上游充通大学 Resistance to anticancer drugs Shanghai Jiao Tong University primary resistance Acquired resistance multidrug resistance,associated with increased expression of a normal gene (the MDR1 gene)for a cell surface glycoprotein (P-glycoprotein)involved in drug efflux
Shanghai Jiao Tong Unive R rsity esistance to anticancer drugs primary resistance Acquired resistance multidrug resistance, associated with increased expression of a normal gene (the MDR1 gene) for a cell surface glycoprotein (P-glycoprotein) involved in drug efflux
h 上游充通大￥ Anticancer drug toxicity 后 Shanghai Jiao Tong University inhibition and killing of normal tissues, eg.bone marrow,mucosa, reproductive cells,hair
Shanghai Jiao Tong University Anticancer drug toxicity inhibition and killing of normal tissues, eg. bone marrow, mucosa, reproductive cells, hair, …
上克通大睾 alkylating agents (烷化剂) Shanghai Jiao Tong University cyclophosphamide(环磷酰胺) mechlorethamine(氮芥)，melphalan(美法 仑)，chlorambucil(苯丁酸氮芥)，thiotepa (塞替哌)，busulfan（白消安) carmustine(卡莫司汀)，lomustine(洛莫司汀)， semustine(司莫司汀) Related platinum analogs:cisplatin, oxaliplatin Mechanism:alkylation of DNA within the nucleus represent the major interactions that lead to cell death
Shanghai Jiao Tong University alkylating agents （烷化剂） cyclophosphamide（环磷酰胺）, mechlorethamine（氮芥）, melphalan（美法 仑）, chlorambucil（苯丁酸氮芥），thiotepa （塞替哌），busulfan（白消安）， carmustine (卡莫司汀), lomustine (洛莫司汀), semustine（司莫司汀） Related platinum analogs: cisplatin, oxaliplatin Mechanism: alkylation of DNA within the nucleus represent the major interactions that lead to cell death
Sugar-phosphate backbone A=== The effects of bifunctional C三三G Bifunctional alkylating agents alkylating agents on DNA.Note the can cause intrastrand linking cross-linking of T-A and cross-linking two guanines. =CE三三三G A,adenine; G:三三C C,cytosine; G,guanine; T,thymine. 三三三三 Elsevier.Rang et al:Pharmacology 6e-www.studentconsult.com
Shanghai Jiao Tong University The effects of bifunctional alkylating agents on DNA. Note the cross-linking of two guanines. A, adenine; C, cytosine; G, guanine; T, thymine
上泽充通大学 Shanghai Jiao Tong Univer.... Discovery of cis-platinu It all started by accident over 40 years ago in the laboratory of physicist- turned-biophysicist Barnett Rosenberg at Michigan State University,East Lansing,United States.Rosenberg was interested in applying electromagnetic radiation to bacterial and mammalian cells to investigate whether electric or magnetic dipole fields might be involved in cell division. Inadvertently,in the early experiments using Escherichia coli,a set of platinum electrodes(considered to be inert)was included in the growth chamber.When the field was turned on,the bacteria appeared as very long filaments(300 times the usual length)rather than as the normal short rods. This effect was shown not to be due to the electric field but,rather,to electrolysis products arising from the platinum electrodes(TIMELINE) Detailed chemical analysis identified two active complexes-the neutral cis- isomer [PtII (NH3)2C12],which went on to be cisplatin,and a platinum(I analogue,cis-diamminetetrachloroplatinum(IV)
Discovery of cis-platinum It all started by accident over 40 years ago in the laboratory of physicistturned-biophysicist Barnett Rosenberg at Michigan State University, East Lansing, United States. Rosenberg was interested in applying electromagnetic radiation to bacterial and mammalian cells to investigate whether electric or magnetic dipole fields might be involved in cell division. Inadvertently, in the early experiments using Escherichia coli, a set of platinum electrodes (considered to be inert) was included in the growth chamber. When the field was turned on, the bacteria appeared as very long filaments (300 times the usual length) rather than as the normal short rods. This effect was shown not to be due to the electric field but, rather, to electrolysis products arising from the platinum electrodes (TIMELINE). Detailed chemical analysis identified two active complexes — the neutral cisisomer [PtII (NH3)2Cl2], which went on to be cisplatin, and a platinum(IV) analogue, cis-diamminetetrachloroplatinum( IV)