Thread: Brain mets
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Old 12-01-2009, 09:17 PM   #4
Rich66
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Re: Brain mets

Anticancer Res. 2005 May-Jun;25(3A):1531-7.
Brain metastases in breast cancer--an in vitro study to evaluate new systemic chemotherapeutic options.

Honig A, Rieger L, Sutterlin A, Kapp M, Dietl J, Sutterlin MW, Kämmerer U.
Department of Obstetrics and Gynecology, University of Wuerzburg, Germany. arnd_hoenig@hotmail.com
BACKGROUND: Fifteen-30% of breast cancer patients develop central nervous system (CNS) metastases. The most potent drugs for the treatment of breast cancer like taxanes, anthracyclines and trastuzumab have limited efficacy for brain metastases. No standardized therapy has yet been established for this condition. Drugs with proven efficacy in the CNS and which are commonly used for primary brain tumors were applied. We evaluated the capacity of these drugs to inhibit breast tumor cell growth in vitro. MATERIALS AND METHODS: Twelve primary cell cultures of pulmonary/pleural metastases of breast cancer and 3 commercially available cell lines were used for non-radioactive cytotoxicity assays to evaluate the efficacy of 3 different concentrations of Topotecan, Cisplatin, Nimustine, Vincristine, Irinothecan, Caelyx (pegylated liposomal Doxorubicin) and Etoposide. RESULTS: Topotecan, Cisplatin, Caelyx and Vincristine showed significantly higher cytostatic activity in vitro than Irinotecan, Etoposide and Nimustine. With regard to the median cytotoxicity, the order of drugs in our assays was Topotecan, Cisplatin, Vincristine, Caelyx, Irinotecan, Etoposide and Nimustine. Nimustine showed almost no efficacy against breast cancer cells. CONCLUSION: Topotecan, Cisplatin, Vincristine and Caelyx seem to be suitable candidates for further clinical evaluation. The data and the "liposomal packaging" suggest that Caelyx might be effective in the CNS. Since pulmonary metastases are often associated with brain metastases, evaluating primary cell cultures from malignant pleural effusions could be a valuable approach for the testing of new cytostatic drugs for brain metastases.

PMID: 16033055 [PubMed - indexed for MEDLINE]


Web address:
http://www.sciencedaily.com/releases/2009/12/
091202131633.htm


Brain Tumor Cells Made More Responsive to Radiation

ScienceDaily (Dec. 2, 2009) — Duke University Medical Center researchers have figured out how stem cells in the malignant brain cancer glioma may be better able to resist radiation therapy. And using a drug to block a particular signaling pathway in these cancer stem cells, they were able to kill many more glioma cells with radiation in a laboratory experiment.

The work builds off earlier research which showed that cancer stem cells resist the effects of radiation much better than other cancer cells.
The Duke team identified a known signaling pathway called Notch as the probable reason for the improved resistance. Notch also operates in normal stem cells, where it is important for cell-cell communication that controls cell growth and differentiation processes. The study was published in late November by Stem Cells journal.
"This is the first report that Notch signaling in tumor tissue is related to the failure of radiation treatments," said lead author Jialiang Wang, Ph.D., a research associate in the Duke Division of Surgery Sciences and the Duke Translational Research Institute. "This makes the Notch pathway an attractive drug target. The right drug may be able to stop the real bad guys, the glioma stem cells."
Stem cells in a cancer are the source of cancer cell proliferation, Wang said. Hundreds of cancer stem cells can quickly become a million tumor cells.
The Duke researchers, in collaboration with a team led by Dr. Jeremy Rich at Cleveland Clinic, used drugs called gamma-secretase inhibitors that target a key enzyme involved in Notch signaling pathway on gliomas in a lab dish. These inhibitors are being studied by other researchers for their ability to fight tumors in which Notch is abnormally activated, such as leukemia, breast and brain tumors.
"In our study, gamma-secretase inhibitors alone only moderately slowed down tumor cell growth," said senior author Dr. Bruce Sullenger, Duke Vice Chair for Research and Joseph W. and Dorothy W. Beard Professor of Surgery. "But when we looked at these molecules combined with radiation at clinically relevant doses, the combination caused massive cell death in the tumors and significantly reduced survival of glioma stem cells. These findings often correlate with better tumor control."
Wang said ongoing clinical trials are testing gamma-secretase inhibitors as stand-alone therapy for breast and brain tumors. "Our study suggests that Notch inhibition using these drugs would provide significant therapeutic benefits if combined with radiotherapy, and I hope that future research will study this combination therapy in this vulnerable patient population," Wang said. "More effective radiation may be attainable if we can stop Notch signaling in the tumor stem cells."
Other authors include Timothy P. Wakeman and Xiao-Fan Wang of the Duke Department of Pharmacology and Cancer Biology; Rebekah R. White of the Duke Department of Surgery and the Duke Translational Research Institute; and Justin D. Lathia and Anita B. Hjelmeland of the Department of Stem Cell Biology and Regenerative Medicine at Cleveland Clinic, and Jeremy Rich, Dr. Wang's mentor who was at Duke and now heads that department at the Cleveland Clinic.
The research was supported by a Basic Research Fellowship from the American Brain Tumor Association, a Howard Hughes Medical Institute Early Career Award, NIH grants, the Childhood Brain Tumor Foundation, the Pediatric Brain Tumor Foundation of the United States, Accelerate Brain Cancer Cure, the Alexander and Margaret Stewart Trust, Brain Tumor Society, the Goldhirsh Foundation, the Sidney Kimmel Foundation, and the Damon Runyon Cancer Research Foundation.
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For the First Time, a Glioma - Brain Cancer - may be Eliminated by a Chinese Research/Medical Team, Using a Novel Stem Cell Based Therapy of Cellonis Biotech, Beijing


