Posts Tagged ‘white’

Research reveals mechanism behind cell protein remodeling

According to the National Cancer Institute, more than a third of all human cancers are driven by mutations in the Ras family of genes. When Ras is activated, it promotes tumor growth but also activates autophagy which helps to sustain that growth. These cancers remodel proteins using the cellular self-cannibalization process known as autophagy to capture and degrade intracellular proteins and protein-containing organelles. Since Ras-driven cancers often rely on autophagy for growth and survival, this raised the question: Is proteome remodeling by autophagy important, and if so, by what mechanism?

This question was answered in research published in the current online edition of Molecular Cell, by senior author Eileen White, PhD, associate director for basic science at the Cancer Institute of New Jersey, and colleagues. They compared the global proteome (all of the expressed proteins) of Ras-driven cancer cells where autophagy was present to those where autophagy was deficient.

In this latest study researchers found that autophagy affects a majority of the proteins in Ras-driven cancers, yet the process is highly selective as to which proteins are targeted. For instance, investigators found that autophagy eliminates proteins involved in non-essential pathways or those deemed toxic under stressful conditions. Meanwhile, autophagy-resistant proteins involved in pathways needed for stress survival and autophagy maintenance were spared. The authors say these sets of proteins can serve as biomarkers for monitoring autophagy in the clinical setting. The study also revealed that defects in the autophagy process caused accumulation of certain proteins that prompted activation of an immune response in cancer cells and led to cell death.

“This remodeling process of the cell proteome by autophagy is an important immune-suppressive survival mechanism for Ras-driven cancers, and inhibiting autophagy can provide a means to target these aggressive cancers,” notes White, who is also a distinguished professor of molecular biology and biochemistry at Rutgers School of Arts and Sciences.

source : http://www.sciencedaily.com/releases/2014/08/140828135240.htm

Making an IMPACT: Donation keeps innovative trials going

The effort is known as the Institutional Multidisciplinary Paradigm to Accelerate Collaboration and Translation (IMPACT). The aim — as illustrated in the acronym — is to enhance the way cancer discoveries are translated from the laboratory bench to patient bedside and back again. Further development of the IMPACT initiative will require increasing scientific depth to enable new approaches to improve the prevention, early detection, diagnosis and treatment of cancers.

Showing its commitment to clinical research and making a significant investment in this effort, the Cancer Institute earlier this year recruited a new Associate Director for Clinical Science. Howard L. Kaufman, MD, FACS, a leader in clinical and translational research, is nationally known for his work in cancer immunotherapy and melanoma. As part of the IMPACT initiative, Dr. Kaufman will lead six new specialized clinical trials aimed at molecular targets, as opposed to a specific tumor type, utilizing the strengths and capabilities of the Cancer Institute. The Jewels of Charity gift will enable $100,000 to be devoted to each of the six studies.

One of the six clinical trials will focus on a new approach that utilizes T cells (part of the white blood cells) from cancer patients in which the cells are genetically modified to attack only cancer cells. This approach requires specialized centers such as the Cancer Institute that have the capability of preparing these cells. These cells already have shown major clinical responses in patients with certain blood cancers, such as B cell lymphomas, chronic lymphocytic leukemias and in Hodgkin’s lymphoma patients that have not responded to other treatments. It is expected that this approach will first be tested in patients with lymphoma and then in solid tumors, such as melanoma, ovarian cancer and lung cancer. The aim is to confirm the effectiveness and safety of these new agents and provide the best possible care for patients with difficult to treat cancers or those that have not responded to more established treatment options.

source : http://www.sciencedaily.com/releases/2014/08/140804102938.htm

Potential ‘universal’ blood test for cancer discovered

The test will enable doctors to rule out cancer in patients presenting with certain symptoms, saving time and preventing costly and unnecessary invasive procedures such as colonoscopies and biopsies being carried out. Alternatively, it could be a useful aid for investigating patients who are suspected of having a cancer that is currently hard to diagnose.

Early results have shown the method gives a high degree of accuracy diagnosing cancer and pre-cancerous conditions from the blood of patients with melanoma, colon cancer and lung cancer. The research is published online in FASEB Journal, the US journal of the Federation of American Societies for Experimental Biology.

The Lymphocyte Genome Sensitivity (LGS) test looks at white blood cells and measures the damage caused to their DNA when subjected to different intensities of ultraviolet light (UVA), which is known to damage DNA. The results of the empirical study show a clear distinction between the damage to the white blood cells from patients with cancer, with pre-cancerous conditions and from healthy patients.

Professor Diana Anderson, from the University’s School of Life Sciences led the research. She said: “White blood cells are part of the body’s natural defence system. We know that they are under stress when they are fighting cancer or other diseases, so I wondered whether anything measureable could be seen if we put them under further stress with UVA light.We found that people with cancer have DNA which is more easily damaged by ultraviolet light than other people, so the test shows the sensitivity to damage of all the DNA — the genome — in a cell.”

The study looked at blood samples taken from 208 individuals. Ninety-four healthy individuals were recruited from staff and students at the University of Bradford and 114 blood samples were collected from patients referred to specialist clinics within Bradford Royal Infirmary prior to diagnosis and treatment. The samples were coded, anonymised, randomised and then exposed to UVA light through five different depths of agar.

The UVA damage was observed in the form of pieces of DNA being pulled in an electric field towards the positive end of the field, causing a comet-like tail. In the LGS test, the longer the tail the more DNA damage, and the measurements correlated to those patients who were ultimately diagnosed with cancer (58), those with pre-cancerous conditions (56) and those who were healthy (94).

“These are early results completed on three different types of cancer and we accept that more research needs to be done; but these results so far are remarkable,” said Professor Anderson. “Whilst the numbers of people we tested are, in epidemiological terms, quite small, in molecular epidemiological terms, the results are powerful. We’ve identified significant differences between the healthy volunteers, suspected cancer patients and confirmed cancer patients of mixed ages at a statistically significant level of P<0.001. This means that the possibility of these results happening by chance is 1 in 1000. We believe that this confirms the test’s potential as a diagnostic tool.”

Professor Anderson believes that if the LGS proves to be a useful cancer diagnostic test, it would be a highly valuable addition to the more traditional investigative procedures for detecting cancer.

A clinical trial is currently underway at Bradford Royal Infirmary. This will investigate the effectiveness of the LGS test in correctly predicting which patients referred by their GPs with suspected colorectal cancer would, or would not, benefit from a colonoscopy — currently the preferred investigation method.

source : http://www.sciencedaily.com/releases/2014/07/140728094410.htm