High-Quality Biospecimens : Cancer : Conversant
February 8th, 2010CELL LINES FAIL, new study reveals: Cancer
January 15th, 2010By Amanda Gardner
HealthDay Reporter – Thu Jan 14, 11:48 pm ET
THURSDAY, Jan. 14 (HealthDay News) — Cancer researchers rely on specific tumor cell lines when developing new treatments, but those samples aren’t always what they’re advertised to be, a Dutch team reports.
Their study found that three of 13 human esophageal cancer cell lines widely used for worldwide research were actually cell lines from lung, colorectal and other malignancies.
Two of the contaminated or misidentified cell lines were involved in research published in more than 100 papers and in the issuance of 11 U.S. patents, which led to clinical trials in patients.
One of those trials involved testing the drug Nexavar (sorafenib) on patients with Barrett-related esophageal adenocarcinoma. Nexavar is approved for kidney and liver cancer but not yet for this indication.
While earlier-phase studies using these cell lines are still “scientifically sound,” the clinical trials should be revisited, said Winand N.M. Dinjens, senior author of a short paper published online Jan. 14 in the Journal of the National Cancer Institute and head of molecular diagnostics in the department of pathology at the Josephine Nefkens Institute, University Medical Center Rotterdam in The Netherlands.
“Widespread use of contaminated cell lines threatens the development of treatment strategies for EAC,” he and his colleagues wrote.
Other experts expressed less concern, saying the unintentional misidentification or contamination of the cell lines is not critical and is even a fairly common occurrence.
“From the scientific point of view, it’s not a huge deal, but it’s certainly something you’re glad you found out,” said Charles Saxe, scientific director of the Program in Cancer Cell Biology and Metastasis at the American Cancer Society in Atlanta. “This probably doesn’t surprise anybody. The surprise is probably that there were only three.”
And clinical trials shouldn’t necessarily be stopped, Saxe said, but researchers “need to go back to the other 10 cell lines that are good and see how much of this stuff holds up. They’re not saying pull the plug.”
“The issue of misidentification/crosscontamination is not a new thing,” agreed Robert H. Shoemaker, chief of the screening technologies branch at the U.S. National Cancer Institute and author of an editorial accompanying the study, who also did not deem the finding a huge catastrophe.
Previous estimates gauge that up to one-third of all cell lines have been somehow mischaracterized, the authors stated.
The good news is that advancing technologies will make it easier to identify incorrect cell lines, Saxe stated.
Only 14 cell lines exist for research on esophageal adenocarcinoma which, although not the world’s number-one cancer killer, is increasing sharply in incidence (the authenticity of the 14th line may also be in question). No animal models and few human samples are available for research into the disease, the authors stated, making the existence of such cell lines a critical part of devising new therapies.
So why isn’t this mixup more significant, according to experts?
One reason is that the two signaling pathways looked at in these studies are common to many types of cancer. “Both of those pathways are known to be involved in a very wide number of cancers,” Saxe said. In other words, it’s not inconceivable that research results done in these “bogus” cell lines would be equally valid for esophageal adenocarcinoma.
Paul Sanberg is professor of neurosurgery and director at the University of South Florida Center for Aging and Brain Repair in Tampa. He pointed out that only experimental drugs were tested on this type of cell — not drugs already approved for use with this type of cancer.
But identifying the mistake “sets the stage for seeking targets that are unique to this disease,” Shoemaker said.
The challenge now is to ensure the identities of these cells, experts said.
“These things can happen,” Sanberg said. “This is just more evidence that it’s a good idea to check the characteristics of cells, especially those used in therapeutics.”
Conversant Medical Director | News | Breast Cancer
October 22nd, 2009Cancer doctor says he’s ‘lucky’ because he sees people at their best
By Lee Roop of the Huntsville Times
Mike Mercier / The Huntsville TimesDr. Marshall Schreeder
HUNTSVILLE, AL — He spends his days helping people fight a disease whose name — cancer — may be the scariest word in the English language, but oncologist Dr. Marshall Schreeder is one of Huntsville’s biggest optimists.
