Most recent edit on 2007-11-23 11:39:34 by KathyFromEngland

Additions:
~*BEMA Fentanyl Demonstrates Substantial Transmucosal Delivery

*How Curcumin Helps Fight Cancer

How Curcumin Helps Fight Cancer
Article Date: 31 May 2007 - 10:00 PDT
Scientists showed that curcumin, the main ingredient of the Indian herb turmeric, restores key immune cells that fight off cancer.
The immune system of patients with advanced cancer is significantly weakened, mostly because the main cells that fight off tumors either cannot proliferate anymore or have died off. Curcumin was previously shown to have anti-tumor activity but its effects on the immune system were unknown - until now.
Gaurisankar Sa and colleagues showed that curcumin boosts the immune system of tumor-bearing mice by restoring key immune cells called CD4 and CD8 T cells. The scientists also showed that curcumin increases the production of proteins that cause immune cells to proliferate and reduces the production of proteins that destroy immune cells.
Article: "Curcumin Prevents Tumor-Induced T Cell Apoptosis through Stat-5a-mediated Bcl-2 Induction" by Sankar Bhattacharyya, Debaprasad Mandal, Baisakhi Saha, Gouri Sankar Sen, Tanya Das, and Gaurisankar Sa
http://www.medicalnewstoday.com/articles/72129.php∞

Deletions:
~*BEMA Fentanyl Demonstrates Substantial Transmucosal Delivery

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Edited on 2007-11-14 00:08:43 by KathyFromEngland

Additions:
~*Targeting Tumors The Natural Way

*BEMA Fentanyl Demonstrates Substantial Transmucosal Delivery

BEMA Fentanyl Demonstrates Substantial Transmucosal Delivery
BioDelivery Sciences International, Inc. (Nasdaq:BDSI) have announced the results of a 12 subject, crossover study comparing the absorption of fentanyl from both single and multiple BEMA? Fentanyl discs, as well as oral and intravenous doses of fentanyl. The data demonstrates that the absolute bioavailability (i.e. the total amount absorbed from the delivery system) of fentanyl through the BEMA disc was more than 70%, with 50% absorbed through the buccal mucosa (the inner lining of the cheek). The study further demonstrates that equal doses administered as either a single disc or multiple discs produced nearly identical plasma concentrations (i.e. two 200 mcg discs provided nearly equivalent plasma concentrations as one 400 mcg disc, etc.)

Deletions:
~*Targeting Tumors The Natural Way

BEMA Fentanyl Demonstrates Substantial Transmucosal Delivery
BioDelivery Sciences International, Inc. (Nasdaq:BDSI) have announced the results of a 12 subject, crossover study comparing the absorption of fentanyl from both single and multiple BEMA? Fentanyl discs, as well as oral and intravenous doses of fentanyl. The data demonstrates that the absolute bioavailability (i.e. the total amount absorbed from the delivery system) of fentanyl through the BEMA disc was more than 70%, with 50% absorbed through the buccal mucosa (the inner lining of the cheek). The study further demonstrates that equal doses administered as either a single disc or multiple discs produced nearly identical plasma concentrations (i.e. two 200 mcg discs provided nearly equivalent plasma concentrations as one 400 mcg disc, etc.)

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Edited on 2007-11-14 00:07:32 by KathyFromEngland

