Biosimilars: where we were and where we are.

Recent progress in biosimilars development is overviewed, with attention to the history of issues and processes leading to current regulations, and to scientific considerations, including progress on design and operational implementation issues that arise and are peculiar to biosimilars trial design and implementation.

CD44 expression in cervical intraepithelial neoplasia (CIN) and carcinoma.

Background: The expression of the CD44 gene is markedly changed in many neoplastic tissues. The identification of tumor-specific CD44 expression patterns may aid tumor diagnosis.

Methods And Results: The transcription and translation of the CD44 gene were analyzed by reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization and by immunohistochemistry.

Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres.

The mammalian Ku70 and Ku86 proteins form a heterodimer that binds to the ends of double-stranded DNA in vitro and is required for repair of radiation-induced strand breaks and V(D)J recombination [1,2]. Deletion of the Saccharomyces cerevisiae genes HDF1 and HDF2--encoding yKu70p and yKu80p, respectively--enhances radiation sensitivity in a rad52 background [3,4]. In addition to repair defects, the length of the TG-rich repeat on yeast telomere ends shortens dramatically [5,6].

Chromosome ends: all the same under their caps.

The recent characterisation of subtelomeric regions from a variety of organisms from yeast to man has led to the realisation that all chromosome ends are similar in structure although maintenance of the terminus varies. The mosaic of repeats and proteins associated with telomeres has an architectural role which divides the genome into two domains, allowing for the adaptive use of the region as well as the evolution of non-telomerase-mediated telomere maintenance.

Rapid analysis of distinctive CD44 RNA splicing preferences that characterize colonic tumors.

In normal tissues, the steady-state level of CD44 mRNA is low, and the variety of alternatively spliced transcripts produced by this complex gene is limited. Conversely, increased and disorderly expression of this gene has been observed in a number of types of cancer. This study analyzed the order in which the CD44 variant exons are spliced together in gastrointestinal tumor cell lines and in 20 colonic carcinomas and matched normal mucosa.