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Discovery Medicine / No 017


High-Dose Chemotherapy Combined with Stem Cell Transplantation in the Treatment of Breast Cancer

New studies published recently cast doubts on the effectiveness of high-dose chemotherapy plus bone marrow stem cell transplantation for the treatment of breast cancer.

Women with primary breast cancer and local lymph node metastasis have a poor prognosis. Even with the aggressive treatments involving surgical removal of the tumors and post-operative (adjuvant) chemotherapies, only 20 to 30 percent of these patients are likely to survive for five years or longer. Doctors and researchers are actively searching for better treatment methods. In the early 1980s, interest in using bone marrow hematopoietic stem cell transplantation bone marrow or well defined stem cells was ... Read more

PEG-Modified Liposome for Efficient Drug Delivery

Benefiting from the recent advances in biotechnology, polypeptides (peptides and proteins) contribute to about a third of drug candidates currently in clinical trials. In the US market alone, there are over 80 polypeptide drugs currently marketed, and 350 more are under different stages of clinical studies.

The limitations of polypeptide drugs include destruction by proteolysis, short circulation half-life (partly as a consequence of rapid clearance by the kidneys), short shelf life, low solubility, and induction of immunity. Among the methods developed to overcome the above weaknesses of polypeptide drugs, polyethylene glycol (PEG)-modification or pegylation holds significant benefit. The PEG coat prevents ... Read more

Tolerance and Autoimmunity: An Intricate Balance Orchestrated by Co-stimulatory Factors

The immune system is a complex network evolutionarily designed to combat infection, cancer and other systems deemed dangerous to the host. The strategic focus of immunity is to prolong survival of the host. Two alternative hypotheses have been proposed to account for activation of the primary immune response. The first is based on the ability of the host to identify self from non-self tissues. The alternative hypothesis suggests that the host’s ability to distinguish danger from non-danger (Matzinger 1994) is responsible. The distinction of self from non-self has been the focus of intense debate. However, it is clear that the ... Read more

In Vivo Imaging Tools Push Frontiers of Medical Discoveries

In medical sciences, an ever-lasting challenge is to visualize what is happening inside a living being without causing more procedural damages. Technical advances in medical radiology have revolutionized both the health care practice and basic research; computed tomography (CT) scanning, positron-emission tomography (PET), and functional magnetic resonance imaging (fMRI), just to name a familiar few.

The desire to “see through” skin keeps driving scientists and engineers to innovate on new technologies to allow us to see more with better resolution and clarity. For instance, a particular organ, tissue or cell needs to be monitored in the living animal for studying their ... Read more

Water-in-Oil Microemulsion: Single DNA Molecule Detection by PCR

Detection of a single DNA molecule is useful for genetic studies and diagnosis. There are a number of technologies that were devised to meet this challenge. These technologies such as fluorescence resonance energy transfer (FRET), evanescent wave scattering, nanoparticle composite, surface plasmon resonance, fiber-optics arrays, conductivity/capacitance measurements, and molecular beacons have increasingly gained depth in their sophistication and height in cost. Occasionally a simple idea proves uplifting and powerful in solving a particular problem. Water-in-oil emulsion for polymerase chain reaction is one such idea.

Polymerase chain reaction is capable of amplifying a single copy of a DNA molecule into millions and ... Read more

Specificity of RNA Interference: Prerequisite for Gene Research and Therapeutics

In the last few years, there have been dramatic advances in research and therapeutic developments for RNA interference (RNAi) since the discovery of silencing of transgenes in plants and interference of gene expression by double-stranded RNA in the worm C. elegans. Based on the recent flourish of research activities, an ever-growing number of companies are formed to explore the therapeutic potentials of RNA interference.

RNAi holds promise both in gene function studies and targeted gene therapy. For RNAi to have any of these utilities, it needs to suppress its target in a very specific way and it does not affect surrounding genes or ... Read more

Drug Profile: Advate

Other Names: Antihemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM).

Maker: Baxter International, Inc.

Disease Treated: Hemophilia A (classical hemophilia).

Approval Status: Approved by the U.S. FDA on July 25, 2003.

Chemical/Biological Nature: ADVATE is the molecularly engineered human Factor VIII glycoprotein consisting of 2,332 amino acids. It is produced by genetically engineered Chinese hamster ovary cells without the presence of any human or animal components in the cells or in the culture medium, in order to eliminate the chances that viruses or viral DNA could have been carried with the human or animal additives. The purification process has a viral inactivation solvent-detergent treatment step that ... Read more

Drug Profile: Emtriva

Other Names: emtricitabine.

Maker: Gilead Sciences, Inc.

Disease Treated: HIV-1 infection in adults.

Approval Status: Approved by the U.S. FDA on July 2, 2003.

Chemical/Biological Nature: EMTRIVA is a synthetic cytosine analogue. It is the (-) enantiomer of a thio analogue of cytidine. It has a fluorine in the 5-position, distinguishing it from other cytidine analogues. It has a molecular weight of 247.24 daltons.

Administration: 200 mg of EMTRIVA (one capsule) is taken orally with or without food.

Mechanism of Disease: HIV-1 infection leads to AIDS and other immunodeficiency related complications.

Mechanism of Drug Action: EMTRIVA is a nucleoside analogue reverse transcriptase inhibitor (NRTI). Following ... Read more

Drug Profile: UroXatral

Other Names: alfuzosin HCl, Xatral.

Maker: Sanofi-Synthelabo, France.

Disease Treated: Benign prostatic hyperplasia (BPH), also known as benign prostatic enlargement (BPE).

Approval Status: Approved for marketing by the U.S. FDA on June 16, 2003. Alfuzosin was approved for marketing in more than 80 countries throughout Europe, Latin America, Africa and Asia. Outside U.S., the once-daily formulation is marketed as XATRAL OD, which is currently available for prescription in 14 countries in Europe and in more than 35 other countries. Sanofi-Synthelabo claimed that it has 15 years of clinical experience in marketing the drug, with approximately 1.35 billion days of treatment (3.7 million patient ... Read more

Drug Profile: Xolair

Other Names: omalizumab, rhuMAb-E25, monoclonal antibody E25.

Maker: Genentech, Roche, and Tanox.

Disease Treated: Moderate to severe persistent asthma in patients (12 years of age and above) who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled by inhaled corticosteroids.

Approval Status: Approved by the U.S. FDA on June 20, 2003.

Chemical/Biological Nature: Xolair is a humanized monoclonal antibody (IgG1k) that binds specifically to human immunoglobulin E (IgE). It is produced by recombinant DNA technology in Chinese hamster ovary cells.

Administration: 150-375 mg of Xolair is given by subcutaneous injection once every 2 or 4 ... Read more

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