Optimism is almost a job requirement, Schreeder said recently, but it’s more than that. It’s the natural result of what he sees every day.
“I’m astounded by the soul of man,” Schreeder said.
The soul of man?
Perhaps an unexpected observation from a man of science who first wanted to be a systems engineer, then ended up Huntsville’s best-known breast cancer doctor.
Schreeder, 63, discussed his life path late last month at Clearview Cancer Institute, the state of the art cancer clinic he, Dr. Jeremy Hon, and several other oncologists opened in 2006.
Hon and Schreeder have practiced together since the early 1980s at Clearview’s predecessor, the Comprehensive Cancer Institute.
The soul isn’t what Schreeder was looking for when he entered Tulane University medical school. But it’s close.
“I liked engineering, but I liked working with people a good bit more,” Schreeder said. “I thought that, maybe, I could do both by doing medicine.”
Why cancer?
“I picked oncology because I thought it had a long way to go,” Schreeder said, “and I thought I might be able to play a role in that development in my lifetime.”
The first decade “was pretty slow-going,” Schreeder conceded, but things have accelerated rapidly. He ticked off major developments in the field:
- Improvements in chemotherapy making intense nausea almost a thing of the past.
- Earlier detection at a time when a “cure” is a realistic expectation.
- An increase in active cancer-fighting drugs from four or five when Schreeder started to “a hundred or more” today.
- The development of targeted drugs, or “the concept that you can identify the critical target in a disease, hit nothing but that and have an excellent result.”
Even now, after a career that began in Phoenix in the 1970s, Schreeder still leans forward in excitement when he talks about the future.
“This last 10 years has really been a watershed,” he said, “and there’s a lot of excitement in the years to come.”
He plans to be a part of it. He knows where he wants oncology to go. That’s the big picture.
But how does an oncologist handle the daily disappointments, the inevitable death?
For Schreeder, it starts with his sense of the physician’s role.
“Oftentimes, I see myself as an educator,” Schreeder said, “and then let (the patients) tell me what they want to do.”
“We can’t guarantee the result,” he said. “All I can do is guarantee that, patient by patient, we’ll do the best we can.”
Rather than annoyed, Schreeder is fine when patients come armed with information about their malignancy gleaned from the Web.
“That’s what we want,” Schreeder said, “People to be informed, people to look at the options.
“When everything is said and done, peace of mind is part of the outcome. I think that’s very important to satisfaction.”
There are bad days, no doubt.
“Sometimes, it’s overwhelming,” Schreeder said. “And sometimes you have periods that you are humbled by how helpless you really are.
“On the other hand, it’s almost as if, those people you help, they make it all worthwhile,” he said, “even if they have an extra six months, or an extra year, an extra two years, an extra two decades.”
Cancer patients have “a greater appreciation for life,” Schreeder said, and they teach him every day.
“I get to know people at their very best,” he said, “and at a level that you don’t know in a different way … in a sense where everything is stripped off.”
The people. They get Schreeder up at 4 a.m. — still — for a half-hour’s hard bicycle ride on dark streets before breakfast. They fuel the morning hospital rounds, patient appointments at Clearview, administrative duties and research.
Two of his sons chose medicine as a career, Schreeder said, “and I did not encourage them at all. I said, ‘You see what I do. You see what the cost is. You’d better be sure this is really what you’d like to do, because you’re not going to be doing a whole lot else.”
“Maybe I’ve made it more than it needs to be,” he admitted, “I think I’ll just say I am what I am. As Popeye would say.”
And what is he?
“I’m lucky,” Schreeder said. “I’m lucky to be associated with the type of people I meet. You’d just be astounded at how wonderful people are and how brave they are and how every day it’s like that.”
Conversant in the news | Cancer Stem Cells, B-Cells | Conversant
October 8th, 2009Conversant as well as some of our fellow HudsonAlpha researchers and associate companies received some great press from the Huntsville Times for breast cancer awareness week.
HudsonAlpha Institute for Biotechnology wages quiet, personal war on breast cancer
By Patricia C. McCarter
October 04, 2009, 9:44AM
Inside the building situated in a former cotton field, there’s a war going on.
