Home About us Contact
|
Home About us Contact | ||
|
|
||
Molecular Therapeutics (molecular + therapeutics)
Selected AbstractsMolecular Therapeutics: 21st century medicine by Pamela Greenwell and Michelle McCulleyBIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION, Issue 6 2008Robert H. Glew No abstract is available for this article. [source] Stromelysin-3 expression is an early event in human oral tumorigenesisINTERNATIONAL JOURNAL OF CANCER, Issue 2 2003Shilpi Soni Abstract Stromelysin-3 (ST3/MMP11) is associated with human tumour progression. To determine the clinical significance of ST3 in oral tumorigenesis, its expression was analysed in different stages of tobacco-associated oral cancer. Immunohistochemical analysis of ST3 expression in 79 oral precancerous lesions, 177 SCCs and 35 histologically normal oral tissues was carried out and corroborated by immunoblotting and RT-PCR. ST3/MMP11 protein expression was observed in 45/79 (57%) precancerous lesions [28/48 (58%) with hyperplasia and 17/31 (55%) with dysplasia] and in 123/177 (70%) oral SCCs. In precancerous lesions, ST3 expression was higher compared to normal oral tissues (p = 0.000) and associated with MVD (p = 0.05), a marker for angiogenesis. ST3 was also expressed in cells cultured from precancerous and cancerous lesions that had undergone epithelial-to-mesenchymal transition. In oral cancer patients, ST3 positivity was associated with lymph node involvement (p = 0.025) and increased intratumoral MVD (p = 0.009). Ninety-eight oral SCC patients were followed up for a period of 94 months (median 22.5 months). Kaplan-Meier survival analysis showed that ST3 expression was not a significant prognostic indicator. ST3 expression in oral hyperplastic and dysplastic lesions suggests its association with progression of phenotypic alterations acquired early during the malignant transformation pathway of oral epithelium and implicates it not only in angiogenesis and invasion but also in tumorigenesis. Thus, ST3 may serve as a potential target for developing molecular therapeutics for early intervention in oral tumorigenesis. © 2003 Wiley-Liss, Inc. [source] Antisense applications for biological controlJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006Wei-Hua Pan Abstract Although Nature's antisense approaches are clearly impressive, this Perspectives article focuses on the experimental uses of antisense reagents (ASRs) for control of biological processes. ASRs comprise antisense oligonucleotides (ASOs), and their catalytically active counterparts ribozymes and DNAzymes, as well as small interfering RNAs (siRNAs). ASOs and ribozymes/DNAzymes target RNA molecules on the basis of Watson-Crick base pairing in sequence-specific manner. ASOs generally result in destruction of the target RNA by RNase-H mediated mechanisms, although they may also sterically block translation, also resulting in loss of protein production. Ribozymes and DNAzymes cleave target RNAs after base pairing via their antisense flanking arms. siRNAs, which contain both sense and antisense regions from a target RNA, can mediate target RNA destruction via RNAi and the RISC, although they can also function at the transcriptional level. A considerable number of ASRs (mostly ASOs) have progressed into clinical trials, although most have relatively long histories in Phase I/II settings. Clinical trial results are surprisingly difficult to find, although few ASRs appear to have yet established efficacy in Phase III levels. Evolution of ASRs has included: (a) Modifications to ASOs to render them nuclease resistant, with analogous modifications to siRNAs being developed; and (b) Development of strategies to select optimal sites for targeting. Perhaps the biggest barrier to effective therapies with ASRs is the "Delivery Problem." Various liposomal vehicles have been used for systemic delivery with some success, and recent modifications appear to enhance systemic delivery, at least to liver. Various nanoparticle formulations are now being developed which may also enhance delivery. Going forward, topical applications of ASRs would seem to have the best chances for success. In summary, modifications to ASRs to enhance stability, improve targeting, and incremental improvements in delivery vehicles continue to make ASRs attractive as molecular therapeutics, but their advance toward the bedside has been agonizingly slow. J. Cell. Biochem. 98: 14,35, 2006. © 2006 Wiley-Liss, Inc. [source] Induction of bone formation by transforming growth factor-,2 in the non-human primate Papio ursinus and its modulation by skeletal muscle responding stem cellsCELL PROLIFERATION, Issue 3 2010U. Ripamonti Objectives:, Four adult non-human primates Papio ursinus were used to study induction of bone formation by recombinant human transforming growth factor-,2 (hTGF-,2) together with muscle-derived stem cells. Materials and methods:, The hTGF-,2 was implanted in rectus abdominis muscles and in calvarial defects with and without addition of morcellized fragments of striated muscle, harvested from the rectus abdominis or temporalis muscles. Expression of osteogenic markers including osteogenic protein-1, bone morphogenetic protein-3 and type IV collagen mRNAs from generated specimens was examined by Northern blot analysis. Results:, Heterotopic intramuscular implantation of 5 and 25 ,g hTGF-,2 combined with 100 mg of insoluble collagenous bone matrix yielded large corticalized mineralized ossicles by day 30 with remodelling and induction of haematopoietic marrow by day 90. Addition of morcellized rectus abdominis muscle to calvarial implants enhanced induction of bone formation significantly by day 90. Conclusions:, In Papio ursinus, in marked contrast to rodents and lagomorphs, hTGF-,2 induced large corticalized and vascularized ossicles by day 30 after implantation into the rectus abdominis muscle. This striated muscle contains responding stem cells that enhance the bone induction cascade of hTGF-,2. Induction of bone formation by hTGF-,2 in the non-human primate Papio ursinus may occur as a result of expression of bone morphogenetic proteins on heterotopic implantation of hTGF-,2; the bone induction cascade initiated by mammalian TGF-, proteins in Papio ursinus needs to be re-evaluated for novel molecular therapeutics for induction of bone formation in clinical contexts. [source] | ||||||||||