HISTORY OF CANCER CHEMOTHERAPY MAJID MOHIUDDIN
HISTORY OF CANCER CHEMOTHERAPY <ul><li>Refers to the use of medication and drugs for treatment of Cancer. </li></ul><ul><l...
SULFUR MUSTARD <ul><li>Mustard gas (cytotoxic, Vesicant Chemical warfare agents – Large blisters) </li></ul><ul><li>Pure f...
<ul><li>Sulfur Mustards are variations of “Mustard Gas”  (Bis(2-Chloroethyl)sulfide). </li></ul><ul><li>SCL 2  + 2 C 2 H 4...
 
<ul><li>Properties </li></ul><ul><li>Molecular formula =C4H8Cl2S </li></ul><ul><li>Molar mass 159 g/mol </li></ul><ul><li>...
<ul><li>Several varieties and mixtures of sulfur mustard have been employed. Some of those varieties are listed below: </l...
<ul><li>The complete list of effective sulfur mustard agents commonly stock-piled is as follows: </li></ul><ul><li>1,2-Bis...
<ul><li>Physiological effects of Mustard gas: </li></ul><ul><li>Strong vesicant (blister-causing agent)-alkylating propert...
 
 
<ul><li>HISTORY: </li></ul><ul><li>Developed as early as 1822 by M.Depretz (1798 – 1863). </li></ul><ul><li>described the ...
ALBERT NIEMANN <ul><li>Born  =  May 20, 1834   Goslar, Germany </li></ul><ul><li>Died  =  January 19, 1861    (aged 26)   ...
Friedrich Wöhler   <ul><li>Born  =  31 July 1800) Eschersheim,  Frankfurt am Main,  Germany </li></ul><ul><li>Died  =  23 ...
VIKTOR MEYER <ul><li>Born  =  September 8, 1848   Berlin, Germany </li></ul><ul><li>Died  =  August 8, 1897 (aged 48)   He...
Hans T. Clarke 1887—1972 <ul><li>1913 </li></ul><ul><li>English Chemist  </li></ul><ul><li>Replaced Phosphorus trichloride...
<ul><li>Mustard gas was first used effectively in World War I by the German army against British soldiers near Ypres in Ju...
<ul><li>The Hindenburg Line (also known as the  Siegfried Line ) was a vast system of defenses in northeastern France duri...
<ul><li>Mustard gas was dispersed as an aerosol in a mixture with other chemicals. </li></ul><ul><li>That gave yellow-brow...
<ul><li>Counter measures   against the gas were relatively   ineffective,  since  a soldier wearing a   gas mask  was  not...
<ul><li>mustard gas was a persistent agent  </li></ul><ul><li>remain in the environment for days and can cause sickness. <...
<ul><li>Since Then, Mustard gas reportedly been used in several wars: </li></ul>
<ul><li>United Kingdom against the Red Army in 1919 </li></ul><ul><li>Spain against Rif insurgents in Morocco in 1921-1927...
<ul><li>Soviet Union in Xinjiang,  China  against  Japan  in 1934 and 1936-1937 </li></ul><ul><li>Italy  against  Abyssini...
<ul><li>Germany against Poland and the Soviet Union in a few erroneous uses during the Second World War </li></ul>
<ul><li>Japan against China in 1937-1945  </li></ul>
<ul><li>Egypt against North Yemen in 1963-1967 </li></ul>
<ul><li>Iraq against Iran in 1983-1988 </li></ul>
<ul><li>Possibly Sudan against insurgents in the civil war, in 1995 and 1997  </li></ul>
<ul><li>Possibly Sudan against insurgents in the civil war, in 1995 and 1997  </li></ul>
<ul><li>In 1943, a U.S. Stock pile was bombed in Bari, Italy, accidentally exposing thousands of civilians and 628 Allied ...
<ul><li>White cell counts decreased  </li></ul><ul><li>Mustard gas was investigated as therapy for Hodgkin’s lymphoma. </l...
<ul><li>The Use of poison gas, including mustard gas, during warfare, a practice known was chemical warfare, was prohibite...
 
 
<ul><li>Most of the Mustard gas found in Germany after World War II was dumped into the Baltic Sea. Between 1966 and 2002....
<ul><li>Fishermen have found around 700 chemical weapons outside Bornholm, most of which were mustard gas bombs. </li></ul>
<ul><li>When Mustard gas is exposed to seawater, it forms a tar-like gel and maintains its lethality for at least five yea...
<ul><li>In 1972, the United States Congress banned the practice of disposing Chemical weapons into the Ocean. </li></ul>
<ul><li>However, 64 million pounds of nerve and mustard gas agents had already been dumped into the Ocean waters off the U...
<ul><li>According to a 1998 report created by William Brankowitz, a deputy project manager in the U.S. army Chemical Mater...
 
