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Sialyltransferase Inhibitors for the Cancer Metastasis: Latest Difficulties as well as Upcoming Views.
Study test included the two tasks designated by the NIOSH protocol, with additional steps added to the evaluation. Tasks were repeated 10 times for each device. Results Only three of the six tested CSTDs (Equashield®, HALO®, and PhaSealTM) had an average IPA vapor release below the quantifiable performance threshold (1.0 ppm) for all tasks performed. This value was selected by NIOSH to represent the performance threshold for successful containment. The remaining three CSTDs had vapor release above 1 ppm at various times during the IPA manipulation process. Conclusion Equashield®, HALO®, and PhaSealTM devices tested met the 2015 NIOSH protocol quantifiable performance threshold, functioning as a truly closed system. Quantifiable effective data may be useful in product selection.Auto-antibodies against apoA-1 (anti-apoA-1 IgGs) have been identified as important actors of atherosclerosis development through pro-inflammatory and pro-atherogenic properties and to also induce apoptosis in tumoral neuronal and lymphocyte derived cell lines through unknown mechanisms. The purpose of this study was to explore the cellular pathways involved in tumoral cell survival modulated by anti-apoA-1 antibodies. We observed that anti-apoA-1 antibodies induce growth arrest (in G2/M phase) and cell apoptosis through caspase 3 activation, accompanied by a selective p53 phosphorylation on serine 15. RNA sequencing indicated that anti-apoA-1 IgGs affect the expression of more than 950 genes belonging to five major groups of genes and respectively involved in i) cell proliferation inhibition, ii) p53 stabilisation and regulation, iii) apoptosis regulation, iv) inflammation regulation, and v) oxidative stress. In conclusion, anti-apoA-1 antibodies seem to have a role in blocking tumoral cell proliferation and survival, by activating a major tumor suppressor protein and by modulating the inflammatory and oxidative stress response. Further investigations are needed to explore a possible anti-cancer therapeutic approach of these antibodies in very specific and circumscribed conditions.KSHV-associated cancers have poor prognoses and lack therapeutics that selectively target viral gene functions. We developed a screening campaign to identify known drugs that could be repurposed for the treatment of KSHV-associated cancers. Selleck B022 We focused on primary effusion lymphoma (PEL), which has particularly poor treatment outcomes. We developed a luciferase reporter assay to test the ability of drugs to inhibit DNA binding of the KSHV LANA DNA binding domain (DBD). In parallel, we screened drugs for selective inhibition of a KSHV+ PEL cells. While potent hits were identified in each assay, only one hit, Mubritinib, was found to score in both assays. Mubritinib caused PEL cells to undergo cell cycle arrest with accumulation of sub-G1 population and Annexin V. Mubritinib inhibited LANA binding to KSHV terminal repeat (TR) DNA in KSHV+ PEL cells, but did not lead to KSHV lytic cycle reactivation. Mubritinib was originally identified as a receptor tyrosine kinase (RTK) inhibitor selective for HER2/ErbB2. But recent studies have revealed that Mubritinib can also inhibit the electron transport chain (ETC) complex at nanomolar concentrations. We found that other related ETC complex inhibitors (Rotenone and Deguelin) exhibited PEL cell growth inhibition while RTK inhibitors failed. Seahorse analysis demonstrated that Mubritinib selectively inhibits the maximal oxygen consumption (OCR) in PEL cells and metabolomics revealed changes in ATP/ADP and ATP/AMP ratios. These findings indicate that PEL cells are selectively sensitive to ETC complex inhibitors and provide a rationale for repurposing Mubritinib for selective treatment of PEL.Prostate cancer (PCa) is one of the leading causes of cancer-related deaths worldwide. Prostate tumorigenesis and PCa progression involve numerous genetic as well as epigenetic perturbations. Histone modification represents a fundamental epigenetic mechanism that regulates diverse cellular processes, and H3K4 methylation, one such histone modification associated with active transcription, can be reversed by dedicated histone demethylase KDM5B (JARID1B). Abnormal expression and functions of KDM5B have been implicated in several cancer types including PCa. Consistently, our bioinformatics analysis reveals that the KDM5B mRNA levels are upregulated in PCa compared to benign prostate tissues, and correlate with increased tumor grade and poor patient survival, supporting an oncogenic function of KDM5B in PCa. Surprisingly, however, when we generated prostate-specific conditional Kdm5b knockout mice using probasin (Pb) promoter-driven Cre loxP system, we observed that Kdm5b deletion did not affect normal prostate development but instead induced mild hyperplasia. These results suggest that KDM5B may possess context-dependent roles in normal prostate development vs. PCa development and progression.The Campbell University Drug Information Center supports health professionals by providing responses to drug-related inquiries. An inquiry was received by the Drug Information Center for a comprehensive list of oral solutions which should be protected from light. In investigating this request for information, a list of light-sensitive oral prescription drug products published in Hospital Pharmacy in 2009 was identified. This discovery highlighted the need for both an updated list and one which distinguished oral solid products and oral liquid products. The purpose of this project was to update the previously published list and to distinguish between oral solid and liquid dosage forms. The process of updating this list entailed several professional resources. A list of all oral products was obtained and then sorted to clearly identify which products were available in oral solid dosage form only, oral liquid dosage form only, and both dosage forms. Once delineated, the