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The evolving role of DNA inter-strand crosslinks in chemotherapy.

DNA crosslinking agents make up a broad class of chemotherapy agents that target rapidly dividing cancer cells by disrupting DNA synthesis. These drugs differ widely in both chemical structure and biological effect. In cells, crosslinking agents can form multiple types of DNA lesions with varying efficiencies. Inter-strand crosslinks (ICLs) are considered to be the most cytotoxic lesion, creating a covalent roadblock to replication and transcription. Despite over 50 years in the clinic, the use of crosslinking agents that specialize in the formation of ICLs remains limited, largely due to high toxicity in patients. Current ICL-based therapeutics have focused on late-stage and drug-resistant tumors, or localized treatments that limit exposure. In this article, we review the development of clinical crosslinking agents, our understanding of how cells respond to different lesions, and the potential to improve ICL-based chemotherapeutics in the future.

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Diagnostic accuracy of MDCT in differentiating gallbladder cancer from acute and xanthogranulomatous cholecystitis.

To determine the diagnostic accuracy of multi-detector CT (MDCT) for differentiating gallbladder cancer from acute and xanthogranulomatous cholecystitis using previously described imaging features.

1759 related Products with: Diagnostic accuracy of MDCT in differentiating gallbladder cancer from acute and xanthogranulomatous cholecystitis.

Cancer Apoptosis Phospho- Top five cancer tissue ar Multiple organ cancer tis Lung cancer tissue array, Lung cancer tissue array Colon cancer and normal t Colon cancer and normal t Colon cancer, metastasize Colon cancer and matched Colon cancer tissue array Rectum disease spectrum ( Kidney disease spectrum (

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Scavenger receptor B promotes bacteria clearance by enhancing phagocytosis and attenuates white spot syndrome virus proliferation in Scylla paramamosian.

Phagocytosis and apoptosis are key cellular innate immune responses against bacteria and virus in invertebrates. Class B scavenger receptors (SRBs), which contain a CD36 domain, are critical pattern recognition receptors (PRRs) of phagocytosis for bacteria and apoptotic cells. In the present study, we identified a member of SRB subfamily in mud crab Scylla paramamosain, named Sp-SRB. The full-length cDNA of Sp-SRB is 2593 bp with a 1629 bp open reading frame (ORF) encoding a putative protein of 542 amino acids, and predicted to contain a CD36 domain with two transmembrane regions at the C- and N-terminals. Real-time qPCR analysis revealed that Sp-SRB was widely expressed in all tissues tested, and the expression of Sp-SRB was up-regulated upon challenge with Vibrio parahaemolyticus, white spot syndrome virus (WSSV), lipopolysaccharides (LPS) and polyinosinic polycytidylic acid (PolyI:C). Moreover, in vitro experiments indicated that recombinant Sp-SRB protein (rSp-SRB) could bind to fungi, Gram-positive and Gram-negative bacteria. RNA interference of Sp-SRB resulted in significant reduction in the expression level of phagocytosis related genes, antimicrobial peptides (AMPs) and Toll-like receptors (TLRs), which consequently led to impairment in both bacterial clearance and the phagocytotic activity of hemocytes. In addition, we found that Sp-SRB had the ability to attenuate the replication of WSSV proliferation in mud crab S. paramamosain. Collectively, this study has shown that Sp-SRB contributed to bacteria clearance by enhancing phagocytosis and up-regulating the expression of AMPs possibly in a TRLs (SpToll 1 and SpToll 2)-dependent manner. Besides, Sp-SRB inhibited the replication of WSSV in S. paramamosian probably through enhancement of hemocytes phagocytosis of apoptotic cells.

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Human Epstein-Barr Virus Mouse Epstein-Barr Virus Influenza A Virus Hemaggl BYL-719 Mechanisms: PI3K- IGF-1R Signaling Phospho- Insulin Receptor Phospho- Nuclear Membrane Receptor T-Cell Receptor Signaling Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep

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MYH9: Structure, functions and role of non-muscle myosin IIA in human disease.

