Chemicals,viruses,irradiation,etc. Acquired mutations Inherited mutations" Simplified outline of the Altered gene expression genesis of cancer.The Proto-oncogenes Oncogenes Decreased expression of tumour sis,erbB,ras,myc,gene for cyclin D,etc suppressor genes:p53,Rb1,etc. genesis of cancer is usually multifactorial,involving more Other factors than one genetic change. Uncontrolled cell proliferation, Decreased apoptosis, 'Other factors',as specified dedifferentiation alterations in telomerase above,may involve the actions of promoters, Development of primary tumour cocarcinogens,hormones, etc.which,while not Production of metalloproteinases etc. themselves carcinogenic, increase the likelihood that genetic mutation(s)will Invasion of nearby tissue by tumour cells result in cancer. Angiogenesis Metastasis Development of secondary tumours Elsevier.Rang et al:Pharmacology 6e-www.studentconsult.com
Shanghai Jiao Tong University Simplified outline of the genesis of cancer. The genesis of cancer is usually multifactorial, involving more than one genetic change. 'Other factors', as specified above, may involve the actions of promoters, cocarcinogens, hormones, etc. which, while not themselves carcinogenic, increase the likelihood that genetic mutation(s) will result in cancer
上商充通大 alkylating agents(烷化剂) 后 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==T =C三G= C2G The effects of Bifunctional bifunctional alkylating agents alkylating agents can cause on DNA.Note the intrastrand linking T==A三 and cross-linking cross-linking of two C三三三G guanines.A, G:三三三C adenine;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
It all started by accident over 40 years ago in the laboratory of physicist-turned- 上浒克通大睾 biophysicist Barnett Rosenberg at 后 Shanghai Jiao Tong Uni 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 [Ptll (NH3)2C12],which went on to be cisplatin
Shanghai Jiao Tong University Discovery of cis-platinum 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)2Cl2], which went on to be cisplatin, and a platinum(IV) analogue, cis- diamminetetrachloroplatinum( IV)
上克通大睾 Discovery of cis-platinum Shanghai Jiao Tong University 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 [Ptll(NH3)2CI2],which went on to be cisplatin,and a platinum(IV)analogue,cis- diamminetetrachloroplatinum(IV)
Shanghai Jiao Tong University Discovery of cis-platinum ü 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. ü 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)2Cl2], which went on to be cisplatin, and a platinum(IV) analogue, cis- diamminetetrachloroplatinum( IV)