They showed cancer cells were able to recover even after exposure to a chemical cocktail which triggers suicide in normal cells.

The ability may help cancer cells to block the effect of chemotherapy drugs.

The study, by the Chinese University of Hong Kong, appears in the British Journal of Cancer.

Programmed cell suicide - or apoptosis - plays a key role in keeping the body healthy, by ridding it of damaged or defective cells.

If these cells are not destroyed, then they can may continue to divide, developing into a tumour.

The researchers treated human cervical, skin, liver and breast cancer cells each with three different chemicals - jasplakinolide, staurosporine and ethanol - which triggers apoptosis in normal cells.

They wanted to see if cancer cells could survive once they have passed the point of no return for normal cell death.

The researchers found the cancer cells recovered once the chemical cocktail had been removed - even after the cells had passed normal critical checkpoints.

Changing shape

When the chemicals were removed, the cancer cells regained their shape, function and continued to divide.

They only lost the ability to recover once the nucleus at the very heart of the cell containing key genetic material had started to disintegrate - an event right at the end of the normal cell suicide process.

Researcher Professor Ming-Chiu Fung said the study suggested that cancer cells could use this ability to survive assault by chemotherapy drugs.

He said the discovery could potentially help the development of new, more effective anti-cancer drugs.

Dr Lesley Walker, of the charity Cancer Research UK, said: “This eye-opening discovery has created an entire map of new routes to explore in the search for new therapy targets.

“It is an intriguing advance and one that we hope will play a useful part in our efforts to beat cancer.”

Source: BBC NEWS

“The lack of many signals with strong credibility that emerged from our analysis, despite an enormous amount of work in this area over the years, needs careful consideration,” the authors write in a synopsis published online December 30 in the Journal of the National Cancer Institute. “The ability of the candidate gene approach to identify genetic risk factors may have been overestimated.

“Alternatively, the importance of the DNA repair pathway may have been exaggerated. However, there is increasing recognition that genetic risks of cancer conferred by single variants are almost always very modest. This means that even if the DNA repair pathway is essential for carcinogenesis, extremely large-scale evidence would be necessary to establish with high confidence the presence of specific associations.”

The scientists identified 241 previously reported associations between gene variants and the risk of cancer and reexamined these associations from 1,087 data sets. Initially 31 of the 241 associations appeared to be statistically significantly associated with cancer risk in the meta-analysis. Only XRCC1 allele (-77 T>C) and an allele of ERCC2 (codon 751), however, remained statistically significant after the researchers adjusted for multiple comparisons.

Thirtyone nominally statistically significant (i.e., P < .05 without adjustment for multiple comparisons) associations were recorded for 16 genes in dominant and/or recessive model analyses (BRCA2, CCND1, ERCC1, ERCC2, ERCC4, ERCC5, MGMT, NBN, PARP1, POLI, TP53, XPA, XRCC1, XRCC2, XRCC3, and XRCC4). XRCC1, XRCC2, TP53, and ERCC2 variants were each nominally associated with several types of cancer.

Three associations were graded as having strong credibility, another four had modest credibility, and 24 had weak credibility based on Venice criteria.

Requiring more stringent P values to account for multiplicity of comparisons, only the associations of ERCC2 codon 751 (recessive model) and of XRCC1 –77 T>C (dominant model) with lung cancer had P less than or equal to 0.0001 and retained P   less than or equal to 0.001 even when the first published studies on the respective associations were excluded.

Source: GEN News

The hormone deprivation therapy that prostate cancer patients often take gives them only a temporary fix, with tumors usually regaining their hold within a couple of years. Now, researchers at Johns Hopkins have discovered critical differences in the hormone receptors on prostate cancer cells in patients who no longer respond to this therapy. The findings, reported in the Jan. 1 issue of Cancer Research, could lead to a way to track disease progression, as well as new targets to fight prostate cancer.

Prostate cancer cells rely on androgens, male hormones that include testosterone, to survive and grow, explains Jun Luo, Ph.D., an assistant professor at Johns Hopkins’ James Buchanan Brady Urological Institute. Since 1941, doctors have taken advantage of this dependency to battle prostate cancer by depriving patients of androgens, either by castration or chemical methods. For most patients, this hormone deprivation therapy causes tumors to shrink, sometimes dramatically. However, it’s never a curetumors eventually regrow into a stronger form, becoming resistant to this and other forms of treatment.

Seeking the reason why this therapy eventually fails, Luo and his colleagues at the Johns Hopkins University School of Medicine, the University of Washington and Puget Sound VA Medical Center looked to a key player: the androgen receptors on prostate cancer cells.