The MYH9 gene encodes the heavy chain of non-muscle myosin IIA, a widely expressed cytoplasmic myosin that participates in a variety of processes requiring the generation of intracellular chemomechanical force and translocation of the actin cytoskeleton. Non-muscle myosin IIA functions are regulated by phosphorylation of its 20 kDa light chain, of the heavy chain, and by interactions with other proteins. Variants of MYH9 cause an autosomal-dominant disorder, termed MYH9-related disease, and may be involved in other conditions, such as chronic kidney disease, non-syndromic deafness, and cancer. This review discusses the structure of the MYH9 gene and its protein, as well as the regulation and physiologic functions of non-muscle myosin IIA with particular reference to embryonic development. Moreover, the review focuses on current knowledge about the role of MYH9 variants in human disease.

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Identification of differential phosphorylation and sub-cellular localization of the metastasis suppressor, NDRG1.

The metastasis suppressor, N-myc downstream regulated gene-1 (NDRG1), exhibits pleiotropic activity, inhibiting metastasis of various tumor-types, while being correlated with metastasis in others. Notably, NDRG1 phosphorylation and cleavage are associated with its function, although it is unclear if these modifications occur universally, or selectively, in different cancer cell-types and if it contributes to its pleiotropy. Considering the suggested DNA repair role of nuclear NDRG1, the effects of the above post-translational modifications on its nuclear localization was examined. Herein, the full-length (FL) and truncated (T) NDRG1 isoforms were detected using a C-terminus-directed antibody, while only the FL isoform was identified using an N-terminus-directed antibody. For the first time, we demonstrate that the expression of the NDRG1 FL and T forms occurs in all cancer cell-types examined, as does its phosphorylation (p-NDRG1) at Ser330 and Thr346. The FL isoform localized highly in the nucleus compared to the T isoform. Moreover, p-NDRG1 (Ser330) was also markedly localized in the nucleus, while p-NDRG1 (Thr346) was predominantly cytoplasmic in all cell-types. These results indicate the N-terminus region and phosphorylation at Ser330 could be crucial for NDRG1 nuclear localization and function. PTEN silencing indicated that p-NDRG1 (Thr346) could be regulated differentially in different tumor cell-types, indicating PTEN may be involved in the mechanism(s) underlying the pleiotropic activity of NDRG1. Finally, therapeutics of the di-2-pyridylketone thiosemicarbazone class increased nuclear NDRG1 isoforms (FL and T) detected by the C-terminus-directed antibody in HepG2 cells, while having no significant effect in PC3 cells, indicating differential activity depending on the cell-type.

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Molecular phylogeny and comparative morphology indicate that odontostomatids (Alveolata, Ciliophora) form a distinct class-level taxon related to Armophorea.

The odontostomatids are among the least studied ciliates, possibly due to their small sizes, restriction to anaerobic environments and difficulty in culturing. Consequently, their phylogenetic affinities to other ciliate taxa are still poorly understood. In the present study, we analyzed newly obtained ribosomal gene sequences of the odontostomatids Discomorphella pedroeneasi and Saprodinium dentatum, together with sequences from the literature, including Epalxella antiquorum and a large assemblage of ciliate sequences representing the major recognized classes. The results show that D. pedroeneasi and S. dentatum form a deep-diverging branch related to metopid and clevelandellid armophoreans, corroborating the old literature. However E. antiquorum clustered with the morphologically discrepant plagiopylids, indicating that either the complex odontostomatid body architecture evolved convergently, or the positioning of E. antiquorum as a plagiopylid is artifactual. A new ciliate class, Odontostomatea n. cl., is proposed based on molecular analyses and comparative morphology of odontostomatids with related taxa.

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Bitter and sweet tasting molecules: it's complicated.