Additions:
BEMA Fentanyl Demonstrates Substantial Transmucosal Delivery
12 May 2007
BioDelivery Sciences International, Inc. (Nasdaq:BDSI) have announced the results of a 12 subject, crossover study comparing the absorption of fentanyl from both single and multiple BEMA? Fentanyl discs, as well as oral and intravenous doses of fentanyl. The data demonstrates that the absolute bioavailability (i.e. the total amount absorbed from the delivery system) of fentanyl through the BEMA disc was more than 70%, with 50% absorbed through the buccal mucosa (the inner lining of the cheek). The study further demonstrates that equal doses administered as either a single disc or multiple discs produced nearly identical plasma concentrations (i.e. two 200 mcg discs provided nearly equivalent plasma concentrations as one 400 mcg disc, etc.)
These findings follow the Company's announcement of statistically significant results with BEMA Fentanyl in treating cancer patients with breakthrough pain in the company's Phase III efficacy clinical trial. BDSI plans to include today's study results, the efficacy trial results and other materials in its planned submission of a New Drug Application (NDA) to the FDA for BEMA Fentanyl. The NDA submission is expected during third quarter of 2007.
BEMA Fentanyl consists of a small, dissolvable polymer disc, formulated with the opioid narcotic fentanyl, for application to the buccal membranes. Upon administration, BEMA Fentanyl is designed to deliver a rapid, reliable dose of drug across mucous membranes. BEMA Fentanyl is being developed for the treatment of "breakthrough" cancer pain (i.e. episodes of severe pain which "break through" the medication already in use to control the persistent pain).
Dr. Andrew Finn, Executive Vice President of Product Development for BDSI, stated "The results of this study confirm, and are an expansion of, the information obtained in our 2006 pharmacokinetic study which demonstrated that fentanyl absorption from the BEMA delivery system was better than that seen with Actiq?. This study showed that the absolute bioavailability from BEMA Fentanyl and the amount of fentanyl absorbed directly through the buccal mucosa was substantial (70% and 50%, respectively). Although the study announced today was not a direct comparative study, our bioavailability results are greater than those previously reported with Actiq? (50% and 22%), and similar to those previously reported with Fentora? (65% and 48%). Given the linear increase in plasma concentrations with increases in dose, and the nearly identical plasma concentrations when a dose is administered as a single disc or with multiple discs, we believe doctors will have the needed flexibility in titrating the dose of BEMA Fentanyl to meet the changing analgesic requirements of patients with breakthrough cancer pain."
Actiq?, marketed by Cephalon, Inc., is the leading fentanyl product for the treatment of breakthrough cancer pain in the U.S. market. Cephalon introduced a second fast dissolving fentanyl product, Fentora?, in 2006. The reported combined sales of these products in 2006 were $659 million.
Dr. Mark Sirgo, President and CEO of BDSI, stated "These results continue to demonstrate the consistency in the performance of the BEMA delivery system. The principal purpose of a transmucosal delivery system is to have the majority of the drug absorbed through that membrane, thereby allowing for a rapid onset of action while minimizing the amount of drug that is swallowed. These results show that the BEMA technology and our BEMA Fentanyl product specifically meet this principle. These results, when combined with the recent announcement of achieving our primary efficacy endpoint in our breakthrough cancer pain Phase III efficacy study, give us continued confidence that the commercial value for BEMA Fentanyl remains on target with our expectations. In addition, we believe these continued positive findings with our BEMA technology lend support to the continued development of other products in the technology, including our next pain product in development, BEMA LA."
http://www.medilexicon.com/medicalnews.php?newsid=70251∞

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Edited on 2007-11-13 00:13:46 by JasonD [Restored to Original Version by Kathy]