LINK


BEIJING, Dec. 17 /PRNewswire-Asia/ -- Using a novel stem cell based technology of Cellonis Biotechnologies, Beijing, a Chinese research/medical team may eliminate a glioma -- brain cancer -- of a 36 year old Norwegian patient in a hospital in Beijing. The treatment shows that the activated immune system can directly kill tumor stem cells as well as cancer daughter cells. The amazing outcome of this novel treatment within a Comprehensive Cancer Therapy tells Cellonis that the future vaccination therapies may be targeted towards cancer stem cell lysates to improve the antigen-presenting Dendritic Cell response.
(Photo: http://www.newscom.com/cgi-bin/prnh/20091217/CNTH007)


Arve Johnsen , 36, from Norway, a patient diagnosed with glioma in 2006 and relapsed in 2009 after surgical resection. He arrived in Beijing in August 2009 with his wife Vanja and a one-year-old daughter, with the hope that the doctors in Norway were wrong. They told the family there is no other option anymore in the Scandinavian countries or in Europe for Arve to control the progress of disease and prolong his life. Driven by the hope that their daughter could grow up with a father, the Johnsen family started a research campaign to find other treatments worldwide, to give Arve a new hope.

Comprehensive Cancer Therapy in China
The Johnsen's, having heard about the sustainable success of a Comprehensive Cancer Therapy (CCT) in China, decided to try for this last chance in a country 10,000 km away from Norway. This kind of CCT had been developed in the past few years by a Chinese team of scientific researchers and clinical doctors in Beijing, combining conventional cancer treatments with Traditional Chinese Medicine (TCM) and cell therapies.
The role of cancer stem cells in the tumors
Scientists previously believed that tumors are lumps of cancer tissue that must be completely removed or destroyed to cure a patient. But over the past few years, researchers have learned that cancer stem cells (CSCs), comprising a small population of cells, appear to be responsible for the initiation, upkeep and relapse of malignant tumors. Even if a tumor is almost completely obliterated, it will regenerate from the surviving CSCs and become even more resistant to treatment than before.
Current therapies, including cell therapy, generally do not target CSCs. This allows CSCs to survive until after chemotherapy or radiation treatments. Killing those cells is a promising strategy to eliminate tumors and prevent them from re-growing.

Prof.
Lily Shum : Perfect integration of stem cells and immunotherapies


"The CSCs may explain why common treatments, particularly chemotherapy, are not sufficient to kill tumors. In fact, despite the continuous development of new chemotherapeutic agents, brain tumors can develop and remain resistant to those therapies. The integration of stem cells and immune technologies seems to give us a chance to find out a new way to target at CSCs," says Prof.
Lily Shum , PhD, the chief scientist of Cellonis.

"The difficult issue in our project is how to capture and classify CSCs. With our patented technologies, we are able to isolate the CSCs from patient's brain tumor tissues, culture them and induce the multi-drug and radiation resistance. These cells possess very strong carcinogenicity, self-renewal, and also a very strong drug and radiation resistance."


Lily Shum adds, "The Dendritic Cell (DC) is a very useful tool to conduct a specific immune response against brain CSCs." As we know, DC is an antigen-presenting cell that stimulates the innate immune system, as a messenger, it transfers "the information of cancer cell - antigen" to "the killers of the immune system - the T cells," and then T cells can recognize and lyse cells bearing those antigens. "We educate the DC with the brain CSCs, and then conduct the specific immune response which targets the CSCs."


Dr.
Dinggang Li : Comprehensive Cancer Therapies


"The outcome of the first pilot study with Johnsen is amazing. The PET-CT scan for Johnsen shows that all the tumor disappeared after the treatment," says Dr.
Dinggang Li, M.D. PhD. He has developed and conducted CCT for more than 100 international cancer patients in the past few years. DCs loaded with different kinds of brain cancer related antigens that target cancer cells and the CIK cell treatment are the main elements of his comprehensive treatment for cancer. "In the first cycle of treatment, we treated him with comprehensive approaches including SHG-44 loading DC, CIK cell therapy and TCM, but we had not been able to control the progression of the disease, the tumors continued to grow. We gave him the DC therapy which targets brain CSCs in the 2nd cycle of treatment, and it showed a very promising response."

Dr. Cindy HAO: More clinical trials to confirm the outcome
Cindy HAO, M.D., CEO of Cellonis Biotechnologies is optimistic for the future of this new brain cancer approach. "It gives us a strong confidence to make more efforts toward this direction. This pilot treatment study shows us that the activated immune system can directly kill tumor stem cells as well as tumor daughter cells. But first of all we need to extend our further clinical trials to confirm the outcome. And it also tells us that the future vaccination therapies may be targeted toward Cancer Stem Cell Lysates to improve the antigen-presenting DC response."

For more information, please contact:

Urs. J. Lienert, M.B.A.
Director International
Cellonis Biotechnologies Co., Ltd.
Floor 7, Huizhong Science & Technology Center
No 1, Shangdi Seventh Road
Haidian District Beijing, 100085
P.R. China
Email: urs.lienert@cellonis.com; Lienert.Cellonis@yahoo.com
Phone: +86-10-6296-2795; Cell: +86-150-1054-7487
Cell: +41-76-584-87-60 (Switzerland)
(from 20 December 2009 to 15 January 2010)
SOURCE Cellonis Biotechnologies


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