Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer‐related deaths. Thus, understanding the mechanism of lung cancer metastasis ...will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF‐elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients.
CD109 promotes lung cancer metastasis through promoting EGFR‐AKT‐mTOR signaling and CD109 is an independent prognostic marker for lung adenocarcinoma.
Cone-beam computed tomography (CBCT) integrated with a linear accelerator is widely used to increase the accuracy of radiotherapy and plays an important role in image-guided radiotherapy (IGRT). For ...comparison with fan-beam computed tomography (FBCT), the image quality of CBCT is indistinct due to X-ray scattering, noise, and artefacts. We proposed a deep learning model, "Cycle-Deblur GAN", combined with CycleGAN and Deblur-GAN models to improve the image quality of chest CBCT images. The 8706 CBCT and FBCT image pairs were used for training, and 1150 image pairs were used for testing in deep learning. The generated CBCT images from the Cycle-Deblur GAN model demonstrated closer CT values to FBCT in the lung, breast, mediastinum, and sternum compared to the CycleGAN and RED-CNN models. The quantitative evaluations of MAE, PSNR, and SSIM for CBCT generated from the Cycle-Deblur GAN model demonstrated better results than the CycleGAN and RED-CNN models. The Cycle-Deblur GAN model improved image quality and CT-value accuracy and preserved structural details for chest CBCT images.
Obesity is a well‐known risk factor for breast cancer formation and is associated with elevated mortality and a poor prognosis. An obesity‐mediated inflammatory microenvironment is conducive to the ...malignant progression of tumors. However, the detailed molecular mechanism is still needed to be clarified. Herein, we identified that breast cancer cells from mice with diet‐induced obesity exhibited increased growth, invasiveness, and stemness capacities. A transcriptome analysis revealed that expressions of interleukin 33 (IL33) signaling pathway‐related genes were elevated in obesity‐associated breast cancer cells. Importantly, IL33 expression was significantly associated with the yes‐associated protein (YAP) signature, and IL33 was transcriptionally regulated by YAP. Suppression of IL33 reduced tumor migration and invasion, while the addition of IL33 activated nuclear factor (NF)‐κB signaling and revived tumor mobility in YAP‐silenced cells. Furthermore, suppression of YAP attenuated IL33 expression which was accompanied by relief of obesity‐mediated immunosuppression. Clinical analyses showed that IL33 expression was markedly associated with macrophage and regulatory T cell infiltration. These findings reveal a crucial role of the YAP/IL33 axis in promoting aggressiveness and immunosuppression of obesity‐associated breast cancer progression.
Multifunctional nanoplatforms combined with photodynamic therapy (PDT) and anticancer drugs have shown great promising in cancer therapy. However, their efficacy is limited by the low specificity, ...low oxygen levels, and a tolerant tumor immune microenvironment. Herein, we developed a biocompatible theranostic nanoplatform (FM@VP) based on co-assembly of a nanocomplex formed by a functional polysaccharide fucoidan and a bioreducible polyamidoamine (PAMAM) dendrimer, a photosensitizer verteporfin (VP), and MnO2 nanoparticles (a tumor microenvironment responsive oxygen evolving nanomaterial) into a multifunctional nanoparticle cluster. The dendrimer-fucoidan polyionic nanocomplex (DFPN) specifically targeted P-selectin-overexpressed triple-negative breast cancer (TNBC) and the tumor-associated vasculature, and was sensitive to glutathione (GSH) in tumor. More importantly, this FM@VP nanocomplex simultaneously overcame tumor hypoxia, suppressed oncogenic signaling, and attenuated tumor-mediated immunosuppression, resulting in improving therapeutic efficacy of PDT while enhancing antitumor immunity and anti-metastasis. This discovery provides a powerful strategy for synergetic cancer targeting/photodynamic/immunotherapy and could serve as a safe clinical translational approach.
Radiotherapy treatment planning (RTP) is time-consuming and labor-intensive since medical physicists must devise treatment plans carefully to reduce damage to tissues and organs for patients. ...Previously, we proposed the volume-based algorithm (VBA) method, providing optimal partial arcs (OPA) angle to achieve the low-dose volume of lungs in dynamic arc radiotherapy. This study aimed to implement the VBA for esophageal cancer (EC) patients and compare the lung dose and delivery time between full arcs (FA) without using VBA and OPA angle using VBA in volumetric modulated arc therapy (VMAT) plans. We retrospectively included 30 patients diagnosed with EC. RTP of each patient was replanned to 4 VMAT plans, including FA plans without (FA-C) and with (FA + C) dose constraints of OARs and OPA plans without (OPA-C) and with (OPA + C) dose constraints of OARs. The prescribed dose was 45 Gy. The OARs included the lungs, heart, and spinal cord. The dose distribution, dose-volume histogram, monitor units (MUs), delivery time, and gamma passing rates were analyzed. The results showed that the lung V
and V
in OPA + C plans were significantly lower than in FA + C plans (p < 0.05). No significant differences were noted in planning target volume (PTV) coverage, lung V
, lung V
, mean lung dose, heart V
, heart V
, mean heart dose, and maximal spinal cord dose between FA + C and OPA + C plans. The delivery time was significantly longer in FA + C plans than in OPA + C plans (237 vs. 192 s, p < 0.05). There were no significant differences between FA + C and OPA + C plans in gamma passing rates. We successfully applied the OPA angle based on the VBA to clinical EC patients and simplified the arc angle selection in RTP. The VBA could provide a personalized OPA angle for each patient and effectively reduce lung V
, V
and delivery time in VMAT.
