Anti-PD-1/PD-L1 treatment has achieved durable responses in TNBC patients, whereas a fraction of them showed non-sensitivity to the treatment and the mechanism is still unclear.
Objective To investigate the role of P53 gene in radiation induced cell death of non-small-cell lung cancerMethods Select the H1299(p53-/-),H1299-P53,H1299-175H cells for the studing.Flow cytometry was used to detect the apoptosis rate,western bolt was used to detect the expression of related autophagy and apoptosis protein.Results When treated with 4 GY、8 GY H1299(P53-/-) manifest the lower apoptosis rate by 68.4%and 50%respectively compared with sham-irradiation group.When treated with 4GY 、8GY H1299-P53 manifest the highter apoptosis rate by 1.7 times and 8.1 times respectively compared with sham-irradiation group .When treated with 4 GY、8 GY H1299-175H manifest the highter apoptosis rate by 1.5 times and 2 times respectively compared with sham-irradiation group.The expression of akt is decreasing in dose dependent manner in H1299,the same in H1299-175H,but in H1299-p53 and,the expression of akt elevated in 4 GY,decreased in 8GY but higher compared with sham-irradiation group.The expression of MDM2 show positive dose-dependent manner in H1299(P53-/-),the trend of the expression of MDM2 in H1299-P53 show the same tread as expression of akt,but in H1299-175H the expression of MDM2 increased in 4GY,decreased in 8GY.The expression of LC3 show positive dose-dependent manner in H1299(P53-/-),but show negative dose-dependent manner in H1299-P53 and H1299-175H.The expression of caspase-3 show no clear difference in H1299(P53-/-),in H1299-P53 the expression of caspase-3 increasing in dose dependent manner,in H1299-175H the expression of caspase-3 increased in 0 GY,decreased in 4 GY.Conclusion The effect of X-ray in H1299(P53-/-)promote autophagy,but promote apoptosis in H1299-P53 and H1299-175H.
The malignant tumor is a multi-etiological, systemic and complex disease characterized by uncontrolled cell proliferation and distant metastasis. Anticancer treatments including adjuvant therapies and targeted therapies are effective in eliminating cancer cells but in a limited number of patients. Increasing evidence suggests that the extracellular matrix (ECM) plays an important role in tumor development through changes in macromolecule components, degradation enzymes and stiffness. These variations are under the control of cellular components in tumor tissue via the aberrant activation of signaling pathways, the interaction of the ECM components to multiple surface receptors, and mechanical impact. Additionally, the ECM shaped by cancer regulates immune cells which results in an immune suppressive microenvironment and hinders the efficacy of immunotherapies. Thus, the ECM acts as a barrier to protect cancer from treatments and supports tumor progression. Nevertheless, the profound regulatory network of the ECM remodeling hampers the design of individualized antitumor treatment. Here, we elaborate on the composition of the malignant ECM, and discuss the specific mechanisms of the ECM remodeling. Precisely, we highlight the impact of the ECM remodeling on tumor development, including proliferation, anoikis, metastasis, angiogenesis, lymphangiogenesis, and immune escape. Finally, we emphasize ECM "normalization" as a potential strategy for anti-malignant treatment.
Background: Breast ultrasound is the first choice for breast tumor diagnosis in China, but the Breast Imaging Reporting and Data System (BI-RADS) categorization routinely used in the clinic often leads to unnecessary biopsy. Radiologists have no ability to predict molecular subtypes with important pathological information that can guide clinical treatment. Materials and Methods: This retrospective study collected breast ultrasound images from two hospitals and formed training, test and external test sets after strict selection, which included 2,822, 707, and 210 ultrasound images, respectively. An optimized deep learning model (DLM) was constructed with the training set, and the performance was verified in both the test set and the external test set. Diagnostic results were compared with the BI-RADS categorization determined by radiologists. We divided breast cancer into different molecular subtypes according to hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression. The ability to predict molecular subtypes using the DLM was confirmed in the test set. Results: In the test set, with pathological results as the gold standard, the accuracy, sensitivity and specificity were 85.6, 98.7, and 63.1%, respectively, according to the BI-RADS categorization. The same set achieved an accuracy, sensitivity, and specificity of 89.7, 91.3, and 86.9%, respectively, when using the DLM. For the test set, the area under the curve (AUC) was 0.96. For the external test set, the AUC was 0.90. The diagnostic accuracy was 92.86% with the DLM in BI-RADS 4a patients. Approximately 70.76% of the cases were judged as benign tumors. Unnecessary biopsy was theoretically reduced by 67.86%. However, the false negative rate was 10.4%. A good prediction effect was shown for the molecular subtypes of breast cancer with the DLM. The AUC were 0.864, 0.811, and 0.837 for the triple-negative subtype, HER2 (+) subtype and HR (+) subtype predictions, respectively. Conclusion: This study showed that the DLM was highly accurate in recognizing breast tumors from ultrasound images. Thus, the DLM can greatly reduce the incidence of unnecessary biopsy, especially for patients with BI-RADS 4a. In addition, the predictive ability of this model for molecular subtypes was satisfactory,which has specific clinical application value.
BackgroundBreast cancer is the most widespread malignant tumor worldwide. Single-cell sequencing technology offers novel insights and methods to understand the onset, progression, and treatment of tumors. Nevertheless, there is currently an absence of a thorough and unbiased report on the comprehensive research status of single-cell sequencing in breast cancer. This study seeks to summarize and quantify the dynamics and trends of research on breast cancer single-cell sequencing by bibliometric analysis.MethodsResearch articles and reviews related to breast cancer single-cell sequencing were selected from the WoSCC database. Visualization of data regarding countries, institutions, authors, references, and keywords was performed by CiteSpace and VOSviewer software.Results583 articles and reviews were analyzed in this study. The quantity of publications related to breast cancer single-cell sequencing has been increasing annually. These studies originate from 302 institutions in 46 countries, with YMAX S WICHA producing the most publications and WANG Y being the most cited author. Nature Communications is the most researched journal, while Nature holds the highest number of citations. These journals predominantly cover topics in the molecular/biological/immunological fields. Moreover, an analysis of reference and keyword bursts revealed that current research trends in this area are primarily centered on "clonal evolution," "tumor microenvironment," and "immunotherapy."ConclusionBreast cancer single-cell sequencing is a rapidly growing area of scientific interest. Future research requires more frequent and in-depth collaborations among countries, institutions, and authors. Furthermore, "clonal evolution," "tumor microenvironment," and "immunotherapy" are likely to become major focal points in upcoming research on breast cancer single-cell sequencing.
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