Archive for the ‘Breast Cancer’ Category

Substance in greens shrinks cancer again

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Posted 19 May 2012 — by James Street
Category apigenin, Breast Cancer
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A University of Missouri researcher has once again found that a natural substance extracted from celery and parsley can shrink a type of aggressive breast cancer.

A year ago, Salman Hyder, a professor of biomedical sciences, discovered that rats exposed to the substance, apigenin, experienced significant delays in tumor formation compared to those that weren’t exposed.

This time around, his study used human cells that were injected into mice.

In the study, Hyder and his research team implanted cells of a deadly fast-growing breast cancer and then treated some of the mice with a common hormone therapy that’s known to cause cancer cells to grow more aggressively. Among that group, some mice were then given apigenin.

Cancerous tumors grew rapidly in mice that did not receive apigenin, but those treated with the substance saw cancer growth drop to the same rate of the control group that never received the hormone treatment.

“We don’t know exactly how apigenin does this on a chemical level,” Hyder said in a statement. “We do know that apigenin slowed the progression of human breast cancer cells in three ways: by inducing cell death, by inhibiting cell proliferation, and by reducing expression of a gene associated with cancer growth. Blood vessels responsible for feeding cancer cells also had smaller diameters in apigenin-treated mice compared to untreated mice. Smaller vessels mean restricted nutrient flow to the tumors and may have served to starve the cancer as well as limiting its ability to spread.”

In the future, apigenin injections could be a safe alternative to chemotherapy, he said. But Hyder fears funding for clinical testing in humans could be difficult: Because the substance is easy to extract from plants, pharmaceutical companies don’t stand to profit from the treatment.

Reach Janese Silvey at 573-815-1705 or e-mail jsilvey@columbiatribune.com.

Vaccine may cut breast cancer recurrence risk in half

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Posted 19 May 2012 — by James Street
Category Breast Cancer, Vaccine

Posted: May 17, 2012 3:43 PM PDT Updated: May 19, 2012 11:00 AM PDT

HOUSTON (KPRC/NBC) – A new breast cancer vaccine has been shown to cut the risk of recurrence by nearly half.

The clinical trial involving about 200 breast cancer patients started back in 2007.

Anne Allen of Topeka, KS was diagnosed with breast cancer in 2010.

A second opinion at The University of Texas MD Anderson Cancer Center confirmed it was worse than she thought.

“It turned out to be stage three that involved my lymph nodes,” Allen said.

With no known history of breast cancer, Allen was vigilant about getting yearly mammograms.

With dense breasts, the two lumps were overlooked.

“Calcifications are white. Dense breast tissue is white. It’s like looking for a rabbit in a snowstorm sometimes,” Allen said.

After a total mastectomy, removal of her lymph nodes, 16 rounds of chemotherapy and six weeks of radiation, Allen enrolled in a clinical trial at MD Anderson for a breast cancer vaccine.

“Hopefully, if this doesn’t help me, it gives more information so that down the road, a vaccine would be tremendous for other cancer patients,” she said.

Patients are inoculated under the skin once a month for six months. Then they receive a booster shot every six months for three years.

That time period is when the chance of recurrence is the highest.

“It’ll teach the T cells to recognize that HER2 protein. So the thought would be that if the T cells were educated in this way, if the tumor cell were to come back, the immune system could identify it, attack it and destroy it before the patient would have, as we see, a measurable recurrence,” said Dr. Elizabeth Mittendorf, surgical oncologist at MD Anderson and the trial’s national principal investigator.

Mittendorf said the results of the study were extraordinary, with a recurrence rate of 10 percent compared to 18 percent in the control group. That works out to be a 43 percent reduction in the risk of recurrence.

The next phase of the trial would include even more patients.

The results of the study will be presented in June at the annual meeting of the American Society of Clinical Oncology.

Trial enrollment is expected to end this fall.

RF Ablation After Excision Can Prevent Tumor Recurrence

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Posted 10 May 2012 — by James Street
Category Breast Cancer, Radio Frequency RF

Nancy A. Melville

May 8, 2012 (Phoenix, Arizona) — The use of intraoperative radiofrequency ablation to create a disease-free zone after the excision of a breast cancer tumor can significantly reduce the need for repeat surgeries and adjuvant radiation, according to the results of a study presented here at the American Society of Breast Surgeons 13th Annual Meeting.

Despite advances in tumor localization technology, the ability to identify a specific size or grade of invasive cancer that can be reliably addressed with lumpectomy alone is still an inexact science; patients often require reexcision of positive margins or adjuvant radiation, which increase cost and morbidity.

“Even with our best efforts, 20% to 40% of patients require reincision for closed or positive margins,” said lead author Misti Wilson, MD, a surgical oncologist at the University of Arkansas in Little Rock.