product labels for each medication were scoured for language indicating the product is light sensitive.Introduction Medication errors are more likely to occur in chronically ill children, who are highly dependent on caregivers for medication administration. This study aimed to explore the issues related to medication safety among pediatric outpatients in Malaysia from the caregivers' perspective. Methods This was a qualitative study conducted between May and June 2018 at a pediatric clinic of a regional referral hospital. Caregivers of children who (1) were under 6 years of age and (2) had hypothyroidism, epilepsy, thalassemia, asthma, or other chronic diseases were recruited via purposive sampling. Each selected disease was represented by at least 3 caregivers, who were identified from the medical records of their children. Face-to-face interviews were conducted with each of them, facilitated by a semi-structured interview guide. All the interviews were audio-recorded, transcribed verbatim, and analyzed using the thematic analysis approach. Results A total of 15 mothers with a median age of 34 years were interviewed. Three themes emerged from the interviews (I) actual experiences with medication errors, (II) underlying risk factors for medication errors, and (III) recommendations to improve medication safety. Several cases of administration errors, including missed doses and self-decided dose adjustment, were detected. Furthermore, the caregivers were found to have inadequate understanding of the medications in general. Conclusions While children were shown to be consistently exposed to medication errors at home in Malaysia, the recommendations of the caregivers, including the use of written instructions and a diary, could be effective strategies to improve the out-of-hospital medication safety in children.Neuroblastoma is the most common extracranial solid tumor in childhood. Patients in high-risk group often have poor outcomes with low survival rates despite several treatment options. This study aimed to identify a genetic signature from gene expression profiles that can serve as prognostic indicators of survival time in patients of high-risk neuroblastoma, and that could be potential therapeutic targets. RNA-seq count data was downloaded from UCSC Xena browser and samples grouped into Short Survival (SS) and Long Survival (LS) groups. Differential gene expression (DGE) analysis, enrichment analyses, regulatory network analysis and machine learning (ML) prediction of survival group were performed. Forty differentially expressed genes (DEGs) were identified including genes involved in molecular function activities essential for tumor proliferation. DEGs used as features for prediction of survival groups included EVX2, NHLH2, PRSS12, POU6F2, HOXD10, MAPK15, RTL1, LGR5, CYP17A1, OR10AB1P, MYH14, LRRTM3, GRIN3A, HS3ST5, CRYAB and NXPH3. An accuracy score of 82% was obtained by the ML classification models. SMIM28 was revealed to possibly have a role in tumor proliferation and aggressiveness. Our results indicate that these DEGs can serve as prognostic indicators of survival in high-risk neuroblastoma patients and will assist clinicians in making better therapeutic and patient management decisions.Gliomas are the most common primary malignant brain tumors associated with a low survival rate. Even after surgery, radiotherapy, and chemotherapy, gliomas still have a poor prognosis. Extracellular vesicles are a heterogeneous group of cell-derived membranous structures. Exosomes are a type of extracellular vesicles, their size ranges from 30 nm to 100 nm. Recent studies have proved that glioma cells could release numerous exosomes; therefore, exosomes have gained increasing attention in glioma-related research. Recent studies have confirmed the importance of extracellular vesicles, particularly exosomes, in the development of brain tumors, including gliomas. Exosomes mediate intercellular communication in the tumor microenvironment by transporting biomolecules (proteins, lipids, deoxyribonucleic acid, and ribonucleic acid); thereby playing a prominent role in tumor proliferation, differentiation, metastasis, and resistance to chemotherapy or radiation. Given their nanoscale size, exosomes can traverse the blood-brain barrier and promote tumor progression by modifying the tumor microenvironment. Based on their structural and functional characteristics, exosomes are demonstrating their value not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting glioma cells. Therefore, exosomes are a promising therapeutic target for the diagnosis, prognosis, and treatment of malignant gliomas. More research will be needed before exosomes can be used in clinical applications. Here, we describe the exosomes, their morphology, and their roles in the diagnosis and progression of gliomas. In addition, we discuss the potential of exosomes as a therapeutic target/drug delivery system for patients with gliomas.BACKGROUND An epithelial inclusion cyst within a lymph node denotes a heterotopic phenomenon. Nodal epithelial inclusion cysts have been reported in a variety of anatomical locations including pelvic, abdominal, mediastinal, and axillary regions. While nodal melanocytic nevus (also known as nevus cell aggregates) is the most common heterotopic phenomena involving the axillary lymph nodes, the presence of benign epithelial inclusion cysts in axillary lymph nodes is a rare but well-reported finding. Such documentation is in part due to assessment of sentinel lymph nodes in breast cancer becoming standard of care. These epithelial inclusion cysts offer a diagnostic pitfall in evaluation of sentinel lymph node in the setting of breast carcinoma. They also complicate assessment of sentinel lymph node during intraoperative frozen sections analysis. CASE REPORT We report a case of co-existent of benign squamous-type and glandular-type epithelial inclusions cysts in 2 sentinel lymph nodes in a patient with grade III invasive ductal carcinoma involving the left breast.
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