Archive for the ‘Cancer Types’ Category

This Week in the Journal of the National Cancer Institute

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Posted 18 May 2012 — by James Street
Category Osteosarcoma
May 17, 2012

In the Journal of the National Cancer Institute this week: glycogen synthase kinase-3β in human osteosarcoma, staging systems for pancreatic neuroendocrine neoplasms, and more.

Full article at GenomeWeb  (Requires login)

J&J’s Zytiga Helps Eliminate Early-Stage Prostate Cancer

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Posted 17 May 2012 — by James Street
Category Prostate Cancer, Zytiga
By Michelle Fay Cortez – May 17, 2012

Johnson & Johnson (JNJ)’s Zytiga, approved last year to treat metastatic prostate cancer, helped eliminate tumors in high-risk patients whose malignancy hadn’t yet spread, a small study found.

The pill was given as an initial therapy before surgery to 58 patients with aggressive tumors that were confined to the prostate gland, a group typically treated with radiation. These patients are rarely cured by surgery and previous studies using older drugs failed to improve survival, said Mary-Ellen Taplin, an associate professor at Harvard Medical School in Boston.

One-third of those on Zytiga for six months showed no cancer or only trace levels when the prostate gland was removed, said Taplin, who is the lead researcher. Fifteen percent of men on it for three months had a similar benefit. The drug, with $200 million in worldwide sales in 2011, may eventually generate $1 billion annually, said Larry Biegelsen, an analyst at Wells Fargo Securities in New York, in a May 1 note to investors.

“What we’ve shown is that the concept is valid, that in some patients you can eliminate the cancer completely,” Taplin said in a telephone interview. “To really prove what the overall benefit is to a patient with this type of approach, you would have to do a very large trial.”

J&J rose less than 1 percent to $63.74 at 10:44 am. in New York. Dendreon Corp., which makes a rival medicine to Zytiga, dropped 8.2 percent to $7.91, after previously declining to $7.40, its lowest intraday price since Jan. 4.

$5,000 Cost

J&J’s once-a-day drug, which costs about $5,000 a month, targets a protein to block production of the androgen hormone that fuels prostate cancer growth. While other medications can stop androgen production in the testes and adrenal glands, Zytiga also shuts it down inside the tumor itself.

Participants in the study were also given the generic hormone therapy leuprolide and steroids.

Prostate cancer is the most-common tumor in men, according to the American Cancer Society. Fifteen percent of the 218,000 Americans diagnosed with it each year have it spread beyond the walnut-sized gland that lies between the bladder and urethra, according to the National Cancer Institute.

J&J, which helped fund the initial study, isn’t planning any additional research on the use of Zytiga as an initial therapy in men with high-risk, local disease that hasn’t spread, said Kellie McLaughlin, a spokeswoman for the New Brunswick, New Jersey-based company.

The Prostate Cancer Foundation also helped fund the study, which was conducted by the Department of Defense-supported Prostate Cancer Clinical Trial Consortium.

Further Studies

Taplin, an oncologist at the Dana-Farber Cancer Institute in Boston, said she is working on a trial that adds the experimental medication ARN-509 from closely held Aragon Pharmaceuticals Inc., based in San Diego, to the mixture of Zytiga and the steroid prednisone used in the current study. She is also exploring the use of Medivation Inc. (MDVN)’s prostate cancer drug MDV3100, which also blocks androgen production, before surgery in high-risk patients.

The findings released yesterday will be presented at the American Society of Clinical Oncology meeting in Chicago on June 2. The results were released ahead of the event by the organizers to coincide with the publication of the study’s abstract.

Among the 29 men who received Zytiga for the entire six months, three had no signs of cancer once the prostate was eliminated, while seven had very low levels, Taplin said. One of the 27 men treated for three months had no cancer, and three had only a smattering of cancer cells, she said.

Results from a pivotal trial examining the use of Zytiga before chemotherapy in patients with prostate cancer that has spread will also be presented at the meeting. The studies may boost use of the drug in patients who aren’t formally approved to receive it, making it one of several medicines to accelerate J&J’s sales growth, Biegelsen, of Wells Fargo, wrote.