Using a large database, the researchers searched for variations of the nucleic acid RNA that prostate cells use to create androgen receptors, eventually identifying seven RNA sequences different from the “normal” androgen receptor already known to scientists. When they looked for these sequences in cells isolated from 124 prostate cancer patients, they found over-production of these outlaw variants in prostate cancer cells taken from patients whose disease had become resistant to hormone deprivation therapy. One variationknown as AR-V7, was also prevalent in a select group of patients who had never taken hormone therapy, but whose cancer aggressively regrew after surgery to remove their tumors.

To see how androgen receptors made from AR-V7 differ from others, the researchers forced lab-grown prostate cancer cells to produce only the AR-V7 sequence. Unlike cells with other androgen receptors, those with only AR-V7 receptors acted as if they were continually receiving androgensturning on at least 20 genes that rely on androgens for activationeven though no androgens were present.

The results suggest that hormone therapy might encourage prostate cancer cells to overproduce the AR-V7 receptors over time, leading them to survive and grow aggressively even without androgens, explains Luo. In some patients, he adds, AR-V7 receptors might already be prevalent even without hormone therapy, predisposing them to an already-aggressive form of prostate cancer that won’t respond as well to hormone deprivation therapy.

“We may eventually be able to develop an assay to test for this androgen receptor variant, giving us a way to test which patients are good candidates for hormone deprivation therapy and providing a way to monitor disease progression in patients already on this therapy,” Luo says.

Examining the differences between AR-V7 and other androgen receptor variants may also provide researchers with new ideas to develop prostate cancer-fighting pharmaceuticals, he adds.

Other researchers who contributed to this study include Rong Hu, Thomas A. Dunn, Shuanzeng Wei, Sumit Isharwal, Robert W. Veltri, Elizabeth Humphreys, Misop Han, Alan W. Partin, William B. Isaacs and G. Steven Bova, all of the Johns Hopkins University School of Medicine; and Robert L. Vessella of the University of Washington and Puget Sound VA Medical Center.

This research was funded by a grant from the David H. Koch Foundation.

For more information, go to: http://urology.jhu.edu/

Source: GEN

In lab experiments, scientists found that the extract stimulated leukaemia cells to commit suicide.

Within 24 hours, 76% of leukaemia cells exposed to the extract were killed off, while healthy cells were unharmed, Clinical Cancer Research reports.

The study raises the possibility of new cancer treatments, but scientists said it was too early to recommend that people eat grapes to ward off cancer.

Grape seeds contain a number of antioxidants, including resveratrol, which is known to have anti-cancer properties, as well as positive effect on the heart.

Previous research has shown grapeseed extract has an effect on skin, breast, bowel, lung, stomach and prostate cancer cells in the laboratory.

It can also reduce the size of breast tumours in rats and skin tumours in mice.

However, the University of Kentucky study is the first to test its impact on a blood cancer.

Lead researcher Professor Xianglin Shi said: “These results could have implications for the incorporation of agents such as grapeseed extract into prevention or treatment of haematological (blood) malignancies and possibly other cancers.

“What everyone seeks is an agent that has an effect on cancer cells but leaves normal cells alone, and this shows that grapeseed extract fits into this category.”

The researchers exposed leukaemia cells to grape extract in a range of different doses.

Apoptosis

One of the higher doses produced a marked effect, causing large numbers of the cells to commit suicide in a process known as apoptosis.

This is a natural method of getting rid of damaged and potentially dangerous cells.

When the mechanism behind apoptosis breaks down, cancerous cells can survive and multiply.

The researchers found grapeseed extract activates a protein called JNK which helps to regulate apoptosis.

When they exposed the leukaemia cells to an agent that inhibits JNK, the grapeseed extract effect was cancelled out.

Silencing the gene that makes JNK also blocked the extract’s ability to kill cancer cells.

Kat Arney, Cancer Research UK’s senior cancer information officer, warned against jumping to firm conclusions.

She said: “This is yet another story highlighting the potential cancer-fighting properties of naturally-occurring chemicals.

“Although interesting, it’s still a long way from being a treatment that we can give to patients.”

Source: BBC NEWS

The protein cyclophilin B affects cell division, motility, and death, all of which are altered in cancerous cells. To explore the role of cyclophilin B-mediated gene regulation in breast cancer, Dr. Clevenger and colleagues inhibited cyclophilin B expression in breast cancer cells. They found that absence of cyclophilin B impacted 27 different protein networks and decreased cell proliferation, motility, and tumorigenesis. In addition, in human breast tissue, increases in cyclophilin B protein levels correlated with the presence of breast cancer metastases.

