Purpose: Discriminating radiation encephalopathy (REP) from brain tumor recurrence is often difficult. This study aims to develop and validate an approach to distinguish REP from post-radiation brain tumor recurrence using machine learning. Methods: This study involved 102 patients diagnosed and treated in our institution between 2020 and 2023. A total of 2153 radiomics features were extracted from contrast-enhanced MRI by using 3D-Slicer software and Pycharm platform. Nine diagnostic models were built and compared based on three selection methods and three classification algorithms. The sensitivity, specificity, accuracy, and area under curve (AUC) of each model were calculated, and based on these the optimal model was chosen. Results: The least absolute shrinkage and selection operator with correlation (LASSO+corr) was chosen as the optimal selection method, which selected 17 important radiomics features. The most promising model was a combination of LASSO+corr as the selection method and logistic regression (LR) as the classification algorithm. The combination models of LASSO+corr with LR, random forest (RF) and support vector machine (SVM) showed sensitivities of 0.88, 0.86 and 0.97, and specificities of 0.98, 0.93 and 0.90 with AUC of 0.9805, 0.9452 and 0.9743, respectively. Conclusion: Radiomics-based machine learning has potential to be utilized in differentiating REP from recurrent brain tumor after radiotherapy accurately.

This paper is focused on studying adaptive algorithms which can be applied to identification and equalization of underwater acoustic (UWA) channels, which often present non-stationary and sparse impulse response with multipath. Long-tap adaptive filters to meet the channel sparseness can cause unnecessary computation when they apply classical adaptive algorithms such as the normalized least-mean-square (NLMS) and recursive least-squares (RLS). Proportionate NLMS (PNLMS) and improved PNLMS algorithms have been investigated to deal with sparse channel identification. Dichotomous Coordinate Descent (DCD)-RLS is implemented to provide fast convergence and lower steady state on mean square deviation (MSD) in channel modeling. The numerical simulation results indicated l 1 -PNLMS and l 0 -norm IPNLMS converged faster than PNLMS in highly sparse channel and l 1 -norm IPNLMS showed the greatest initial convergence among NLMS and its variants. In addition, DCD-RLS presented an outstanding convergence in a wide range of channel sparsity although its tracking capacity was inferior in condition of channel varying. The equalization performance of the algorithms were evaluated by comparison on mean square error (MSE) and impulse response convolution.

Neoadjuvant chemoradiation (nCRT) followed by radical surgery is the preferred option for locally advanced colorectal cancer (CRC) treatment. However, chemo/radio-resistance remains a main obstacle in CRC therapy. In the study, we analyzed the mRNA expression profiling of CRC patients and revealed that the aberrant expression of fibronectin type III domain containing 1 (FNDC1) was associated with disease progression and poor prognosis in CRC. FNDC1 expression was consistently increased in multiple independent cohorts of CRC. Upregulated FNDC1 in pretreated primary tumor tissues predicted a poor response to nCRT, recurrence, and poor disease-free survival in nCRT-treated CRC patients. FNDC1 overexpression accelerated CRC cell survival on 5-FU or radiation treatment both in vitro and in vivo, whereas FNDC1 inhibition sensitized CRC cells to chemoradiation. In addition, FNDC1 accelerated stem cell-like properties of CRC cells. Furthermore, tumor tissues from non-responders exhibited higher activation of PI3K/Akt signaling than those from responders. FNDC1 depletion repressed 5-FU or irradiation-induced activation of PI3K/AKT in CRC cells. More importantly, pharmacological inhibition of PI3K/Akt signaling effectively decreased the effect of FNDC1 on chemoradiation resistance. Taken together, our study reveals the potential function of FNDC1 as a biomarker to predict nCRT sensitivity in CRC and a therapeutic target in CRC treatment.