<ul><li>GOOD BYE </li></ul>MAJID MOHIUDDIN
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HISTORY OF CANCER CHEMOTHERAPY

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HISTORY OF CANCER CHEMOTHERAPY

  1. 1. HISTORY OF CANCER CHEMOTHERAPY MAJID MOHIUDDIN
  2. 2. HISTORY OF CANCER CHEMOTHERAPY <ul><li>Refers to the use of medication and drugs for treatment of Cancer. </li></ul><ul><li>Soldiers were exposed to chemical warfare. </li></ul><ul><li>Sulfur Mustard lowered their White blood cells (Lymphocytes). </li></ul><ul><li>Nitrogen Mustard – Less toxic agent- used in patients with Lymphoid Leukemia and then in Lymphomas. </li></ul><ul><li>Using for treatment of Hodgkin’s Disease. </li></ul><ul><li>Can we cure cancer more successfully? Can we cure more patients? </li></ul>
  3. 3. SULFUR MUSTARD <ul><li>Mustard gas (cytotoxic, Vesicant Chemical warfare agents – Large blisters) </li></ul><ul><li>Pure for of sulfur mustards are colorless, odorless, viscous liquids at R/T. </li></ul><ul><li>For War – Yellow-brown, odor mustard plants, garlic or horseradish. </li></ul>
  4. 4. <ul><li>Sulfur Mustards are variations of “Mustard Gas” (Bis(2-Chloroethyl)sulfide). </li></ul><ul><li>SCL 2 + 2 C 2 H 4 (CLCH 2 CH 2 ) 2 S </li></ul><ul><li>Sulfur dichloride + Ethylene Bis (2-Chloroethyl) sulfide </li></ul><ul><ul><li>Names: </li></ul></ul><ul><ul><ul><li>HD </li></ul></ul></ul><ul><ul><ul><li>Senfgas, </li></ul></ul></ul><ul><ul><ul><li>Sulfur mustard, </li></ul></ul></ul><ul><ul><ul><li>Blister gas </li></ul></ul></ul><ul><ul><ul><li>S-lost </li></ul></ul></ul><ul><ul><ul><li>Lost </li></ul></ul></ul><ul><ul><ul><li>Kampfstoff LOST </li></ul></ul></ul><ul><ul><ul><li>Yellow cross liquid </li></ul></ul></ul><ul><ul><ul><li>Yperite. </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Lommel and Steinkoff – react thiodiglycol with hydrochloric acid – at German company Bayer AG for war. </li></ul></ul></ul></ul></ul>
  5. 6. <ul><li>Properties </li></ul><ul><li>Molecular formula =C4H8Cl2S </li></ul><ul><li>Molar mass 159 g/mol </li></ul><ul><li>AppearanceColorless if pure. Normally ranges from pale yellow to dark brown. Slight garlic or horseradish type odor </li></ul><ul><li>[1] Density 1.27 g/ml, liquid </li></ul><ul><li>Melting point 14.4 °C </li></ul><ul><li>Boiling point 217 °C (decomposes) </li></ul><ul><li>Solubility in water = Negligible </li></ul>
  6. 7. <ul><li>Several varieties and mixtures of sulfur mustard have been employed. Some of those varieties are listed below: </li></ul><ul><li>H  – Also known as HS (&quot;Hun Stuff&quot;) or Levinstein mustard . - dry ethylene + sulfur monochloride = HS under controlled conditions. Undistilled sulfur mustard contains 20–30% impurities,- cannot stored. </li></ul><ul><li>HD  – Codenamed Pyro by the British, and Distilled Mustard by the US. Distilled sulfur mustard (bis(2-chloroethyl) sulfide); approximately 96% pure. The term &quot;mustard gas&quot; usually refers to this variety of sulfur mustard . </li></ul><ul><li> thiodiglycol + hydrochloric acid = HD </li></ul><ul><li>HT  – Codenamed Runcol by the British, and Mustard T- mixture by the US. A mixture of 60% sulfur mustard (HD) and 40% T (bis[2-(2-chloroethylthio)ethyl] ether). </li></ul><ul><li>HL  – A blend of distilled mustard (HD) and Lewisite (L)- antifreeze. </li></ul><ul><li>HQ  – A blend of distilled mustard (HD) and sesquimustard (Q) (Gates and Moore 1946). </li></ul>
  7. 8. <ul><li>The complete list of effective sulfur mustard agents commonly stock-piled is as follows: </li></ul><ul><li>1,2-Bis(2-chloroethylthio) ethane </li></ul><ul><li> (aka Sesquimustard; Q) </li></ul><ul><li>1,3-Bis(2-chloroethylthio)-n-propane </li></ul><ul><li>1,4-Bis(2-chloroethylthio)-n-butane </li></ul><ul><li>1,5-Bis(2-chloroethylthio)-n-pentane </li></ul><ul><li>2-Chloroethylchloromethylsulfide </li></ul><ul><li>Bis(2-chloroethyl) sulfide (HD) </li></ul><ul><li>Bis(2-chloroethylthio) methane </li></ul><ul><li>Bis(2-chloroethylthiomethyl) ether </li></ul><ul><li>Bis(2-chloroethylthioethyl) ether (O Mustard) </li></ul>