"Bitter" and "sweet" are frequently framed in opposition, both functionally and metaphorically, in regard to affective responses, emotion, and nutrition. This oppositional relationship is complicated by the fact that some molecules are simultaneously bitter and sweet. In some cases, a small chemical modification, or a chirality switch, flips the taste from sweet to bitter. Molecules humans describe as bitter are recognized by a 25 member subfamily of class A G-protein coupled receptors (GPCRs) known as TAS2Rs. Molecules humans describe as sweet are recognized by a TAS1R2/TAS1R3 heterodimer of class C GPCRs. Here we characterize the chemical space of bitter and sweet molecules: the majority of bitter compounds show higher hydrophobicity compared to sweet compounds, while sweet molecules have a wider range of sizes. Critically, recent evidence indicates that TAS1Rs and TAS2Rs are not limited to the oral cavity; moreover, some bitterants are pharmacologically promiscuous, with the hERG potassium channel, cytochrome P450 enzymes and carbonic anhydrases as common off-targets. Further focus on polypharmacology may unravel new physiological roles for tastant molecules.

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Mortality in Pulmonary Arterial Hypertension Patients Treated with Continuous Prostanoids.

Parenteral prostanoids are considered the treatment of choice for patients with severe pulmonary arterial hypertension (PAH). Prognostic studies for patients treated in the modern era are limited.

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circRNA expression analysis in lung adenocarcinoma: Comparison of paired fresh frozen and formalin-fixed paraffin-embedded specimens.

Circular RNA (circRNAs) is a novel class of endogenous non-coding RNAs which is widely involved in carcinogenesis. Archived formalin-fixed paraffin-embedded (FFPE) specimens represent valuable resources for cancer research. Currently there is a lack of systematic analysis on the feasibility of circRNAs expression analysis using FFPE samples. Here, we reported the first comparison study of circRNA expression from paired fresh frozen and FFPE specimens of lung adenocarcinoma. circRNAs expression of paired lung adenocarcinoma and adjacent normal samples, starting from either fresh frozen or FFPE materials, were analyzed via a high-throughput circRNA microarray. Hierarchical clustering was performed on samples. qRT-PCR was used to confirm the differentially expressed circRNAs. The circRNA regulation networks were built by bioinformatics tools for several candidate circRNAs. Our results demonstrated that there was a good correlation in circRNAs expression analysis utilizing fresh frozen or FFPE tissues. Tumors and adjacent normal tissues can be clustered correctly by the differentially expressed circRNAs in fresh frozen or FFPE groups. Furthermore, three differentially expressed circRNAs, hsa_circRNA_100421, hsa_circRNA_104329 and hsa_circRNA_101969 were verified by qRT-PCR assay. Bioinformatics analysis was also applied to predict the circRNA-miRNA-protein coding gene interaction network for each of above circRNAs. To the best of our knowledge, this is the first report demonstrating that the circRNAs microarray analysis, starting from FFPE specimens, is comparable with that based on fresh frozen samples. Therefore FFPE specimen represents a good substitute for fresh frozen tissue, especially when fresh frozen specimen is limited.

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Mouse Anti-Ca19.9 Sialyl Lung adenocarcinoma and n Lung adenocarcinoma tissu Frozen colorectal adenoca Lung adenocarcinoma tissu Lung adenocarcinoma tissu DNA (cytosine 5) methyltr Stomach adenocarcinoma wi Lung disease spectrum tis Lung cancer tissue array, Lung carcinoma and normal Lung carcinoma and normal

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Determinants of Reverse Remodeling of the Left Atrium Following Transaortic Myectomy.

In patients with hypertrophic cardiomyopathy (HCM), enlargement of the left atrium (LA) is associated with increased morbidity and mortality due to risk of atrial fibrillation (AF), stroke, and heart failure. In this study, we investigated whether LA reverse remodeling occurs following septal myectomy.

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