[MOL] Re: Bile duct Cancer??? [02362] Medicine On Line

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[MOL] Re: Bile duct Cancer???

Hi everyone; Lillian told me that someone had written in for info on bile 
duct cancer and she told them I would respond after my vacation as I also 
have this type. BUT, I don't have the e-mail that was sent...I must have 
deleted it by mistake. If this person gets this message or if anyone else 
has any info on them (or a copy of their e-mail) please let me know. This is 
a very rare type of cancer and I feel terrible that this person has been 
waiting for a response from me and I'm not able to find them. Please help 
Your friend,

>From: "Lillian" <firefly@islc.net>
>Reply-To: mol-cancer@lists.meds.com
>To: "Nancy J." <mol-cancer@lists.meds.com>
>Subject: [MOL] Turning the tables on pancreatic tumors.....
>Date: Sat, 29 Apr 2000 21:42:46 -0700
>       Lead Investigator: Daniel Von Hoff
>       Turning the Tables on Pancreatic Tumors
>       by Dan Ferber
>       It's one of the deadliest cancers around and more than 100 
>anticancer drugs have failed to stop it. But now, pancreatic cancer appears 
>vulnerable, because new information about the genetics of cancer cells is 
>leading researchers to create novel drug strategies, according to results 
>presented April 2, at the 91st annual conference of the American 
>Association of Cancer Research.
>       Of the 29,800 people who are projected to develop pancreatic cancer 
>in 2000 in the United States, all but about 800 will die of the disease, 
>often just months after they're diagnosed. That makes the disease the 
>single most lethal form of cancer, says Daniel Von Hoff, director of the 
>Arizona Cancer Center in Tucson. Decades of drug-discovery effort and 
>testing have yielded only one drug that has shown results for most 
>patients, without any side effects such as allergic reactions. However, he 
>says the effectiveness of that drug, 5-fluorouracil, has been debated.
>       With pancreatic cancer, "the creed has been, 'let the patient pass 
>away and hope the period of suffering is not too long," he says, adding: 
>"There's a lot of people who don't want to believe this creed."
>       To identify new drugs to treat pancreatic cancer, he says, 
>researchers are trying to turn the tables on cancer cells, by taking 
>advantage of their propensity to become genetically unstable and accumulate 
>mutations. For example, cancer cells in patients treated with 
>5-fluorouracil evolve to resist the drug by overexpressing its molecular 
>target, an enzyme called thymidylate synthase (ST). So researchers have 
>screened for and found a new agent that is activated by the enzyme, and 
>will therefore target cancer cells preferentially.
>       To test the new drug, Von Hoff and his colleagues used a screen 
>called the human tumor-cloning assay, which allows them to identify those 
>agents that kill pancreatic cancer cells cultured from pancreatic tumors 
>that have been removed surgically. "The results were very impressive," Von 
>Hoff says. The researchers are planning to test the drug, called NB1011, in 
>a phase I clinical trial.
>       To identify new drug targets, Von Hoff and other researchers are 
>taking advantage of rapidly accumulating knowledge about the specific 
>genetic alterations in pancreatic cancer cells. For example, 14% of 
>pancreatic tumors are deficient in an enzyme called MLH1/MSH2 that fixes 
>small mistakes during DNA replication.
>       By creating a strain of yeast deficient for that enzyme and 
>screening for drugs that kill it, the Arizona team identified a drug called 
>MGI-114 that kills pancreatic cancer cells that are also deficient in that 
>enzyme. The Arizona team has begun a clinical trial to test the safety of 
>the compound in pancreatic cancer patients.
>       The researchers also used similar yeast strains to identify the 
>molecular target of a drug used to treat the disease for years, with 
>unimpressive results. Cultured cancer cells and yeast cells with a 
>defective DNA-copying enzyme are susceptible to gemcitibine, but cells with 
>intact enzyme are not. This might explain why only 18 percent of pancreatic 
>cancer patients respond to gemcitibine, Von Hoff says.
>       Genetics can also identify entirely new and unexpected drug targets, 
>Von Hoff says. Sometimes, mutations in cancer cells eliminate the function 
>of a protein, and it is difficult to design a therapy to replace a missing 
>protein. So researchers are using yeast to find unexpected new drug 
>targets. For example, certain mutations weaken the ability of yeast to 
>repair its DNA, but don't kill the cell. Those same mutations make cancer 
>cells unstable. By screening for mutations that kill the mutant yeast but 
>not normal yeast, researchers can spot new targets for anticancer drugs.
>       With the exploding amount of genetic information about pancreatic 
>tumors, Von Hoff is optimistic that new drugs can be developed to treat 
>this deadly cancer. "The molecular genetic approach has given us 
>substantial therapy leads," he says.
>We invite you to take a look at our Album.
>   ( Very informational, good tips, Molers pictures, art work and much 

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