Immunogene therapy combined with standard treatment is safe for patients with brain tumors, study suggests

ScienceDaily (Sep. 6, 2011) — A clinical trial has shown that a form of gene therapy is safe for treating a deadly form of brain cancer, even when combined with radiation therapy.

The phase 1b trial was conducted at the Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) and at Methodist at Hospital in Houston, TX.

The novel treatment uses an adenovirus vector called AdV-tk. The vector is taken up by cancer cells where it activates a drug that kills the cells. The vector is applied in the operating room after removing brain tumors such as glioblastoma multiforme, the most common and dangerous form of brain cancer.

The findings, published online in the Journal of Clinical Oncology, suggest that the therapy might also stimulate an immune response against the tumor.

"This is the first time that a gene therapy approach was combined with radiation in patients with newly diagnosed glioblastoma," says first author Dr. E. Antonio Chiocca, professor and chair of neurological surgery and co-director of the Dardinger Center for Neuro-oncology and Neurosciences at Ohio State.

"There had been a concern that combining these two treatments could be too toxic for patients, but this was not the case. We do not know yet if this will improve survival, but these findings are encouraging," he says.

Glioblastomas occur in about 18,500 Americans annually and kill nearly 13,000 of them yearly. Glioblastoma multiforme is the most common and lethal form of the malignancy, with an average survival of 15 months after diagnosis.

The tumors often recur because cancer cells typically migrate into adjacent brain tissue where they can give rise to a recurrent tumor. This study examines an immunogene therapy approach that is designed to kill these undetected cancer cells and prevent recurrence.

This clinical trial involved 10 patients with glioblastoma multiforme and two patients with anaplastic astrocytoma. The procedure works as follows:

After removing the tumor, the neurosurgeon injects the tumor bed with 1 milliliter (1/30th oz) of a solution containing the AdV-tk vector. The vector carries a gene from herpes simplex virus for an enzyme called thymidine kinase (the '-tk' in AdV-tk). Cancer cells infected with the vector begin making the enzyme.Patients then take the anti-herpes virus drug valacyclovir for two weeks.Inside the cancer cells, the herpes thymidine kinase enzyme converts valacyclovir into DNA building blocks that the rapidly growing cancer cells cannot use to make DNA, and this kills them.Radiation therapy begins halfway through the course of valacyclovir. The radiation damages the DNA in the cancer cells, which then try to repair it, using the toxic valacyclovir building blocks.

In addition to improved overall survival, studies revealed a significant rise in the number of T lymphocytes in the tumors. This suggests that the gene therapy stimulated an immune response against the tumor, producing an "immunogene therapy" effect.

Cancer immunogene therapy refers to genetically manipulating cancer cells to stimulate an immune response against a tumor. (Note: This differs from "immunotherapy," which attempts to stimulate the immune system directly against tumor cells.)

"If the results of another recently completed phase 2 efficacy trial are also encouraging, the next step will be to compare this therapy head-to-head with the current standard of care," Chiocca says.

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The above story is reprinted from materials provided by Ohio State University Medical Center, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

E. A. Chiocca, L. K. Aguilar, S. D. Bell, B. Kaur, J. Hardcastle, R. Cavaliere, J. McGregor, S. Lo, A. Ray-Chaudhuri, A. Chakravarti, J. Grecula, H. Newton, K. S. Harris, R. G. Grossman, T. W. Trask, D. S. Baskin, C. Monterroso, A. G. Manzanera, E. Aguilar-Cordova, P. Z. New. Phase IB Study of Gene-Mediated Cytotoxic Immunotherapy Adjuvant to Up-Front Surgery and Intensive Timing Radiation for Malignant Glioma. Journal of Clinical Oncology, 2011; DOI: 10.1200/JCO.2011.35.5222

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Patients with COPD have higher risk of shingles, study finds

ScienceDaily (Feb. 23, 2011) — Patients with chronic obstructive pulmonary disease (COPD) are at greater risk of shingles compared with the general population, according to a study published in CMAJ (Canadian Medical Association Journal). The risk is greatest for patients taking oral steroids to treat COPD.

Shingles, or herpes zoster, is a reactivation of the chicken pox virus resulting in a painful rash with lesions.

People with a compromised immune system are at greater risk of developing shingles although it has not been previously studied in patients with COPD.

There is increasing evidence that COPD is an autoimmune disease. "Given that various immune-mediated diseases, such as rheumatoid arthritis and inflammatory bowel disease, have been reported to be associated with an increased risk of herpes zoster, it is reasonable to hypothesize that immune dysregulation found in COPD may put patients at higher risk of developing herpes zoster," writes Dr. Hui-Wen Lin, Taipei Medical University, Taiwan with coauthors.

This study, using data from the Taiwan Longitudinal Health Insurance Database, included 8486 patients with COPD and 33 944 subjects from the comparison cohort. Of the total sample of 42 430 patients, 1080 had incident of herpes zoster during the follow-up period. There were 321 cases of shingles identified in the COPD cohort, 16.4 per 1000 person years, and 759 cases in the comparison cohort, 8.8 per 1000 person years.

"Our cohort study demonstrated that patients with COPD are at an increased risk of developing herpes zoster compared with the general population, after controlling for other herpes zoster risk factors," write the authors. "The risk of herpes zoster associated with COPD is greater for patients with inhaled or oral corticosteroids therapy than patients without."

The authors conclude it is possible that "increased disease severity further contributes to the increased risk of herpes zoster associated with COPD."

