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.
This study seeks to assess quality of life (QOL) and utility scores of head and neck cancer survivors.
We compared QOL as indicated by EORTC QLQ-C30, QLQ-H&N35, utility scores by time trade off (TTO) ...with previous published reference values and tested series characteristics related to global QOL and utility.
A total of 127 patients were recruited. Of the patients, 102 (80%) completed the utility assessment. Cancer survivors had lower scores compared with norm values. Patients without a spouse had a lower utility than those with a spouse. Patients with a low annual family income also had lower global QOL and utility scores (p < 0.05). Other factors were not significantly related to QOL and utility scores.
Disease and treatment of head and neck cancer lead to disability and poor health-related QOL and utility. Economic status may contribute to health-related QOL and utility, while marital status is related to utility for head and neck cancer patients.
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.
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.
Mitochondrial-targeting therapy is considered an important strategy for cancer treatment. (3-Carboxypropyl) triphenyl phosphonium (CTPP) is one of the candidate molecules that can drive drugs or ...nanomedicines to target mitochondria via electrostatic interactions. However, the mitochondrial-targeting effectiveness of CTPP is low. Therefore, pH-sensitive polymer-liposome complexes with charge-conversion copolymers and CTPP-containing cationic liposomes were designed for efficiently delivering an anti-cancer agent, ceramide, into cancer cellular mitochondria. The charge-conversion copolymers, methoxypoly(ethylene glycol)-block-poly(methacrylic acid-g-histidine), were anionic and helped in absorbing and shielding the positive charges of cationic liposomes at pH 7.4. In contrast, charge-conversion copolymers became neutral in order to depart from cationic liposomes and induced endosomal escape for releasing cationic liposomes into cytosol at acidic endosomes. The experimental results reveal that these pH-sensitive polymer-liposome complexes could rapidly escape from MCF-7 cell endosomes and target MCF-7 mitochondria within 3 h, thereby leading to the generation of reactive oxygen species and cell apoptosis. These findings provide a promising solution for cationic liposomes in cancer mitochondrial-targeting drug delivery.
This study aims to develop a volume-based algorithm (VBA) that can rapidly optimize rotating gantry arc angles and predict the lung V
preceding the treatment planning. This phantom study was ...performed in the dynamic arc therapy planning systems for an esophageal cancer model. The angle of rotation of the gantry around the isocenter as defined as arc angle (θ
), ranging from 360° to 80° with an interval of 20°, resulting in 15 different θ
of treatment plans. The corresponding predicted lung V
was calculated by the VBA, the mean lung dose, lung V
, lung V
, mean heart dose, heart V
, the spinal cord maximum dose and conformity index were assessed from dose-volume histogram in the treatment plan. Correlations between the predicted lung V
and the dosimetric indices were evaluated using Pearson's correlation coefficient. The results showed that the predicted lung V
and the lung V
in the treatment plan were positively correlated (r = 0.996, p < 0.001). As the θ
decreased, lung V
, lung V
, and the mean lung dose decreased while the mean heart dose, V
and the spinal cord maximum dose increased. The V
and the mean lung dose also showed high correlations with the predicted lung V
(r = 0.974, 0.999, p < 0.001). This study successfully developed an efficient VBA to rapidly calculate the θ
to predict the lung V
and reduce the lung dose, with potentials to improve the current clinical practice of dynamic arc radiotherapy.
Despite a considerable expansion in the present therapeutic repertoire for other malignancy managements, mortality from head and neck cancer (HNC) has not significantly improved in recent decades. ...Moreover, the second primary cancer (SPC) diagnoses increased in patients with HNC, but studies providing evidence to support SPCs prediction in HNC are lacking. Several base classifiers are integrated forming an ensemble meta-classifier using a stacked ensemble method to predict SPCs and find out relevant risk features in patients with HNC. The balanced accuracy and area under the curve (AUC) are over 0.761 and 0.847, with an approximately 2% and 3% increase, respectively, compared to the best individual base classifier. Our study found the top six ensemble risk features, such as body mass index, primary site of HNC, clinical nodal (N) status, primary site surgical margins, sex, and pathologic nodal (N) status. This will help clinicians screen HNC survivors before SPCs occur.
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