Near-Infrared MAO A Inhibitor (NMI) Outperformed FDA-Approved Chemotherapeutic Agents in Brain and Other Cancers: A Bioinformatic Analysis of NCI60 Screening Data

Our previous work has shown that monoamine oxidase A (MAO A) is overexpressed in glioma and prostate cancer. Near-infrared dye conjugate MAO A Inhibitor (NMI) inhibited the growth of these cancers. This study investigated the effects of NMI on other cancers by NCI60 screening. Our results showed that 48 out of 59 screened cell lines from nine types of cancer had 100% growth inhibition at 10 μM NMI treatment. The in vitro efficacy of NMI determined by growth inhibition (GI50 and TGI) and lethal doses (LC50) has been further studied in various cell lines of CNS cancer, prostate cancer, and non-small cell lung cancer (NSCLC), these three cancers showed increased MAO A expression in tumors compared to normal tissues. Based on the waterfall plots and the 3D scatter plot of GI50, TGI, and LC50 data, NMI showed higher potency to several CNS cancer and NSCLC cell lines than prostate cancer cell lines. In vitro efficacy of NMI outperformed FDA-approved drugs for CNS cancer, prostate cancer, and NSCLC, respectively. The Pairwise Pearson Correlation Coefficient (PCC) showed that NMI has a unique mechanism compared to the existing anticancer drugs. This study shows that NMI is a novel theragnostic drug with high potency and unique mechanisms for brain, prostate, NSCLC, and other cancers.

Computational Method Using Heterogeneous Graph Convolutional Network Model Combined With Reinforcement Layer For MiRNA-Disease Association Prediction

Background: A large number of evidences from biological experiments have confirmed that miRNAs play an important role in the progression and development of various human complex diseases. However, the traditional experiment methods are expensive and time-consuming. Therefore, it is a challenging task that how to develop more accurate and efficient methods for predicting potential associations between miRNA and disease. Results: In the study, we developed a computational model that combined Heterogeneous Graph Convolutional Network with Enhanced Layer for miRNA-Disease Association prediction (HGCNELMDA). The major improvement of our method lies in through restarting the random walk optimized the original features of nodes and adding a Reinforcement layer to the hidden layer of graph convolutional network retained similar information between nodes in the feature space. In addition, the proposed approach recalculated the influence of neighborhood nodes on target nodes by introducing the attention mechanism. The reliable performance of the HGCNELMDA was certified by the AUC of 93.47% in global leave-one-out cross-validation (LOOCV), and the average AUCs of 93.01% in fivefold cross-validation. Meanwhile, we compared the HGCNELMDA with the state‑of‑the‑art methods. Comparative results indicated that o the HGCNELMDA is very promising and may provide a cost‑effective alternative for miRNA-Disease Association prediction. Moreover, we applied HGCNELMDA to 3 different case studies to predict potential miRNAs related to lung cancer, prostate cancer, and pancreatic cancer. Results showed that 48, 50, and 50 of the top 50 predicted miRNAs were supported by experimental association evidence. Therefore, the HGCNELMDA is a reliable method for predicting disease-related miRNAs. Conclusions: The results of the HGCNELMDA method in the LOOCV (leave-one-out cross validation, LOOCV) and 5-cross validations were 93.47% and 93.01%, respectively. Compared with other typical methods, the performance of HGGCNMA is higher. Three cases of lung cancer, prostate cancer, and pancreatic cancer were studied. Among the predicted top 50 candidate miRNAs, 48, 50, and 50 were verified in the biological database HDMMV2.0.Therefore; this further confirms the feasibility and effectiveness of our method. To facilitate extensive studies for future disease-related miRNAs research, we developed a freely available web server called HGCNELMDA is available at http://132.232.17.50:8080/HGCNELMDA.jsp.

Clival Metastases in Cancer Patients

Purpose This study aimed to describe clinical features, radiotherapy (RT), and symptom outcomes in cancer patients with cranial nerve palsies associated with clival metastases. Methods A retrospective record review for the period in between 2000 and 2020 was conducted for patients with primary metastatic cancers, who developed distal clival metastases, or were treated with RT at the Karmanos Cancer Institute (Detroit, Michigan). The patients’ demographics and clinical characteristics, including their symptoms and improvement of symptoms after RT are described. Results Forty-four patients were identified who met inclusion criteria. The most common primary cancers were breast cancer, prostate cancer, and multiple myeloma. Magnetic resonance images and computed tomography scans were used for the diagnosis of clival metastasis, as well as for the evaluation after RT. Thirty-two patients (73%) with clival metastases also had cervical spine metastases. Prevailing neurologic symptoms were headache, diplopia, lateral gaze paralysis, blurry vision, chin numbness, and tongue deviation. Fifteen of 23 RT-treated patients (65%) received clivus only RT, and 8 patients (35%) were given whole brain RT. Post-RT symptom improvement was observed in patients with diplopia (5/6; 83%), headache (8/10; 80%), chin numbness (2/4; 50%), blurry vision (2/5; 40%), lateral gaze deficit (2/6; 33%), and tongue deviation (1/4; 25%). Conclusions These results suggest that early detection and rigorous cranial nerve examination, in addition to RT treatment, should be considered in patients with breast cancer, prostate cancer, and multiple myeloma, who developed bone metastasis, especially cervical spine metastasis.

2D exfoliated black phosphorus influences healthy and cancer prostate cell behaviors

Nowadays, prostate cancer is the most widespread tumour in worldwide male population. Actually, brachytherapy is the most advanced radiotherapy strategy for the local treatment of prostate cancer. It consists in the placing of radioactive sources closed to the tumour side thus killing cancer cells. However, brachytherapy causes the same adverse effects of external-beam radiotherapy. Therefore, alternative treatment approaches are required for enhancing radiotherapy effectiveness and reducing toxic symptoms. Nanostructured exfoliated black phosphorus (2D BP) may represent a strategic tool for local cancer therapy because of its capability to induce singlet oxygen production and act as photosensitizer. Hence, we investigated 2D BP in vitro effect on healthy and cancer prostate cell behavior. 2D BP was obtained through liquid exfoliation. 2D BP effect on healthy and cancer prostate cell behaviors was analyzed by investigating cell viability, oxidative stress and inflammatory marker expression. 2D BP inhibited prostate cancer cell survival, meanwhile promoted healthy prostate cell survival in vitro by modulating oxidative stress and immune response with and without near-infrared light (NIR)-irradiation. Nanostructured 2D BP is able to inhibit in vitro prostate cancer cells survival and preserve healthy prostate cell vitality through the control of oxidative stress and immune response, respectively.