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Gene Ther. 2002 Oct;9(19):1326-32.
Human foamy virus integrase fails to catalyse the integration of a circular DNA molecule containing an LTR junction sequence.
Russell RA, Critchley R, Vassaux G, McClure MO.
Jefferiss Research Trust Laboratories, Wright-Fleming Institute, Imperial College School of Medicine at St Mary's Hospital, Norfolk Place, London W2 1PG, UK.
The presence of closed circular forms of the linear DNA genome of human foamy virus (HFV) has not been established. The ability of the HFV integrase (IN) to catalyse the integration of these circular forms (termed 2 long terminal repeat (LTR) circles) was investigated, with a view to producing a novel hybrid vector. To this end, a construct was made containing, in addition to the enhanced green fluorescent protein (eGFP) marker gene, the last 27 bp of the 3' U5 LTR region of HFV fused to the first 28 bp of the 5' U3 LTR, the latter representing a 2LTR circle. Marker gene expression following transfection of both 293 and 293T cells indicated that the level of integration was not significantly increased by the HFV IN. Moreover, correctly integrated provirus-like forms of the input plasmid could not be detected by PCR. Taken together, these results show that the HFV IN is not able to integrate a circular molecule containing an LTR junction and, hence, the technique is not exploitable as a tool to produce hybrid vectors for gene therapy.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12224016&dopt=Abstract
Gene Ther. 2002 Oct;9(19):1333-7.
Viral and non-viral gene therapy partially prevents experimental cisplatin-induced neuropathy.
Pradat PF, Kennel P, Naimi-Sadaoui S, Finiels F, Scherman D, Orsini C, Delaere P, Mallet J, Revah F.
Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus Neurodegeneratifs (LGN), UMR C9923, Centre National de la Recherche Scientifique, Hopital de la Pitie-Salpetriere, Paris, France.
Sensory neuropathies are a frequent and dose-limiting complication resulting from treatment with cisplatin. Neurotrophin-3 (NT-3) promotes the survival of the large fiber sensory neurones that are impaired in cisplatin-induced neuropathy, and may therefore serve as a preventive agent. However, the short half-life of recombinant NT-3 after systemic administration limits its clinical applications. We compared two muscle-based gene transfer strategies for the continuous delivery of NT-3 to the bloodstream in an experimental model of cisplatin-induced neuropathy. Electrophysiological studies showed that the intramuscular injection of an adenovirus encoding NT-3 partially prevented the cisplatin-induced increase in sensory distal latencies. Similar effects were observed in cisplatin-treated mice that received intramuscular injections of a plasmid encoding NT-3 associated with in vivo electroporation. The two techniques were well tolerated and induced only slight muscle toxicity. Measurement of renal function, weight and survival showed that neither technique increased the toxicity of cisplatin. Our study shows that gene therapy, using either a viral or a non-viral vector, is a promising strategy for the prevention of cisplatin-induced neuropathy.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12224017&dopt=Abstract
Cancer Gene Ther. 2002 Oct;9(10):807-12.
p53 alone or in combination with antisense cyclin D1 induces apoptosis and reduces tumor size in human melanoma.
Sauter ER, Takemoto R, Litwin S, Herlyn M.
Tumor Biology Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA. edward.sauteail.tju.edu
Melanoma incidence is growing at a faster rate than any other human malignancy. Wild-type (wt) p53 is important in both G(1) and G(2) cell cycle arrest, and cyclin D1 (CD1) is necessary for G(1)-->S progression in melanoma cells. We reported that an adenoviral vector containing wt p53 significantly reduced [(3)H]thymidine uptake in melanoma cells containing mutant but not wt p53. Subsequently we showed that CD1 decreased melanoma proliferation and increased apoptosis. We now extend these findings by evaluating the effect on preformed melanomas of (1) intratumoral therapy with wt p53 alone, (2) wt p53 in combination with antisense (AS) CD1, both short (< or =14 days) and longer term, and (3) doubling the dose or repeat doses of wt p53 or AS CD1. Two melanoma cells lines that metastasize in SCID mice (451 and 1205) were used, one containing a p53 mutation (451) and the other a normal p53 gene sequence (1205). Compared to injection with a control adenoviral vector containing beta-galactosidase (LacZ), intratumoral injection of wt p53 slowed the growth of tumors formed from 451 cells. Using 5 x 10(8) plaque forming units as our standard intratumoral dose, neither doubling the dose of LacZ, p53 or AS CD1, nor repeat doses of the vectors, was as effective as combined therapy with wt p53+AS CD1, which resulted in the shrinkage of all tumors treated and 4/7 (57%) tumors vanished. No tumors treated with wt p53 or AS CD1 alone vanished. Wt p53+AS CD1 treatment resulted in significantly more cells undergoing apoptosis compared to either therapy alone. In summary, combining the separately effective treatment vectors p53 and AS CD1 led to an enhanced growth-suppressive and apoptotic effect, supporting a role for combination gene therapy to treat human malignant melanoma.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12224020&dopt=Abstract
Cancer Gene Ther. 2002 Oct;9(10):819-24.
Adenovirus-mediated combined P16 gene and GM-CSF gene therapy for the treatment of established tumor and induction of antitumor immunity.
Wang L, Qi X, Sun Y, Liang L, Ju D.
The Department of Urology, Changhai Hospital, The Second Military Medical University, Shanghai, China. wlhunline.sh.cn
Antitumor effects of combined transfer of P16 and cytokine genes were investigated in this study. The adenovirus harboring the P16 gene (AdP16) and murine granulocyte-macrophage colony-stimulating factor gene (AdGM-CSF) were utilized for the treatment of established tumors. The mice were inoculated subcutaneously with Renca cells and, 6 days later, received an intratumoral injection of AdP16 in the presence or absence of AdGM-CSF. The results demonstrated that tumor-bearing mice treated with AdP16 in combination with AdGM-CSF showed more potent inhibition of tumor growth and survived much longer than did mice treated with AdP16, AdGM-CSF, adenovirus expressing beta-galactosidase, or phosphate-buffered saline alone (P<.01). The tumor mass showed obvious necrosis and inflammatory cell infiltration, and more CD(4)(+) and CD(8)(+) T cells infiltrating the tumor after combined therapy. After combined therapy, the expression of MHC-1 (H-2K(d)) and Fas molecules on freshly isolated tumor cells increased greatly. The activity of specific cytotoxic T lymphocytes was also found to be induced more significantly after the combined therapy (P<.01). Our results demonstrated that combined therapy with P16 and GM-CSF genes can inhibit the growth of established tumors in mice significantly and induce antitumor immunity of the host efficiently.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12224022&dopt=Abstract
Vitamins, amino acids, oils for topical application, and prescription medications...
There are a number of approaches to hair loss problems.
Hair Million is an herbal alternative. It is a formula made of traditional, edible herbs
and has been anecdotally demonstrated the efficacy to ward off hair loss
problems.
There is no singular medical or alternative cure for hair loss since the
biology of hair growth is a highly complicated phenomenon.
It is unknown how Hair Million stops hair loss,
The advantages of Hair Million over other approaches are, firstly, Hair Million is comparatively inexpensive,
and secondly, it is made only of traditionally used safe and healthy herbs that promote hair growth
according to Chinese pharmacopoeia. In addition, Hair Million is cardiotonic, meaning that Hair Million consists of herbs
that strengthens your heart, according to Chinese medicine. There is an interesting research paper which correlates baldness
to heart diseases: people with alopecia or hair loss
problems are significantly more likely to develop heart attacks.
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