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The above story is reprinted from materials provided by Canadian Medical Association Journal, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Yang, Ya-Wen, Chen, Yi-Hua, Wang, Kuo-Hsien, Wang, Chen-Yi, Lin, Hui-Wen. Risk of herpes zoster among patients with chronic obstructive pulmonary disease: a population-based study. Canadian Medical Association Journal, 2011; DOI: 10.1503/cmaj.101137

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Eczema Patients Most At Risk For Dangerous Viral Infections

ScienceDaily (June 25, 2009) — Eczema patients at risk for serious viral infections have more severe disease, are more likely to be allergic to food and other allergens, and have a frequent history of staph infections, according to researchers at National Jewish Health and other institutions in the NIH-funded Atopic Dermatitis Vaccinia Network.

The findings, published June 22 in the online version of The Journal of Allergy and Clinical Immunology, could help identify people at risk for serious complications of smallpox vaccinations, and point to defects in the skin barrier and antimicrobial-protein production as possible causes for the increased susceptibility.

"Previous studies have suggested that eczema is not only becoming more prevalent, but that patients have increased susceptibility to disseminated viral infections," said senior author Donald Leung, MD, PhD, Edelstein Family Chair of Pediatric Allergy and Clinical Immunology at National Jewish Health. "Our study is the largest and first in the United States to carefully characterize eczema patients who have suffered widespread herpes simplex viral infections of their skin. It is also the first to report that these patients are more susceptible to staphylococcus and other infections of the skin and eye."

A subset of the estimated 6 million eczema patients in the United States are susceptible to widespread infections of their skin by herpes simplex and vaccinia viruses. The herpes simplex virus is common but only rarely causes disseminated skin infections that can spread to the eye and bloodstream sometimes leading to encephalitis and meningitis. The widespread herpes simplex skin infection is known as eczema herpeticum.

Vaccinia virus, which is used in smallpox vaccinations, can also cause a serious and life-threatening skin infections in a smaller subset of patients. People who have eczema or had it in the past are susceptible to this infection when they receive a smallpox vaccination. This situation could limit the ability of those people to safely receive vaccinations in case of a smallpox bioterrorism event.

The Atopic Dermatitis Vaccinia Network (ADVN) is an NIH-funded multi-center network charged with better understanding the susceptibility of eczema patients to the vaccinia infection and to search for ways to protect against it. Atopic dermatitis is another name for eczema, an allergic skin condition that causes itchy, inflamed and cracked skin.

The ADVN researchers believed that they might be able to identify eczema patients at high risk for these infections and to obtain clues about the mechanisms of susceptibility by studying a large cohort of patients who had suffered eczema herpeticum, the herpes simplex viral skin infections. They examined a wide variety of demographic, pathologic and biologic characteristics  in 901 subjects, 138 of whom had suffered eczema herpeticum.

They found that eczema patients susceptible to herpes simplex infections had more severe disease, earlier age of disease onset, more frequent history of other allergic diseases such as food allergy, asthma and hay fever, more allergic biomarkers, and more frequent skin infections with other microbes.

"These characteristics associated with eczema herpeticum should help us identify young patients at greater risk for eczema herpeticum so that we can be more vigilant with them and better equipped to prevent this serious complication of eczema," said Dr. Leung.

The greater allergic disease and sensitization, as well as infection by other microbes,  point to a potential mechanism for the increased susceptibility to viral skin infections. An emerging model of eczema highlights the importance of skin-barrier defects and a lack of antimicrobial proteins among eczema patients. The skin-barrier defect is believed to result in the greater allergic sensitization among eczema patients in general. The even higher allergic sensitization among EH patients suggests the skin-barrier defect is particularly acute in those patients.

The higher levels of infections with staphylococcus and other microbes suggests that EH patients may be particularly lacking in antimicrobial proteins.

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The above story is reprinted from materials provided by National Jewish Medical and Research Center.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Patients with COPD have higher risk of shingles, study finds

ScienceDaily (Feb. 22, 2011) — Patients with chronic obstructive pulmonary disease (COPD) are at greater risk of shingles compared with the general population, according to a study published in CMAJ (Canadian Medical Association Journal). The risk is greatest for patients taking oral steroids to treat COPD.

Shingles, or herpes zoster, is a reactivation of the chicken pox virus resulting in a painful rash with lesions.

People with a compromised immune system are at greater risk of developing shingles although it has not been previously studied in patients with COPD.

There is increasing evidence that COPD is an autoimmune disease. "Given that various immune-mediated diseases, such as rheumatoid arthritis and inflammatory bowel disease, have been reported to be associated with an increased risk of herpes zoster, it is reasonable to hypothesize that immune dysregulation found in COPD may put patients at higher risk of developing herpes zoster," writes Dr. Hui-Wen Lin, Taipei Medical University, Taiwan with coauthors.

This study, using data from the Taiwan Longitudinal Health Insurance Database, included 8486 patients with COPD and 33 944 subjects from the comparison cohort. Of the total sample of 42 430 patients, 1080 had incident of herpes zoster during the follow-up period. There were 321 cases of shingles identified in the COPD cohort, 16.4 per 1000 person years, and 759 cases in the comparison cohort, 8.8 per 1000 person years.

"Our cohort study demonstrated that patients with COPD are at an increased risk of developing herpes zoster compared with the general population, after controlling for other herpes zoster risk factors," write the authors. "The risk of herpes zoster associated with COPD is greater for patients with inhaled or oral corticosteroids therapy than patients without."

The authors conclude it is possible that "increased disease severity further contributes to the increased risk of herpes zoster associated with COPD."

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by Canadian Medical Association Journal, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Yang, Ya-Wen, Chen, Yi-Hua, Wang, Kuo-Hsien, Wang, Chen-Yi, Lin, Hui-Wen. Risk of herpes zoster among patients with chronic obstructive pulmonary disease: a population-based study. Canadian Medical Association Journal, 2011; DOI: 10.1503/cmaj.101137

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here