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

Prognostic factors in canine appendicular osteosarcoma – a meta-analysis

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Posted 17 May 2012 — by James Street
Category Dog Osteosarcoma

Appendicular osteosarcoma is the most common malignant primary canine bone tumor. When treated by amputation or tumor removal alone, median survival times (MST) do not exceed 5 months, with the majority of dogs suffering from metastatic disease.

This period can be extended with adequate local intervention and adjuvant chemotherapy, which has become common practice. Several prognostic factors have been reported in many different studies, e.g.

age, breed, weight, sex, neuter status, location of tumor, serum alkaline phosphatase (SALP), bone alkaline phosphatase (BALP), infection, percentage of bone length affected, histological grade or histological subtype of tumor. Most of these factors are, however, only reported as confounding factors in larger studies.

Insight in truly significant prognostic factors at time of diagnosis may contribute to tailoring adjuvant therapy for individual dogs suffering from osteosarcoma.The objective of this study was to systematically review the prognostic factors that are described for canine appendicular osteosarcoma and validate their scientific importance.

Results: A literature review was performed on selected studies and eligible data were extracted. Meta-analyses were done for two of the three selected possible prognostic factors (SALP and location), looking at both survival time (ST) and disease free interval (DFI).

The third factor (age) was studied in a qualitative manner. Both elevated SALP level and the (proximal) humerus as location of the primary tumor are significant negative prognostic factors for both ST and DFI in dogs with appendicular osteosarcoma.

Increasing age was associated with shorter ST and DFI, however, was not statistically significant because information of this factor was available in only a limited number of papers.

Conclusions: Elevated SALP and proximal humeral location are significant negative prognosticators for canine osteosarcoma.

Author: Ilse BoermanGayathri T SelvarajahMirjam NielenJolle Kirpensteijn
Credits/Source: BMC Veterinary Research 2012, 8:56

Melanoma: Whole-genome sequencing of 25 tumors confirms role of sun damage, reveals new genetic alterations

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Posted 10 May 2012 — by James Street
Category Gene sequencing, genetic research, Melanoma, Melanoma

May 9, 2012 by Elizabeth Cooney in Cancer

Melanoma – the deadliest and most aggressive form of skin cancer – has long been linked to time spent in the sun. Now a team led by scientists from the Broad Institute and Dana-Farber Cancer Institute has sequenced the whole genomes of 25 metastatic melanoma tumors, confirming the role of chronic sun exposure and revealing new genetic changes important in tumor formation.

In an article published online May 9 in Nature, the authors provide the first high-resolution view of the genomic landscape of human tumors. Previous genetic analyses have focused on the exomes of many types of cancer tumors, concentrating on the tiny fraction of the genome that provides the genetic code for producing proteins. Whole genomes contain a wealth of genetic information, and by sequencing and analyzing 25 metastatic melanoma tumors – a significant technical and computational feat – scientists can learn vastly more about the variety of genetic alterations that matter in melanoma.

“Sequencing the whole genome certainly adds a richness of discovery that can’t be fully captured with a whole exome,” said Levi A. Garraway, a senior associate member of the Broad Institute, an associate professor at Dana-Farber Cancer Institute and Harvard Medical School, and co-senior author of the paper.

“By looking across the entire genome you can more accurately determine the background mutation rate and the different classes of mutations, and more confidently describe the pattern of ultraviolet-induced mutagenesis in melanoma,” said Michael F. Berger, co-first author of the paper. He worked in the Broad’s cancer genome analysis group and with Garraway as a research scientist and computational biologist before moving to Memorial Sloan-Kettering Cancer Center.

When the scientists explored the whole genome data generated and analyzed at the Broad, they found that the rates of genetic mutations rose along with chronic sun exposure in patients, confirming the role of sun damage in disease development.

“Whole-genome analysis of human melanoma tumors shows for the first time the existence of many structural rearrangements in this tumor type,” said Lynda Chin, a senior associate member of the Broad and co-senior author of the paper. Formerly at Dana-Farber and Harvard Medical School, she is now chair of the Department of Genomic Medicine at the University of Texas MD Anderson Cancer Center.