In multiple offices along the high-ceiling corridors of the HudsonAlpha Institute for Biotechnology, nonprofit research groups and private companies are waging serious battle against breast cancer.
Some are embroiled in research to help them understand which proteins cancer cells are drawn to. Others are developing tests that will predict whether a particular breast cancer will likely reoccur, so that a woman and her doctor can select the best course of therapy.
Still others are seeking an actual cure, as well as other drugs that can help make the grueling task of fighting breast cancer a little less awful.
And for so many of these bright minds, the battle against breast cancer is more than a little bit personal.
Applied Genomics Inc.
Rob Seitz was a high school senior when his mother was diagnosed with breast cancer. She got well, then sick, well, then sick again, and she died when he was 28.
He and Doug Ross founded Applied Genomics in 2000, with the goal of subtyping breast cancers so that oncologists could determine which chemotherapy worked best for each patient. In 2007, Mammastrat was ready for the market.
“It predicts recurrence in (estrogen responsive) positive, node negative breast cancer,” Seitz said. “As breast cancer goes, that’s the one you’d rather have.”
Mammastrat was developed by looking at thousands of breast cancer samples and determining which proteins correlated with negative outcomes. Samples came from Huntsville, Cleveland, Vancouver, Australia, Norway and elsewhere around the world.
If the test says “yes,” the oncologist can ramp up the chemotherapy process.
“You don’t want to have to get extra chemo if you don’t need it,” Seitz said. “It’s very difficult on the body.”
Seitz, who also has a master’s degree in divinity, and Ross are also working on a test called Mammotax, which will predict if a patient will respond to chemotherapies known as Taxotere and Taxol. Those are often added to “regular” chemotherapy, Seitz said, even though they’re only helpful if a patient expresses a particular protein.
“Ninety percent of breast cancer patients are getting this additional chemo, but not all of them need it,” he said. “Knowing you don’t need it can be very helpful.”
Mammastrat impacts about 43 percent of women with breast cancer, he said. But Mammotax will be able to impact the treatment of almost every breast cancer patient.
It is going through final clinical evaluation now and should be market ready within a year, he said. It will also be useful in the diagnosis of lung cancer patients.
“My mom is why I do this,” he said. “I know I will make a difference in this disease, and that is very important to me.”
Conversant
All the brilliant medical minds in the world couldn’t develop life-saving breast cancer treatments or tests if they didn’t initially have blood, tissue and tumor samples from afflicted patients.
That’s where companies such as Conversant come in. Founded nearly three years ago by Marshall Schreeder Jr. and Luke Doiron, Conversant gets permission from patients to collect their medical waste and turn it into samples for researchers.
Almost always, they say yes.
“Even though we tell them that this won’t improve their current treatment, that it might takes years for the research to yield something applicable to future cancer patients, they say yes,” Schreeder said.
It doesn’t alter their treatment course, and it doesn’t mean more needle sticks, “which are the two things they always ask about.”
In its lab space at HudsonAlpha, Conversant isolates cell types and puts those samples on slides and in tubes in preparation for researchers. The patients’ names are replaced with a series of numbers and letters, through which Conversant maintains updated files on how they’re responding to certain treatments.
All of that is pertinent for scientists trying to find better ways of treating the disease.
“The National Cancer Institute says getting good samples is the No. 1 impediment to cancer research,” Schreeder said. “It’s raw material for researchers around the world.”
Many of the samples are procured from Clearview Cancer Institute, where Schreeder’s namesake is one of the city’s premier oncologists. Doiron’s father is a physician in Knoxville, and other samples come from a hospital there.
“We are sensitive to not approach patients on the first visit to their physicians,” he said. “But we do have to talk to them before their first treatments.”
Currently, there are no blood tests to determine if a patient has breast cancer. In his best dream, such a test is developed using samples from Conversant.
“This isn’t an immediate-gratification kind of thing,” he said. “Researchers have to make a discovery, validate it, test, test, test, do animal trials, human trials, validate some more,” he said. “It’s a long-term fight.”
