Health
Scientists at USC have discovered a new type of drug for the treatment of ovarian cancer that works in a way that should not only decrease the number of doses that patients need to take, but also may make it effective for patients whose cancer has become drug-resistant.
The drug, which so far has been tested in the lab on ovarian cancer cells and on mice tumors, was unveiled last month in the Proceedings of the National Academy of Sciences (PNAS).
“We need a new generation of drugs,” said Shili Xu, a USC graduate student and lead author of the PNAS paper. “We need to overcome the drug-resistance issue.”
The drug is a member of a new class of cytotoxic agents abbreviated as PACMA that was discovered by testing roughly 10,000 chemical compounds on cancer cells in the lab of Nouri Neamati, professor of pharmacology and pharmaceutical sciences at the USC School of Pharmacy, and a co-corresponding author of the paper.
These initial findings led to a collaboration with Nicos Petasis, co-corresponding author of the paper and professor of chemistry at the USC Dornsife College of Letters, Arts and Sciences, with appointments at the School of Pharmacy and the USC Norris Comprehensive Cancer Center of the Keck School of Medicine of USC. This joint effort led to a study of PACMA compounds that was reported last year in the Journal of Medicinal Chemistry.
In order to investigate and optimize the anticancer properties of PACMAs, co-author Alexey Butkevich, a graduate student in the Petasis lab, synthesized more than 80 newly designed compounds. One of these, called PACMA31, was eventually found to be very toxic to ovarian cancer cells and was shown to be a potentially effective drug.
In the PNAS paper, Xu and his co-authors reported that PACMA31 is a potent and selective inhibitor of a protein called Protein Disulfide Isomerase (PDI) that is highly expressed in ovarian cancer.
PACMA31 can be taken orally and accumulates in cancer cells, which means that it is less likely to cause harmful side effects in normal tissues. It is also what is known as an “irreversible” drug, meaning that it permanently latches on to its target, PDI, and refuses to wear off until the protein is degraded.
That irreversibility may result in prolonged duration of drug action that could translate into giving the patients lower doses of drugs.
“We are exploring combination studies in order to find synergy between our drug and first-line therapy for ovarian cancer,” Neamati said.
Currently, there are two major types of drugs in the first-line treatment of ovarian cancer: paclitaxel, which hinders cancer cell division by inhibiting the disassembly of microtubules; and carboplatin, which binds to and causes crosslinking of DNA that results in the death of cancer cells.
PACMA31 attacks cancer cells in yet a different way, targeting PDI and thus interrupting the folding process during which proteins assume the shapes that allow them to function properly. Accumulation of misfolded proteins in a cell causes cellular stress and eventually cancer cell death.
Because PACMA31’s strategy is different than that of current anticancer drugs, it has the potential to help patients who do not respond to paclitaxel or cisplatin.
“When the patient has no other choice, we could potentially treat them with our drug,” Neamati said.
Other co-authors of the PNAS paper included Roppei Yamada, Yu Zhou, Bikash Debnath and Professors Roger Duncan and Ebrahim Zandi. Additional contributors to the PACMA project and co-authors to the team’s first paper included Xuefei Cao, Melissa Millard, Srinivas Odde, Nick Mordwinkin, Rambabu Gundla and Professor Stan Louie.
“The discovery of this new drug and its novel mechanism of action is a great example of the power of interdisciplinary collaborations between chemists, biologists, pharmacologists and other biomedical researchers,” Petasis said.
The drug will still require additional testing, but so far it appears to be nontoxic and effective at halting tumor growth. It may also have potential for treating other types of cancer, Neamati noted.
“Obviously, we think that it will go beyond ovarian cancer,” he said.
- Details
- Written by: Editor
ROCHESTER, Minn. – Melanoma is on the rise nationally, and transplant recipients and lymphoma patients are far likelier than the average person to get that form of skin cancer and to die from it, a Mayo Clinic review has found.
That is because their immune systems tend to be significantly depressed, making early detection of melanoma even more important, said co-author Jerry Brewer, M.D., a Mayo dermatologist.
The findings are published in the October issue of Mayo Clinic Proceedings.
Melanoma strikes roughly 1 in 50 people in the general population, Dr. Brewer said.
The odds of getting melanoma are up to 2.5 times higher in people who have received a transplant or who have lymphoma, and melanoma also is likelier to be fatal in those patients, he added.