As expected, the scientists detected known BRAF and NRAS mutations in 24 of the 25 tumors. Both genes are involved in sending signals important in cell growth.

One other gene leaped out: PREX2, previously implicated in breast cancer for blocking a tumor-suppressor pathway, was altered in 44 percent of patients. In a larger validation cohort of 107 tumors, the frequency of the mutation was 14 percent.

PREX2 is mutated in a convergence of genetic disruption that appears to accelerate tumor development. Its mutations occurred not just at hot spots that typically turn on an oncogene, a type of cancer-causing gene, and drive cancer forward. The alterations were also scattered across the length of the gene in a pattern typically seen when another type of cancer-causing gene, known as tumor suppressors, are turned off.

“The pattern of mutations here looks a lot more like a tumor suppressor gene, but from the functional experiments, it behaved more like an oncogene,” Berger said.

When PREX2 functions normally, it interacts with the protein PTEN. PTEN is well known as a tumor suppressor, controlling growth in normal cells. Mouse experiments in Chin’s lab at Dana-Farber showed that PREX2 mutations spurred tumor growth in ways that are not fully understood.

“We still can’t say we know exactly how it works,” Garraway said. “PREX2 may be in a very interesting new category of mutated cancer genes that point us to at least one and maybe more pathways that would be worth targeting therapeutically in melanoma.”

The identification of PREX2 may be the tip of the iceberg.

“New melanoma genes remain to be discovered by this unbiased approach, as illustrated by the discovery of PREX2 and the demonstration of its oncogenicity in vivo,” said Chin.

More information: Berger, Hodis, Heffernan, Deribe, Lawrence et al. “Melanoma genome sequencing reveals frequent PREX2 mutations.” Nature, May 10, 2012. doi:10.1038/nature11071

Provided by Massachusetts Institute of Technology (news : web)

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.

Beehive remedy may slow prostate cancer

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Posted 09 May 2012 — by James Street
Category propolis, propolis, propolis, Prostate Cancer

U. CHICAGO (US) — An over-the-counter remedy derived from honeybee hives stalls the growth of prostate cancer cells in mice.

Caffeic acid phenethyl ester, or CAPE, is a compound isolated from honeybee hive propolis, the resin used by bees to patch up holes in hives.

Propolis has been used for centuries as a natural remedy for conditions ranging from sore throats and allergies to burns and cancer. But the compound has not gained acceptance in the clinic due to scientific questions about its effect on cells.

In a paper published in Cancer Prevention Research, researchers from the University of Chicago combined traditional cancer research methods with cutting-edge proteomics to find that CAPE arrests early-stage prostate cancer by shutting down the tumor cells’ system for detecting sources of nutrition.

“If you feed CAPE to mice daily, their tumors will stop growing. After several weeks, if you stop the treatment, the tumors will begin to grow again at their original pace,” says Richard B. Jones, assistant professor in the Ben May Department for Cancer Research and Institute for Genomics and Systems Biology and senior author of the study.

“So it doesn’t kill the cancer, but it basically will indefinitely stop prostate cancer proliferation.”

Natural remedies isolated from plant and animal products are often marketed as cure-alls for a variety of maladies, usually based on vague antioxidant and anti-inflammatory claims.

While substances such as ginseng or green tea have been occasionally tested in laboratories for their medicinal properties, scientific evidence is commonly lacking on the full biological effects of these over-the-counter compounds.

“It’s only recently that people have examined the mechanism by which some of these herbal remedies work,” Jones says. “Our knowledge about what these things are actually doing is a bit of a disconnected hodge-podge of tests and labs and conditions. In the end, you’re left with a broad, disconnected story about what exactly these things are doing and whether or not they would be useful for treating disease.”

To study the purported anti-cancer properties of CAPE, first author Chih-Pin Chuu (now at the National Health Research Institutes in Taiwan) tested the compound on a series of cancer cell lines. Even at the low concentrations expected after oral administration, CAPE successfully slowed the proliferation of cultured cells isolated from human prostate tumors.

