Further Probing the Properties of a Unique Sponge-derived Alkaloid Through the Isolation of a New (-)-(5)-(8)-(14)-Mycothiazole Analogue.

Scale-up isolation of (+)-(5)-(8)-(14)-mycothiazole () from Vanuatu specimens of to semisynthesize (+)-(5)-(8)-8--acetyl-(14)-mycothiazole () revealed a new diastereomer, (-)-(5)-(8)-(14)-mycothiazole (). The structure of was determined using HRMS, NMR, and comparing optical rotation to (-)-(5)-(8)-(14)-mycothiazole () and . The maximum tolerated dose of in mice was 0.

Portobelamides A and B and Caciqueamide, Cytotoxic Peptidic Natural Products from a sp. Marine Cyanobacterium.

Three new compounds, portobelamides A and B ( and ), 3-amino-2-methyl-7-octynoic acid (AMOYA) and hydroxyisovaleric acid (Hiva) containing cyclic depsipeptides, and one long chain lipopeptide caciqueamide (), were isolated from a field-collection of a sp. marine cyanobacterium obtained from Panama as part of the Panama International Cooperative Biodiversity Group Program. Their planar structures were elucidated through analysis of 2D NMR and MS data, especially high resolution (HR) MS/MS fragmentation methods.

Reinvestigation of Mycothiazole Reveals the Penta-2,4-dien-1-ol Residue Imparts Picomolar Potency and 8 Configuration.

Reinvestigation of mycothiazole () revealed picomolar potency (IC = 0.00016, 0.00027, 0.

Inhibition of 5-lipoxygenase downregulates stemness and kills prostate cancer stem cells by triggering apoptosis via activation of c-Jun N-terminal kinase.

The cancer stem cell (CSC) concept suggests that neoplastic clones are maintained exclusively by a rare group of cells possessed with stem cell properties. CSCs are characterized by features that include self-renewal, pluripotency and tumorigenicity, and are thought to be solely responsible for tumor recurrence and metastasis. A hierarchically organized CSC model is becoming increasingly evident for various types of cancer, including prostate cancer.

Intraoperative Raman Spectroscopy.

Surgical excision of brain tumors provides a means of cytoreduction and diagnosis while minimizing neurologic deficit and improving overall survival. Despite advances in functional and three-dimensional stereotactic navigation and intraoperative MRI, delineating tissue in real time with physiologic confirmation is challenging. Raman spectroscopy has potential to be an important modality in the intraoperative evaluation of tissue during surgical resection.

Wedelolactone, an Anti-inflammatory Botanical, Interrupts c-Myc Oncogenic Signaling and Synergizes with Enzalutamide to Induce Apoptosis in Prostate Cancer Cells.

The c-Myc gene encodes an oncoprotein transcription factor that is frequently upregulated in almost all cancer types and is the subject of intense investigation for management of cancer because of its pleiotropic effects controlling a spectrum of cellular functions. However, due of its nonenzymatic nature, development of suitable strategies to block its protein-protein or protein-DNA interaction is challenging. Thus, c-Myc has been recognized as an elusive molecular target for cancer control, and various approaches are in development to inhibit c-Myc transcriptional activity.

Shining light on neurosurgery diagnostics using Raman spectroscopy.

Surgical excision of brain tumors provides a means of cytoreduction and diagnosis while minimizing neurologic deficit and improving overall survival. Despite advances in functional and three-dimensional stereotactic navigation and intraoperative magnetic resonance imaging, delineating tissue in real time with physiological confirmation is challenging. Raman spectroscopy is a promising investigative and diagnostic tool for neurosurgery, which provides rapid, non-destructive molecular characterization in vivo or in vitro for biopsy, margin assessment, or laboratory uses.

MiR-129-5p-mediated Beclin-1 suppression inhibits endothelial cell autophagy in atherosclerosis.

Endothelial cell injury and subsequent death play an essential role in the pathogenesis of atherosclerosis. Autophagy of endothelial cells antagonizes the development of atherosclerosis, whereas the underlying molecular mechanisms are unclear. MicroRNA-129-5p (miR-129-5p) is a well-defined tumor suppressorin some types of cancer, while it is unknown whether miR-129-5p may also play a role in the development of atherosclerosis.

