Treating tumors with salmonella bacteria can induce an immune response that kills cancer cells, scientists have found — a discovery that may help them create tumor-killing immune cells to inject into patients.

Researchers from Italy and the United States who worked with mouse and human cancer cells in laboratories said their work might help in developing a new drug in a class of cancer treatments called immunotherapies or therapeutic vaccines, which harness the body’s immune system to fight disease.

“We did experiments first in mice and then in cancer cells and immune cells from human patients, and found that the salmonella was doing exactly the same job,” Maria Rescigno of European Institute of Oncology in Milan, who worked on the study, said in a telephone interview. “Now we are ready to go into (testing on) humans, but we are waiting for authorization.”

The scientists said they thought the salmonella bacteria, which they used in a safe form that did not cause illness itself, helped to flag up cancer cells to the body’s immune system, which was then able to find and kill them.

In the very earliest stages of cancer, patrolling immune cells often recognize cancer cells as abnormal and destroy them, they explained in their study, which was published in the journal Science Translational Medicine on Wednesday.

PROTEIN

This process relies on connexin 43, a protein that forms tiny communication channels between different types of cells. Fragments of tumor proteins called peptides escape through these channels, enter immune cells and act as “red flags” triggering a specific immune response against the disease.

But as cancer cells grow and proliferate, they can become invisible to immune cells because not enough connexin 43 is made to keep the “red flag” process going.

In this study, the scientists looked mainly at cells from melanoma — the deadliest form of skin cancer and one which has no cure and few effective treatments.

Rescigno and colleagues found that injecting salmonella into cancerous mice and melanoma cells from humans increased the amount of connexin 43 in the tumor cells. As a result, new communication channels formed, and immune cells were activated and went on to kill the tumor cells.

The technique also protected mice from cancer spreading to other parts of the body, Rescigno said, suggesting a potential “vaccination-style” preventative strategy.

Immunotherapy drugs — medicines that enlist the help of the body’s immune system to fight disease — are a relatively new form of cancer treatment.

In April, the U.S. Food and Drug Administration medicines regulators approved Dendreon Corp’s Provenge, a therapeutic vaccine designed to stimulate the immune system to attack prostate cancer, as the first vaccine to treat tumors.

An experimental immunotherapy drug called ipilimumab being developed by Bristol-Myers Squibb showed promise in fighting melanoma in trial data released in June.

Rescigno said the team used melanoma cells in the study because it was one of the deadliest forms of the disease, but the same technique could also be trialed in other types of cancer.

via:Source

Tamoxifen, the longtime gold standard, is more effective and longer lasting, the results show. But a newer drug _ raloxifene, sold as Evista _ is safer.

“I don’t see a clear winner,” but two good choices with different risks and benefits, said Dr. Scott Lippman, a cancer specialist at the University of Texas M. D. Anderson Cancer Center.

He is editor of Cancer Prevention Research, a journal that published long-term results from the federally funded study on Monday. They also were being presented at an American Association for Cancer Research meeting in Washington.

Tamoxifen is widely used to treat cancer once it’s diagnosed, and Evista is used to treat osteoporosis. But the drugs have not found wide acceptance so far as cancer preventives. Doctors hope the findings will spur more high-risk women to consider taking one of the drugs.

They’re not recommended for women at average risk of breast cancer. But for the millions who are at higher risk because of gene mutations, family history or other factors, they can make a dramatic difference.

“Between 27 million and 30 million women in the United States might have a high enough risk to qualify for one of these drugs,” including any woman over age 60, said Dr. Gabriel Hortobagyi, a breast cancer specialist at the M. D. Anderson Cancer Center.

Tamoxifen cut the chances of developing the most serious forms of breast cancer in half, the research shows, but with a higher risk of uterine cancer. Evista cut the cancer risk by 38 percent, with fewer uterine problems and other serious side effects……

“We’ve now documented that it’s far less toxic” than tamoxifen, said study leader Dr. D. Lawrence Wickerham. He is a cancer specialist at Allegheny General Hospital in Pittsburgh who has consulted for makers of both drugs.

Tamoxifen has long been used to treat and prevent breast cancer. It blunts estrogen, which fuels the growth of most tumors that occur after menopause.

Evista, sold by Indianapolis-based Eli Lilly & Co., more selectively blocks estrogen. It is only for use after menopause; its safety and effectiveness before then are unknown.

Generic tamoxifen costs about 30 cents a day, versus up to $3 for Evista. Both can cause hot flashes.

The study, called STAR, compared them in nearly 20,000 postmenopausal women at higher risk of breast cancer. They took one drug or the other for about five years and then stopped (longer use is not known to be safe or good).

After about seven years of follow-up, there were 310 cases of invasive breast cancer among women on Evista versus 247 in those on tamoxifen. That works out to a 24 percent higher cancer rate for Evista users.

Uterine cancer developed in 65 tamoxifen users but in only 37 women on Evista. Twice as many women on tamoxifen had abnormal uterine growths that led to hysterectomies. Blood clots and cataracts also were less common with Evista.