CAPE was also effective at slowing the growth of human prostate tumors grafted into mice. Six weeks of treatment with the compound decreased tumor volume growth rate by half, but when CAPE treatment was stopped, tumor growth resumed its prior rate. The results suggested that CAPE stopped cell division rather than killing cancerous cells.

To determine the cellular changes that mediated this effect, the researchers then used an innovative proteomics technique invented by Jones and colleagues called the “micro-western array.”

Western blots are a common laboratory tool used to measure the changes in protein levels and activity under different conditions. But whereas only one or a few proteins at a time can be monitored with Western blots, micro-western arrays allow researchers to survey hundreds of proteins at once from many samples.

Chuu, Jones, and their colleagues ran micro-western arrays to assess the impact of CAPE treatment on the proteins of cellular pathways involved in cell growth—experiments that would have been prohibitively expensive without the new technique.

“What this allowed us to do is screen about a hundred different proteins across a broad spectrum of signaling pathways that are associated with all sorts of different outcomes. You can pick up all the pathways that are affected and get a global landscape view, and that’s never been possible before,” Jones says.

“It would have taken hundreds of Westerns, hundreds of technicians, and a very large amount of money for antibodies.”

The micro-western array results allowed researchers to quickly build a new model of CAPE’s cellular effects, significantly expanding on previous work that studied the compound’s mechanisms.

Treatment with CAPE at the concentrations that arrested cancer cell growth suppressed the activity of proteins in the p70S6 kinase and Akt pathways, which are important sensors of sufficient nutrition that can trigger cell proliferation.

“It appears that CAPE basically stops the ability of prostate cancer cells to sense that there’s nutrition available,” Jones says. “They stop all of the molecular signatures that would suggest that nutrition exists, and the cells no longer have that proliferative response to nutrition.”

The ability of CAPE to freeze cancer cell proliferation could make it a promising co-treatment alongside chemotherapies intended to kill tumor cells. Jones cautioned that clinical trials would be necessary before CAPE could be proven effective and safe for this purpose in humans. But the CAPE experiments offer a precedent to unlock the biological mechanisms of other natural remedies as well, perhaps allowing these compounds to cross over to the clinic.

“A typical problem in bringing some of these herbal remedies into the clinic is that nobody knows how they act, nobody knows the mechanism, and therefore researchers are typically very hesitant to add them to any pharmaceutical treatment strategy,” Jones says.

“Now we’ll actually be able to systematically demonstrate the parts of cell physiology that are affected by these compounds.”

Research was supported by grants from the Cancer Research Foundation, American Cancer Society, National Institutes of Health, U.S. Department of Health, and National Science Council.

More news from the University of Chicago: http://news.uchicago.edu/

Moffitt Cancer Center researchers identify drivers of sarcoma growth and survival

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Posted 06 May 2012 — by James Street
Category Kinase, Osteosarcoma, Proteomics, Sarcoma, Tyrosine Kinase

Posted On: May 1, 2012 – 9:00pm

To better understand the signaling pathways active in sarcomas, researchers at Moffitt Cancer Center used state-of-the-art mass spectrometry-based proteomics to characterize a family of protein enzymes that act as “on” or “off” switches important in the biology of cancer. The tyrosine kinases they identified, the researchers said, could act as “drivers” for the growth and survival of sarcomas.

Sarcomas are relatively rare forms of cancer. In contrast to carcinomas, which arise from epithelial cells (in breast, colon and lung cancers, for example), sarcomas are tumors derived from bone, fat, muscle or vascular tissues.

“Sarcomas are rare, diverse malignancies that arise from connective tissues,” said study lead author Eric B. Haura, M.D., program leader for Experimental Therapeutics. “We hypothesized that we could identify important proteins that drive the growth and survival of these poorly understood sarcomas using an approach to characterize signaling proteins using mass spectrometry.”

According to Haura, whose lab focuses on signaling pathways in cancer and understanding the role of kinases, protein phosphorylation plays a significant role in a wide range of cellular processes and is commonly disrupted in diseases such as cancer. The study approach is novel by engaging proteomics, an emerging and increasingly powerful approach to study proteins in disease in a more global and unbiased manner.

