FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1597946639> ?p ?o ?g. }

• W1597946639 abstract "Cancer-specific survival has changed remarkably little over the past half century, mainly because metastases that are occult at diagnosis and generally resistant to chemotherapy subsequently develop months, years or even decades following definitive therapy. Targeting the dormant micrometastases responsible for these delayed or occult metastases would represent a major new tool in cancer patient management. Our hypothesis is that these metastases develop from micrometastatic cells that are suppressed by normal extracellular matrix (ECM). A new screening method was developed that compared the effect of drugs on the proliferation of cells grown on a normal ECM gel (small intestine submucosa, SISgel) to cells grown on plastic cell culture plates. The desired endpoint was that cells on SISgel were more sensitive than the same cells grown as monolayers. Known cancer chemotherapeutic agents show the opposite pattern. Screening 13,000 compounds identified two leads with low toxicity in mice and EC50 values in the range of 3–30 μM, depending on the cell line, and another two leads that were too toxic to mice to be useful. In a novel flank xenograft method of suppressed/dormant cells co-injected with SISgel into the flank, the lead compounds significantly eliminated the suppressed cells, whereas conventional chemotherapeutics were ineffective. Using a 4T1 triple negative breast cancer model, modified for physiological metastatic progression, as predicted, both lead compounds reduced the number of large micrometastases/macrometastases in the lung. One of the compounds also targeted cancer stem cells (CSC) isolated from the parental line. The CSC also retained their stemness on SISgel. Mechanistic studies showed a mild, late apoptotic response and depending on the compound, a mild arrest either at S or G2/M in the cell cycle. In summary we describe a novel, first in class set of compounds that target micrometastatic cells and prevent their reactivation to form recurrent tumors/macrometastases." @default.
• W1597946639 created "2016-06-24" @default.
• W1597946639 creator A5010743791 @default.
• W1597946639 creator A5014175543 @default.
• W1597946639 creator A5016405661 @default.
• W1597946639 creator A5027150874 @default.
• W1597946639 creator A5031463022 @default.
• W1597946639 creator A5039649862 @default.
• W1597946639 creator A5044511340 @default.
• W1597946639 creator A5054877292 @default.
• W1597946639 creator A5060676110 @default.
• W1597946639 creator A5069496915 @default.
• W1597946639 date "2015-05-14" @default.
• W1597946639 modified "2023-09-25" @default.
• W1597946639 title "Identification of novel drugs to target dormant micrometastases" @default.
• W1597946639 cites W144939485 @default.
• W1597946639 cites W1495945591 @default.
• W1597946639 cites W1561537870 @default.
• W1597946639 cites W1572028736 @default.
• W1597946639 cites W1778790658 @default.
• W1597946639 cites W1969801754 @default.
• W1597946639 cites W1970944737 @default.
• W1597946639 cites W1981268896 @default.
• W1597946639 cites W1981717673 @default.
• W1597946639 cites W1983075270 @default.
• W1597946639 cites W1987148306 @default.
• W1597946639 cites W1988556290 @default.
• W1597946639 cites W1992324708 @default.
• W1597946639 cites W1993497779 @default.
• W1597946639 cites W1996191723 @default.
• W1597946639 cites W1997575697 @default.
• W1597946639 cites W2003626047 @default.
• W1597946639 cites W2004280628 @default.
• W1597946639 cites W2007303912 @default.
• W1597946639 cites W2012789793 @default.
• W1597946639 cites W2013072786 @default.
• W1597946639 cites W2014119944 @default.
• W1597946639 cites W2019922740 @default.
• W1597946639 cites W2021292361 @default.
• W1597946639 cites W2029938510 @default.
• W1597946639 cites W2033278321 @default.
• W1597946639 cites W2041888522 @default.
• W1597946639 cites W2044702943 @default.
• W1597946639 cites W2045927961 @default.
• W1597946639 cites W2046068483 @default.
• W1597946639 cites W2054547141 @default.
• W1597946639 cites W2057359010 @default.
• W1597946639 cites W2070332197 @default.
• W1597946639 cites W2076679216 @default.
• W1597946639 cites W2082539367 @default.
• W1597946639 cites W2085360323 @default.
• W1597946639 cites W2090399120 @default.
• W1597946639 cites W2093814531 @default.
• W1597946639 cites W2093829133 @default.
• W1597946639 cites W2093973650 @default.
• W1597946639 cites W2104604857 @default.
• W1597946639 cites W2104666893 @default.
• W1597946639 cites W2119120345 @default.
• W1597946639 cites W2131756681 @default.
• W1597946639 cites W2138542824 @default.
• W1597946639 cites W2142232788 @default.
• W1597946639 cites W2143176313 @default.
• W1597946639 cites W2150902592 @default.
• W1597946639 cites W2156408464 @default.
• W1597946639 cites W2156555688 @default.
• W1597946639 cites W2159173343 @default.
• W1597946639 cites W2161867610 @default.
• W1597946639 cites W2169344919 @default.
• W1597946639 cites W2180964475 @default.
• W1597946639 cites W2415808476 @default.
• W1597946639 cites W4246491089 @default.
• W1597946639 doi "https://doi.org/10.1186/s12885-015-1409-4" @default.
• W1597946639 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4434572" @default.
• W1597946639 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25971923" @default.
• W1597946639 hasPublicationYear "2015" @default.
• W1597946639 type Work @default.
• W1597946639 sameAs 1597946639 @default.
• W1597946639 citedByCount "11" @default.
• W1597946639 countsByYear W15979466392016 @default.
• W1597946639 countsByYear W15979466392017 @default.
• W1597946639 countsByYear W15979466392018 @default.
• W1597946639 countsByYear W15979466392019 @default.
• W1597946639 countsByYear W15979466392020 @default.
• W1597946639 countsByYear W15979466392021 @default.
• W1597946639 countsByYear W15979466392022 @default.
• W1597946639 crossrefType "journal-article" @default.
• W1597946639 hasAuthorship W1597946639A5010743791 @default.
• W1597946639 hasAuthorship W1597946639A5014175543 @default.
• W1597946639 hasAuthorship W1597946639A5016405661 @default.
• W1597946639 hasAuthorship W1597946639A5027150874 @default.
• W1597946639 hasAuthorship W1597946639A5031463022 @default.
• W1597946639 hasAuthorship W1597946639A5039649862 @default.
• W1597946639 hasAuthorship W1597946639A5044511340 @default.
• W1597946639 hasAuthorship W1597946639A5054877292 @default.
• W1597946639 hasAuthorship W1597946639A5060676110 @default.
• W1597946639 hasAuthorship W1597946639A5069496915 @default.
• W1597946639 hasBestOaLocation W15979466391 @default.
• W1597946639 hasConcept C121608353 @default.
• W1597946639 hasConcept C126322002 @default.
• W1597946639 hasConcept C142724271 @default.

• next