Although radiation can significantly reduce recurrence after lumpectomy, it is associated with significant adverse effects, including breast fibrosis and decreased cosmesis, and can be inconvenient and even impossible for rural or poor patients to obtain, she explained.

The use of radiofrequency ablation following excision (eRFA) allows surgeons to create an extra tumor-free zone extending beyond the lumpectomy cavity, which approximates the zone treated by brachytherapy.

eRFA-treated breast

Dr. Wilson and her colleagues evaluated 73 patients with invasive cancer and an average tumor size of 1.1 cm (range, 0.2 to 2.5 cm) who were treated with eRFA.

The mean age of the patients was 69 years, and all started out with tumors 3 cm or less and clinically negative nodes.

The radiofrequency procedure involves deploying the probe, maintained at 100 °C, for 15 minutes to circumferentially extend the lumpectomy cavity margin by 1 cm. Doppler sonography was used to determine the final ablation size.

Follow-up, involving a mammogram and physician exam, was done every 6 months in the first 2 years, and yearly thereafter.

Of the 73 patients, 68 had invasive ductal carcinoma and 5 had invasive lobular carcinoma; 93% of patients had grade 1 to 2 disease.

None of the patients received radiation therapy; for cosmesis, their Radiation Therapy Oncology Group (RTOG) score was reported as good to excellent. The only patients requiring reresection were those with grossly positive margins or residual calcifications on postoperative mammography.

Nineteen of the patients had adequate margins, defined as 2 mm or less. Of those, 16 (84%) had close or positive margins and were spared reexcision.

“In general, only 3 patients of 73 returned to the operating room for reexcision after eRFA,” Dr. Wilson said.

Postoperatively, there were 2 hematomas that resolved on their own and 4 infections requiring antibiotics, incision, and drainage, she noted.

In the 55-month follow-up period, disease-free survival at 1 year was 100%, at 3 years was 92%, and at 5 years was 86%. There were 8 deaths overall, but none were related to the primary disease.

“The findings indicate that eRFA reduces the need for second surgeries for inadequate margins,” Dr. Wilson concluded.

“Long-term follow-up suggests that in patients with breast cancer or who can’t or won’t have radiation, eRFA can reduce local recurrence without the need of radiation therapy, and these patients reported good to excellent cosmesis.”

This study is important in demonstrating the potential of eRFA to benefit breast cancer patients and allow for potential breast conservation, said Peter Beitsch, MD, a surgical oncologist at the Dallas Surgical Group in Texas.

“This small study, with relatively short follow-up, is very innovative and [demonstrates that eRFA allows] complete local treatment in one setting,” said Dr. Beitsch.

“Not only is it extremely convenient for patients, eRFA may allow more women the opportunity of breast preservation when the logistics of travel to and from the radiation center makes mastectomy their only option.”

“I look forward to the larger study and continued follow-up of this cohort to ensure the persistence of local control,” he said.

Dr. Wilson’s team has opened a multicenter trial — ABLATE (Adjunctive Breast Lumpectomy With RF Ablation Treatment to Reduce Re-Excision & Recurrence) — and recruiting is underway at 5 centers.

The study was funded by research grant from AngioDynamics and the Fashion Footwear Association of NY and QVC.

American Society of Breast Surgeons (ASBS) 13th Annual Meeting: Abstract 0136. Presented May 4, 2012.

Breast Cancer Redefined into 10 Genetic Subtypes, May Lead to Better Treatment

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Posted 20 Apr 2012 — by James Street
Category Breast Cancer, genetic research

A group of scientists have reclassified breast cancer as having 10 genetic subtypes, instead of having four as previously thought, in a breakthrough study that could change the way that breast cancer is currently diagnosed and treated.

By Christine Hsu | April 18, 2012

A group of scientists have reclassified breast cancer as having 10 genetic subtypes, instead of having four as previously thought, in a breakthrough study that could change the way that breast cancer is currently diagnosed and treated.

The discovery published in April 18 the journal Nature, which found breast cancer to be a culmination of at least 10 diseases also identified several completely new genes that drive breast cancer, offering potential targets for new kinds of drugs.

These newly identified genes that impact the function of cell signaling pathways, networks that control cell growth and division, could enable researchers to pinpoint how these gene faults disrupt important cell processes to cause cancer.

Researchers said that the latest findings mean that people should now see cancer as an “umbrella term” for a larger number of diseases.

The findings will also allow doctors to better predict survival times in patients and personalize treatment to match specific tumor types, said co-author Carlos Caldas at Cancer Research UK’s Cambridge Research Institute.

“Essentially we’ve moved from knowing what a breast tumor looks like under a microscope to pinpointing its molecular anatomy,” Caldas said in a statement.

“This research won’t affect women diagnosed with breast cancer today. But in the future, breast cancer patients will receive treatment targeted to the genetic fingerprint of their tumor.”