The neurokinin-1 receptor (NK-1R) antagonists are approved as treatment for chemotherapy-associated nausea and vomiting in cancer patients. The emerging role of the substance P-NK-1R system in oncogenesis raises the possibility of repurposing well-tolerated NK-1R antagonists for cancer treatment. This study reports that human colorectal cancer (CRC) patients with high NK-1R expression have poor survival, and NK-1R antagonists SR140333 and aprepitant induce apoptotic cell death in CRC cells and inhibit CRC xenograft growth. This cytotoxicity induced by treatment with NK-1R antagonists is mediated by induction of endoplasmic reticulum (ER) stress. ER stress triggers calcium release, resulting in the suppression of prosurvival extracellular signal-regulated kinase (ERK)-c-Myc signaling. Along with ER calcium release, one ER stress pathway mediated by protein kinase RNA-like ER kinase (PERK) is specifically activated, leading to increased expression of proapoptotic C/EBP-homologous protein (CHOP). Moreover, NK-1R antagonists enhance the efficacy of chemotherapy by increasing the sensitivity and overcoming resistance to 5-fluorouracil in CRC cells through the induction of sustained ER stress and the consequent suppression of ERK-c-Myc signaling both in vitro and in vivo. Collectively, the findings provide novel mechanistic insights into the efficacy of NK-1R antagonists either as a single agent or in combination with chemotherapy for cancer treatment.

In a recent paper in Cell Metabolism,Xu et al.provide new insights whether and how caspase-4/11 involves in pyroptotic cell death implicated in non infective diseases.They discovered a novel mechanism of GSDME-dependent pyroptosis,which was induced by mitochondrial permeability transition(MPT)-activated Apaf-1/caspase-4 pyroptosome assembly.1 These findings provide impor-tant implications for understanding the pathogenesis of chole-static liver failure(Fig.1).

Resistance to radiotherapy is the main reason causing treatment failure in locally advanced rectal cancer. MicroRNAs (miRNAs) have been well demonstrated to regulate cancer development and progression. However, how miRNAs regulate radiotherapy resistance in colorectal cancer remains unknown. Herein, we established two human colorectal cancer cell lines resistant to radiotherapy, named HCT116-R and RKO-R, using the strategy of fractionated irradiation. The radioresistant phenotypical changes of the two cell lines were validated by cell viability assay, colony formation assay and apoptosis assay. The miRNA expression profilings of HCT116-R and RKO-R were determined using RNA-seq analyses, and further confirmed by quantitative real-time PCR. Multiple miRNAs, including miR-423-5p, miR-7-5p, miR-522-3p, miR-3184-3p, and miR-3529-3p, were identified with altered expression in both of the radiotherapy-resistant cells, compared to the parental cells. The downregulation of miR-423-5p was further validated in the rectal cancer tissues from radiotherapy-resistant patients. Silencing of miR-423-5p in parental HCT116 and RKO cells decreased the sensitivity to radiation treatment, and inhibited the radiation-induced apoptosis. In consistence, overexpression of miR-423-5p in HCT116-R and RKO-R cells partially rescued their sensitivity to radiotherapy, and promoted the radiation-induced apoptosis. Bcl-xL (Bcl-2-like protein 1) was predicted to be a potential target gene for miR-423-5p, and miR-423-5p/Bcl-xL axis could be a critical mediator of radiosensitivity in colorectal cancer cells. The current finding not only revealed a novel role of miR-423-5p in regulating the radiosensitivity in colorectal cancer, but also suggested miR-423-5p as a molecular candidate for combination therapy with radiation to treat colorectal cancer.

BackgroundEarly diagnosis of breast cancer can reduce the high fatality rate. Thus novel diagnostic methods are urgently required for breast cancer patients. The research aimed at checking potential correlation for serum microRNA-124-3p ( miR-124-3p ) expression with breast cancer, and exploring its competence as a promising potential biomarkers for breast cancer.MethodsQuantitative real-time PCR (qRT-PCR) assay detected miR-124-3p levels. Possible relationship between miR-124-3p degree and clinical features of breast cancer patients was measured by Chi-square analysis. Sensitivity, specificity and area under the curve (AUC) for serum miR-124-3p degree were settled adopting receiver operating characteristics (ROC) analyses.ResultsRelative degree for serum miR-124-3p notably reduced among breast cancer sufferers in comparison with healthy persons ( P =0.000). Moreover, miR-124-3p degree held tight connection to clinical stage ( P =0.034), histological grade ( P =0.002), and lymph node metastasis ( P =0.001). ROC curve analyses unveiled at the optimal cut-off of 0.935, serum miR-124-3p expression reached a sensitivity of 78.4% and a specificity of 84.8% in discriminating between breast cancers sufferers and healthy persons, achieving an area under the curve (AUC) of 0.872 (95% CI: 0.752-0.871).ConclusionSerum miR-124-3p degree might represent one non-invasive indicator in diagnosing breast cancer.