HudsonAlpha researchers
If you know why a disease has attacked your body, you can treat it more effectively than if you don’t.
Looking at all of the genes of 100 breast cancer patients, HudsonAlpha post-doctoral fellow K-T Varley hopes to one day determine why those 100 women got sick.
“New technologies allow us to look at all of a person’s genes at one time, so it’s not as daunting as was even just a few years ago,” said Varley, whose mother died of breast cancer.
She’s teamed up with researchers and oncologists at the University of Alabama at Birmingham to look at how women respond to treatment and determine why some get better and others do not.
Genomic markers should show how aggressive the cancer is and lead doctors to a better understanding of which patients need what drugs. Some drugs impede a blood vessel’s ability to form and deliver nutrients to the tumor, but it impacts other parts of the body as well.
Others try to trick estrogen-receptive cancer cells into binding to a substance that mimics estrogen, but won’t give the cancer what it needs to reproduce.
“Currently, there’s a terrible time problem as well as horrible side effects in how cancer is treated,” said Dr. Rick Myers, president and director of HudsonAlpha. “So much of the time, doctors just don’t know which kind of chemo a patient is going to respond to best.
“So, they’ll be on one medicine for months, and when the doctors realize that one isn’t working, they have to switch to another. You can literally lose months using the wrong treatment because, currently, you just don’t always know.”
Myers said the word “cancer” actually refers to “a thousand different diseases” in which cells mutate and replicate. There will never be “one magic bullet” to take out all cancer because the disease isn’t just one thing.
“The dream is for there to be one annual blood test that can check for all sorts of tumors,” Varley said.
To which Myers added, “We’re not there yet, but we’re seeing how to design the pathway to get us there.”
Serina Therapeutics
It’s not just the medicine that matters. It’s also how the medicine is delivered to your body that determines how well the drug will work.
Serina Therapeutics was founded in 2006 by scientists who have already made their mark in drug efficacy, through the companies Shearwater Polymers and Nektar, by developing polyethylene glycol (PEG) technology. PEG allows certain pain medicines to be absorbed in the gut and then block pain receptors in the brain without causing bowel dysfunction.
Chemist Mike Bentley, 70, sparked the idea behind NKTR-118 and NKTR-119, developed when he was at Nektar, and now being late-stage tested and marketed by AstraZeneca.
He said the drugs will benefit breast cancer patients, as well as other patients who take opioids such as Hydrocodone and morphine for pain. With NKTR-118 and 119, patients will see the benefits of the pain inhibitor without suffering from constipation, which 40 to 90 percent of opioid users do.
“People like to make jokes about constipation, but it can be a serious, costly problem,” he said. “You’re not allowed to leave the hospital after surgery until you’ve had a bowel movement, but the opioids keep you from being able to go.
“So, you have to stay in the hospital longer, and you’re just feeling worse and worse. A drug that lets you leave the hospital sooner can save a ton of money.”
Bentley, an Alabama native who spent a couple decades teaching chemistry at the University of Maine, said the idea came to him almost 10 years ago. It involved using polymers to encourage proteins to circulate longer in the body and continue the “rippling effect” in the gut that allows for proper body function.
“I do the ‘thought chemistry,’ ” said the Serina Therapeutic cofounder. “And I oversaw the team as it was being developed. I’ve never had more fun on a project, and I know it’s going to improve lives.
“I don’t even take a salary now. I’m just here because it’s fun.”
Human Cancer Plasma and Serum | Oncology Solid Tumor Samples | Conversant
September 7th, 2009Systematic exploration of human plasma and serum for circulating proteins as biomarkers for cancer, hematologic diseases, rheumatoid arthritis, and lupus has been actively pursued for decades.
The problem is, not much has been found that holds up to the rigors of sensitivity and specificity on a large scale.
We’re aware of the myriad theories about the “why”… like…- selection of appropriate patient poulations
- availability of accurately matched controls
- sample collection
- sample handling and storage
- quality and depth of available clinical information
- variable profiling techniques
- etc.