  8. 9. <ul><li>Physiological effects of Mustard gas: </li></ul><ul><li>Strong vesicant (blister-causing agent)-alkylating properties. </li></ul><ul><li>Strongly mutagenic </li></ul><ul><li>Carcinogenic </li></ul><ul><li>Takes 4 to 24hrs – deep, itching or burning blister – on Skin </li></ul><ul><li>If Eyes – sore and the eyelids swollen, conjunctivitis and blindness. </li></ul><ul><li>Very high conc. Inhaled- bleeding and blistering within the respiratory system, damage mucous membrane and cause pulmonary edema. </li></ul><ul><li>50% body surface exposure is fatal. </li></ul><ul><li>(povidone iodine in a base of glycofurol is rapidly applied – reduces damage) </li></ul><ul><li>Oxidation or chlorination: household bleach (sodium hypochlorite) or decontamination solution “DS2” (2% NaOH, 70% diethylenetriamine, 28% ehtylene glycol monomethyl ether) can be used for neutralize. </li></ul>
  9. 12. <ul><li>HISTORY: </li></ul><ul><li>Developed as early as 1822 by M.Depretz (1798 – 1863). </li></ul><ul><li>described the reaction of Sulfur dichlorde and ethene – irritating properties not mentioned. </li></ul><ul><li>In 1854, French Chemist Alfred Riche (1829-1908)- repeated the procedure but not describe adverse physiological properties. </li></ul>
  10. 13. ALBERT NIEMANN <ul><li>Born = May 20, 1834 Goslar, Germany </li></ul><ul><li>Died = January 19, 1861 (aged 26) Goslar, Germany </li></ul><ul><li>Residence = Germany </li></ul><ul><li>Nationality = German </li></ul><ul><li>Fields = Chemist </li></ul><ul><li>Alma mater = University of Göttingen </li></ul><ul><li>Doctoral advisor = Friedrich Wöhler </li></ul><ul><li>Known for Isolating cocaine from coca leaves </li></ul><ul><li>REPEATED THE REACTION BUT THIS TIME BLISTER FORMING PROPERTIES WERE RECORDED. </li></ul>
  11. 14. Friedrich Wöhler <ul><li>Born = 31 July 1800) Eschersheim, Frankfurt am Main, Germany </li></ul><ul><li>Died = 23 September 1882 (aged 82) Göttingen, Germany </li></ul><ul><li>Residence = Germany </li></ul><ul><li>Fields = organic chemistry biochemistry </li></ul><ul><li>Institutions = Polytechnic School in Berlin,Polytechnic School at Kassel, University of Göttingen. </li></ul><ul><li>Known for Wöhler synthesis of urea. </li></ul><ul><li>IN 1860 He also noted its irritating properties of Mustard gas. </li></ul>
  12. 15. VIKTOR MEYER <ul><li>Born = September 8, 1848 Berlin, Germany </li></ul><ul><li>Died = August 8, 1897 (aged 48) Heidelberg, Germany </li></ul><ul><li>Residence = Germany, Switzerland </li></ul><ul><li>Nationality = German </li></ul><ul><li>Institutions = Polytechnikum of Stuttgart, Polytechnikum of Zurich, University of Heidelberg, University of Göttingen </li></ul><ul><li>In 1886, he published a paper describing a synthesis which produced good yields. </li></ul><ul><li>2-chloroethanol + aqueous potassium sulfide and treated the resulting thiodiglycol with phosphorus trichloride. </li></ul><ul><li>Higher purity and adverse health effects and severe. </li></ul><ul><li>Tested on Assistant – mental illness and Rabbits – consequently died. </li></ul>
  13. 16. Hans T. Clarke 1887—1972 <ul><li>1913 </li></ul><ul><li>English Chemist </li></ul><ul><li>Replaced Phosphorus trichloride by hydrochloric acid </li></ul><ul><li>2-chloroethanol + aqueous potassium sulfide and treated the resulting thiodiglycol with HCL. While working with Emil Fisher. </li></ul><ul><li>He hospitalized for 2 months for burns after a flask broke. </li></ul>German Chemical Society set Germany on Chemical Weapon track. after this incident. Meyer-Clarke Method
  14. 17. <ul><li>Mustard gas was first used effectively in World War I by the German army against British soldiers near Ypres in July 1917. </li></ul><ul><li>Later also against the French Second Army. </li></ul><ul><li>The name Yperite comes from its usage by the German army near the city of Ypres . </li></ul><ul><li>The Allies did not use mustard until November 1917 at Cambrai, after they captured a large stock of German mustard-filled shells. </li></ul><ul><li>It took the British over a year to develop their own mustard gas weapon (their only option was the Despretz–Niemann–Guthrie process), first using it in September 1918 during the breaking of the Hindenburg Line . </li></ul>