Immunotherapy: A New Approach to Treating Multiple Myeloma with Daratumumab and Elotuzumab.

Objective: To review the clinical pharmacology, efficacy, and safety of daratumumab and elotuzumab for the treatment of relapsed refractory multiple myeloma (RRMM).

Data Sources: A literature search of MEDLINE, PubMed, the US National Institutes of Health Clinicaltrials.gov, the Food and Drug administration, and relevant meeting abstracts was conducted using the terms daratumumab, elotuzumab, multiple myeloma, anti-CD38, HuMax-CD38, HuLuc63, SLAMF7, and anti-CS1 STUDY SELECTION/DATA EXTRACTION: Human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of daratumumab and elotuzumab for MM were identified.

Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study.

Design, synthesis, and evaluation of α-methylene-γ-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNFα-induced NF-κB activity, cancer cell growth and tumor growth in an ovarian cancer model. A second iteration of synthesis and screening identified 29 which inhibited cancer cell growth with low-μM potency.

Topoisomerase IIα mediates TCF-dependent epithelial-mesenchymal transition in colon cancer.

Aberrant T-cell factor (TCF) transcription is implicated in the majority of colorectal cancers (CRCs). TCF transcription induces epithelial-mesenchymal transition (EMT), promoting a tumor-initiating cell (TIC) phenotype characterized by increased proliferation, multidrug resistance (MDR), invasion and metastasis. The data presented herein characterize topoisomerase IIα (TopoIIα) as a required component of TCF transcription promoting EMT.

'Sailing in troubled waters': a review of the use of anticoagulation in adult cancer patients with thrombocytopenia.

Simply providing anticoagulation therapy is not as straightforward of a solution in cancer patients who have concurrent thrombocytopenia owing to the increased risk of bleeding complications. Currently, few guidelines are in place to assist clinicians in safely managing thrombocytopenic cancer patients on anticoagulation. The purpose of this review is to critically examine the available body of biomedical literature surrounding anticoagulant use against the backdrop of cancer-related thrombocytopenia in adult patients.

Kalkipyrone B, a marine cyanobacterial γ-pyrone possessing cytotoxic and anti-fungal activities.

Bioassay-guided fractionation of two marine cyanobacterial extracts using the H-460 human lung cancer cell line and the OVC-5 human ovarian cancer cell line led to the isolation of three related α-methoxy-β, β'-dimethyl-γ-pyrones each containing a modified alkyl chain, one of which was identified as the previously reported kalkipyrone and designated kalkipyrone A. The second compound was an analog designated kalkipyrone B. The third was identified as the recently reported yoshinone A, also isolated from a marine cyanobacterium.

Identification of regions of normal grey matter and white matter from pathologic glioblastoma and necrosis in frozen sections using Raman imaging.

In neurosurgical applications, a tool capable of distinguishing grey matter, white matter, and areas of tumor and/or necrosis in near-real time could greatly aid in tumor resection decision making. Raman spectroscopy is a non-destructive spectroscopic technique which provides molecular information about the tissue under examination based on the vibrational properties of the constituent molecules. With careful measurement and data processing, a spatial step and repeat acquisition of Raman spectra can be used to create Raman images.

Clues to the Blues: Predictors of Self-Reported Mental and Emotional Health Among Older African American Men.

The mental health needs of aging African American men have been overlooked and few studies have distinguished between more severe clinically diagnosable mental health challenges and less severe emotional states for this population. African American men may not identify with or internalize the terminology of "depression" despite exhibiting the symptom criteria. This exploratory cross-sectional study examined correlates of "downheartedness" as an alternative indicator of emotional health.

MK591, a second generation leukotriene biosynthesis inhibitor, prevents invasion and induces apoptosis in the bone-invading C4-2B human prostate cancer cells: implications for the treatment of castration-resistant, bone-metastatic prostate cancer.

Castration-resistant prostate cancer (CRPC) is a major clinical challenge for which no cure is currently available primarily because of the lack of proper understanding about appropriate molecular target(s). Previously we observed that inhibition of 5-lipoxygenase (5-Lox) activity induces apoptosis in some types of prostate cancer cells, suggesting an important role of 5-Lox in the viability of prostate cancer cells. However, nothing is known about the role of 5-Lox in the survival of castration-resistant, metastatic prostate cancer cells.

