Encouse B. Golden, Philip Y. Lam, Adel Kardosh, Kevin J. Gaffney, Enrique Cadenas, Stan G. Louie, Nicos A. Petasis, Thomas C. Chen, and Axel H. Schonthal*
Department of Pathology, University of Southern California (USC) Keck School of Medicine (KSOM), Los Angeles, CA, United States
Department of Molecular Pharmacology and Toxicology, USC School of Pharmacy (SoP), Los Angeles, CA, United States
Department of Molecular Microbiology and Immunology, USC KSOM, Los Angeles, CA, United States
Department of Chemistry, USC College of Letters, Arts and Sciences, Los Angeles, CA, United States
Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, USC SoP, Los Angeles, CA, United States
Department of Neurosurgery, USC KSOM, Los Angeles, CA, United States
* Corresponding author; email: email@example.com.
The anticancer potency of green tea and its individual components is being intensely investigated, and some cancer patients already self-medicate with this ‘miracle herb’ in hopes of augmenting the anticancer outcome of their chemotherapy. Bortezomib (Velcade®) is a proteasome inhibitor in clinical use for multiple myeloma. Here, we investigated whether the combination of these compounds would yield increased antitumor efficacy in multiple myeloma and glioblastoma cell lines in vitro and in vivo. Unexpectedly, we discovered that various green tea constituents, in particular (-)-epigallocatechin gallate (EGCG) and other polyphenols with 1,2-benzenediol moieties, effectively prevented tumor cell death induced by bortezomib in vitro and in vivo. This pronounced antagonistic function of EGCG was only evident with boronic acid-based proteasome inhibitors (bortezomib, MG-262, PS-IX), but not with several non-boronic acid proteasome inhibitors (MG-132, PS-I, nelfinavir). EGCG directly reacted with bortezomib and blocked its proteasome inhibitory function; as a consequence, bortezomib could not trigger endoplasmic reticulum stress or caspase-7 activation, and did not induce tumor cell death. Taken together, our results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of bortezomib and suggest that consumption of green tea products may be contraindicated during cancer therapy with bortezomib.
My doc gave me an rx for Lyrica a few weeks ago to help with the neuropathy. I posted on the mailing list to get an idea of what kinds of side effects others had experienced when they used it. Mostly, I’d say they were not very positive responses. Almost everyone quit taking Lyrica because of side effects such as edema. One patient’s experience was pretty severe. I won’t be taking it. My PN isn’t present 100% of the time (although the numbness is). I’ll just take tramadol or some other medication PRN.
The issue is that I plan on making a very long trip out of the country in the spring. The PN is worse when I can’t either be moving or have my legs up, so I was concerned about taking an extremely long flight. It might just be best for me to be prepared with some vicodin (someone recommended this). Once I’m there, I’ll just need a good night’s sleep to recover and all will be well.
If you have any experience with chemo-induced PN, let me know how you handle it.
Message: Hi Beth,
Here are some data highlights from The 50th Annual American Society
of Hematology (ASH) Meeting this week:
Updated results from the ECOG study evaluating Revlimid plus low-dose dexamethasone in newly diagnosed patients was presented by Dr. Rajkumar in a joint symposium of the American Society of Clinical Oncology and ASH. The results are the highest 3 year overall survival rates ever reported in this patient group.
Data presented by Dr. San Miguel showed that relapsed/refractory patients who received continuous treatment with Revlimid and dexamethasone after achieving their best response lived longer and had increased time to disease progression compared to those who discontinued treatment after ten months or less.
Dr. Lacy presented data which showed that pomalidomide with dexamethasone has promising activity for patients with relapsed/refractory MM. Results from this ongoing trial showed high remission rates.
Online support communities for high survival rate cancers contain a greater amount of emotional support content than online support communities for cancers with low survival rates, according to a new study from the U-M Health System (UMHS) and the VA Ann Arbor Healthcare System.
The researchers also found that support communities for low survival rate cancers contain a greater amount of informational support content than online support communities for high survival rate cancers.
“Online communities have become an important resource for individuals seeking emotional and informational social support related to cancer,” says senior author Dr. Caroline Richardson, assistant professor in the Department of Family Medicine at UMHS.
The study — led by Lorraine Buis, a postdoctoral research fellow at the VA Ann Arbor Healthcare System — assessed differences in emotional and informational social support content in online communities for cancers with high and low survival rates.
The researchers also found that, overall, emotional support was more prevalent than informational support across all communities and all types of cancers.
Both emotional and informational support widely is available within online communities for cancer, but not all of these sites are created equally, Buis says.
“When primary care providers refer individuals to online communities for support, they should be aware that there might be differing amounts of support based on the survival rare of a particular cancer,” she says. Buis also explains that not only are such online communities for patients, “but they help family and friends cope with the struggles that cancer presents.”
Until Richardson’s and Buis’s most recent study, there had been no previous research on the influence of patients’ cancer survival rates on social support content within online support communities for cancer.
Participants in this study all were reviewed under the same time period, were online community members who participated in online support communities for four different types of cancer — lung cancer, pancreatic cancer, thyroid cancer and melanoma — and participated in eight different online communities in the investigation.
The study was presented last week at the annual meeting of the North American Primary Care Research Group. In addition to Buis and Richardson, Pamela Whitten of Michigan State University also was an author of the study.