Patients who have the form of lymphoma called chronic lymphocytic leukemia and develop melanoma are 2.8 times more likely to die from metastatic melanoma, in which the cancer has spread from the skin to other parts of the body, such as internal organs.
The take-home message, Dr. Brewer said: If melanoma is found earlier in such patients, they will likely have better chances of survival. Melanoma can develop anywhere on the body. The first signs are often a change in a mole’s appearance or the development of a new pigmented or unusual-looking growth.
“How you catch melanoma earlier is to be very aware of your skin,” Dr. Brewer said. “These patients with immunosuppression should be looking themselves over head-to-toe once a month, they should be seeing a dermatologist once or twice a year, and if they have a lot of other risk factors, maybe more often than that.”
Dr. Brewer also advises using sunscreen, trying to avoid the sun and steering clear of tanning beds.
The melanoma risk is so high in immunosuppressed patients that they should use sunscreen not only every day, but “almost as often as you brush your teeth,” he said.
- Details
- Written by: Editor
Daily low dose aspirin could slow the decline in brain power among elderly women at high risk of heart disease, indicates observational research published in the online journal BMJ Open.
The researchers base their findings on 681 women between the ages of 70 and 92, 601 of whom were at high risk of heart disease and stroke, defined as a 10 percent or greater risk on a validated risk scale.
All the women were subjected to a battery of tests to measure their physical health and intellectual capacity, including verbal fluency and memory speed, and dementia.
Their health was tracked over a period of five years, at the end of which the intellectual capacity of 489 women was assessed again.
Some 129 women were taking low dose aspirin (75 to 160 mg) every day to ward off a heart attack or stroke when the monitoring period started. A further 94 were taking various other non-steroidal anti-inflammatory drugs (NSAIDs).
The MMSE score fell, on average, across the whole group at the end of the five years, but this decline was considerably less in the 66 women who had taken aspirin every day over the entire period.
This held true, even after taking account of age, genetic factors, the use of other NSAIDs, and the cardiovascular risk score.
The researchers then divided up the group into those who had taken aspirin for the entire five years (66); those who had stopped taking it by 2005-6 (18); those who were taking it by 2005-6 (67); and those who hadn't taken the drug at any point (338).
Compared with women who had not taken aspirin at all, those who had done so for all five years, increased their MMSE score, while those who had taken aspirin at some point, registered only insignificant falls in MMSE score.
The test results for verbal fluency and memory speed indicated similar patterns, although the findings weren't statistically significant.
There were no differences, however, in the rate at which the women developed dementia.
The researchers then looked only at the women with a Framingham risk score of more than 10 percent. Again, similar patterns were evident.
The fall in MMSE score was less among those taking aspirin than those who weren't, and there was no difference between those taking other NSAIDs and those who weren't. The same was true of the verbal and memory tests, although the differences were not statistically significant.
The authors caution that theirs was an observational study, and that the MMSE can't detect subtle changes in cognitive ability. But they suggest their findings indicate that aspirin may protect the brain – at least in women at high risk of a heart attack or stroke.
- Details
- Written by: Editor
WILLITS, Calif. – Frank R. Howard Memorial Hospital (HMH) Chief Financial Officer Carlton Jacobson has been appointed vice president of finance for Adventist Health’s St. Helena Region, according to HMH Chief Executive Officer Rick Bockmann.
“We will miss Carlton terribly, but are so pleased for him. His new position will allow him to share his financial and operational talent and experience with a much broader market,” Bockmann said.
In 1987, Jacobson began his career in hospitals as the controller at Valley Community Hospital in Santa Maria, Calif.
In 1993, he became controller at Simi Valley Hospital and Health Care Services, and in 2000, Jacobson relocated to Northern California to assume the position of HMH CFO, vice president of finance.
Jacobson has been responsible for all HMH financial operations, as well as information systems, materials management, maintenance, laboratory and dietary.
He also was instrumental in the development of the new hospital, to be completed by December 2014.
“I consider myself an entrepreneurial/business development CFO. At Howard Memorial Hospital we have increased net revenue through growth, program development and strategic investments in equipment four fold from $10 million to over $40 million,” said Jacobson.
Jacobson will be based at the St. Helena Hospital Napa Valley campus.
The process is under way to identify a financial leader for Howard Hospital.
- Details
- Written by: Editor