  15. 18. <ul><li>The Hindenburg Line (also known as the Siegfried Line ) was a vast system of defenses in northeastern France during World War I. It was constructed by the Germans during the winter of 1916–17. The line stretched from Lens to beyond Verdun . </li></ul>
  16. 19. <ul><li>Mustard gas was dispersed as an aerosol in a mixture with other chemicals. </li></ul><ul><li>That gave yellow-brown color and a distinctive odor. </li></ul><ul><li>Mustard gas has also been dispersed in such munitions as aerial bombs, land mines, mortar rounds, artillery shells , and rockets. </li></ul><ul><li>Mustard gas was lethal in only about 1% of cases. </li></ul>
  17. 20. <ul><li>Counter measures against the gas were relatively ineffective, since a soldier wearing a gas mask was not protected against absorbing it through the skin. </li></ul>
  18. 21. <ul><li>mustard gas was a persistent agent </li></ul><ul><li>remain in the environment for days and can cause sickness. </li></ul><ul><li>If mustard gas contaminated a soldier's clothing and equipment, then other soldiers he came into contact with would also be poisoned. </li></ul><ul><li>Towards the end of the war it was even used in high concentrations as an area-denial weapon, which often forced soldiers to abandon heavily contaminated positions. </li></ul>
  19. 22. <ul><li>Since Then, Mustard gas reportedly been used in several wars: </li></ul>
  20. 23. <ul><li>United Kingdom against the Red Army in 1919 </li></ul><ul><li>Spain against Rif insurgents in Morocco in 1921-1927 </li></ul><ul><li>Italy in Libya in 1930 </li></ul>
  21. 24. <ul><li>Soviet Union in Xinjiang, China against Japan in 1934 and 1936-1937 </li></ul><ul><li>Italy against Abyssinia (now Ethiopia) from 1935 to 1940 </li></ul><ul><li>Poland against Germany in 1939 during an isolated incident, British product </li></ul>
  22. 25. <ul><li>Germany against Poland and the Soviet Union in a few erroneous uses during the Second World War </li></ul>
  23. 26. <ul><li>Japan against China in 1937-1945 </li></ul>
  24. 27. <ul><li>Egypt against North Yemen in 1963-1967 </li></ul>
  25. 28. <ul><li>Iraq against Iran in 1983-1988 </li></ul>
  26. 29. <ul><li>Possibly Sudan against insurgents in the civil war, in 1995 and 1997 </li></ul>
  27. 30. <ul><li>Possibly Sudan against insurgents in the civil war, in 1995 and 1997 </li></ul>
  28. 31. <ul><li>In 1943, a U.S. Stock pile was bombed in Bari, Italy, accidentally exposing thousands of civilians and 628 Allied Troops. </li></ul>
  29. 32. <ul><li>White cell counts decreased </li></ul><ul><li>Mustard gas was investigated as therapy for Hodgkin’s lymphoma. </li></ul>
  30. 33. <ul><li>The Use of poison gas, including mustard gas, during warfare, a practice known was chemical warfare, was prohibited by THE GENEVA PROTOCOL OF 1925. </li></ul><ul><li>The subsequent Chemical Weapons Convention of 1993, which also prohibits the development, production and stockpiling of such weapons. </li></ul>
  31. 36. <ul><li>Most of the Mustard gas found in Germany after World War II was dumped into the Baltic Sea. Between 1966 and 2002. </li></ul>
  32. 37. <ul><li>Fishermen have found around 700 chemical weapons outside Bornholm, most of which were mustard gas bombs. </li></ul>
  33. 38. <ul><li>When Mustard gas is exposed to seawater, it forms a tar-like gel and maintains its lethality for at least five years. </li></ul>
  34. 39. <ul><li>In 1972, the United States Congress banned the practice of disposing Chemical weapons into the Ocean. </li></ul>
  35. 40. <ul><li>However, 64 million pounds of nerve and mustard gas agents had already been dumped into the Ocean waters off the United States by the U.s. Army. According </li></ul>
  36. 41. <ul><li>According to a 1998 report created by William Brankowitz, a deputy project manager in the U.S. army Chemical Materials Agency, the Army created at least 26 Chemical weapons dump sites in the Ocean. </li></ul>
  37. 43. <ul><li>GOOD BYE </li></ul>MAJID MOHIUDDIN

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