Recent advances in research on aspartate β-hydroxylase (ASPH) in pancreatic cancer: A brief update

Pancreatic cancer (PC) is a highly aggressive tumor, often difficult to diagnose and treat. Aspartate β-hydroxylase (ASPH) is a type II transmembrane protein and the member of α-ketoglutarate-dependent dioxygenase family, found to be overexpressed in different cancer types, including PC. ASPH appears to be involved in the regulation of proliferation, invasion and metastasis of PC cells through multiple signaling pathways, suggesting its role as a tumor biomarker and therapeutic target. In this review, we briefly summarize the possible mechanisms of action of ASPH in PC and recent progress in the therapeutic approaches targeting ASPH

Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets

Unitary matrix completion-based DOA estimation of noncircular signals in nonuniform noise

In this paper, a novel direction-of-arrival (DOA) estimation algorithm is proposed for noncircular signals with nonuniform noise by using the unitary matrix completion (UMC) technique. First, the proposed method utilizes the noncircular property of signals to design a virtual array for approximately doubling the array aperture. Then, the virtual complex-valued covariance matrix with the unknown nonuniform noise is transformed into the real-valued one by utilizing the unitary transformation to improve the computational efficiency. Next, a novel UMC method is formulated for the DOA estimation to remove the influence of nonuniform noise. Finally, the DOA without the influence of the unknown noncircularity phase is obtained by using the modified estimation of signal parameters via rotational invariance technique (ESPRIT). Especially, for handling the coherent sources, the forward-backward spatial smoothing technique is utilized to reconstruct a full-rank covariance matrix so that the signal subspace and the noise subspace can be correctly separated. Due to utilizing the extended array aperture and the unitary transformation, the proposed method can identify more sources than the number of physical sensors and provides higher angular resolution and better estimation performance. Compared with the existing DOA estimation algorithms for noncircular signals, the proposed one can effectively suppress the influence of the nonuniform noise. The simulation results are provided to verify the effectiveness and superiority of the proposed method.Published versio

Tumor-derived extracellular vesicle drug delivery system for chemo-photothermal-immune combination cancer treatment

Summary: Tumor extracellular vesicles (EVs) demonstrate considerable promise for medication delivery and tumor targeting owing to their natural long-term blood circulation and tissue targeting capabilities. We extracted EVs from mouse breast cancer cell 4T1 using UV stimulation and differential centrifugation. To create a new nano-drug delivery system, the vesicle delivery system (EPM) loaded with melanin and paclitaxel albumin (PA), the collected EVs were repeatedly compressed on a 200 nm porous polycarbonate membrane with melanin and PA. Our findings suggest that EPM is readily absorbed by breast cancer and dendritic cells. EPM generates significant photoacoustic signals and photothermal effects when exposed to near-infrared light and can enhance the infiltration of CD8+ T cells in mouse tumor tissues. EPM is more cytotoxic than PA in in vivo and in vitro investigations. The efficacy of EPM in clinical transformation when paired with chemotherapy/photothermal/immunotherapy treatment is demonstrated in this study

Hepatic G Protein-Coupled Receptor 180 Deficiency Ameliorates High Fat Diet-Induced Lipid Accumulation via the Gi-PKA-SREBP Pathway

Single-nucleotide polymorphisms in G protein-coupled receptor 180 (GPR180) are associated with hypertriglyceridemia. The aim of this study was to determine whether hepatic GPR180 impacts lipid metabolism. Hepatic GPR180 was knocked down using two approaches: Gpr180-specific short hairpin (sh)RNA carried by adeno-associated virus 9 (AAV9) and alb-Gpr180−/− transgene established by crossbreeding albumin-Cre mice with Gpr180flox/flox animals, in which Gpr180 was specifically knocked down in hepatocytes. Adiposity, hepatic lipid contents, and proteins related to lipid metabolism were analyzed. The effects of GPR180 on triglyceride and cholesterol synthesis were further verified by knocking down or overexpressing Gpr180 in Hepa1-6 cells. Gpr180 mRNA was upregulated in the liver of HFD-induced obese mice. Deficiency of Gpr180 decreased triglyceride and cholesterol contents in the liver and plasma, ameliorated hepatic lipid deposition in HFD-induced obese mice, increased energy metabolism, and reduced adiposity. These alterations were associated with downregulation of transcription factors SREBP1 and SREBP2, and their target acetyl-CoA carboxylase. In Hepa1-6 cells, Gpr180 knockdown decreased intracellular triglyceride and cholesterol contents, whereas its overexpression increased their levels. Overexpression of Gpr180 significantly reduced the PKA-mediated phosphorylation of substrates and consequent CREB activity. Hence, GPR180 might represent a novel drug target for intervention of adiposity and liver steatosis

Genomic analyses reveal mutational signatures and frequently altered genes in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers world wide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G> A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal

Supplemental Material, Table_S2_PH-assumption_tests_of_different_variables - High TSTA3 Expression as a Candidate Biomarker for Poor Prognosis of Patients With ESCC

<p>Supplemental Material, Table_S2_PH-assumption_tests_of_different_variables for High TSTA3 Expression as a Candidate Biomarker for Poor Prognosis of Patients With ESCC by Jie Yang, Pengzhou Kong, Jian Yang, Zhiwu Jia, Xiaoling Hu, Zianyi Wang, Heyang Cui, Yanghui Bi, Yu Qian, Hongyi Li, Fang Wang, Bin Yang, Ting Yan, Yanchun Ma, Ling Zhang, Caixia Cheng, Bin Song, Yaoping Li, Enwei Xu, Haiyan Liu, Wei Gao, Juan Wang, Yiqian Liu, Yuanfang Zhai, Lu Chang, Yi Wang, Yingchun Zhang, Ruyi Shi, Jing Liu, Qi Wang, Xiaolong Cheng, and Yongping Cui in Technology in Cancer Research & Treatment</p

Supplemental Material, Table_S1_Information_of_104_ESCC_patients - High TSTA3 Expression as a Candidate Biomarker for Poor Prognosis of Patients With ESCC

<p>Supplemental Material, Table_S1_Information_of_104_ESCC_patients for High TSTA3 Expression as a Candidate Biomarker for Poor Prognosis of Patients With ESCC by Jie Yang, Pengzhou Kong, Jian Yang, Zhiwu Jia, Xiaoling Hu, Zianyi Wang, Heyang Cui, Yanghui Bi, Yu Qian, Hongyi Li, Fang Wang, Bin Yang, Ting Yan, Yanchun Ma, Ling Zhang, Caixia Cheng, Bin Song, Yaoping Li, Enwei Xu, Haiyan Liu, Wei Gao, Juan Wang, Yiqian Liu, Yuanfang Zhai, Lu Chang, Yi Wang, Yingchun Zhang, Ruyi Shi, Jing Liu, Qi Wang, Xiaolong Cheng, and Yongping Cui in Technology in Cancer Research & Treatment</p