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Showing posts with label neuroblastoma. Show all posts
Showing posts with label neuroblastoma. Show all posts

Wednesday, July 10, 2013

New Strategy For Defeating Neuroblastoma

Main Category: Pediatrics / Children's Health
Also Included In: Cancer / Oncology;??Neurology / Neuroscience
Article Date: 05 Jun 2013 - 2:00 PDT Current ratings for:
New Strategy For Defeating Neuroblastoma
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Researchers at Karolinska Institutet in Sweden have found a promising strategy for defeating neuroblastoma - a malignant form of cancer in children - that focuses on the so-called MYCN protein. A specific chemical molecule helps to break down MYCN, which either kills the cancer cell or makes it mature into a harmless neuron. The discovery, which is published in the scientific journal PNAS, raises hopes for new and more effective treatments in the future.

Neuroblastoma is the third most common form of cancer in children. It usually develops before the age of two and affects around two dozen children per year in Sweden and around 800 in the US. The tumours are normally located in the peripheral nervous system, but in very young infants they can sometimes spread over the entire body. Current therapies are tough and have serious side effects, and for many of the patients the prognosis is poor. In its most aggressive form only a minority survive, which makes finding alternative treatments particularly urgent.

In the case of neuroblastoma, extra copies of the gene that encodes the MYCN protein are normally found in the cancer cell. This in turn is a clear indication of a poor prognosis, as it has long been known that the incorrect activation of the MYCN and similar MYC genes causes cancer. The strategy of the research group for defeating the disease was therefore to identify substances that prevent MYC-triggered cell division or that kill cancer cells in an MYC-specific manner.

-"We have found that a small chemical molecule, that is known from previous studies to inhibit the activity of the c-MYC-protein, also inhibits the activity of MYCN," says Principal Investigator Marie Arsenian Henriksson, Professor of molecular tumour biology at Karolinska Institutet. "The substance disrupts the binding between MYCN and another protein called Max, which results in the degradation of MYCN and subsequently either to cell death in neuroblastoma cells with extra copies of the MYCN gene, or to their development into neurons, at which point their malignity disappears. Small chemical molecules that knock out MYCN are therefore a possible therapy option for children with neuroblastoma as well as for other MYC-driven tumours."

The molecule used by the researchers is no drug candidate; instead the finding is to be seen as a model that can inspire future cancer therapies. However, the researchers did find that the survival rate increased when they applied test treatments on mice with neuroblastoma. The study also led to a new discovery on what happens inside the cancer cell, where the treatment caused an accumulation of fat droplets, suggesting that the MYC proteins affect tumour cell metabolism and the normal breakdown of fatty acids.

"This is an original finding," says Professor Arsenian Henriksson. "It has not previously been observed that the inhibition of MYC affects tumour cells in this way. This does not only open new avenues for novel therapies for certain forms of cancer, but may also have implications for metabolic diseases, such as diabetes."

The study was financed with grants from several bodies, including the Swedish Childhood Cancer Foundation, the Swedish Cancer Society, the Swedish Research Council, Karolinska Institutet, and the Hedlund Foundation.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our pediatrics / children's health section for the latest news on this subject. “MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells”,
Hanna Zirath, Anna Frenzel, Ganna Oliynyk, Lova Segerstrom, Ulrica K. Westermark, Karin Larsson, Matilda Munksgaard Person, Kjell Hultenby, Janne Lehtio, Christer Einvik, Sven Pahlman, Per Kogner, Per-Johan Jakobsson, and Marie Arsenian Henriksson.
PNAS 3-7 June 2013 Please use one of the following formats to cite this article in your essay, paper or report:

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5 Jun. 2013. APA

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'New Strategy For Defeating Neuroblastoma'

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Sunday, July 7, 2013

Autophagy Protects Neuroblastoma From Chemotherapy

Main Category: Cancer / Oncology
Also Included In: Neurology / Neuroscience;??Pediatrics / Children's Health
Article Date: 03 Jul 2013 - 1:00 PDT Current ratings for:
Autophagy Protects Neuroblastoma From Chemotherapy
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Neuroblastomas are pediatric tumors that originate from cells of the embryonic nervous system. The disease can take widely varying clinical courses that range from spontaneous regression to fatal outcomes. Highly aggressive neuroblastomas rarely respond well to chemotherapy. Understanding and overcoming the resistance mechanisms of highly aggressive neuroblastomas are considered essential to the development of effective treatments.

Scientists from the department headed by Professor Dr. Olaf Witt at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and at Heidelberg University Hospital are searching for more effective methods to treat neuroblastomas. The researchers are particularly focusing on the role of 18 different HDAC enzymes which appear to promote the aggressiveness of neuroblastomas in various ways. Dr. Ina Oehme and her colleagues from Witt's department have now studied whether a member of the HDAC family might be linked to the sensitivity of tumors to chemotherapy in high-risk neuroblastomas. She discovered that the high-risk tumors that responded well to therapy were those which had produced only small quantities of HDAC10 prior to treatment.

The Heidelberg researchers subsequently used an experimental agent or a method of blocking the gene to turn off HDAC10 experimentally in cell cultures developed from highly aggressive neuroblastomas. They subsequently treated the cells with the chemotherapy agent doxorubicin. In neuroblastoma cells, this treatment normally induces a self-digestion process known as autophagy, a kind of recycling of endogenous cellular components. This is a biologically ancient program for survival that protects cells during starvation. Highly aggressive cancer cells use autophagy to overcome stress caused by cytotoxic agents.