Genetic variants in the DNA of patients with multiple myeloma appear to strongly influence survival, a groundbreaking new genomic study has concluded.
In this first pass at identifying genetic markers for survival, treatment response, and complications in the disease, a group of 3,400 variants predicted early or late mortality 76% of the time, Dr. Brian Van Ness said in an interview about the initial report (BMC Medicine 2008 Sept. 8 [doi: 10.1186/1741-7015-6-26]).
“Clearly, inherited genetics influenced survival,” said Dr. Van Ness
of the University of Minnesota, Minneapolis. “What we have not yet done is identify which specific variants are responsible for these differences. Our hypothesis is that it won’t be a single variant driving response or survival, but a complex interaction of many.”
After narrowing down the initial 3,404 candidate single nucleotide polymorphisms (SNPs), Dr. Van Ness and his colleagues are now focusing on 1,000 SNPs found to be most strongly associated with the outcome
measures. More studies are on the way using this genetic panel, he said.
Indeed, just 2 weeks after the first study appeared, a coinvestigator, Dr. Gareth Morgan of London’s Royal Marsden Hospital, published findings on the association between certain SNPs and the incidence of
treatment-associated venous thromboembolism (VTE). The analysis showed that some of the variants associated with thalidomide-related VTE occurred in pathways important in drug transport and metabolism.
“The effects of the SNPs associated with thalidomide-related VTE may be functional at the level of the tumor cell, the tumor-related microenvironment, and the endothelium,” Dr. Morgan and his colleagues wrote (Blood 2008 Sept. 19 [Epub ahead of print]).
“Another study, currently submitted, has identified an association between some of the variants and the development of severe myeloma bone disease,” Dr. Van Ness said.
The initial investigation used a genetic screen developed from two DNA data sets: cells from the Coriell Institute for Medical Research, and samples obtained from multiple myeloma patients enrolled in two
randomized drug trials, as well as some unaffected spouses. The samples came from white, black, Hispanic, and Asian patients from North America and Europe. The candidate SNPs, occurring on 983 genes, were chosen based on the most recent genetic research and included on a myeloma-specific gene-testing chip.
The investigators chose extremes of survival as the first test of the panel, because this comparison was most likely to show the effects of any genetic variant. “We took the worst outcomes – people who died in
the first year of their disease – and the best outcomes – those who survived at least 3 years without progression,” Dr. Van Ness said. After repeatedly running the screen on both data sets, the team concluded that, as a whole, it discriminated the survival groups correctly 76% of the time.
Further drilling down identified several SNPs of particular interest, including some associated with drug metabolism, transport, and export; a variant that induces myeloma apoptosis; one associated with cellular
migration and angiogenesis; and several linked to proliferative responses.
Although not designed to detect racial differences, the initial screen did identify some interesting variations: 401 of the SNP variants occurred only in black patients. In whites, there was no difference in these SNPs between cases and controls.
“We know that African Americans have a two- to threefold increase in the incidence of myeloma, but we don’t yet know why,” Dr. Van Ness said. “We’ll be trying to identify those genetic variants that might uniquely increase the risk for one race to develop myeloma over another.”
Neither this initial analysis nor subsequent ones will examine the possible interplay of environment with genetics. But, Dr. Van Ness said, such studies may be forthcoming. The International Myeloma Foundation of North Hollywood, Calif., is conducting a patient survey to begin assessing what role – if any – environmental exposure plays in disease development. The 36-page survey asks patients to detail their environmental, dietary, and geographical exposures. The National Cancer Institute will collaborate with the group in evaluating the data.
The International Myeloma Foundation is also the curator of the DNA samples used in the analysis through its Bank on a Cure program. “Bank on a Cure was developed by an international group of physicians and scientists to deal with a disease that’s difficult to deal with,” Dr. Van Ness said. “It’s not a high-incidence cancer, so it’s not easy to research.”
The Bank on a Cure group developed cooperative agreements with national and international clinical trial groups, and the studies were funded by the International Myeloma Foundation. While exploration of genetic variants relevant to multiple myeloma is in its infancy, Dr. Van Ness predicted the effect could be profound.
Dallas attorney, Fred Baron, lost his battle with multiple myeloma on Thursday. He was 61 years old. Mr. Baron made the news when he tried to get the Biogen drug Tsyabri to treat the myeloma that was taking his life. There aren’t any reports about whether or not Mr. Baron actually was treated with the drug.
I had never heard of Mr. Baron before a few weeks ago even though he was a supporter of and fundraiser for John Edwards. Edwards was a democratic candidate for president this year and vice president in 2004. He was a North Carolina senator whose affair with a woman who produced videos for his campaign probably ruined his future in politics. According to the Dallas News, Mr. Baron was the friend who got Mr. Edwards’s mistress out of Dodge when it was feared knowledge of the affair would go public.
Elizabeth Edwards, wife of John Edwards, has breast cancer with bone metastasis. It was discovered during his presidential campaign after she fractured a rib while moving some furniture, according to the News and Observer.
Have you read about the furor over Fred Baron’s quest to get Tysabri to attempt to treat his myeloma?
According to his son’s blog, they believe it could help prolong his life. Andrew Baron says that Biogen, the maker of Tysabri (a drug used to treat MS), will not allow him to have the drug. It is, however, being tested on MM patients in a phase I trial.
I still have to do some reading on this drug. The side effects are potentially serious, but, when you have only weeks left to live, I don’t suppose that matters.