In this study, the Moffitt researchers identified 1,936 unique tyrosine phosphorylated peptides corresponding to 844 unique phospho-tyrosine proteins and found 39 tyrosine kinases in sarcoma cells. Of the 99 tyrosine kinases present in the human genome, the research team identified peptides corresponding to nearly 40 percent of the tyrosine kinome.

“Tyrosine kinases play an important role in controlling the hallmarks of cancer, and they have a proven track record as druggable targets for cancer treatment. Our goal was to produce a ‘landscape’ of tyrosine phosphorylated proteins and tyrosine kinases prioritized for subsequent functional validation,” Haura said. “In our study, we identified numerous tyrosine kinases that can be important for cellular signaling in human sarcomas that could drive the natural progression of sarcoma and, therefore, could be targeted by small molecule inhibitors aimed at altering sarcoma progression.”

Questions remain, however, about which, if any, of the 40 tyrosine kinases the researchers identified in sarcoma tumor cell lines act to regulate sarcoma tumor cell growth and tumor survival.

“The answers to this question can help prioritize which potential targets to examine further, including advancement into trials of patients with advanced sarcoma,” explained Haura. “As a first step, we screened sarcoma cell lines against a number of inhibitors selected, all based on the tyrosine kinases we identified, and identified some active drugs.”

While the researchers found kinases in sarcoma cells that deserved further study, they also concluded that the sarcoma cells tested expressed multiple tyrosine kinases. That great number may limit the effectiveness of targeted agents.

“We think this approach could hold promise in profiling tumors directly from patients and can complement existing genetic data on sarcomas. Our results show this is feasible in tumor tissues, and we hope to advance this further by directly studying additional tumors from sarcoma patients.”

 

Small Molecular Bodyguards Kill HPV-Infected Cancer Cells by Protecting Tumor-Suppressor

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Posted 28 Apr 2012 — by James Street
Category Cervical, human papillomavirus (HPV)

ScienceDaily (Apr. 26, 2012) — Researchers at The Wistar Institute announce the discovery of small molecules that kill cancer cells caused by infection with human papillomavirus (HPV). Their results, in both cell and mouse models, demonstrate that the small molecule inhibitors protect a tumor-suppressing protein targeted by viral proteins, thus killing the infected tumor cells.

The Wistar scientists presented their findings in the April 20 issue of the journal Chemistry & Biology. The researchers believe that, with further testing and refinement, their inhibitors could provide a therapeutic for HPV-caused tumors, such as those seen in cervical cancer.

“While there is an effective vaccine for preventing HPV infection, there is currently no therapeutic that specifically targets cancers caused by the virus,” said Ronen Marmorstein, Ph.D., senior author, Hilary Koprowski, M.D. Professor, and leader of The Wistar Institute Cancer Center’s Gene Expression and Regulation program.

“HPV often turns cells cancerous for the virus’s own reproductive advantage, and we have found a class of small molecules that effectively prevents a key HPV protein from allowing cells to become cancerous,” Marmorstein said. “We think that this could be the start of an effective drug strategy for cancers caused by HPV.”

HPV is one of the primary infectious causes of cancer, responsible for most cases of cervical cancer, nearly 20 percent of all head and neck cancers, and has been implicated in cancers of the vagina, penis, and anus. American Cancer Society statistics estimate that over 4,000 women will die this year from cervical cancer alone.

The US Centers for Disease Control estimates that about 50 percent of sexually active men and women will be infected with HPV at one point in their lives. While most infected people will naturally fight off the infection, the virus frequently becomes “latent,” residing within the body for decades at a time. When HPV re-emerges from its latent state, it may cause host cells to become cancerous as the virus replicates.

According to Marmorstein, research has shown that the HPV protein, E7, targets an important tumor-suppressing protein called the retinoblastoma protein (pRb). When E7 binds to pRb, it disturbs the normal process of cell division, allowing the cells to grow out of control and unhindered and thus become cancerous.

In this latest study, the Wistar researchers describe the results of an exhaustive search for potential small molecule drug candidates to prevent E7 from binding to pRb. They screened a library of over 88,000 molecular compounds to find a class of small molecules that can prevent HPV-E7 from disabling pRb. Surprisingly, these inhibitors work by binding to pRb itself, yet do not seem to keep pRb from doing its normal job within the cell.

