the biological behavior of hub gene PLOD1. Result: Two definite anoikis subgroups were identified. Compared to ARGcluster A, patients assigned to ARGcluster B were characterized by an immunosuppressive microenvironment and worse prognosis. Then, the anoikis-related model, including PLOD1, EHBP1, and CSPG4, was constructed, and BLCA patients in the low-risk group were characterized by a better prognosis. Next, the accurate nomogram was built to improve the clinical applicability by combining the age, tumor stage and risk Score. Moreover, immune infiltration and clinical features differed significantly between high- and low-risk groups. We also found that the low-risk group exhibited a lower tumor immune dysfunction and exclusion score, a higher immunophenoscore (IPS), had more sensitivity to immunotherapy. Eventually, the expression levels of three genes were verified by our experiment, and knockdown of PLOD1 could inhibit invasion and migration abilities in BLCA cell lines. Conclusion: These results demonstrated a new direction in precision therapy for BLCA, and indicated that the ARGs might be helpful to in predicting prognosis and as therapeutic targets in BLCA. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the application value of contrast‐enhanced transthoracic echocardiography (cTEE) in the diagnosis of patent foramen ovale (PFO) under different states of stimulation, with the goal of enhancing the accuracy and efficiency of PFO diagnosis. Methods: This research consecutively enrolled patients suspected of having PFO from October 2022 to February 2024, presenting primary clinical symptoms such as unexplained syncope, headache, dizziness, and stroke. Patients underwent standard transthoracic echocardiography (TTE) and cTEE under three different states of stimulation (resting state, coughing, and Valsalva maneuver). Based on the presence of microbubbles in the left heart and their initial appearance time, patients were classified into PFO and control groups, with further diagnostic confirmation via transesophageal echocardiography (TEE) or foramen ovale closure procedures. Results: The study results revealed significant differences between the PFO and control groups regarding age (p = 0.034) and headache symptoms (p = 0.001). In the PFO group, TTE showed a higher positivity rate both at rest and during coughing, highlighting the association between PFO and specific clinical symptoms. The number of microbubbles observed during TTE increased significantly under various stimulation states, particularly during the Valsalva maneuver (p < 0.05). This increase became more pronounced as the duration of the maneuver was extended, underscoring the differential response of PFO patients under varied physiological testing conditions, especially during prolonged Valsalva maneuvers. Conclusion: The study confirms the significant value of cTEE in diagnosing PFO under different stimulation states, particularly emphasizing the application of the Valsalva maneuver to significantly improve the sensitivity and specificity of PFO detection. Thus, incorporating cTEE examinations under various stimulation states holds significant clinical importance for enhancing the accuracy and efficiency of PFO diagnosis. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells (CSCs) are a subset of cells within tumors that possess the unique ability to self-renew and give rise to diverse tumor cells. These cells are crucial in driving tumor metastasis, recurrence, and resistance to treatment. The objective of this study was to pinpoint the essential regulatory genes associated with CSCs in prostate adenocarcinoma (PRAD) and assess their potential significance in the diagnosis, prognosis, and immunotherapy of patients with PRAD., Method: The study utilized single-cell analysis techniques to identify stem cell-related genes and evaluate their significance in relation to patient prognosis and immunotherapy in PRAD through cluster analysis. By utilizing diverse datasets and employing various machine learning methods for clustering, diagnostic models for PRAD were developed and validated. The random forest algorithm pinpointed HSPE1 as the most crucial prognostic gene among the stem cell-related genes. Furthermore, the study delved into the association between HSPE1 and immune infiltration, and employed molecular docking to investigate the relationship between HSPE1 and its associated compounds. Immunofluorescence staining analysis of 60 PRAD tissue samples confirmed the expression of HSPE1 and its correlation with patient prognosis in PRAD., Result: This study identified 15 crucial stem cell-related genes through single-cell analysis, highlighting their importance in diagnosing, prognosticating, and potentially treating PRAD patients. HSPE1 was specifically linked to PRAD prognosis and response to immunotherapy, with experimental data supporting its upregulation in PRAD and association with poorer prognosis., Conclusion: Overall, our findings underscore the significant role of stem cell-related genes in PRAD and unveil HSPE1 as a novel target related to stem cell., Competing Interests: The authors declare the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Ma, He, Gu and Zhu.)

Melatonin is an amine hormone produced by mammals and the human pineal gland. Modern biomedical research has shown that melatonin has antitumor effects. However, the underlying mechanisms of these effects remain unclear. In this study, we explore the effect of melatonin on TE-1 esophageal cancer cells metastasis and study the roles of the NF-κB signaling pathway and MMP9 in this process. We found that melatonin significantly suppressed the migration and invasion of TE-1 esophageal cancer cells, inhibited the activation NF-κB signaling pathway, and decreased the expression of MMP9. When adding NF-κB inhibitor, the results show that the expression of MMP9 decreased while E-cadherin increased. Taken together, the results indicate that melatonin inhibits esophageal cancer cell metastasis by down-regulating the NF-κB signaling pathway and MMP9. Therefore, melatonin may be a new drug for the effective treatment of esophageal cancer., (© 2020 by the Association of Clinical Scientists, Inc.)

Genistein, an isoflavone isolated from soybean, has been found to be a potent antitumor agent. However, both the effect of genistein on human uveal melanoma cells and the precise mechanism by which genistein suppresses tumorigenesis remain unclear. In the present study, we explored the possible activity of genistein to inhibit human uveal melanoma cell growth and investigated the possible role of genistein on microRNA-27a (miR-27a) as well as its target gene zinc finger and BTB domain containing 10 (ZBTB10) expression levels. The results suggested a significant inhibition of uveal melanoma cell growth in a time- and dose-related manner. In vivo study also indicated treatment groups with genistein could significantly inhibit the growth of xenografts. Further functional assays revealed that the levels of miR-27a and its target gene ZBTB10 were significantly different based on the dose of genistein. In conclusion, the present study demonstrates that genistein exerts growth inhibitory activities in human uveal melanoma cells. Moreover, we for the first time report a correlation between antitumor activity of genistein and miR-27a mediated regulatory mechanism.