Salivary gland carcinomas are a heterogeneous group of tumors with many histological subtypes which occur in both major and minor salivary glands. However, they have a relatively low of incidence. ...Their rarity limits study size and the ability to perform phase III trials. Therefore, to date, the entire management is usually varied. Certain published studies have paid more attention to the systemic therapy in the management of metastatic or locally recurrent salivary gland cancer, while little effort has been made to study the entire management for this lesions. Although results of treatment for patients with salivary gland carcinoma have improved in recent years, the treatment of salivary gland cancers is still not standardized. And some patients who haven't received optimal treatment strategies had a reduced survival. In this review, the topics covered include surgery and radiotherapy, selective neck dissection, chemotherapy, and targeted therapy, which aimed to summarize the optimal management approaches and to develop recommendations for managing this lesions. For these rare cancers, there is also a need for a determined, coordinated effort to conduct high-quality clinical trials.
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•Prodrug and nanotechnology strategies were investigated in this study.•GSH-responsive and pH-responsive cisplatin prodrug was synthesized.•Cisplatin prodrug and paclitaxel co-loaded ...nanoparticles were constructed.•DDP-P/PTX NPs could be applied as promising anticancer system.
Platinum-based combination therapy is more effective and less toxic, but lack of targeting, and is not capable to enrich in the tumor zone. To obstacle these drawbacks, prodrug and nanotechnology strategies have been investigated in this study. GSH-responsive and pH-responsive cisplatin prodrug was synthesized. Cisplatin prodrug and paclitaxel co-loaded nanoparticles: DDP-P/PTX NPs were constructed. The drug release behavior and cytotoxicity of nanoparticles was assessed in vitro. In vivo anticancer efficiency and toxicity were evaluated on lung cancer bearing mice animal model. DDP-P/PTX NPs had a nanoscale size of 112.9 ± 3.5 nm. A reduction and pH triggered drug release with a synergistic tumor cell inhibition ability was observed by DDP-P/PTX NPs. DDP-P/PTX NPs also exhibited high tumor distribution, low systemic toxicity and remarkable antitumor effects in vivo. DDP-P/PTX NPs could be applied as promising anticancer system for the treatment of NSCLC.
Pathological cardiac hypertrophy is associated with cardiac dysfunction and is a key risk factor for heart failure and even sudden death. This study investigates the function of Mycn in cardiac ...hypertrophy and explores the interacting molecules.
A mouse model of cardiac hypertrophy was induced by isoproterenol (ISO). The cardiac dysfunction was assessed by the heart weight-to-body weight ratio (HW/BW), echocardiography assessment, pathological staining, biomarker detection, and cell apoptosis. Transcriptome alteration in cardiac hypertrophy was analyzed by bioinformatics analysis. Gain- or loss-of-function studies of MYCN proto-oncogene (Mycn), ubiquitin specific peptidase 2 (USP2), and junction plakoglobin (JUP) were performed. The biological functions of Mycn were further examined in ISO-treated cardiomyocytes. The molecular interactions were verified by luciferase assay or immunoprecipitation assays.
Mycn was poorly expressed in ISO-treated mice, and its upregulation reduced HW/BW, cell surface area, oxidative stress, and inflammation while improving cardiac function of mice. It also reduced apoptosis of cardiomyocytes in mice and those in vitro induced by ISO. Mycn bound to the USP2 promoter to activate its transcription. USP2 overexpression exerted similar myocardial protective functions. It stabilized JUP protein by deubiquitination modification, which blocked the Akt/β-catenin pathway. Knockdown of JUP restored phosphorylation of Akt and β-catenin protein level, which negated the protective effects of USP2.
This study demonstrates that Mycn activates USP2 transcription, which mediates ubiquitination and protein stabilization of JUP, thus inactivating the Akt/β-catenin axis and alleviating cardiac hypertrophy-induced heart failure.
In this study, we set out to characterize the expression status of long non-coding RNA (lncRNA) Myocardial Infarction Associated Transcript (MIAT) in non-small cell lung cancer (NSCLC) and elucidate ...its mechanistic contribution to this disease. Relative expression levels of MIAT, Pellino E3 Ubiquitin Protein Ligase Family Member 3 (PELI3), and microRNA (miR)-128-3p were analyzed by real-time polymerase chain reaction. PELI3 protein level was determined by immunoblotting. Cell viability and proliferation were evaluated by the MTT assay and colony formation assay, respectively. Cell invasion and migration were assessed by wound-healing closure and transwell assays, respectively. The regulatory actions of miR-128-3p on both MIAT and PELI3 were interrogated by luciferase reporter assay. We demonstrated the aberrant upregulation of MIAT in NSCLC and its association with tumor progression. We further uncovered the negative correlation among MIAT, PELI3, and miR-128-3p. MIAT deficiency significantly compromised cell viability, proliferation, invasion, and migration, while increased miR-128-3p and decreased PELI3 expressions. Application of miR-128-3p inhibitor significantly stimulated luciferase activities driven by both MIAT and PELI3 promoter and phenotypically promoted cell viability, proliferation, migration, and invasion. Our study highlighted the mechanistic contribution of the MIAT/miR-128-3p/PELI3 signaling cascade in NSCLC.