Breast cancer accounts for 16 percent of all female cancer cases, making it the most common cancer among women worldwide, according to the World Health Organization.

The Institute for Health Metrics and Evaluation in the United States conducted a study last year and found that the breast cancer cases around the world have more than doubled in the last 30 years, from 641,000 cases in 1980 to 1.6 million cases in 2010, a growing rate that dramatically exceeds the global population growth.

Researchers at Cancer Research UK’s Cambridge Research Institute and the BC Cancer Agency in Vancouver analyzed the genetic material, DNA and RNA, of 2,000 frozen tumor samples from patients diagnosed with the disease at five different hospitals for mutations and other changes and grouped them into 10 subtypes with common genetic features that correlate with survival.

Researchers explained that the combined analysis of DNA and RNA, which translates DNA into proteins, uncover the identity of oncogenes, genes that drive cancer, and of tumor suppressor genes, which protect against the disease.

The current method of diagnosing and treating women with breast cancer involves analyzing tumor samples for the presence of biomarkers such as estrogen receptors or the cell surface receptor HER2, Caldas said in a news conference.

While the results of current test only determine which of the four existing subtypes of breast cancer a patient has, depending on the presence of two hormone receptors ER and HER-2, which ultimately influences the treatment and prognosis the patient receives, the new classification of 10 subtypes means that patients will know more precisely which type of cancer they have and as newer and more targeted drugs are developed, patients should be able to receive more effective or tailored treatments.

Caldas said that seven of the new subtypes found in the study were defined as ER-positive and HER-2 negative, and cancer survival time for each of the seven genetic subtypes varied widely from 80 percent to less than 40 percent after 15 years from diagnosis.

Researchers said that more research is needed to determine how tumors in each subgroup behave, like how they grow and how fast they spread. Other research is needed in the laboratory and in patients to find the most effective way to treat each of the 10 subtypes of the disease.

“The new molecular map of breast cancer points us to new drug targets for treating breast cancer and also defines the groups of patients who would benefit most,” co-author Professor Samuel Aparicio at the BC Cancer Agency in Vancouver said in a statement. “The size of this study is unprecedented and provides insights into the disease such as the role of immune response, which will stimulate other avenues of research.”

“This landmark study will completely change the way we look at breast cancer. It’s the result of decades of research by our scientists to identify the causes and drivers of the disease, which included a pivotal role in decoding the well-known BRCA genes,” Harpal Kumar, Cancer Research UK’s chief executive added.

Parker Waichman LLP Warns that Cancer Research Study Reports Injectable Contraceptive Doubles Breast Cancer Risk

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Posted 15 Apr 2012 — by James Street
Category Birth Control, Breast Cancer, Carcinogens, Legal Issues

Cancer researchers are reporting that young women who have been taking Depo-Provera for more than a year may be twice as likely to develop invasive breast cancer. Parker Waichman LLP is currently investigating this possible Depo-Provera side effect, and is actively assessing potential Depo-Provera breast cancer lawsuit claims.

New York, New York (PRWEB) April 09, 2012

Parker Waichman LLP, a national law firm representing victims of defective drugs and medical devices, is evaluating potential lawsuit claims related to Depo-Provera (depo-medroxyprogesterone acetate or DMPA) and breast cancer. The birth control shots, which are given once every three months, prevent pregnancy solely through progestin; many other contraceptives incorporate a progestin-estrogen combination. According to a new study published in the April 15th issue of Cancer Research, the injectable contraceptive can double the risk of invasive breast cancer in young women. [cancerres.aacrjournals.org/content/early/2012/02/25/0008-5472.CAN-11-4064.abstract?sid=b94f53d7-cd3e-4624-af50-5a8b0a5cc970]

This is not the first time Depo-Provera has been associated with an increased risk of breast cancer. According to the Cancer Research study, the contraceptives shot contains the same progestin as the menopausal hormone therapy regimen found to increase breast cancer risk among postmenopausal women in the Women’s Health Initiative clinical trial. Lead researcher on the Cancer Research study and breast cancer epidemiologist Christopher I. Li M.D., Ph.D, of the Fred Hutchinson Cancer Research Center, also notes that multiple studies involving young women and DPMA have produced mixed findings. “Our study adds to the body of knowledge from international studies conducted in a diverse group of countries – Kenya, New Zealand, Thailand, Mexico and Costa Rica – which have shown that one of the risks associated with DMPA use may be an increased risk of breast cancer,” Dr. Li said in a press release issued by the Fred Hutchinson Cancer Center. Dr. Li’s study is the first major U.S. based study showing that Depo-Provera can also pose this danger to younger women; his team studied nearly 2,000 women between the ages of 20 to 44, the release said. [fhcrc.org/content/public/en/news/releases/2012/04/dmpa-breast-cancer-risk-chris-li.html]