Biosynthetic products from a nearshore-derived gram-negative bacterium enable reassessment of the kailuin depsipeptides.

Sampling of California nearshore sediments resulted in the isolation of a Gram-negative bacterium, Photobacterium halotolerans, capable of producing unusual biosynthetic products. Liquid culture in artificial seawater-based media provided cyclic depsipeptides including four known compounds, kailuins B-E (2-5), and two new analogues, kailuins G and H (7 and 8). The structures of the new and known compounds were confirmed through extensive spectroscopic and Marfey's analyses.

Fatalistic Beliefs About Cancer Prevention Among Older African American Men.

Objectives: Evidence suggests that minority groups are more likely to exhibit fatalistic beliefs about cancer prevention (FBCP), which are defined as confusion, pessimism, and helplessness about one's ability to prevent cancer. This study examines the socioeconomic and psychosocial predictors of FBCP among older African American men (AAM).

Methods: AAM (N = 1,666) enrolled in Medicare and participating in a longitudinal study on patient navigation were surveyed.

Inhibition of 5-lipoxygenase selectively triggers disruption of c-Myc signaling in prostate cancer cells.

Myc is up-regulated in almost all cancer types and is the subject of intense investigation because of its pleiotropic effects controlling a broad spectrum of cell functions. However, despite its recognition as a stand-alone molecular target, development of suitable strategies to block its function is hindered because of its nonenzymatic nature. We reported earlier that arachidonate 5-lipoxygenase (5-Lox) plays an important role in the survival and growth of prostate cancer cells, although details of the underlying mechanisms have yet to be characterized.

Characteristics associated with genetic counseling referral and BRCA1/2 testing among women in a large integrated health system.

Background: Evidence shows underutilization of cancer genetics services. To explore the reasons behind this underutilization, this study evaluated characteristics of women who were referred for genetic counseling and/or had undergone BRCA1/2 testing.

Methods: An ovarian cancer risk perception study stratified 16,720 eligible women from the Henry Ford Health System into average-, elevated-, and high-risk groups based on family history.

Enzyme inhibition by hydroamination: design and mechanism of a hybrid carmaphycin-syringolin enone proteasome inhibitor.

Hydroamination reactions involving the addition of an amine to an inactivated alkene are entropically prohibited and require strong chemical catalysts. While this synthetic process is efficient at generating substituted amines, there is no equivalent in small molecule-mediated enzyme inhibition. We report an unusual mechanism of proteasome inhibition that involves a hydroamination reaction of alkene derivatives of the epoxyketone natural product carmaphycin.

Modeling the sustainability of community health networks: novel approaches for analyzing collaborative organization partnerships across time.

Sustainability is important if community health organizations are to be effective in collaborating to achieve long term health goals. We present a multi-method set of longitudinal analyses examining structural markers applied to a group of organizations brought together to reduce cancer disparities among older African American adults. At the overall network level, sustainability was seen in the growth of outgoing connections and multiplexity.

Discovery and development of anticancer agents from marine sponges: perspectives based on a chemistry-experimental therapeutics collaborative program.

A collaborative program was initiated in 1990 between the natural product chemistry laboratory of Dr. Phillip Crews at the University of California Santa Cruz and the experimental therapeutics laboratory of Dr. Fred Valeriote at the Henry Ford Hospital in Detroit.

Overcoming docetaxel resistance in prostate cancer: a perspective review.

The treatment of metastatic castrate-resistant prostate cancer has been historically challenging, with few therapeutic successes. Docetaxel was the first cytotoxic therapy associated with a survival benefit in castrate-resistant prostate cancer. Toxicity is typical of other cytotoxic agents, with myelosuppression being the dose-limiting toxicity and neurotoxicity also a notable side effect for some patients.

Non-steroidal anti-inflammatory drug use and colorectal polyps in the Prostate, Lung, Colorectal, And Ovarian Cancer Screening Trial.

Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs) have been documented in animal and human studies to reduce risk for colorectal cancer and adenomatous polyps, but risk modification for subgroups of the population and effects on hyperplastic polyps have been less studied.

Methods: Data on recent use of two frequently ingested NSAIDs, aspirin and ibuprofen, were collected at baseline from participants aged 55-74 years in the 10 centers of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Participants randomized to the intervention arm of the trial received a flexible sigmoidoscopy during a baseline examination.