Mcneilabbott2139

Streptomyces sp. GET02.ST and Achromobacter sp. GET02.AC were isolated together from the gut of the wharf roach, Ligiaexotica, inhabiting the intertidal zone of the west coast of Korea. The co-cultivation of these two strains significantly induced the production of two new metabolites, ligiamycins A (1) and B (2), which were barely detected in the single culture of Streptomyces sp. GET02.ST. The planar structures of ligiamycins A (1) and B (2) were elucidated as new decalins coupled with amino-maleimides by the analysis of various spectroscopic data, including nuclear magnetic resonance (NMR), ultraviolet (UV), and mass (MS) data. The assignment of two nitrogen atoms in amino-maleimide in 1 was accomplished based on 1H-15N heteroatom single quantum coherence spectroscopy (HSQC) NMR experiments. The relative configurations of the ligiamycins were determined using rotating frame Overhauser effect spectroscopy (ROESY) NMR data, and their absolute configurations were deduced by comparing their experimental and calculated optical rotations. Ligiamycin A (1) displayed antibacterial effects against Staphylococcus aureus and Salmonella enterica, while ligiamycin B (2) exhibited mild cell cytotoxicity against human colorectal cancer cells.To enhance the biological activity of the natural product geodin (1), isolated from the marine-derived fungus Aspergillus sp., a series of new ether derivatives (2-37) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the insecticidal and antibacterial activities of all geodin congeners were evaluated systematically. Most of these derivatives showed better insecticidal activities against Helicoverpa armigera Hübner than 1. In particular, 15 showed potent insecticidal activity with an IC50 value of 89 μM, comparable to the positive control azadirachtin (IC50 = 70 μM). Additionally, 5, 12, 13, 16, 30 and 33 showed strong antibacterial activity against Staphylococcus aureus and Aeromonas salmonicida with MIC values in the range of 1.15-4.93 μM. The preliminary structure-activity relationships indicated that the introduction of halogenated benzyl especially fluorobenzyl, into 1 and substitution of 4-OH could be key factors in increasing the insecticidal and antibacterial activities of geodin.Palytoxin (PLTX) is a highly toxic polyether identified in various marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. In addition to adverse effects in humans, negative impacts on different marine organisms have been often described during Ostreopsis blooms and the concomitant presence of PLTX and its analogues. Considering the increasing frequency of Ostreopsis blooms due to global warming, PLTX was investigated for its effects on Artemia franciscana, a crustacean commonly used as a model organism for ecotoxicological studies. At concentrations comparable to those detected in culture media of O. cf. ovata (1.0-10.0 nM), PLTX significantly reduced cysts hatching and induced significant mortality of the organisms, both at larval and adult stages. Adults appeared to be the most sensitive developmental stage to PLTX significant mortality was recorded after only 12 h of exposure to PLTX concentrations > 1.0 nM, with a 50% lethal concentration (LC50) of 2.3 nM (95% confidence interval = 1.2-4.7 nM). The toxic effects of PLTX toward A. franciscana adults seem to involve oxidative stress induction. Indeed, the toxin significantly increased ROS levels and altered the activity of the major antioxidant enzymes, in particular catalase and peroxidase, and marginally glutathione-S-transferase and superoxide dismutase. On the whole, these results indicate that environmentally relevant concentrations of PLTX could have a negative effect on Artemia franciscana population, suggesting its potential ecotoxicological impact at the marine level.Eight trichothecenes, including four new compounds 1-4 and four known entities 5-8, together with one known cyclonerane (9) were isolated from the solid-state fermentation of Trichodermabrevicompactum NTU439 isolated from the marine alga Mastophora rosea. The structures of 1-9 were determined by 1D/2D NMR (nuclear magnetic resonance), MS (mass spectrometry), and IR (infrared spectroscopy) spectroscopic data. All of the compounds were evaluated for cytotoxic activity against HCT-116, PC-3, and SK-Hep-1 cancer cells by the SRB assay, and compound 8 showed promising cytotoxic activity against all three cancer cell lines with the IC50 values of 3.3 ± 0.3, 5.3 ± 0.3, and 1.8 ± 0.8 μM, respectively. Compounds 1-2, 4-6, and 7-8 potently inhibited LPS-induced NO production, and compounds 5 and 8 showed markedly inhibited gelatinolysis of MMP-9 in S1 protein-stimulated THP-1 monocytes.Seven new compounds, namely talaromanloid A (1), talaromydene (2), 10-hydroxy-8-demethyltalaromydine and 11-hydroxy-8-demethyltalaromydine (3 and 4), talaromylectone (5), and ditalaromylectones A and B (6 and 7), together with seven known compounds were identified from a marine-derived fungus, Talaromyces mangshanicus BTBU20211089, which was isolated from a sediment sample collected from the South China Sea. Their chemical structures were determined using spectroscopic data, including HRESIMS, 1D, and 2D NMR techniques. The absolute configurations of 1 and 2 were elucidated by comparing experimental and calculated ECD spectra. Compounds 1, 2, 6, and 7 are new compounds possessing a novel carbon skeleton. Compound 6 is a dimeric molecule of 3 and 9. Compound 7 shared a unique structure of the cyclized dimer of 3 and 4. All the compounds were tested for their bioactivities against Staphylococcus aureus, Escherichia coli, and Candida albicans.Malignant gastrointestinal neuroectodermal tumor (GNET) is an ultra-rare soft tissue sarcoma, therefore often misdiagnosed and has no