Evista clearly is the safer drug, said V. Craig Jordan of Georgetown University, the scientist who led development of tamoxifen. However, Evista’s breast cancer prevention benefits wane over time much more than tamoxifen’s do.

Lippman, the Texas cancer specialist, agreed.

“It may be that with raloxifene, you need to continue to take it,” he said. And even counting the additional uterine cancers that occurred with tamoxifen, its users still had 35 fewer invasive cancers overall than women on Evista.

It sets up a choice, he said. For example, women might choose tamoxifen if they are at very high risk of breast cancer and have had hysterectomies so that uterine cancer is not a concern.

Marty Smith, 55, an insurance agent in Grandville, Mich., has used both drugs. Her sister and mother had breast cancer and a grandfather had male breast cancer. She switched to Evista after two years on tamoxifen because of worries about side effects.

“I thought, if there’s something else that’s going to give me equal and possibly better breast cancer prevention with less risk, then I was going to get on it,” she said.

Via:townhall.com/news/health

The mid-stage study, conducted at the University of Texas M.D. Anderson Cancer Center in Houston and funded by the U.S. Army, enrolled 255 patients with advanced lung cancer who had previously been treated with chemotherapy.

“We are still in the dark ages with how we treat lung cancer patients,” said Dr. Edwin Kim, associate professor at the center’s thoracic/head and neck oncology department and the study’s lead investigator. Currently, they are separated only into “histologic” categories such as small cell or non-small cell lung cancer, with subtypes like squamous or non-squamous.

“As far as molecular testing nothing is standardly done in lung cancer at this time,” Kim said.

For other types of cancer — such as breast and colon — such testing has become common in recent years amid the development of biologic drugs designed to work only against tumors with specific genetic or molecular characteristics.

Patients in the MD Anderson trial had their lung tumors biopsied and tested for several “biomarkers” including epidermal growth factor receptor, or EGFR; vascular endothelial growth factor, or VEGF; a gene known as KRAS; and another that encodes for a protein called Cyclin D1.

Erlotinib, sold by Roche Holding AG and OSI Pharmaceuticals Inc under the brand name Tarceva, is designed to block EGFR, a protein found in high amounts on many types of cancer cells….

Tarceva is cleared for treating lung cancer that has gotten worse following at least one chemo regimen and the companies’ are seeking approval for its use in patients whose disease has remained stable after chemotherapy.

The M.D. Anderson trial also looked at treatment with AstraZeneca PLC’s Zactima, or vandetanib, which has targets including VEGF, a protein tumors need to grow vessels to supply blood. AstraZeneca last year pulled its regulatory applications for Zactima in lung cancer after an updated analysis found no overall survival advantage when the drug was added to chemotherapy.

Other drugs in the study were Nexavar, or sorafenib, sold by Onyx Pharmaceuticals Inc and Bayer AG, for treatment of kidney and liver cancers, and bexarotene, sold under the brand name Targretin as a treatment for a type of lymphoma.

The trial’s end point was disease control at eight weeks, which is seen as an indicator of overall survival. “In our study, if you made it to eight weeks, survival was 11.5 months. if not, it was 7.5 months,” Kim said, noting that as patients were enrolled they were directed to regimens which proved successful for earlier patients with similar tumor types.

The study found that 61 percent of patients with a KRAS mutation in their tumors who took Nexavar had no tumor growth at eight weeks, compared with 32 percent for the other three drugs.

Tarceva did best against EGFR mutations, Zactima for high VEGF expression and the Tarceva-Targretin fared best with Cyclin D1 defects or amplified numbers of the EGFR gene, the researchers said.

Overall, 46 percent of patients on the trial had disease control at 8 weeks, compared with a historical experience of around 30 percent for late-stage lung cancer patients.

Researchers said toxicities from the four drugs were minimal, with 6.5 percent of patients having a significant side effect.

Kim said future trials are needed to test combinations of therapies as well as single agents, including trials in earlier-stage lung cancer patients.

Roche is conducting a late-stage trial looking at the effectiveness of Tarceva as a first-line treatment for lung cancer patients with EGFR mutations.

Results were to be presented in Washington on Sunday at a meeting of the American Association for Cancer Research.

(Reporting by Deena Beasley; editing by Carol Bishopric)

The research by The Cancer Genome Atlas (TCGA), published online in the journal Cancer Cell, used epigenomics to determine that tumor DNA methylation profiles were distinctly different in about 10 percent of patients with glioblastoma multiforme (GBM).

“Most GBM patients survive fewer than 15 months, and fewer than 10 percent live more than five years,” said Peter W. Laird of the USC Epigenome Center, who led the TCGA team in collaboration with Dr. Kenneth Aldape at M.D. Anderson Cancer Center, Dr. Stephen B. Baylin at Johns Hopkins School of Medicine and many other TCGA consortium members. “With this research, we have identified a subset of patients with a distinct type of GBM that have substantially better clinical outcomes, with a median survival time of more than three years from the time of diagnosis.”