Depo-Provera has also been linked to other serious side effects, such as bone loss. The risks associated with the injectable birth control appeared so severe that the FDA has advised it as a last resort, stating that “Depo-Provera Contraceptive should be used as a long-term birth control method (eg, longer than 2 years) only if other birth control methods are inadequate.” [fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm154784.htm?utm_campaign=Google2&utm_source=fdaSearch&utm_medium=website&utm_term=depo-provera&utm_content=1]

The new study, however, shows that the risk of breast cancer in young women can increase 2.2-fold after only one year. The study also found that the risk seemed to decline months after women stopped taking Depo-Provera, which only strengthens the correlation. Li’s findings echo the FDA’s cautioning advice about Depo-Provera. “In the United States many women have numerous options for contraception, and so it is important to balance their risks and benefits when making contraceptive choices” Dr. Li said, according to the statement from the Fred Hutchinson Cancer Center.

In addition to reviewing cases concerning Depo-Provera and breast cancer, Parker Waichman LLP also helps victims affected by other contraceptives, including Yaz, Yasmin andNuvaRing.

Parker Waichman LLP offers free legal consultations to breast cancer patients attributing their diagnosis to Depo-Provera. If you or a loved one were diagnosed with breast cancer and you believe it to be a result of Depo-Provera injections, please contact their office by visiting the firm’s at Depo-Provera page http://www.yourlawyer.com. Free case evaluations are also available by calling 1 800 LAW INFO (1-800-529-4636).

For more information regarding Depo-Provera breast cancer lawsuits and Parker Waichman LLP, please visit: http://www.yourlawyer.com or call 1-800-LAW-INFO (1-800-529-4636).

Contact: Parker Waichman LLP

Herbert Waichman, Partner
(800) LAW-INFO
(800) 529-4636

http://www.yourlawyer.com

Freezing Cancer In Its Tracks

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Posted 31 Mar 2012 — by James Street
Category Breast Cancer

Friday, March 30, 2012 1:03 PM

Doctors have been able to freeze tumors in a small number of breast cancer patients, effectively destroying them to stop the disease’s growth and spread.

A team of Detroit researchers that reported progress in refining the technique – called “percutaneous cryoablation” – said it may offer doctors a new weapon in the arsenal of treatments for patients with advanced breast cancer that has spread to other parts of the body.

“If you envision cancer treatment as a three-legged stool: you have radiation therapy, surgery and chemotherapy,” said Dr. Peter J. Littrup, director of radiology research at the Karmanos Cancer Institute in Detroit. “We are introducing the fourth leg on the stool of cancer care: tumor [freezing].”

In a presentation at the Society of Interventional Radiology’s 37th Annual Scientific Meeting in San Francisco this week, Littrup and colleagues reported the results of a small study involving breast cancer patients whose disease had spread to other areas of the body.

The new freezing procedure was used to destroy secondary tumors in the liver, lung and kidney.

“There were no serious complications and all procedures were considered successful. All individual tumors remaining in the body were found and the local cancer did not recur,” the researchers concluded

“This therapy provides a minimal rate of cancer recurrence and no major complications, making these ice balls ideal for targeting metastatic tumors that are limited in number and location,” said Littrup.

He said he hopes the Detroit research will be “a stepping stone for a bigger study” involving more patients.

“If we can get more data that supports percutaneous cryoablation for metastatic breast cancer, it could be a huge finding,” he added.

Researchers noted breast cancer is the most common cancer in women, causing 1 million new cases and killing 370,000 people worldwide each year.

 

New medical device headed to KU could be ‘revolutionary’ tool for breast cancer

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Posted 19 Mar 2012 — by James Street
Category Breast Cancer, Gamma Ray, Gamma Ray, Physics and Engineering

KU Cancer Center to conduct trials on GammaPod, a device said to eliminate small breast tumors without surgery.

By ALAN BAVLEY

The Kansas City Star

It hasn’t been tried on a single patient yet, and already doctors are calling this new radiation therapy device for breast cancer “paradigm-changing” and “revolutionary.”

It’s the GammaPod, coming later this year to the University of Kansas Cancer Center.

Enthusiastic doctors say this $3 million-plus piece of technology could make it possible for the first time to eradicate early-stage breast tumors without surgery; they’ll be nuked to oblivion by just a week of intensely focused radiation treatments. No risk of scars, infections or breast deformities.

That’s sure to pique the interest of the roughly 150,000 women who undergo lumpectomies each year in the United States.

But don’t get your hopes up just yet, more skeptical doctors counsel. Nobody before has been able to destroy breast tumors with radiation alone. And it will take years of clinical trials before there’s proof that GammaPod works as well as the conventional combination of an operation to remove a lump in the breast followed by about six weeks of radiation therapy.