Purpose Acute myeloid leukemia (AML) is a complex malignancy characterized by the clonal expansion of immature myeloid precursors. The standard treatment for newly diagnosed AML is chemotherapy consisting of cytosine arabinoside (Ara-C) and anthracyclines with disappointing clinical outcomes and severe adverse effects, such as symptomatic bradycardia, neurotoxicity. Thus, it is promising to treat AML through combination drug therapy to reduce the adverse effects of chemotherapeutics. In our recent published PNAS paper, we reported that NK-1R antagonists, both Aprepitant and SR140333, induce apoptosis of myeloid leukemia cells by inducing oxidative stress through mitochondrial calcium overload. We, therefore, tested the hypothesis of the combination Ara-C with NK-1R antagonist could enhance the efficacy of Ara-C. Methods MTT assay was employed to detect the cell proliferation. Flow cytometry was applied to detect the cell cycle and necrosis. PI uptake and LDH release assay were used to detect the disintegration of the plasma membrane. Xenograft model was constructed to explore the effect of combination Ara-C with Aprepitant in vivo. Results Our results showed that Aprepitant sensitizes HL60 cells to the cytotoxic effects of Ara-C more than 5-fold by enhancing G0/G1 cell cycle arrest and necrosis in vitro. Furthermore, Nec-1, a specific inhibitor of necroptosis, could recover the cell proliferative viability significantly. Attractively, once every 2-days regimen of Ara-C (5 mg/kg) and Aprepitant (10 mg/kg) via in situ injection dramatically reduced the tumor volume from 2175.0 ± 341.9 mm3 in the vehicle group to 828.4 ± 232.4 mm3 in the combination group without obvious toxicity in human myeloid leukemia xenograft mice. Conclusion Taken together, reduced dose of Ara-C combination with moderate Aprepitant provides more effective therapeutical methods for AML treatment in vitro and in vivo with the elimination of the toxicity of Ara-C, which may pay new avenue for the usage of the routine chemotherapy drug Ara-C with low dose to enhance efficacy and reduce toxicity in clinical practice.

Epidermal growth factor receptor (EGFR) mutations are common in non-small cell lung cancers, but rare in small cell lung cancers (SCLCs). In previous reports, some SCLC patients with EGFR mutations could benefit from EGFR tyrosine kinase inhibitors (TKIs). In this study, we reported a case in which an SCLC patient with EGFR exon 19 deletion (19-Del) mutation did not benefit from EGFR-TKIs. Interestingly, the standard treatment strategies for SCLC also failed to control tumor progression. Moreover, we screened 43 SCLC patients in China and found that the frequency of EGFR mutations in Chinese SCLC patients was about 4.65% by next-generation sequencing (NGS). Collectively, this case illustrated a rare subtype of SCLCs which harbored EGFR mutations and was intrinsically resistant to standard treatments and EGFR-TKIs. We also tried to explore the mechanisms underlying drug resistance. The literature concerning SCLCs with EGFR mutations is reviewed.

Objective: The purpose of this study was to explore the functional roles of SOX2 in the progression of breast cancer and relevant molecular mechanism. Methods: A total of 108 breast cancer patients were included, and breast cancer cell line MDA-MB-231 was selected for this research. Real time-qualitative polymerase chain reaction (RT-qPCR) was conducted to measure the expression level of SOX2 mRNA. MTT and Transwell assays were used to detected the proliferation, migration and invasion of breast cancer cells, respectively. Luciferase reporter assay was conducted to reveal the relationship of SOX2 with PTEN. Western blot was performed to detect the expressions of Wnt/beta-catenin pathway-related proteins. Results: The expression of SOX2 mRNA was up-regulated in breast cancer tissues and cells (P < 0.001). SOX2 expression was significantly associated with TNM stage and lymph node metastasis of breast cancer patients (P < 0.05). SOX2 knockdown significantly inhibited the proliferation, migration and invasion of breast cancer cells (P < 0.05). PTEN was a direct target of SOX2. The inhibition of PTEN could significantly suppress the progression of breast cancer cells with SOX2 overexpression. SOX2 knockdown also inhibited the expressions of beta-catenin, TCP-4, FZD7, C-myc and MMP-7 proteins. Moreover, PTEN knockdown reversed the results caused by SOX2 overexpression, that is, increased expressions of beta-catenin, TCP-4, FZD7, C-myc and MMP-7 proteins (P < 0.05). Conclusion: SOX2 promotes the progression of breast cancer through activating Wnt/beta-catenin signaling pathway via regulating PTEN.