IGF system, CD99 and tumor-specific chromosomal translocations: evaluation of their cross-talk and definition of their role in Ewing sarcoma and prostate cancer

Aberrant expression of ETS transcription factors, including FLI1 and ERG, due to chromosomal translocations has been described as a driver event in initiation and progression of different tumors. In this study, the impact of prostate cancer (PCa) fusion gene TMPRSS2-ERG was evaluated on components of the insulin-like growth factor (IGF) system and the CD99 molecule, two well documented targets of EWS-FLI1, the hallmark of Ewing sarcoma (ES). The aim of this study was to identify common or distinctive ETS-related mechanisms which could be exploited at biological and clinical level. The results demonstrate that IGF-1R represents a common target of ETS rearrangements as ERG and FLI1 bind IGF-1R gene promoter and their modulation causes alteration in IGF-1R protein levels. At clinical level, this mechanism provides basis for a more rationale use of anti-IGF-1R inhibitors as PCa cells expressing the fusion gene better respond to anti-IGF-1R agents. EWS-FLI1/IGF-1R axis provides rationale for combination of anti-IGF-1R agents with trabectedin, an alkylator agent causing enhanced EWS-FLI1 occupancy on the IGF-1R promoter. TMPRSS2-ERG also influences prognosis relevance of IGF system as high IGF-1R correlates with a better biochemical progression free survival (BPFS) in PCa patients negative for the fusion gene while marginal or no association was found in the total cases or TMPRSS2-ERG-positive cases, respectively. This study indicates CD99 is differentially regulated between ETS-related tumors as CD99 is not a target of ERG. In PCa, CD99 did not show differential expression between TMPRSS2-ERG-positive and –negative cells. A direct correlation was anyway found between ERG and CD99 proteins both in vitro and in patients putatively suggesting that ERG target genes comprehend regulators of CD99. Despite a little trend suggesting a correlation between CD99 expression and a better BPFS, no clinical relevance for CD99 was found in the field of prognostic biomarkers.

The meaning and measurement of neuroticism and anxiety

Bibliography: p. 503-512.

A grammatical analyzer : or, The derivation and definition of words with their grammatical classification for the use of schools and academies /

Mode of access: Internet.

The ten nequdoth of the Torah; or, The meaning and purpose of the extraordinary points of the Pentateuch (Massoretic text) A contribution to the history of textual criticism among the ancient Jews,

Biography: p. iii.

Analytical concordance to the Bible on an entirely new plan, containing about 311,000 references, subdivided under the Hebrew and Greek originals, with the literal meaning and pronunciation of each, designed for the simplest reader of the English Bible, /

Mode of access: Internet.

The meaning and value of life,

Mode of access: Internet.

Phase I mandates studies and definition of schooling : final staff recommendations presented to the Illinois State Board of Education, Planning and Policy Committee.

Final recommendations for analysis of the mandates in special education, bilingual education, driver education, physical education, and the instructional program in elementary and secondary schools.

Analytical vocabulary, or, Analytical system of teaching orthography : in which the spelling, meaning, and construction of 80,000 words are taught from 8,000 roots /

On cover: 1837.

The great deception, bringing into the light the real meaning and mandate of the Harding vote as to peace,

Mode of access: Internet.

The desk Standard dictionary of the English language, designed to give the orthography, pronunciation, meaning, and etymology of about 83,000 words and phrases in the speech and literature of the English-speaking peoples;

Mode of access: Internet.

A pocket medical dictionary : giving the pronunciation and definition of about 12,000 of the principal words used in medicine and the collateral sciences ... /

Half-title: Gould's Pocket pronouncing medical dictionary.