Standard Operating Procedures and Quality Control/Quality Assurance checks are necessary because there is really no standard out there to guarantee reproducability of new procedures. It’s almost like flying blind, there are so many new variables. From a technical and economic viewpoint, every assay has to be sufficiently robust to be completed in community-based hospitals, physician clinics, and must be transportable over long distances and even days.
From a patient perspective, there is a real feeling that drugs and treatments should be highly adaptable and ultimately relevant to the patient. The days of treating cancer patients with drugs of low toxicity or of high tolerance regardless of their efficacy are quickly coming to an end. In much the same way, there is a growing trend to utilize a panel of biomarkers in the hopes that there will be a marker among the group that works effectively to identify disease in every patient.
Attention do detail makes all the difference.
Cancer Stem Cells | Human Cell Research | Drug Discovery | Conversant
August 31st, 2009Most chemotherapeutic drugs today are targeting mature cancer cells… are these cancer drugs targeted at the wrong kinds of cells?
This is a pretty tough problem. While we know that currently available cancer drugs dramatically reduce the size of tumors, we also know that MOST cancers will eventually recur. There is some amazing, pioneering work being done in universities, non-profits (like HudsonAlpha), and biopharma to address this issue. Some research we’ve reviewed points toward small populations of cells — “cancer stem cells” or “CSC”s — that are ultimately responsible for the growth of tumors and are resistant to current therapies.
Most of our existing cancer treatments have been developed based on animal models, where therapies that can show ability to promote tumor shrinkage were considered effective. Most mice do not live beyond 1-2 years so using that model to assess relapse is not practical.
Also, the efficacy of cancer treatments is, in the initial stages of testing, often measured by the ablation fraction of tumor mass (fractional kill). Since the theory is that CSCs form a very small proportion of a given tumor, this may not necessarily select for drugs that act specifically on the cancer stem cells. Since conventional chemotherapies kill differentiated or differentiating cells – which form the bulk of the tumor but are unable to generate new cells – a population of CSCs, which gave rise to it, could remain untouched and cause a relapse of the disease.
More next time…
HER2 / Neu and Breast Cancer | Refractory Cancer | Conversant
August 24th, 2009Can you collect clinical specimens from Herceptin non-responders? That’s a question we get often. Let me give you a little background then address that question directly…
Breast cancer – including ductal carcinoma in situ, invasive/infiltrating ductal, and invasive/infiltrating lobular – is a common diagnosis at Conversant’s clinical cancer Sites (a “Site” to us is any place where we consent patients and collect samples ie. a hospital, clinic, or physician practice). For example, in 2008 our Sites saw over 275 newly diagnosed breast cancer patients, 25 (or 9%) of which were pre-chemotherapy Stage IV Breast Cancer patients.
9% Stage IV disease is a significant improvement versus previous years. That points to a successful, new, aggressive push for screening plus some major advances in diagnostic technology.
Improved diagnosis is one part; the other part is improved treatment. That’s why I’m posting this blog…
Treatment Options
Everyone who has been around the cancer research world for any period of time has heard about HER2/Neu (also known as ErbB-2, ERBB2) which stands for “Human Epidermal Growth Factor Receptor 2″; a protein giving higher aggressiveness in breast cancers.
We also know Trastuzumab (”Herceptin”) – developed by Genentech and FDA approved in 1998 – is a monoclonal antibody that interferes with the HER2/neu receptor and reverses the effects of an overactive HER2 receptor. In order to be used, physicians will score breast cancer tissue with IHC and FISH… scores of 0 and 1+ are negative (don’t treat), scores of 3+ are positive (treat).
Studies conducted by academia and industry both show that approximately 25% of breast cancer patients have tumors that are HER2+. Herceptin is a highly effective treatment for many of these patients.
What About Herceptin “Non-Responders”
Because the fight for better therapies in breast cancer is always ongoing, many researchers are focused on improving upon the currently available treatment options. That’s where we can help.
Conversant collects clinical specimens from patients at initial diagnosis and follows them throughout their treatment course. Using the Herceptin non-responders example, we can (and do) collect clinical specimens (like PBMC, Serum, Whole Blood, and even Circulating Tumor Cells) from these patients… enabling our research clients to study refractory or n0n-responder patient population.