“Typically, you would think that an inhibitor would bind to the disease-causing ‘bad’ protein, in this case HPV-E7, but instead the inhibitor latches onto pRb itself,” Marmorstein said. “In any event, these inhibitors bind to the same spot on pRb that E7 clamps onto in order to disable pRb.”

Once attached to pRb, these inhibitors allow pRb to trigger the molecular mechanisms of normal cell division without the disruptive effect of E7 upon HPV infection.

In subsequent studies, conducted with Wistar Associate Professor Joseph Kissil, Ph.D., of Wistar’s Molecular and Cellular Oncogenesis program, one of these small molecular bodyguards proved effective in killing HPV-positive cells in mice.

“With this new class of inhibitors, we have a promising scaffold on which we can build therapies to treat HPV-related diseases,” Marmorstein said.

The Marmorstein laboratory is currently involved in additional research towards developing inhibitors that block the ability of another key HPV protein called E6 to inactivate another important tumor suppressor protein called p53, a protein that is inactivated in the majority of human cancers. In addition, refinement of the HPV-E7 inhibitors is continuing. Their work will involve gaining a better molecular understanding of how their HPV-E7 inhibitors bind to pRb, which will enable them to make more informed decisions on how to best refine the inhibitors so that they are both more effective and suitable for human use.

Funding for this project was through the National Institutes of Health’s National Cancer Institute.

The lead author of this study is Daniela Fera, a graduate student working at the Wistar Institute from the University of Pennsylvania Department of Chemistry. Other co-authors of this study include, David C. Schultz, Ph.D., Santosh Hodawadekar, Ph.D., and Scott Troutman from The Wistar Institute; Donna M. Huryn, Ph.D., and Jason Melvin from the University of Pennsylvania’s Department of Chemistry; and Melvin Reichman, Ph.D., and Preston Scott Donover, from the Chemical Genomics Center at The Lankenau Institute for Medical Research.

FDA Approves GSK Cancer Drug Votrient For Soft-Tissue Sarcoma

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Posted 28 Apr 2012 — by James Street
Category Sarcoma, Votrient
  • April 26, 2012, 8:02 p.m. ET

WASHINGTON (Dow Jones)–The Food and Drug Administration on Thursday approved GlaxoSmithKline PLC’s (GSK, GSK.LN) cancer drug Votrient for use in patients with soft-tissue sarcoma, making it the first new treatment for the rare type of cancer in decades.

Votrient, a tablet taken orally, is already on the U.S. market to treat advanced kidney cancer. It was approved to treat several subtypes of advanced soft-tissue sarcoma, after prior chemotherapy. The disease starts in muscle or other connective tissues in the body.

The National Cancer Institute estimates there are about 11,000 cases of soft-tissue sarcomas diagnosed in the U.S. each year.

Votrient’s approval follows the March recommendation of an agency advisory panel, which voted, 11-2, that the drug’s benefits outweighed the risks. Clinical data involving 369 patients showed the drug temporarily slowed tumor growth.

Specifically, the study showed patients being treated with Votrient had a median progression-free survival of 4.6 months compared with 1.6 months on the placebo, or a difference of three months in the time before the cancer starts to worsen.

The FDA noted that Votrient carries the agency’s toughest boxed warning, telling patients and health-care professionals about the potential risk of liver damage, which can be fatal. Patients should be monitored for liver function and treatment should be discontinued if liver function declines, the agency said.

The most common side effects seen in Votrient-treated patients were fatigue, diarrhea, nausea, weight loss, high blood pressure, decreased appetite, vomiting, tumor and muscle pain, hair color changes, headache, a distorted sense of taste, shortness of breath, and skin discoloration, the FDA said.