So far, the GammaPod has stayed under the media’s radar, deliberately, its manufacturer says, to avoid raising public expectations prematurely.

That’s likely to change later this year when the devices are delivered first to the University of Maryland, where it was invented, then to KU and the University of Texas Southwestern Medical Center in Dallas, and shortly after that, to Allegheny General Hospital/Western Pennsylvania Hospital in Pittsburgh and Thomas Jefferson University Hospital in Philadelphia.

These five medical centers will conduct the first clinical trials of the GammaPod to develop the evidence that will be needed before it can be considered a worthwhile alternative to surgery.

But like other high-tech marvels that promise to make medical treatment safer, less painful and more convenient, GammaPods could proliferate at hospitals around the country long before all the data are in.

As early as next year, the GammaPod’s manufacturer, Xcision Medical Systems of Columbia, Md., expects to ask the U.S. Food and Drug Administration to green-light commercial sales of the device. FDA rules allow devices to be sold without clinical trials to back them up.

“Our goal is to make this commercially available in community settings around the world,” said Xcision vice president Will Wells. “A 10 percent (U.S.) market penetration after a few years would be about right.”

That translates into sales of about 200 GammaPod systems in just the first three years that it’s on the market, Wells estimated.

That comes as no surprise to Donald Patrick, a health policy researcher at the University of Washington and co-author of the book “Hope or Hype: The Obsession with Medical Advances and the High Cost of False Promises.”

“All sorts of things are touted as effective. The public demands them,” Patrick said. “We want something that’s easy and helps us live forever. That’s the American way — anything new.”

• • •

Medical devices that have entered the market before there was substantial evidence they improved care range from $1 million surgical robots to $100 million proton cancer therapy centers.

The GammaPod uses a proven technology called stereotactic body radiation therapy to successfully obliterate inoperable brain tumors and hard-to-reach lung and liver cancers. While the technology has never been used on breast tumors, that may not stop Xcision from getting swift FDA approval to go to market.

The FDA usually considers new stereotactic radiation devices as similar to existing ones, said Jim Keller, vice president of the nonprofit ECRI Institute, which does research on the effectiveness of medical devices. As long as a manufacturer can show that its new device is as safe and effective as others already on the market, FDA will give its assent without additional tests on patients.

Stereotactic radiation devices generally are approved for treatment of “lesions, tumors or conditions anywhere in the body,” Keller said.

But ultimately, the FDA’s ruling, Keller said, will “come down to their marketing claims, how the manufacturer plans to market the clinical effects.”

Wells of Xcision is mindful of what he says.

“We don’t want to create a buzz around something we can’t deliver,” he said. “This is early on. It’s best for us to gain data … as to not hype or overdraw our own technology prematurely.”

That hasn’t stopped others from being bolder.

“We can deliver a high enough dose to (neutralize) the tumor,” the GammaPod’s inventor, Cedric Yu, said in a University of Maryland press release from 2010.

“The traditional three-month ordeal can be shortened to three treatments only,” Yu said. “You don’t need surgery. You don’t need standard radiation. No needle, knife, pain, anesthesia, and no scar.”

By last November, in a keynote address to a University of Maryland breast cancer conference, Yu was calling his device “a paradigm-changing technology.”

“I don’t use this word lightly, but I would consider this device revolutionary,” said radiation oncologist Parvesh Kumar, the associate director of clinical research at KU Cancer Center. “This is absolutely huge.”

Kumar will lead research on the GammaPod at KU.

If it’s successful at eradicating tumors, the GammaPod would free women not only from the complications of breast surgery, but the costs as well, about $20,000 to $30,000 for a lumpectomy, Kumar estimated.

The cost of GammaPod treatments would likely be similar to that of conventional radiation, about $20,000 to $40,000, he said.

• • •

 

The five medical centers receiving the first GammaPods are developing a detailed five-year experimental plan called a protocol for testing the device, Kumar said.

The initial patients will be post-menopausal women with less-aggressive, early-stage breast cancer. Only women most likely to have a favorable outcome from treatment — those with small tumors and cancer that hasn’t spread to lymph nodes — will be admitted to the clinical trial.

At first, women in the study will undergo a conventional lumpectomy and receive GammaPod treatments either before or after their operation, Kumar said. Treatments given before surgery will show the researchers how effective the radiation is at killing breast tumors and allow them to determine what dose is needed.

Women will lie face down on the GammaPod’s specially designed table. Through a large gap in the table, a cup will lock onto the breast to keep it absolutely stationary and precisely positioned for the radiation.

From beneath the table, beams of radiation will strike the tumor from different directions. None of the individual beams will be strong enough to harm the healthy tissue they pass through before reaching the tumor. But the combined strength of the beams bombarding the tumor will be calculated to give it a lethal dose.

