<div>Abstract<p>We described previously a human natural killer (NK) cell population that upregulates PD-L1 expression upon recognizing and reacting to tumor cells or exposure to a combination of IL12, IL18, and IL15. Here, to investigate the safety and efficacy of tumor-reactive and cytokine-activated (TRACK) NK cells, human NK cells from umbilical cord blood were expanded, transduced with a retroviral vector encoding soluble (s) IL15, and further cytokine activated to induce PD-L1 expression. Our results show cryopreserved and thawed sIL15_TRACK NK cells had significantly improved cytotoxicity against non–small cell lung cancer (NSCLC) <i>in vitro</i> when compared with non-transduced (NT) NK cells, PD-L1<sup>+</sup> NK cells lacking sIL15 expression (NT_TRACK NK), or NK cells expressing sIL15 without further cytokine activation (sIL15 NK cells). Intravenous injection of sIL15_TRACK NK cells into immunodeficient mice with NSCLC significantly slowed tumor growth and improved survival when compared with NT NK and sIL15 NK cells. The addition of the anti-PD-L1 atezolizumab further improved control of NSCLC growth by sIL15_TRACK NK cells <i>in vivo</i>. Moreover, a dose-dependent efficacy was assessed for sIL15_TRACK NK cells without observed toxicity. These experiments indicate that the administration of frozen, off-the-shelf allogeneic sIL15_TRACK NK cells is safe in preclinical models of human NSCLC and has potent antitumor activity without and with the administration of atezolizumab. A phase I clinical trial modeled after this preclinical study using sIL15_TRACK NK cells alone or with atezolizumab for relapsed or refractory NSCLC is currently underway (NCT05334329).</p></div>
<div>Abstract<p>We described previously a human natural killer (NK) cell population that upregulates PD-L1 expression upon recognizing and reacting to tumor cells or exposure to a combination of IL12, IL18, and IL15. Here, to investigate the safety and efficacy of tumor-reactive and cytokine-activated (TRACK) NK cells, human NK cells from umbilical cord blood were expanded, transduced with a retroviral vector encoding soluble (s) IL15, and further cytokine activated to induce PD-L1 expression. Our results show cryopreserved and thawed sIL15_TRACK NK cells had significantly improved cytotoxicity against non–small cell lung cancer (NSCLC) <i>in vitro</i> when compared with non-transduced (NT) NK cells, PD-L1<sup>+</sup> NK cells lacking sIL15 expression (NT_TRACK NK), or NK cells expressing sIL15 without further cytokine activation (sIL15 NK cells). Intravenous injection of sIL15_TRACK NK cells into immunodeficient mice with NSCLC significantly slowed tumor growth and improved survival when compared with NT NK and sIL15 NK cells. The addition of the anti-PD-L1 atezolizumab further improved control of NSCLC growth by sIL15_TRACK NK cells <i>in vivo</i>. Moreover, a dose-dependent efficacy was assessed for sIL15_TRACK NK cells without observed toxicity. These experiments indicate that the administration of frozen, off-the-shelf allogeneic sIL15_TRACK NK cells is safe in preclinical models of human NSCLC and has potent antitumor activity without and with the administration of atezolizumab. A phase I clinical trial modeled after this preclinical study using sIL15_TRACK NK cells alone or with atezolizumab for relapsed or refractory NSCLC is currently underway (NCT05334329).</p></div>
To develop a risk stratification system that can predict axillary lymph node (LN) metastasis in invasive breast cancer based on the combination of shear wave elastography (SWE) and conventional ultrasound.A total of 619 participants pathologically diagnosed with invasive breast cancer underwent breast ultrasound examinations were recruited from a multicenter of 17 hospitals in China from August 2016 to August 2017. Conventional ultrasound and SWE features were compared between positive and negative LN metastasis groups. The regression equation, the weighting, and the counting methods were used to predict axillary LN metastasis. The sensitivity, specificity, and the areas under the receiver operating characteristic curve (AUC) were calculated.A significant difference was found in the Breast Imaging Reporting and Data System (BI-RADS) category, the "stiff rim" sign, minimum elastic modulus of the internal tumor and peritumor region of 3 mm between positive and negative LN groups (p < 0.05 for all). There was no significant difference in the diagnostic performance of the regression equation, the weighting, and the counting methods (p > 0.05 for all). Using the counting method, a 0-4 grade risk stratification system based on the four characteristics was established, which yielded an AUC of 0.656 (95% CI, 0.617-0.693, p < 0.001), a sensitivity of 54.60% (95% CI, 46.9%-62.1%), and a specificity of 68.99% (95% CI, 64.5%-73.3%) in predicting axillary LN metastasis.A 0-4 grade risk stratification system was developed based on SWE characteristics and BI-RADS categories, and this system has the potential to predict axillary LN metastases in invasive breast cancer.
Prostate cancer (PCa) is among the three main types of cancer. Although prostate-specific antigen (PSA) is routinely tested, it has disadvantages, such as poor prognostic ability. Therefore, finding more PCa markers and therapeutic targets remains a subject of study. CircRNAs have been found to have regulatory roles in various diseases, such as diabetes, Central Nervous System (CNS) neuropathy, etc. where their application in cancer is even more valuable. Therefore, this paper aims to search for differentially expressed circRNAs in PCa and find downstream targeting pathways related to autophagy.
Human life and property are often seriously threatened and lost due to natural disasters such as earthquakes. As a spatial information system, the geographic information system (GIS) can collect, store, and manage the local or whole related physical data of the surface space to be measured with the support of software and hardware. The physical data is collected through GIS for performance testing. The data are collected from the aftershock event records of the Wenchuan earthquake. Among them, 14,000 Wenchuan earthquake events are used as the original data set, and 8,800 aftershock events are used as the test data set. Seismic data involves the detection of multiple physical quantities, which makes the seismic data gradually increase, many data have no obvious linear relationship, and traditional detection methods are difficult to meet the detection requirements. The artificial intelligence method led by a convolutional neural network (CNN) can perform pattern matching on complex nonlinear variables, and models with general characteristics can be generated from different seismic waveforms for the prediction of seismic waveforms. The results show that GIS can effectively intercept and collect seismic physical signals. The training and detection accuracy of CNN combined with GIS physical data is higher than 90%. Compared with traditional training methods, CNN is obviously superior in detection accuracy and recall rate. At the same time, a large number of microseismic events that are easily missed by manual selection can also be found.
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