There’s a whole lot more to it and – if you are interested – I would love to talk with you. Give us a call anytime at (866) 838-2798.
More next week…
Radiation Therapy
July 28th, 2009Radiation therapy is an exciting new technique being used to combat cancer. This fascinating technology is always evolving. It works by damaging the DNA of cells. The damage is caused by directing a beam of photons, protons, electrons, neutrons, or ions which can directly or indirectly ionize the atoms which make up the DNA chain. Although this may seem permanent, cells have mechanisms for repairing DNA after this process has happened, which is why Radiation Therapists now focus on breaking the DNA on each separate strand to ensure the DNA is destroyed. This DNA damage has been observed to be inherited throughout the cell division of tumors leading to cancer cell apoptosis or decrease in the rate of cancer cell division.
While there are also many drawbacks of radiation therapy, the largest one is cells of solid tumors often become deficient in oxygen and cause hypoxia. This causes the radiation to be far less effective because tumor cells in a hypoxic environment have a shown a general resistance to radiation therapy. Currently, researchers are working hard to solve this problem.
By providing researchers with the samples they need, we are hopeful we can contribute to new advances in this exciting field. If you have and question please feel free to comment or fill out the form to the left.
JAK2+ | Conversant
July 16th, 2009The JAK2 (Janus Kinase 2) is becoming very relevant in ongoing cancer studies, mainly in the area of myeloproliferative disorders (MPD’s). These disorders can be classified as diseases where the bone marrow produces excess cells. Coincidentally, many MPD’s are related and often evolve into cancers such as acute myeloid leukemia. Polycythemia vera (PV), one of the more common MPD’s, is a brand of MPD in which the bone marrow produces too many red blood cells.
Amazingly, recent research has shown a mutation in the JAK2, ties all of the above information together. Multiple research facilities recently observed a mutation recognized now as JAK2 V617F, more commonly called the JAK2+ mutation. Many researchers are in agreement that a major breakthrough in MPD therapeutics can be discovered by further understanding this JAK2+ mutation.
Currently, JAK2+ inhibitors are being tested in vitro and through clinical trials. By providing clients with specimens known to be JAK2+ we feel we are fueling advances in MPD’s and PV studies. If you have any questions or comments about our JAK2+ samples please feel to leave a comment or fill out the form to the left
Antigen-specific Targeting
July 14th, 2009Antigen-specific targeting is a promising new technique in cancer therapy. It involves targeting cell surface groups unique to a specific type of cell with a cytotoxic antibody. Since most cell types present receptors unique to them, cancer therapy can be selectively targeted. One area of research in antigen-specific targeting is centered on the clusters of differentiation (CD), cell surface receptors, found on white blood cells. Each class of white blood cells, T-cell, B-cell, macrophages, etc, has a specific CD and can be selectively targeted.
Antigen-specific targeting is currently divided into a few subtypes. One of them involves the use of receptor specific antibodies to target and block the antigen receptor. The cancer therapy drug trastuzumab, is a monoclonal anti-HER2 antibody. Human epidermal growth factor receptor 2 (HER2) is a cell-surface receptor that is commonly over-activated in breast cancer cells and is a factor contributing to the up-regulation of cell proliferation genes. Trastuzumab binds this receptor and shuts it down, limiting breast tumor cell proliferation in individuals whose cancer is related to an over-expression of HER2. Another type of antigen-specific drugs are the antibodies conjugated to truncated peptide toxins, such as diphtheria toxin and pseudomonas exotoxin. These immunotoxins work by binding to a cell surface receptor of the target, and moving the peptide toxin into the cell, whereby it causes apoptosis. RFB4-dgA is a new drug in phase 1 studies that is a fusion of anti-CD22 and modified ricin toxin proposed for B-NHL, and CLL.
Antigen-specific targeting is a promising area of research that has great potential. This is still a need to further research and study this approach to cancer therapy, its efficacy, and safety. Conversant is proud to offer highly annotate, biological specimens for research. In regards to antigen-specific targeting, we also have the ability to enrich samples with regards to certain cells types.