available standard treatment. Here, we report 3 cases of metastatic GNET with variable clinical courses. Our small case series as well as extensive literature review, further support that GNET is a spectrum of diseases with variable inherent biology and prognosis. Surgical management in the setting of recurrent/metastatic disease may be appropriate for GNET with indolent nature. Response to systemic treatments including chemotherapy and targeted treatments is variable, likely related to heterogenous biology as well. Furthermore, we retrospectively identified 20 additional GNET cases from Foundation Medicine's genomic database and expanded on their clinicopathological and genomic features. Comprehensive genomic profiling (CGP) with DNA and RNA sequencing of this cohort, in the course of clinical care, demonstrated recurrent EWSR1 chromosomal rearrangements and a sparsity of additional recurrent or driver genomic alterations. All cases had low tumor mutational burden (TMB) and were microsatellite stable.This study aims to identify the needs and wishes of childhood cancer long-term survivors for digitally mediated emotional peer support. Survivors of childhood cancer (six men, seven women) aged 19-33, participated in semi-structured interviews (November-December 2020). Age of diagnosis ranged from 1 to 13 years. The interviews lasted between 45 and 85 min. A thematic analysis was used to identify three themes for needs processing long-term complications of cancer treatment, processing psychosocial health and meeting others who share similar experiences; and another three themes reflecting wishes digital tools for connecting with people who had had similar experiences, different modes of communication and a safe place with varying degrees of anonymity. The findings emphasized the needs and wishes of childhood cancer survivors to meet others who had had similar experiences using a digital tool that offered a secure place, with options for a variety of communication methods and levels of anonymity. Peer support can serve as an important complement to professional psychosocial support.Population-based cohort studies can be a resource for tumor specimens, annotated with demographic, lifestyle, and health history data, that support innovative studies of cancer. Our aim was to establish and test a process for accessing tumor samples, held at pathology laboratories around British Columbia (BC), for participants of the BC Generations Project (BCGP). Through the BC Cancer Registry, we identified pathology reports for 1100 (93%) of the 1180 incident solid cancer cases diagnosed in BCGP as of 2019. Using manually abstracted data from the reports, we successfully retrieved 183 (92%) of the 200 formalin-fixed, paraffin-embedded (FFPE) blocks (breast, lung, bladder, and pancreas cancer cases) that we requested from pathology laboratories. No important differences in retrieval rates by cancer site, sample location (Greater Vancouver vs. Outside Greater Vancouver), sample type (biopsy vs. excision) or year of diagnosis were identified. A text mining solution recently implemented by the Registry will allow us to automate the process for data abstraction and should capture pathology reports for 100% of all newly diagnosed BCGP cancer cases moving forward. This will further enhance the utility of BCGP as a high-quality tumor tissue research resource.Prior to 1997, ovarian cancer (OC) was a 'poor target' for patient advocacy. At that time, there were only three OC researchers in Canada, little information available for women diagnosed, and no community of survivors existed. Selleckchem ESI-09 The Corinne Boyer Fund to advance OC was founded in 1997 (later renamed the National Ovarian Cancer Association (NOCA) and subsequently Ovarian Cancer Canada (OCC)), and a Blueprint for Action was established. NOCA developed training programs for public education, partnered with clinicians and scientists, established a Tissue Banking Network across Canada In 2015, the Ladyballs awareness campaign was launched nationally, giving the community a presence and voice. Strategic planning by the organization put advocacy for research funding as a top priority and, working with patients and researchers across the country, petitioned the government for C$10 million in research funding. In 2019, OCC received the funding. In 2020, the OvCAN project was launched with the aim to improve the outcomes of women diagnosed with OC. In the first three years of OvCAN, a pan-Canadian team of 25 Patient Partners was established, and 41 projects to date on research models, pre-clinical and clinical trials covering a wide spectrum of OC types have been funded.Front-line bevacizumab (BEV) in combination with taxanes offers benefit in progression-free survival (PFS) in metastatic breast cancer (mBC). The medical records of mBC patients, treated with front-line BEV-based chemotherapy, were retrospectively reviewed in order to generate real life safety and efficacy data. Patients with human epidermal growth factor receptor 2 (HER2)-negative mBC treated with front-line BEV in combination with chemotherapy were eligible. Maintenance therapy with BEV and/or hormonal agents was at the physicians' discretion. Among the 387 included patients, the most common adverse events were anemia (61.9%, mainly grade 1), grade 3/4 neutropenia (16.5%), grade 1/2 fatigue (22.3%), and grade 1/2 neuropathy (19.6%). Dose reductions were required in 164 cycles (7.1%) and toxicity led to treatment discontinuation in 21 patients (5.4%). The median PFS and the median overall survival (OS) were 13.3 (95% CI 11.7-14.8) and 32.3 months (95% CI 27.7-36.9), respectively. Maintenance therapy, with hormonal agents (ET) and/or BEV, was associated with longer OS versus no maintenance therapy (47.