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Int J Mol Med. 2002 Nov;10(5):613-7.
Lipid-mediated gene transfection of intercellular adhesion molecule-1 suppresses the peritoneal metastasis of gastric carcinoma.
Tanaka H, Yashiro M, Sunami T, Ohira M, Hirakawa-Y S Chung K.
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
We have previously reported that a decreased expression level of ICAM-1 in cancer cells frequently led to the development of lymph node metastasis, and suggested that ICAM-1 gene transfection may inhibit lymph node metastasis. In the present study, we investigated whether ICAM-1 gene therapy for the peritoneal metastasis of gastric carcinoma is useful as a new immuno-gene therapy. ICAM-1 gene was transfected into a gastric cancer cell line, OCUM-2MD3 (2MD3), which has a high metastatic ability to the peritoneum. A transfectant cancer cell line, 2MD3/ICAM-1, had high ICAM-1 expression on the cell surface. The adhesion and cytotoxicity abilities of peripheral blood mononuclear cells were significantly increased against 2MD3/ICAM-1 cells in comparison with 2MD3 cells. Mice inoculated with 2MD3/ICAM-1 cells in the peritoneal cavity had a significantly better survival rate than those inoculated with 2MD3 cells (log-rank test, p<0.05). Histologic findings revealed that more mononuclear cells existed around the metastatic nodules in 2MD3/ICAM-1. Although gastric carcinoma frequently causes peritoneal metastasis, no useful therapy for the metastasis of gastric carcinoma has been developed. These findings revealed that ICAM-1 gene transfection to cancer cells could be a useful immuno-gene therapy for the peritoneal metastasis of gastric carcinoma.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12373302&dopt=Abstract
J Math Biol. 2002 Sep;45(3):261-77.
Determination of hammerhead ribozyme kinetic constants at high molar ratio ribozyme-substrate.
Grassi G, Grassi M, Kuhn A, Kandolf R.
Department of Molecular Pathology, Institute for Pathology, University of Tubingen, Liebermeisterstrasse 8, D-72076, Tubingen, Germany. gegrassed.uni-tuebingen.de
Hammerhead ribozymes provide valuable tools in the field of gene therapy due to their cleavage specificity and the broad range of RNA targets. A major prerequisite for the selection of suitable ribozymes for in vivo application is represented by in vitro determination of ribozyme cleavage kinetic constants. From the experimental cleavage data, kinetic constants are usually calculated under the assumption of rapid conversion of the substrate into the ribozyme-substrate complex. However, this condition is often not satisfied for ribozymes carrying additional RNA stretches, due to cloning strategies or necessary for ribozyme expression in the cell. To overcome this problem, we propose a mathematical model which is able to calculate ribozyme kinetic constants in the case of non-rapid conversion of substrate into ribozyme-substrate complex. In addition, our system gives the opportunity to evaluate the nature of the S conversion into ES through the determination of a model parameter. The validity of the proposed model is restricted to the hypothesis of a ribozyme excess over the substrate at the beginning of the cleavage reaction and to the absence of any mass exchange with the external environment.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12373347&dopt=Abstract
Bull Med Ethics. 2001 Nov;(173):13-9.
What do patients, their relatives and medical staff know about genetic therapy?
Holm S, Jayson G.
Institute of Medicine, Law and Bioethics, Manchester University, UK. soren.holan.ac.uk
Objectives: To investigate the knowledge of, and attitudes towards gene therapy of cancer patients, their relatives, and the staff treating the patients. Design: Cross sectional questionnaire study. Subjects: a) One hundred patients with ovarian cancer either 1) in current treatment with chemotherapy, or 2) in follow up after chemotherapy. b) The relatives accompanying these patients to clinic. c) Fifty doctors and fifty nurses at the hospital in question. Main outcome measures: Knowledge about genes and gene therapy, attitudes toward gene therapy and its introduction in the NHS, willingness to accept additional side-effects for a given-therapeutic gain. Results: Patients and relatives have only limited knowledge about genes and gene therapy, but knowledge is also limited about how chemotherapy works. The attitude towards gene therapy is positive, and the worry about gene therapy being like 'playing God' is accepted by less than 10%. There is a strong belief that if gene therapy is effective it should be paid by the NHS (over 85% agree with this).
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12374184&dopt=Abstract
Biochem J. 2003 Jan 15;369(Pt 2):255-62.
Regulatable liver expression of the rabbit apolipoprotein B mRNA-editing enzyme catalytic polypeptide 1 (APOBEC-1) in mice lacking endogenous APOBEC-1 leads to aberrant hyperediting.
Hersberger M, Patarroyo-White S, Qian X, Arnold KS, Rohrer L, Balestra ME, Innerarity TL.
Gladstone Institute of Cardiovascular Disease, University of California, Building 40, Third Floor, P.O. Box 419100, 2550 23rd Street, San Francisco, CA 94141-9100, U.S.A. hmc.unizh.ch
Apolipoprotein (apo) B mRNA editing is the deamination of C(6666) to uridine, which results in translation of the apoB-48 protein instead of the genomically encoded apoB-100. ApoB-48-containing lipoproteins are cleared more rapidly from plasma and are less atherogenic than apoB-100-containing low-density lipoproteins (LDLs). In humans, the intestine predominantly produces apoB-48 whereas the liver secretes apoB-100 only. To evaluate a potential therapeutic use for liver-induced apoB mRNA editing in humans, we investigated the efficiency and safety of transgenic expression of apoB mRNA-editing enzyme catalytic polypeptide 1 (APOBEC-1) in the absence of endogenous editing in the mouse model. Here we show that regulatable tetO-mediated APOBEC-1 expression in the livers of gene-targeted mice lacking endogenous APOBEC-1 results in 30% apoB mRNA editing. In a time-course experiment, the expression of tetO-APOBEC-1 mRNA was suppressed within 2 days after mice were fed doxycycline and apoB mRNA editing and apoB-48 formation were suppressed within 4 days. However, tetO-APOBEC-1 expression resulted in regulatable aberrant hyperediting of several cytidines downstream of C(6666) in apoB mRNA and in novel APOBEC-1 target 1 (NAT1) mRNA. Several of the cytidines in apoB mRNA were hyperedited to a level similar to that of C(6666), although editing at C(6666) was lower than that in wild-type mice. These results demonstrate that even moderate APOBEC-1 expression can lead to hyperediting, limiting the single-gene approach for gene therapy with APOBEC-1.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12374571&dopt=Abstract
Beautiful, dense hair is a dream for many people.
Hair growth is a sophisticated biological process, which has not yet been understood.
A multitude of therapeutic measures, including drugs, surgery, and suppelements have been developed.
However, due to the diversity of the problems underlying hair loss, there is no single solution that
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Hair Million is an alternative solution to cope with hair loss problems.
Anecdotally, it shows prositive results and improvement especially for age-related hair thinning and hair loss
for a large group of people who take it as suggested. Although personal experiences and anecdotal evidences
indicate that it works, we still do not understand the mechanisms of action as to how Hair Million works to
help stop hair loss, and promote hair growth. There has been no clinical trials nor placebo controlled statistical
analysis on the efficacy of Hair Million on hair loss and hair growth. R & D costs dearly, and no one would
afford to research complex herbal ingredients, which are often not patentable at all because they are
made by mother nature.
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