However, in neuroblastoma cells without a functioning form of HDAC10, treatment disrupted the multi-stage process of autophagy of cellular components at a specific point. As expected, these cells were once again rendered sensitive to the anticancer drug. The researchers cross-checked their results by boosting the activity of the HDAC10 gene in neuroblastoma cells. This protected the cells from the consequences of subsequent chemotherapy.

"HDAC10 appears to play a key role in autophagy and resistance to chemotherapy in high-risk neuroblastomas," Olaf Witt summarizes. "In advanced tumors, high levels of HDAC10 may serve as a biomarker for resistance. A drug that specifically turns off HDAC10 might give us a more effective method of treating neuroblastomas that respond very poorly to chemotherapy."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. Ina Oehme, Jan-Peter Linke, Barbara C. Bock, Till Milde, Marco Lodrini, Bettina Hartenstein, Inga Wiegand, Christian Eckert, Wilfried Roth, Marcel Kool, Sylvia Kaden, Herrmann-Josef Grone, Johannes H. Schulte, Sven Lindner, Anne Hamacher-Brady, Nathan R. Brady, Hedwig E. Deubzer and Olaf Witt. Histone deacetylase 10 promotes autophagy-mediated cell survival. Proceedings of the National Academy of Sciences 2013, DOI: 10.1073/pnas.1300113110

The German Cancer Research Center (Deutsches Krebsforschungszentrum, D

Helmholtz Association of German Research Centres

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5 Jul. 2013. APA

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'Autophagy Protects Neuroblastoma From Chemotherapy'

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Wednesday, June 12, 2013

Hope offered by the new treatment for neuroblastoma

Main category: Cancer / Oncology
Also included in: Neurology / neuroscience;??Pediatrics / children's health
Article Date: June 5, 2013-0:00 PDT current ratings for:
Hope offered by the new treatment for neuroblastoma
not yet ratednot yet rated
Researchers at the Karolinska Institutet in Sweden have found a promising strategy to overcome neuroblastoma - a malignant form of cancer in children – which focuses on protein MYCN. A specific chemical molecule to decompose MYCN, which kills cancer cells or makes mature in a harmless neuron. The discovery, published in the journal PNAS, raises hopes of new and more effective treatments in the future.

Neuroblastoma is the third form of childhood cancer. Usually, it develops before the age of two and affects about two dozen children per year in Sweden and about 800 in the United States. Tumours are normally found in the peripheral nervous system, but in very young infants, they can sometimes spread all over the body. Current treatments are hard and have serious side effects, and for many patients, the prognosis is poor. In its most aggressive form survive only a minority, that allows to find particularly urgent alternative treatments.

In the case of neuroblastoma, additional copies of the gene coding for the protein MYCN normally found in the cancer cell. It is a clear indication of a poor prognosis, as it has long been known that the incorrect activation of MYC and MYCN similar genes causes cancer. The strategy of the research group to defeat the disease was therefore to identify substances that prevent the MYC-triggered cell division or that kill cancer cells specifically MYC.

"We found that a small chemical molecule that is known from previous studies, inhibits the activity of c - MYC protein, also inhibits the activity of MYCN," says Principal Investigator Mary Rakesh Henriksson, Professor of molecular biology of tumours in Karolinska Institutet. 'Substance disrupts the connection between MYCN and another protein called Max, which translates the degradation MYCN and, subsequently, either to cell death in cells of neuroblastoma with one copy, of the MYCN gene or their development into neurons how their malignancy disappears. Small chemical molecules that stuns MYCN are therefore a possible treatment for children suffering from neuroblastoma, as well as other option based the MYC tumors. ?

The molecule used by researchers is no drug candidate; the conclusion is rather seen as a model that can inspire future treatments. However, the researchers estimated that the survival rate increased when they applied treatments of test on mice suffering from neuroblastoma. The study has also led to a new discovery about what is happening inside the cancer cell, where treatment resulted in an accumulation of fat droplets, suggesting that MYC proteins affect metabolism of tumor cells and the normal breakdown of fatty acids.

"It's an original conclusion," said Professor Arsenian Henriksson. "Was not already observed that the inhibition of MYC affects tumor cells in this way. This has not only opened new avenues for new treatments for some forms of cancer, but also implications for metabolic diseases, such as diabetes. ?

Article adapted by Medical News Today press release original. Click on "references" tab above for the source.
Visit our cancer / Oncology section for the latest news on this subject. The study was funded by grants from several bodies, including the Swedish Childhood Cancer Foundation, the company Swedish Cancer, the Swedish Research Council, Karolinska Institutet, and the Foundation Hedlund.

Publication: "inhibition of MYC induces metabolic changes leading to the accumulation of lipid droplets in tumor cells, Hanna Zirath, Anna Frenzel, Ganna Oliynyk, Lova Segerstrom, Ulrica K. Westermark, Karin Larsson, Matilda Munksgaard person, Kjell Hultenby, Janne Lehtio, Christer Einvik, Sven Pahlman Per Kogner, Per-Johan Jakobsson and Marie Arsenian Henriksson, PNAS Online 3-7 June 2013.

Karolinska Institutet

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June 5, 2013. APA

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'The hope offered by the new treatment of Neuroblastoma.

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View the original article here