Coastside Bio Resources (United States)

Abstract Identifying and tracking microbial strains as microbiomes evolve is a major challenge in the field of microbiome research. Longitudinal microbiome samples of co-admitted twins from two different neonatal intensive care units (NICUs) were analyzed using a ∼2,500 base amplicon that spans the 16S and 23S rRNA genes, and mapped to a new 16S-23S rRNA database. Amplicon Sequence Variants inferred using DADA2 provided sufficient resolution for differentiation of rRNA variants from closely related, but not previously sequenced Klebsiella, E. coli, and Enterobacter, among the first bacteria colonizing the gut of these infants after admission to the NICU. Distinct ASV groups (fingerprints) were followed between co-admitted twins over time, demonstrating the potential to track the source and spread of both commensals and pathogens.The high-resolution taxonomy obtained from long amplicon sequencing enable tracking of strains temporally and spatially as microbiomes are established in infants in the hospital environment.

Abstract Sea cucumber has been used as a folk medicine for many conditions and recently antitumor activities have been described. Frondoside A, a triterpenoid glycoside isolated from the sea cucumber Cucumaria frondosa, as well as the related compound Frondanol A5 inhibit growth of pancreatic, colon and breast tumor cell lines in vitro and show activity in a primary prevention model of colon cancer. The cyclooxygenase 2 pathway contributes to growth and progression of many solid tumors by multiple mechanisms. The COX-2 product, prostaglandin E2 (PGE2) contributes to malignancy by acting on a family of four G-protein-coupled receptors (EP1, EP2, EP3, EP4). We have shown that both human and murine breast tumor cell lines express all EP receptors and that EP4 contributes to metastatic potential in a syngeneic murine model of metastatic breast cancer. Other laboratories have also provided evidence that EP4 promotes malignancy but a paucity of effective EP4 antagonists has slowed the development of clinically evaluable EP-targeted compounds. Based on the reported anti-inflammatory properties of Frondoside A, we asked if this compound has EP antagonist properties. We now report the novel finding that Frondoside A is a potent antagonist of EP4 and, to a lesser degree, antagonizes EP2. Frondoside A inhibits the binding of radio-labeled PGE2 to Chem-1 cells expressing EP4 or HEK cells transduced to express EP2. Using EP4-expressing MDA-MD-231 human breast cancer or murine mammary tumor cell line 66.1, we show that EP4-mediated activation of adenylate cyclase is also blocked by Frondoside A indicating both pharmacologic and functional EP4 receptor antagonism. We determined the effect of Frondoside A on metastatic potential of line 66.1 tumor cells. Treatment of 66.1 cells with non-cytotoxic concentrations of Frondoside A prior to i.v. administration of tumor cells into syngeneic Balb/cByJ female mice reduced lung colonizing capacity by 58%. These studies describe a potent metastasis inhibitory activity of Frondoside A and show, for the first time, that this compound may be a potent novel EP4/EP2 antagonist with activity in a model of metastatic breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 609. doi:10.1158/1538-7445.AM2011-609

To investigate the effects and mechanism of Frondanol-A5P, a polar extract from Cucumaria frondosa, on growth inhibition and apoptosis in S2013 and AsPC-1 human pancreatic cancer cells. The effects of Frondanol-A5P on proliferation, cell cycle, expression of cell cycle proteins and p21, phosphorylation of MAP kinases, annexin V binding, and caspase-3 activation were examined. Frondanol-A5P inhibited proliferation and induced G2/M phase cell cycle arrest in both cell lines with decreased expression of cyclin A, cyclin B, and cdc25c. Frondanol-A5P induced phosphorylation of stress-activated protein kinase and Janus kinase (SAPK/JAK) and p38 mitogen-activated protein kinase (MAP) within 5 minutes. Frondanol-A5P markedly increased expression of p21 messenger RNA and protein at 3 hours in both cell lines. This effect was reduced by the p38 kinase inhibitor, SB203580. Frondanol-A5P markedly increased annexin V binding and activated caspase-3. Frondanol-A5 causes cell cycle arrest and apoptosis in human pancreatic cancer cells. These changes are associated with decreased expression of cyclin A, cyclin B, and cdc25c and increased expression of p21 that, at least in part, is mediated by a p38 kinase-dependent mechanism. Because Frondanol-A5P is derived from an edible, nontoxic, sea cucumber, it may be valuable for nutritional therapy or prevention of pancreatic cancer.

Pancreatic cancer cells are resistant to the growth-inhibitory and apoptosis-inducing effects of conventional chemotherapeutic agents. There are multiple genetic and epigenetic events during the process of carcinogenesis that enable the cancer cells to avoid normal growth constraints and apoptosis. Investigation of the mechanisms involved has led to multiple strategies that encourage cell death and apoptosis to occur. The pathways involved are summarized in this review, together with some recently developed strategies to promote cell death in this cancer and with a particular focus on the frondoside A, a novel triterpenoid glycoside isolated from the Atlantic sea cucumber, Cucumaria frondosa. Frondoside A inhibited proliferation of AsPC-1 human pancreatic cancer cells in a concentration- and time-dependent manner, as measured by (3)H-thymidine incorporation and cell counting. In concert with inhibition of cell growth, frondoside A induced significant morphological changes consistent with apoptosis. Propidium iodide DNA staining showed an increase of sub-G0/G1 cell population of apoptotic cells induced by frondoside A. Frondoside A-induced apoptosis was confirmed by annexin V binding and TUNEL assay. Furthermore, western blotting showed a decrease in expression of Bcl-2 and Mcl-1, an increase in Bax expression, activation of caspases 3, 7, and 9, and an increase in the expression of the cyclin-dependent kinase inhibitor, p21. These findings show that frondoside A induced apoptosis in human pancreatic cancer cells through the mitochondrial pathway and activation of the caspase cascade. Finally, a very low concentration of frondoside A (10 mug/kg/day) inhibited growth of AsPC-1 xenografts in athymic mice. In conclusion, new chemotherapeutic agents are desperately needed for pancreatic cancer because of the poor responsiveness to currently available treatment options. Frondoside A has potent growth inhibitory effects on human pancreatic cancer cells, and the inhibition of proliferation is accompanied by marked apoptosis. Frondoside A may be valuable for the treatment or chemoprevention of this devastating disease.

The design of an improved acoustic plate mode (APM) biochemical sensing device is reported. The device, fabricated on a 0.5-mm-thick ZX-lithium niobate substrate, consists of a dual delay line configuration which could be used in either a vector voltmeter phase discriminator or a dual oscillator measurement system. The device exhibits excellent adjacent mode rejection without sacrificing the high sensitivity to electrical loadings. The device, which shows a better phase linearity, is currently being evaluated in various measurement systems as a chemical sensor or biosensor. >