Additions:
The drug, called bortezomib or (Velcade?) - when used alone or in combination with other cancer treatments - represents a potential new way to treat malignant glioma, a particularly stubborn and aggressive brain tumor.
Researchers looked at 203 glioma samples and determined that NF-?B was activated. They also noticed that the level of activation was related to the grade of the tumor, suggesting that NF-?B is related to tumor progression. Treatment with bortezomib suppressed both unregulated and signal-oriented activation in NF-kB by inhibiting the breakdown of IkB-alpha. IkB-alpha is one of a series of inhibitory proteins that controls the activation of NF-kB, preventing it from binding to DNA in the nucleus. Bortezomib not only stops the degradation of IkB-alpha, it also suppresses the activation of NF-kB, thus stopping cell growth.
Researchers from The University of Texas M. D. Anderson Cancer Center, Houston, have identified why some women with Her-2 positive breast cancer, an aggressive form of the disease, do not respond to the drug trastuzumab (Herceptin?) or may actually develop a resistance to the treatment.
There are many reasons why potential treatments do not make it to market. Science has progressed so rapidly in recent years that there are more compounds available than commercial resources to investigate them. And because drug development is so time-consuming and expensive - a new anti-cancer drug can take in excess of 10 years and ?500 million to develop - anything that doesn't look extremely promising is not developed by a pharmaceutical company.
Dr Klaus Pors, a Medicinal Chemist based at the University's Institute of Cancer Therapeutics, has been awarded ?96,474 by Yorkshire Cancer Research to develop a medicine that is harmless to the body but will help to eradicate tumours by using the cancer cell to convert a drug from something inactive to a powerful cell-killing agent.

Deletions:
delelrelc4
The drug, called bortezomib or (Velcade®) - when used alone or in combination with other cancer treatments - represents a potential new way to treat malignant glioma, a particularly stubborn and aggressive brain tumor.
Researchers looked at 203 glioma samples and determined that NF-�B was activated. They also noticed that the level of activation was related to the grade of the tumor, suggesting that NF-�B is related to tumor progression. Treatment with bortezomib suppressed both unregulated and signal-oriented activation in NF-kB by inhibiting the breakdown of IkB-alpha. IkB-alpha is one of a series of inhibitory proteins that controls the activation of NF-kB, preventing it from binding to DNA in the nucleus. Bortezomib not only stops the degradation of IkB-alpha, it also suppresses the activation of NF-kB, thus stopping cell growth.
Researchers from The University of Texas M. D. Anderson Cancer Center, Houston, have identified why some women with Her-2 positive breast cancer, an aggressive form of the disease, do not respond to the drug trastuzumab (Herceptin®) or may actually develop a resistance to the treatment.
There are many reasons why potential treatments do not make it to market. Science has progressed so rapidly in recent years that there are more compounds available than commercial resources to investigate them. And because drug development is so time-consuming and expensive - a new anti-cancer drug can take in excess of 10 years and £500 million to develop - anything that doesn't look extremely promising is not developed by a pharmaceutical company.
Dr Klaus Pors, a Medicinal Chemist based at the University's Institute of Cancer Therapeutics, has been awarded £96,474 by Yorkshire Cancer Research to develop a medicine that is harmless to the body but will help to eradicate tumours by using the cancer cell to convert a drug from something inactive to a powerful cell-killing agent.

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Edited on 2007-11-12 23:54:04 by GetdaRacba

Additions:
delelrelc4
The drug, called bortezomib or (Velcade®) - when used alone or in combination with other cancer treatments - represents a potential new way to treat malignant glioma, a particularly stubborn and aggressive brain tumor.
Researchers looked at 203 glioma samples and determined that NF-�B was activated. They also noticed that the level of activation was related to the grade of the tumor, suggesting that NF-�B is related to tumor progression. Treatment with bortezomib suppressed both unregulated and signal-oriented activation in NF-kB by inhibiting the breakdown of IkB-alpha. IkB-alpha is one of a series of inhibitory proteins that controls the activation of NF-kB, preventing it from binding to DNA in the nucleus. Bortezomib not only stops the degradation of IkB-alpha, it also suppresses the activation of NF-kB, thus stopping cell growth.
Researchers from The University of Texas M. D. Anderson Cancer Center, Houston, have identified why some women with Her-2 positive breast cancer, an aggressive form of the disease, do not respond to the drug trastuzumab (Herceptin®) or may actually develop a resistance to the treatment.
There are many reasons why potential treatments do not make it to market. Science has progressed so rapidly in recent years that there are more compounds available than commercial resources to investigate them. And because drug development is so time-consuming and expensive - a new anti-cancer drug can take in excess of 10 years and £500 million to develop - anything that doesn't look extremely promising is not developed by a pharmaceutical company.
Dr Klaus Pors, a Medicinal Chemist based at the University's Institute of Cancer Therapeutics, has been awarded £96,474 by Yorkshire Cancer Research to develop a medicine that is harmless to the body but will help to eradicate tumours by using the cancer cell to convert a drug from something inactive to a powerful cell-killing agent.