...it is essential to promptly diagnose and treat the bleeding site, whether it is from the primary cancer site, vessels, as this can significantly impact patient outcomes 2. ...the occurrence of ...acute bleeding from the carotid artery, known as carotid blowout syndrome (CBS), remains a rare but devastating side effect of salvage re-irradiation in patients with HNC 3. While life-saving interventions such as supportive care and endovascular and surgical procedures can achieve rapid hemostasis and offer high short-term survival rates, patients at risk of developing CBS should be informed about the various treatment options available for hemorrhage control and the anticipated long-term outcomes, which may be influenced by the underlying recurrent and metastatic disease.
Sorafenib is one of the options for advanced hepatocellular carcinoma treatment and has been shown to extend median overall survival. However, sorafenib resistance often develops a few months after ...treatment. Hence, developing various strategies to overcome sorafenib resistance and understand the possible mechanisms is urgently needed. We first established sorafenib-resistant hepatocellular carcinoma (HCC) cells. Then, we found that sorafenib-resistant Huh7 cells (Huh7/SR) exhibit higher glucose uptakes and express elevated fatty acid synthesis and glucose metabolism-related proteins than their parental counterparts (Huh7). The current study investigated whether sorafenib resistance could be reversed by suppressing fatty acid synthesis, using a fatty acid synthase (FASN) inhibitor, orlistat, in HCC cells. FASN inhibition-caused changes in protein expressions and cell cycle distribution were analyzed by Western blot and flow cytometry, and changes in glucose uptakes were also evaluated by 18F-FDG uptake. Orlistat remarkably enhanced the cytotoxicity of sorafenib in both Huh7 and Huh7/SR cells, and flow cytometry showed that combination treatment significantly increased the sub-G1 population in both cell lines. Western blot revealed that the combination treatment effectively increased the ratio of Bax/Bcl-2 and decreased expressions of pERK; additionally, the combination treatment also strongly suppressed fatty acid synthesis-related proteins (e.g., FASN and SCD) in both cell lines. Lastly, the 18F-FDG uptake was repressed by the combination treatment in both cell lines. Our results indicated that orlistat-mediated FASN inhibition could overcome sorafenib resistance and enhance cell killing in HCC by changing cell metabolism.
Non-small cell lung cancer (NSCLC) patients harboring a KRAS mutation have unfavorable therapeutic outcomes with chemotherapies, and the mutation also renders tolerance to immunotherapies. There is ...an unmet need for a new strategy for overcoming immunosuppression in KRAS-mutant NSCLC. The recently discovered role of melatonin demonstrates a wide spectrum of anticancer impacts; however, the effect of melatonin on modulating tumor immunity is largely unknown. In the present study, melatonin treatment significantly reduced cell viability accompanied by inducing cell apoptosis in KRAS-mutant NSCLC cell lines including A549, H460, and LLC1 cells. Mechanistically, we found that lung cancer cells harboring the KRAS mutation exhibited a higher level of programmed death ligand 1 (PD-L1). However, treatment with melatonin substantially downregulated PD-L1 expressions in both the presence and absence of interferon (IFN)-γ stimulation. Moreover, KRAS-mutant lung cancer cells exhibited higher Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) levels, and PD-L1 expression was positively correlated with YAP and TAZ in lung cancer cells. Treatment with melatonin effectively suppressed YAP and TAZ, which was accompanied by downregulation of YAP/TAZ downstream gene expressions. The combination of melatonin and an inhibitor of YAP/TAZ robustly decreased YAP and PD-L1 expressions. Clinical analysis using public databases revealed that PD-L1 expression was positively correlated with YAP and TAZ in patients with lung cancer, and PD-L1 overexpression suggested poor survival probability. An animal study further revealed that administration of melatonin significantly inhibited tumor growth and modulated tumor immunity in a syngeneic mouse model. Together, our data revealed a novel antitumor mechanism of melatonin in modulating the immunosuppressive tumor microenvironment by suppressing the YAP/PD-L1 axis and suggest the therapeutic potential of melatonin for treating NSCLC.
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