“We think there will be virtually no toxicity” beyond the tumor, Kumar said. And nothing in the protocol will result in a poorer outcome for patients than conventional treatment, he said.

But with standard therapy already shown to be effective, entering the protocol for the GammaPod is “perhaps not for the faint of heart,” advised Phillip Devlin, an associate professor of radiation oncology at Harvard Medical School.

“To date, there is no therapy that replaces surgery in the treatment of early breast cancer,” Devlin said.

In the 1950s, researchers tried using high doses of radiation to get rid of breast tumors without surgery, Devlin said. The radiation damaged healthy breast tissue but didn’t kill the tumors.

“One shouldn’t forget history,” he said.

Stereotactic body radiation therapy has worked to good effect against tumors in other organs, Devlin said. It’s not unreasonable to think it might work against breast tumors.

“But it’s a hypothesis to test.” he said. Meanwhile, “the current paradigm (of surgery and radiation) saves a lot of women.”

How will hospitals use their GammaPods before clinical trials can determine whether it eradicates breast tumors?

“That’s a great question, but I can’t answer it,” said Wells of Xcision. “We make a (radiation) system…the actual prescription is not something we dictate.”

To reach Alan Bavley, call 816-234-4858 or send email to abavley@kcstar.com.

How Cancer Cells Change Once They Spread to Distant Organs

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Posted 28 Feb 2012 — by James Street
Category Breast Cancer, EMT, metastases, versican

ScienceDaily (Feb. 22, 2012) — Oncologists have known that in order for cancer cells to spread, they must transform themselves so they can detach from a tumor and spread to a distant organ. Now, scientists at Weill Cornell Medical College have revealed critical steps in what happens next — how these cells reverse the process, morphing back into classical cancer that can now grow into a new tumor.

Their findings, now published online and in a upcoming issue of Cancer Research and funded through a National Cancer Institute grant to the Cornell Center on the Microenvironment and Metastasis and the Neuberger Berman Foundation, show that a single protein, versican, is key to this process in breast cancer, the tumor they studied. When researchers stopped versican from functioning in mice, breast cancer could not “seed” themselves into the lungs and form secondary tumors.

“Our findings both help us understand how breast cancer metastasizes to the lungs and ways to possibly prevent that deadly spread,” says the study’s senior investigator, Dr. Vivek Mittal, an associate professor of cell and developmental biology in cardiothoracic surgery and director of the Neuberger Berman Lung Cancer Laboratory at Weill Cornell Medical College.

“These are exciting insights into a poorly investigated area,” Dr. Mittal says. “There are no clinically approved drugs now that can effectively target metastatic lesions, which is why more than 90 percent of human cancer-related deaths come from spread of the disease from a primary tumor.”

“The results of this study are a critical step in deconstructing the process of metastases — which is critical to curing our patients,” says co-author Dr. Linda T. Vahdat, professor of medicine, chief of the Solid Tumor Service and director of the Breast Cancer Research Program at Weill Cornell. “As a direct result of this study, we are working on ways to interrupt the process by which tumors co-opt the infrastructure in our bodies to grow and spread.”

This important study starts to unravel the mechanistic basis of cancer metastases, not only in breast cancer but possibly in other types of cancer, says Dr. Nasser Altorki, the David B. Skinner Professor of Thoracic Surgery at Weill Cornell Medical College and director of the division of thoracic surgery at NewYork-Presbyterian/Weill Cornell. “The need for a prepared and receptive soil may be required for cancer cell seeding regardless of the primary cancer’s site of origin.”

The Seed and the Soil Cancer researchers have believed that for a cancer to spread, its “seed” must find the right “soil” in a distant organ in order to thrive. And they have hypothesized that this seed is formed through a process known as epithelial-mesenchymal transition (EMT), in which cancer cells lose their sticky grip to other cells in a primary tumor and become more mobile, able to travel through the blood to a distant organ.

But what happens next is conjecture. Scientists have speculated that the cells undergo a reverse process, called mesenchymal-epithelial transition (MET), in which the cancer seeds morph back into epithelial cells that can make contact with tissue and integrate in the new organ. Little is known about MET compared to EMT.

In this study, Dr. Mittal, along with his colleagues at Weill Cornell, studied mouse models of spontaneous breast cancer development. They first discovered that primary breast tumors send a signal that forces bone-marrow-derived hematopoietic cells to move into the lungs of the mice. “This appears to be the soil the cancer seeds need,” says Dr. Mittal. The next question was obvious: What is it about the soil that helps the seed?

The team found that a subtype of these bone marrow cells expressed versican, which allowed the cancer cells, once they traveled to the lungs, to morph back into epithelial cells. “The primary tumor sets up the lung microenvironment to promote metastasis,” he says. “MET resulted not from properties within the cancer cell itself, but due to a unique crosstalk between the microenvironment and tumor cells in the lung.”