The aim of this study was to draw a comprehensive mutational landscape of nasopharyngeal carcinoma (NPC) tumors and identify the prognostic factors for distant metastasis-free survival (DMFS).
A ...total of forty primary nonkeratinizing NPC patients underwent targeted next-generation sequencing of 450 cancer-relevant genes. Analysis of these sequencing and clinical data was performed comprehensively. Univariate Cox regression analysis and multivariate Lasso-Cox regression analyses were performed to identify factors that predict distant metastasis and construct a risk score model, and seventy percent of patients were randomly selected from among the samples as a validation cohort. A receiver operating characteristic (ROC) curve and Harrell's concordance index (C-index) were used to investigate whether the risk score was superior to the TNM stage in predicting the survival of patients. The survival of patients was determined by Kaplan-Meier curves and log-rank tests.
The twenty most frequently mutated genes were identified, such as KMT2D, CYLD, and TP53 et al. Their mutation frequencies of them were compared with those of the COSMIC database and cBioPortal database. N stage, tumor mutational burden (TMB), PIK3CA, and SF3B1 were identified as predictors to build the risk score model. The risk score model showed a higher AUC and C-index than the TNM stage model, regardless of the training cohort or validation cohort. Moreover, this study found that patients with tumors harboring PI3K/AKT or RAS pathway mutations have worse DMFS than their wild-type counterparts.
In this study, we drew a mutational landscape of NPC tumors and established a novel four predictor-based prognostic model, which had much better predictive capacity than TNM stage.
Patients with esophageal small cell carcinoma undergoing definitive chemoradiotherapy (CRT) seem to have disparity in tumor response. The identification of CRT sensitivity-related tumor markers would ...be helpful for selecting patients most likely to benefit from CRT. The aim of this study was to examine the predictive value of biological markers in small cell carcinoma of the esophagus (SCEC) patients treated with definitive CRT. Pretreatment serum levels of neurone-specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), and carcinoembryonic antigen (CEA) were measured by immunoradiometric assays, while the tumor responses were evaluated according to the World Health Organization response criteria. The relationships between pretreatment expression of NSE, CYFRA21-1, CEA, and the tumor response to CRT were analyzed. The effective rates (complete response + partial response) in NSE high and low groups were 10.80 % (9/82) and 37.98 % (31/82), respectively (
P
= 0.003).The results from statistical analysis indicated that the effectiveness of CRT was significantly associated with the serum levels of NSE before treatment (
P
= 0.002). The overall survival (OS) of the patients with high NSE levels was worse than that of those with low NSE levels (
P
= 0.004). In multivariate analysis, low level of NSE was the most significant independent predictor of good OS (
P
= 0.003). The result showed a promising predictive value of NSE regarding to the sensitivity of tumors to CRT. NSE may be a reliable surrogate marker of CRT efficacy in patients with SCEC.
Patients with advanced non-small cell lung cancer (NSCLC) seem to have disparity in prognosis. Accurate prediction of prognosis could be useful in the future to predict individual risk and to develop ...more aggressive or alternative treatment strategies.
To evaluate the prognostic value of metabolic tumor volume (MTV) measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with NSCLC.
We retrospectively reviewed 120 patients with pathologically proven NSCLC (61 squamous cell carcinomas and 59 adenocarcinomas) who underwent pretreatment 18F-FDG PET. MTV and maximum standardized uptake value (SUVmax) for the primary tumors were measured by 18F-FDG PET. Pretreatment variables (age, sex, American Joint Committee on Cancer AJCC stage, histological type, SUVmax, and MTV) were analyzed to identify their correlation with two-year survival. To further evaluate and compare the predictive value of PET parameters, MTV, and SUVmax, time-dependent receiver-operating characteristic curve (ROC) analysis was used.
In the univariate analysis, AJCC stage, histological type, MTV, and SUVmax of primary tumor were significant predictors of survival. On multivariate analysis, independent prognostic factors associated with decreased two-year survival were AJCC stage (hazard ratio HR 2.236, P = 0.003), histological type (HR 2.038, P = 0. 004), and MTV (HR 1.016, P = 0.001). SUVmax was not a significant factor (HR 0.96, P = 0.490). On time-dependent ROC analysis, MTV showed good predictive performance for two-year survival consistently better than SUVmax.