The new studies by Fang et al “demonstrate that a decrease in cyclophilin B levels … can profoundly alter the expression of genes and cellular functions relevant to the pathogenesis and progression of breast cancer. In this regard, the development of additional pharmacologic agents that specifically target each of the cyclophilins may have significant utility in the treatment of this disease.”

Journal reference:

Fang F, Flegler AJ, Du P, Lin S, Clevenger CV. Expression of Cyclophilin B is Associated with Malignant Progression and Regulation of Genes Implicated in the Pathogenesis of Breast Cancer. Am J Pathol, 2009, 174:297-308

Adapted from materials provided by American Journal of Pathology, via EurekAlert!, a service of AAAS.

Source: ScienceDaily

The drug Tarceva (erlotinib) is used to treat patients with non-small-cell lung cancer at an advanced stage when chemotherapy has not helped to stop the disease.

The letter issued by Hoffman-La Roche says a study of patients with advanced cancer and moderate liver impairment found that a higher number of patients died during treatment or within 30 days of the last dose, compared to patients with normal liver function.

Patients on the drug need to consult their doctor immediately if they show signs or symptoms suggesting possible serious liver side-effects, the company said.

These include dark urine, yellowing of the skin, abdominal pain — especially on the right side — general itchiness, less appetite, nausea, vomiting, or fatigue.

Patients should also tell their doctor or pharmacist if they have any liver problems before beginning treatment with Tarceva, says the letter signed by Lorenzo Biondi, the drug company’s vice-president of medical and regulatory affairs.

The company’s letter has been posted on Health Canada’s website, and any suspected adverse reactions can be reported to the marketed health products directorate at Health Canada.

Source: cbc.ac

In November, Genentech filed for FDA approval of Avastin for the expanded indication. Roche and marketing partner Genentech plan to initiate a Phase III study that will evaluate Avastin with standard therapy in patients with newly diagnosed glioblastoma in the first half of next year, the drugmaker said.

Source: FirstWord

The panel members commented that additional analyses may be required to better screen individuals for gene mutations, and suggested that larger clinical studies could be needed to determine other biochemical factors that may affect drug efficacy. Committee chairperson Janice Dutcher indicated that more tissue samples from patients with cancer will also help regulators and physicians in determining which genes may affect treatment.

Eli Lilly and Amgen said that the companies have sufficient data to show that their drugs are most effective in patients with a normal K-ras gene and that they support label modifications to their products to include this information. Panel member Derek Raghavan noted: “Two companies have come to us to try to create a situation where they sell [fewer] products. This is the first time I’ve seen this at the FDA.”

Commenting on the news, Miller Tabak’s Les Funtleyder stated that “as technology gets better, drugs will be paired with a genetic test,” adding that “it’s unclear how this will play out economically.”.

Source: FirstWord

The collaboration, initiated in August 2006 between MedImmune and Infinity, was transferred to AstraZeneca following its acquisition of MedImmune in June 2007.

After reviewing the potential opportunity for these projects within its portfolio and considering competing R&D investment priorities, AstraZeneca has decided to return the responsibility for development and commercialisation of this program to Infinity.

Infinity is fully committed to targeting Hsp90 as a potential new treatment approach to cancer, and to developing both IPI-504 and IPI-493. In particular, Infinity initiated a late stage trial of IPI-504 in patients with refractory gastrointestinal stromal tumors (GIST), a rare tumor of the gastrointestinal tract. IPI-504 and IPI-493 are in additional late- and early-stage ongoing clinical trials.

Source: AstraZeneca, Inc.

Results from previous analyses have demonstrated that Erbitux and Vectibix are less effective in carriers of the genetic mutation than in patients with a wildtype version of the gene. The US regulator said that the companies have proposed retrospective testing of KRAS status from studies that have already been designed and that have begun recruiting participants; however, agency reviewers questioned whether the clinical trials proposed would sufficiently corroborate the earlier findings. Tuesday’s advisory panel will also offer advice on what type of studies the drugmakers should conduct in order to gather appropriate data.

Commenting on the matter, American Society of Clinical Oncology president Richard Schilsky said: “We’re going to see this story played out over and over again,” adding that “this is the kind of change that’s about where cancer drugs should be moving. They shouldn’t be used in those with no chance of benefit.” Meanwhile, Miller Tabak analyst Les Funtleyder speculated that Erbitux sales would not necessarily be reduced if doctors only prescribe the drug for patients with the mutation, as more patients would be tested, potentially increasing the number that would benefit from the treatment.

Source: FirstWord