-Jennifer Corbett Dooren, Dow Jones Newswires; 202-862-9294; jennifer.corbett@dowjones.com

New Veridex Alliance Drives Study Of Circulating Tumor Cells In Men With Metastatic Prostate Cancer

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Posted 25 Apr 2012 — by James Street
Category Circulating Tumor Cells, zoledronic acid

press release

April 23, 2012, 11:13 a.m. EDT

Research will employ the Veridex CELLSEARCH® CTC Test, the only 510(k)-cleared in vitro diagnostic test to capture and count CTCs –

RARITAN, N.J., April 23, 2012 /PRNewswire via COMTEX/ — Veridex, LLC announced today that it has joined with Novartis Pharmaceuticals Corporation in an educational alliance to encourage and facilitate research involving circulating tumor cells, or CTCs, as a potential biomarker in metastatic prostate cancer.

As part of this initiative, Veridex will support a prospective, single arm, open-label study designed to investigate the effect of zoledronic acid* on CTCs in patients with metastatic castration-resistant prostate cancer (CRPC).

Dr. Ekkehardt Bismarck, M.D., of the EuromedClinic, Furth, Germany, one of the lead investigators, comments, “We hope to determine whether zoledronic acid may have an impact on CTC counts in the body. It is known that improvement of CTC counts has been associated with improved clinical outcomes.”

The study population will initially consist of a representative group of 60 CRPC patients with metastatic bone disease from five-to-10 study centers in Germany. The study will investigate the number of CTCs in study patients who receive zoledronic acid 4mg administered every four weeks for three months. The primary objective of the study is to determine the proportion of patients with decreased CTCs at 12 weeks after first infusion of zoledronic acid.

“Our alliance with Novartis further highlights the growing interest in CTCs as a potential biomarker in treating patients with metastatic prostate, breast and colorectal cancers,” said Robert McCormack, Ph.D. and Head of Technology Innovation at Veridex. “We look forward to further investigating the potential predictive benefit of CTCs in metastatic prostate cancer clinical studies as there are currently limited ways of assessing therapeutic benefit in this disease, especially when it has metastasized to the bone.”

“Our agreement with Novartis signifies our desire to collaborate with biopharmaceutical companies both internally and externally,” continued McCormack. “By leveraging our world-leading expertise in rare cell technology and developing current and future collaborations, we can drive to a more informed drug development model and help develop targeted treatments, making a significant difference for patients and their families.”

About Circulating Tumor CellsCirculating tumor cells are cancer cells that have detached from the tumor and are found at extremely low levels in the bloodstream. The potential clinical benefit of capturing and counting CTCs is being investigated as more research data is gathered about the potential utility of these markers in monitoring disease progression and potentially guiding personalized cancer therapy.

About the CELLSEARCH® CTC TestCELLSEARCH® is the first and only United States Food & Drug Administration 510(k)-cleared in vitro diagnostic (IVD) test to capture and count CTCs to determine the prognosis of patients with metastatic breast, colorectal or prostate cancer. The test can be administered at any time during the course of therapy as a routine blood test. It is used in combination with other tests and a clinician’s assessment, to provide a more complete picture of a patient’s prognosis.

About Veridex, LLCVeridex, LLC, a Johnson & Johnson company, is an organization dedicated to providing physicians with high-value diagnostic oncology products. Veridex IVD products may significantly benefit patients by helping physicians make more informed decisions that enable better patient care. Veridex Clinical Research Solutions provide tools and services that may be used for the selection, identification and enumeration of targeted rare cells in peripheral blood for the identification of biomarkers, aiding scientists in their search for new, targeted therapies. For more information, visit www.veridex.com .

*Editor’s Note: zoledronic acid is marketed by Novartis as ZOMETA®. For additional information on the safety and efficacy of ZOMETA and the full Prescribing Information, please visit www.zometa.com .

(This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Veridex, LLC and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to, general industry conditions and competition; economic factors, such as interest rate and currency exchange rate fluctuations; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; challenges to patents; changes in behavior and spending patterns or financial distress of purchasers of health care products and services; changes to governmental laws and regulations and domestic and foreign health care reforms; trends toward health care cost containment; and increased scrutiny of the health care industry by government agencies. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended January 1, 2012. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov , www.jnj.com or on request from Johnson & Johnson. Neither Veridex, LLC nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)

SOURCE Veridex, LLC

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