Posts Tagged ‘method’

Finding keys to glioblastoma therapeutic resistance

“There is a growing interest to guide cancer therapy by sequencing the DNA of the cancer cell,” said Clark Chen, MD, PhD, vice-chairman of Research and Academic Development, UC San Diego Division of Neurosurgery and the principal investigator of the study. “Our study demonstrates that the sensitivity of glioblastoma to a drug is influenced not only by the content of its DNA sequences, but also by how the DNA sequences are organized and interpreted by the cell.”

The team of scientists, led by Chen, used a method called comparative gene signature analysis to study the genetic profiles of tumor specimens collected from approximately 900 glioblastoma patients. The method allows investigators to discriminate whether specific cellular processes are “turned on” or “turned off” in glioblastomas. “Our study showed that not all glioblastomas are the same. We were able to classify glioblastomas based on the type of cellular processes that the cancer cells used to drive tumor growth,” said Jie Li, PhD, senior postdoctoral researcher in the Center for Theoretical and Applied Neuro-Oncology at UC San Diego and co-first author of the paper.

One of these cellular processes involves Epidermal Growth Factor Receptor (EGFR). The study revealed that EGFR signaling is suppressed in a subset of glioblastomas. Importantly, this suppression is not the result of altered DNA sequences or mutations. Instead, EGFR is turned off as a result of how the DNA encoding the EGFR gene is organized in the cancer cell. This form of regulation is termed “epigenetic.” Because EGFR is turned off in these glioblastomas, they become insensitive to drugs designed to inhibit EGFR signaling.

“Our research suggests that the selection of appropriate therapies for our brain tumor patients will require a meaningful synthesis of genetic and epigenetic information derived from the cancer cell,” said co-first author Zachary J. Taich.

The paper’s abstract can be found at: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=2350

source : http://www.sciencedaily.com/releases/2014/08/140825185321.htm

Severing nerves may shrink stomach cancers: Botox injections slow growth of stomach tumors in mice

“Scientists have long observed that human and mouse cancers contain a lot of nerves in and around the tumor cells,” said Dr. Wang, the Dorothy L. and Daniel H. Silberberg Professor of Medicine at Columbia’s Herbert Irving Comprehensive Cancer Center. “We wanted to understand more about the role of nerves in the initiation and growth of cancer, by focusing on stomach cancer.”

Stomach cancer is the fourth-leading type of cancer and the second-highest contributor to cancer mortality worldwide, with a 5-year survival rate of less than 25 percent.

Using three different mouse models of stomach cancer, Dr. Wang’s team found that when they performed a procedure called a vagotomy to cut the nerves, the surgery significantly slowed tumor growth and increased survival rates. Removing nerve connections from only one side of the stomach allowed cancer to continue growing on the other side (with the intact nerves), providing further evidence of the importance of nerves in tumor growth.

Dr. Wang’s team then tried to block transmission of nerve signals pharmacologically. They found that when they injected Botox® into mice, the drug proved to be as effective as surgery at reducing stomach cancer growth. “We found that blocking the nerve signals makes the cancer cells more vulnerable — it removes one of the key factors that regulate their growth,” said Dr. Wang.

Botox® prevents nerve cells from releasing a neurotransmitter called acetylcholine. In the case of cosmetic treatment, for example, blocking acetylcholine helps to lessen facial wrinkles by causing temporary paralysis of the muscles. Because acetylcholine also ordinarily stimulates cell division, using Botox® to prevent acetylcholine release might help slow the growth of cancer.

Dr. Wang’s team also found evidence of the effectiveness of targeting nerves for cancer treatment in human patients when they compared 37 patients who had a recurrence of stomach cancer many years after surgery. Of the 13 patients who had had a vagotomy as part of their procedure, in all but one case, tumors did not develop in regions where the nerve connections had been severed. By contrast, tumors were found in the same region of the stomach in all 24 patients who had not had a vagotomy.

Next, Dr. Wang’s team plans to investigate the effectiveness of nerve-targeted therapy used in combination with other cancer treatments. Initial experiments have shown that blocking nerves makes cancer cells more vulnerable to chemical agents. Botox® used in combination with chemotherapy in mice increases survival rates up to 35 percent, compared with chemotherapy alone.

A limitation of the current studies is that they focus primarily on early stages of stomach cancer. “In the future, we’d really like to look at how we can use this method of targeting nerves to stop the growth of more advanced tumors,” Dr. Wang said. His laboratory hopes to develop drugs that block neurotransmitter receptors. This approach would be more effective than surgery or Botox® on more invasive forms on cancer, as such drugs would be able reach cells that have broken away from the main tumor.

source : http://www.sciencedaily.com/releases/2014/08/140820164315.htm

Lung cancer diagnosis tool shown to be safe and effective for older patients

Half of all lung cancer patients are over 70 years old when first diagnosed, but studies have shown that these older patients are less likely to receive an accurate diagnosis.

A correct assessment of the stage of a patient’s disease — how much their tumor has grown and spread — is key to ensuring they receive the right treatment.

Non-invasive methods of checking whether a patient’s cancer has spread to their lymph nodes have limited sensitivity and until recently the only way to obtain a tissue sample was under general anaesthetic — limiting its use in elderly patients who often present with other conditions that may restrict the use of general anaesthesia.

Now researchers at University Hospital of South Manchester NHS Foundation Trust and The University of Manchester — part of the Manchester Cancer Research Centre — have looked at a newer technique: endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). This method is carried out under sedation while the patient is still conscious and uses ultrasound to guide a sampling needle down and through the airways of the lungs.

Dr Richard Booton, Consultant Respiratory Physician at the North West Lung Centre and senior lecturer at the University’s Institute of Inflammation and Repair who led the study, said: “We wanted to see if there were any differences between patients aged less than 70 years old and those older than 70, in terms of both the safety of the technique and how useful it was for diagnosis.

“The team recently published their results in the Journal of Thoracic Oncology and found that the procedure was well tolerated at all ages — even in those patients aged over 80 years old. They also showed that EBUS-TBNA is effective for assessing whether a patient’s tumor had spread to the lymph nodes.

“Being able to safely take tissue samples will also allow us to test for specific tumor sub-types and better decide the most appropriate treatment for each individual patient,” added Dr Booton.

source : http://www.sciencedaily.com/releases/2014/08/140804065948.htm