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Molecular Therapy
== Localized Molecular Therapy ==
Localized Molecular Therapy (MT) is the cellular modifications at the molecular level. Take the chemotherapy in oncology for example, it aims to kill the cell by delivering toxic agents to the cell, while MT could aim to terminate the cellular division without necessarily killing the cell, such as aiming to reach senescence whose therapeutic procedure, levels of toxic agents, and tools for delivering the toxicity could all be very different from simply killing the cell.
An example of the senescence therapy could be the delivering of 77BrdC to a Herpes specific gene responsible for certain cancer transformation. Helson and Wang applied the radioactive bromide compound that has a K-capture decay mode leading to a mega Gray (Gy) dose with Auger electrons in Situ () at the DNA level that terminates the cellular division and drives the cell into a state of senescence. But the mega Gy dose is limited to a dimension of a few nanometers so that while it modifies both of the DNA duplexes, it does not interrupt other cellular apparatus sufficiently to kill the cell. This in Vitro work was carried out at Sloan- Kettering Cancer Center in the 1970s, and the work was not published as it was meant to be the beginning program of an extensive clinical trial. The Auger dose in mega Gy can be found in Wikipedia under Auger Therapy ().
Using 77BrdC to exclusively inhibit the Herpes specific DNA material, its in Situ mega Gy delivered by the localized low energy Auger electrons with an ionizing range of a few nanometers in water could modify both of the DNA duplexes and terminate cellular division. Phosphide sugar or the BrdC, however, could be separated and deleted by liver enzymes in Vivo to result with the loss of the specific uptake by the Herpes gene exclusively. While “nuclear chemotherapy” using radioactive material for chemo agent, as Lewis Thomas named such an approach, it suffers from the liver interference in Vivo. As a result, a similar in Situ dose has been designed by using an external X-ray beam, the monochromatic Nano Ray X-rays to bypass the liver interference in drug delivery (), and thus the development of the “NanoRay” X-ray tool that could be used to induce the mega Gy Auger dose without using radioactive elements. The external monochromatic X-ray photons are beamed to resonantly react with strategically placed target atoms such as the platinum of cisplatin attaching to the major groves of the DNA adducts, and they could be induced to initiate the mega Gy dose in Situ to modify both of the DNA duplexes and terminate cellular division without necessarily killing the cells. This senescence approach implies a dramatic reduction in systemic chemo toxicity as well as dose reduction in the externally placed ionizing beam radiation. This approach allows the procedure to be applied repeatedly to deliver the localized termination of cellular divisions and the procedure with minimal side effects could be addressed as often as necessary.
We shall use cisplatin, the chemo agent () as a case in point to illustrate the power of this method. Cis (on the same side)-platin has two amino ligands on one side and two chloride ligands on the other side with Pt being centered in the plano molecule, whose Cl-bonds would leave Pt ion upon entering the cytoplasm as the leaving group because of the reduced NaCl concentration and thus the reduced Chloride ionic pressure to form the “leaving group”. The bonds for chloride would be replaced by the aqua bonds which would bind to two purine bases, with Guanine favored over Adenine in the major groves of DNA adducts. The presence of cisplatin would bend the DNA duplexes by 95o and thus the toxicity to DNA, although it is not sufficiently toxic to all cancers such as breast, prostate and colon. With similar leaving groups, transplatin, carboplatin etc. could deliver similar Auger dose under the beam to tumor cells with much reduced chemo side effects to normal tissues beyond the coverage of the beamed radiation. Trans (cross)-platin, for example, would have much reduced cytotoxicity. By inducing the platinum atoms to initiate the soft Auger electrons in Situ, regardless cis or trans or carbo, the platinum could deliver the cellular modification for senescence at the molecular level and such a procedure forms a novel mode of cancer therapy whose side effects could be dramatically reduced. Using certain simple monochromatic X-ray equipment to initiate the mega Gy of soft Auger electrons in Situ will be explained in Section 2 below.
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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