Epigenomics is the study of how DNA is packaged and marked to control which genes can be used in a particular type of cell or tissue. The distribution of one of these marks along the DNA, called DNA methylation, is often abnormal in cancer, contributing to the disease process. The characteristic epigenetic profile discovered by the TCGA team is called G-CIMP (Glioma CpG Island Methylator Phenotype) and was found to occur in much younger patients. G-CIMP tumors have other distinct alterations in their genomic landscape, revealing an interesting association with an acquired mutation in the IDH1 gene.

“Such findings are critical to the detection and treatment of brain cancer based on the genetic or epigenetic profile of each patient’s disease,” said National Institutes of Health (NIH) Director Francis Collins, M.D., Ph.D. “The depth and breadth of expertise in The Cancer Genome Atlas research network, combined with ever-improving genomic technologies, is generating remarkably detailed insights into cancer.”

Noushmehr H., et al., Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma, Cancer Cell (2010), doi:10.1016/j.ccr.2010.03.017

Source:

Leslie Ridgeway

University of Southern California

via:medicalnewstoday.com/

HCC is a primary cancer of the liver. Worldwide, it accounts for approximately 5.4% of all cancers1 and it is the third cause of cancer-related death with more than 660,000 deaths per year1. Only around 20-30% of patients are treated with curative treatments, including resection and local ablation, but recurrence complicated the outcome in more than two thirds of these cases .

Results of this study identified two gene signatures- one coming from the tumor and the other from the cirrhotic liver — able to identify patients with poor disease outcome. The study concluded that these genetic tools can ultimately be used to select patients for preventive therapies. In addition, specific genes included in these signatures should be evaluated as potential targets for adjuvant treatment, following surgical intervention in HCC patients.

Dr Josep Llovet, Professor from the Hospital Clinic of Barcelona-IDIBAPS and Mount Sinai School of Medicine in New York, who led the study and highlighted this topic at EASL’s official press conference said, “The results of our study demonstrate the potential that molecular classification offers to future clinical management of diseases such as HCC. By successfully identifying certain genomic signatures that clearly predict both overall and early recurrence of HCC post-surgery, we now have a clearer focus for future research into therapeutic options that may in time improve patients’ chances of survival.”…

The study was presented at EASL by Augusto Villanueva, MD member of the International HCC Genomic Consortium. The genomic profiles of 287 HCC patients using whole-genome gene expression platforms were analysed. The study focussed on patients with early HCC (n=257, principally male 189/257, with a mean age of 64) with tumoral tissue (n=257) and adjacent non-tumoural cirrhotic tissue (n=209). Patients were on average followed up after 46 months — there were 167 recurrences (64%) and 89 deaths (34%). In total, 20 gene signatures were evaluated with reported ability to predict survival and or recurrence of HCC. Genomic signatures from the tumour (Proliferation-G3) and adjacent tissue (with poor prognosis) of patients with HCC were identified as important in predicting both overall and early recurrence in HCC. The multinodularity gene signature was also identified as a predictor for HCC recurrence while tumor size was identified as predictor for early recurrence

via:sciencedaily.com

The country’s biggest cancer charity has expressed shock at government figures revealing huge variations in patients’ chances of surviving from one area of the UK to another. The biggest survival gap was in lung cancer, where Department of Health figures showed patients in Herefordshire were three times more likely to die within a year of diagnosis than those in Kensington and Chelsea. In the London borough, 44% of patients survived the first year after diagnosis, compared with only 15% in Herefordshire.

In bowel cancer there was also a big gap in survival – 80% in Telford and Wrekin after one year, but only 58% in Waltham Forest and Hastings and Rother. The gap was less pronounced in breast cancer, with the best rate in Torbay, where 99% survived for one year, compared with 89% in Tower Hamlets.

“There is no excuse for such a big difference between different areas,” said Harpal Kumar, chief executive of Cancer Research UK. “It is appalling that someone with lung cancer in Herefordshire should be three times more likely to die within a year than a patient in Kensington, or that a person diagnosed with bowel cancer in Waltham Forest or Hastings should be 22% more likely to die within a year than a patient in Telford. This is the worst kind of postcode lottery.”

Very few primary care trusts (PCTs) had survival rates that were as good as other countries in Europe now or even as good as Europe was achieving 10 years ago, which Kumar called “a disgrace”.

“We’re pleased that the Department of Health have been bold enough to publish these figures,” he said. “The NHS now needs to take them very seriously.”….

One-year survival figures highlight the issues around delayed diagnosis of cancer. That can be partly the responsibility of the GP, who may not see many cancer cases in a year, but is often to do with the reluctance of the patient to seek medical advice when they suspect a problem.

The figures are contained in the Cancer Reform Strategy second annual report from national cancer director Mike Richards, who points out that cancer deaths continue to fall and that prevention efforts, such as the cervical cancer vaccination programme for schoolgirls and better screening, will further help.

Jeremy Hughes, chief executive of Breakthrough Breast Cancer, said the charity shared the concerns. “Although progress has been made in some parts of the country, in others key Cancer Reform Strategy initiatives are still yet to be implemented,” he said. “In particular, urgent action must be taken to ensure that digital mammography is in place by the December 2010 deadline and that, as previously committed by the government, all women with breast problems referred by their GP will see a specialist within two weeks by the end of this year.”