In their next experiment, the researchers blocked versican production by injecting small interfering RNAs (siRNAs) in the bone marrow that silenced the versican gene, which prevented MET and blocked tumor outgrowth in the lung.

Human Tumors Express Versican Next, they investigated human breast metastases to the lung, utilizing lung samples obtained from breast cancer patients contributed by researchers at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University. “We found versican was highly expressed in those lung tumors, which matched what we found in our mice,” Dr. Mittal says. “This all made sense to us, because versican has been linked to cancer progression, although no one knew why.

“This is the first study demonstrating the significance of MET in the formation of macrometastases in distant organs,” Dr. Mittal says. “Given the findings, we now have a potential strategy to stop cancer spread before it starts, or to shut it down if it has already occurred.”

The study was funded by support from the Neuberger Berman Lung Cancer Laboratory, the Robert I. Goldman Foundation and National Cancer Institute support of the Cornell Center on the Microenvironment and Metastasis.

Study co-authors include, from Weill Cornell Medical College: Dingcheng Gao, Natasha Joshi, Hyejin Choi, Seongho Ryu, Mary Hahn, Raul Catena, Patrick Wagner, Linda T. Vahdat, Jeffrey L. Port, Brendon Stiles and Nasser K. Altorki; from Johns Hopkins University: Saraswati Sukumar, Helen Sadik and Pedram Argani; and Shahin Rafii from the Howard Hughes Medical Institute and Weill Cornell Medical College.

Study Reveals How Normal Cells Fuel Tumor Growth

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Posted 22 Dec 2011 — by James Street
Category Breast Cancer, ETS2, miR-320, PTEN, RNAi

Research summary: · The study shows how normal cells in tumors can enhance the growth of the tumor’s cancer cells after losing an important tumor suppressor gene called Pten. · The findings suggest a new strategy for treating breast cancer by interrupting signals between normal cells and cancer cells in tumors.

COLUMBUS, Ohio – A new study published in the journal Nature Cell Biology has discovered how normal cells in tumors can fuel tumor growth.
Led by researchers at the Ohio State University Comprehensive Cancer Center –  Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), the study examines what happens when normal cells called fibroblasts in mouse mammary tumors lose an important tumor-suppressor gene called Pten (pronounced “P-ten”).
The findings suggest new strategies for controlling tumor growth by developing drugs that disrupt the communication between tumor cells and the normal cells within the tumor. They also provide insight into the mechanisms that control the co-evolution of cancer cells and surrounding normal cells in tumors, and they demonstrate how the Pten gene normally suppresses cancer development, the researchers say.
“Our study is the first to define a specific pathway in tumor fibroblasts that reprograms gene activity and the behavior of multiple cell types in the tumor microenvironment, including tumor cells themselves,” says co-principal investigator Dr. Michael Ostrowski, professor and chair of molecular and cellular biochemistry.
“Along with increasing basic knowledge about how tumors grow and spread, these findings have direct translational implications for the treatment of breast-cancer patients,” says Ostrowski, who is a member of the OSUCCC – James Molecular Biology and Cancer Genetics program.
The researchers found that Pten regulates a molecule called microRNA-320 (miR-320), and that the loss of Pten leads to a dramatic drop in levels of that molecule in a tumor fibroblast. With little miR-320 around, levels of a protein called ETS2 (pronounced Ets-two) rise in the fibroblast.
Finally, the abundance of ETS2 activates a number of genes that cause the fibroblast to secrete more than 50 factors that stimulate the proliferation and invasiveness of nearby cancer cells. It also causes the reprogramming of other fibroblasts in the tumor and throughout the mammary gland.
“The cancer field has long focused solely on targeting tumor cells for therapy,” says co-principal investigator Gustavo Leone, associate professor of molecular virology, immunology and medical genetics. “Our work suggests that modulation of a few key molecules such as miR-320 in noncancer cells in the tumor microenvironment might be sufficient to impede the most malignant properties of tumor cells.”
Ostrowski, Leone and their colleagues began this study by examining human invasive breast tumors from 126 patients for microRNA changes after PTEN loss. Key technical findings include the following:
·         Using mouse models, they found that miR-320 levels and ETS2 levels were inversely correlated in human breast-tumor tissue, suggesting that Pten and miR-320 work together to block ETS2 function and suppress tumor growth.
·         miR-320 in mammary fibroblasts influences the behavior of multiple cell types, making it a critical molecule for suppressing epithelial tumors.
·         miR-320 functions as a regulatory switch in normal fibroblasts that operates to inhibit the secretion of more than 50 tumor-promoting factors (i.e., a tumor-promoting secretome). In doing so, it blocks the expression of genes in other cell types in the tumor microenvironment and suppresses tumor-cell growth and invasiveness.
·         Overall, loss of Pten in tumor fibroblasts results in downregulation of miR-320 and release of the secretome factors. This causes the genetic reprogramming of neighboring endothelial and epithelial cells of the mammary gland, inciting profound changes in these cells that are typical of malignant tumors.
“Remarkably, the molecular signature of the miR-320 secretome could distinguish normal breast tissue from tumor tissue, and it predicted the outcome in breast-cancer patients,” says Leone, who is also a member of the OSUCCC – James Molecular Biology and Cancer Genetics program. “This underscores the potential clinical importance of the Pten-miR-320 regulatory pathway on human breast cancer.”
Funding from the National Cancer Institute, National Institute of Child Health and Human Development, the Komen Breast Cancer Foundation and Evelyn Simmers Charitable Trust supported this research.
Other researchers in this study were Agnieszka Bronisz, Jakub Godlewski, Julie A. Wallace, Anand.S. Merchant, Michal O. Nowicki, Haritha Mathsyaraja, R. Srinivasan, Anthony J. Trimboli, Chelsea K. Martin, F. Li, L. Yu, Soledad A. Fernandez, T. Pécot, Thomas J. Rosol, M. G. Piper, Clay B. Marsh, Lisa D. Yee, G. Nuovo and E. Antonio Chiocca of Ohio State; S. Cory and M. Hallett and M. Park of McGill University; R. E. Jimenez14 of Mayo Clinic; and Sean. E Lawler of Leeds Institute of Molecular Medicine.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (cancer.osu.edu) strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only seven centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State’s cancer program as “exceptional,” the highest rating given by NCI survey teams. As the cancer program’s 210-bed adult patient-care component, The James is a “Top Hospital” as named by the Leapfrog Group and one of the top 20 cancer hospitals in the nation as ranked by U.S.News & World Report.