MTV, a volumetric parameter of 18F-FDG PET, is an important independent prognostic factor for survival and a better predictor of survival than SUVmax for the primary tumor in patients with advanced NSCLC.
•ANP32B was high expression in lung cancer tissues.•ANP32B promoted the progression of lung cancer.•ANP32B promoted the proliferation and migration by regulating VDAC1.
It has been reported before ...that acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) plays roles in many cancers, yet no report of its role in lung cancer exists. In this study, we documented an elevation of ANP32B within lung cancer tissues and cells. Knockdown of ANP32B hindered the proliferation as well as migration of lung cancer cells, whereas overexpression of ANP32B helps to promote the malignant progression of lung cancer. ANP32B also regulates lung cancer cells’ apoptosis and cell cycling. In addition, voltage-dependent anion channel 1 (VDAC1) has been found to be a downstream targeted gene of ANP32B and is positively regulated by ANP32B in lung cancer cells. According to our research, the expression of VDAC1 was positively associated with ANP32B expression in lung adenocarcinoma (r = 0.61, P < 0.001) samples by Pearson’s correlation coefficient analysis. Furthermore, rescue experiments demonstrated that VDAC1 could rescue the effect of ANP32B expression on lung cancer cell proliferation and migration. Our results suggest that ANP32B overexpression facilitates lung cancer progression by increasing the expression of VDAC1. As such, we have revealed a novel mechanism regulating the connection between ANP32B and VDAC1 and a potential role of ANP32B as an oncogene and a clinical therapeutic target in lung cancer.
Objectives
The purpose of the study was to identify predictive factors of tumor response to preoperative chemoradiotherapy for rectal adenocarcinoma.
Methods
Ninety-eight patients with nonmetastatic ...rectal adenocarcinoma received preoperative concurrent chemoradiotherapy and underwent mesorectal excision. After treatment, tumor response according to tumor regression grade were evaluated. The correlation of clinicopathologic factors to tumor response was analyzed.
Results
The results from a univariate analysis indicated that pretreatment carcinoembryonic antigen level ≤3.0 ng/ml (P = 0.002), non-fixed tumor (P = 0.001), and tumor circumferential extent ≤50% (P = 0.001) were associated significantly with a good tumor response. They also indicated that pretreatment positive lymph nodes (P = 0.032) were associated significantly with a poor tumor response. In multivariate analysis, the results indicated that pretreatment carcinoembryonic antigen level (hazard ratio, 2.930; P = 0.003), tumor mobility (hazard ratio, 2.651; P = 0.002) and circumferential extent of tumor (hazard ratio, 2.394; P = 0.019) independently predicted a good pathologic response rate. Pretreatment positive lymph nodes were not significantly associated with a good response (hazard ratio, 0.361; P = 0.191).
Conclusions
Pretreatment carcinoembryonic antigen level, tumor mobility and circumferential extent of tumor may be helpful in predicting responsiveness in rectal adenocarcinoma to preoperative chemoradiotherapy, although the results should be confirmed in larger, more homogeneous studies.
•An alternating CNN and transformer network STCNet is proposed to improve the accuracy of COVID-19 CT image segmentation.•ReSwin transformer block is proposed to expand the receptive field to extract ...richer context information in COVID-19 CT images.•SCCA module is used to cross-process encoder and decoder features to recover fine-grained details of the infected area.•STCNet is superior to SOTA in COVID-19 CT image segmentation with less computational cost and parameters.
Since the emergence of the Corona Virus Disease in 2019 (COVID-19), it has become a serious health problem affecting the human respiratory system. At present, automatic segmentation of lung infection areas from Computed Tomography has been playing a crucial role in the diagnosis of this disease because of its ability to perform pathological studies based on the lung infection areas. However, due to the lung infection areas scattered distribution, the existing segmentation methods generally have the problems of missing and incomplete segmentation. The Convolutional Neural Network (CNN)-based approaches generally lack the ability to model explicit long-range relation, and the transformer-based methods are not conducive to capturing the detailed boundaries of infected areas. Whereas the infected regions of the coronavirus images are scattered and boundary information plays an important role, both the boundaries and the global infected areas need to be taken into account. Therefore, we propose a novel coronavirus image segmentation network alternately using Swin transformer and CNN (STCNet). Firstly, to enable network to capture richer features, the ReSwin transformer block is proposed and added after each level of convolution block in the encoder-decoder. Secondly, to effectively retain the infected areas boundary information, the skip connection cross attention module is used to provide spatial information to each decoder. And through the fine-tuned scale-aware pyramid fusion module to fuse multi-scale context information. Experimental results show that STCNet at can achieve state-of-the-art performance on two coronavirus segmentation datasets, with Dice achieves 79.92 % and 82.78 %, respectively. Our code is available at https://github.com/sineagles/STCNet.
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