Scientists have devised a new, experimental vaccine that seems to be effective at shrinking cancerous tumors in mice by up to 80 percent.

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Posted 13 Dec 2011 — by James Street
Category Breast Cancer, MUC1 protein, MUC1 protein, Vaccine

Scientists have devised a new, experimental vaccine that seems to be effective at shrinking cancerous tumors in mice by up to 80 percent.

The vaccine worked at shrinking similar mouse versions of breast and pancreatic tumors, but researchers from the University of Georgia and the Mayo Clinic said that it could be applied to other cancers, too, including colorectal and ovarian cancers and multiple myeloma.

Scientists have been working for decades to find a way to mobilize the immune system to be able to identify cancerous cells. The problem has always been that the immune system doesn’t recognize the cancerous cells as dangerous because they originated from the body in the first place, and therefore doesn’t attack them, researchers said.

But the new vaccine works by targeting the sugar coating of a protein called MUC1 located on the surfaces of the cancerous cells. The sugar coating differentiates the cancerous cells from normal, healthy cells. The mice were engineered so that their cancer cells overexpressed MUC1, just like human cancer cells do.

“This is the first time that a vaccine has been developed that trains the immune system to distinguish and kill cancer cells based on their different sugar structures on proteins such as MUC1,” study researcher Sandra Gendler, a professor at the Mayo Clinic, said in a statement. “We are especially excited about the fact that MUC1 was recently recognized by the National Cancer Institute as one of the three most important tumor proteins for vaccine development.”

The study will appear in the journal Proceedings of the National Academy of Sciences.

The vaccine has potential to be used on a wide variety of cancers because more than 70 percent of deadly cancers have the MUC1 protein, researchers said. AOL Lifestyle reported that researchers hope to try the vaccine in humans in the next couple of years.

And because MUC1 is overexpressed in 90 percent of people who were unresponsive to other therapies like Tamoxifen or Herceptin, the vaccine might in the future be a viable option for people whose cancers are difficult to treat, researchers added.

The experimental cancer vaccines in the works today are different from the preventive vaccines (like ones that ward off cervical cancer-causing HPV), which prevents cervical cancer.

The Daily Beast explains:

By “cancer vaccine,” scientists mean something that will stimulate the immune system to attack malignant cells.

Recently, researchers at the National Cancer Institute developed a promising vaccine that seems to stop the spread of metastatic breast and ovarian cancers in humans. The poxviral vaccine even seemed to be effective at completely ridding one person involved in the study of cancer, WebMD reported.

However, the vaccine wasn’t as overwhelmingly successful in the other 25 patients — for some of those people, the vaccine seemed to extend the amount of time before the cancer progressed by a few months, WebMD noted.

And earlier this year, University of Pennsylvania researchers announced a leukemia treatment that seems effective at obliterating leukemia cells, and was shown to completely rid patients of the cancer or at least significantly decrease their number of cancerous cells.