Deletions:
The drug, called bortezomib or (Velcade?) - when used alone or in combination with other cancer treatments - represents a potential new way to treat malignant glioma, a particularly stubborn and aggressive brain tumor.
Researchers looked at 203 glioma samples and determined that NF-?B was activated. They also noticed that the level of activation was related to the grade of the tumor, suggesting that NF-?B is related to tumor progression. Treatment with bortezomib suppressed both unregulated and signal-oriented activation in NF-kB by inhibiting the breakdown of IkB-alpha. IkB-alpha is one of a series of inhibitory proteins that controls the activation of NF-kB, preventing it from binding to DNA in the nucleus. Bortezomib not only stops the degradation of IkB-alpha, it also suppresses the activation of NF-kB, thus stopping cell growth.
Researchers from The University of Texas M. D. Anderson Cancer Center, Houston, have identified why some women with Her-2 positive breast cancer, an aggressive form of the disease, do not respond to the drug trastuzumab (Herceptin?) or may actually develop a resistance to the treatment.
There are many reasons why potential treatments do not make it to market. Science has progressed so rapidly in recent years that there are more compounds available than commercial resources to investigate them. And because drug development is so time-consuming and expensive - a new anti-cancer drug can take in excess of 10 years and ?500 million to develop - anything that doesn't look extremely promising is not developed by a pharmaceutical company.
Dr Klaus Pors, a Medicinal Chemist based at the University's Institute of Cancer Therapeutics, has been awarded ?96,474 by Yorkshire Cancer Research to develop a medicine that is harmless to the body but will help to eradicate tumours by using the cancer cell to convert a drug from something inactive to a powerful cell-killing agent.

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Edited on 2007-06-04 11:20:38 by KathyFromEngland

Additions:
~*New Method For Making Potential Cancer Fighter
New Method For Making Potential Cancer Fighter
31 Aug 2006
Ras is a protein that works as a molecular switch, triggering biochemical events inside certain cells that lead to cancer. The gene that produces ras gained notoriety as the first known oncogene -- a gene that can cause cancer. Six years ago, Japanese scientists discovered that rasfonin, a compound isolated from a fungus, selectively destroys ras-dependent cells. Normal cells were not harmed.
With the prospect that rasfonin could lead to a new family of anti-cancer drugs, scientists began searching for a way to make enough rasfonin for tests. Scientists now are reporting development of that simpler method in a report scheduled for the Aug. 23 issue of the Journal of the American Chemical Society.
Robert K. Boeckman Jr. and colleagues explain that the only existing synthesis was complicated and not easily adapted for producing larger amounts of rasfonin. Their method involves only 16 steps (compared to 23 in the previous method) and produces 67 percent more rasfonin.
ARTICLE #1: "Toward the development of a General Chiral Auxiliary. Enantioselective Alkylation and a New Catalytic Asymmetric Addition of Silyloxyfurans: Application to a Total Synthesis of (-)-Rasfonin"
DOWNLOAD PDF:
http://pubs.acs.org/cgi-bin/sample.cgi/jacsat/asap/pdf/ja063532+.pdf∞
DOWNLOAD HTML:
http://pubs.acs.org/cgi-bin/sample.cgi/jacsat/asap/html/ja063532+.html∞
Robert K. Boeckman Jr., Ph.D.
University of Rochester
Email: rkb@rkbmac.chem.rochester.edu
http://www.medilexicon.com/medicalnews.php?newsid=50709∞

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Edited on 2007-03-29 08:20:25 by KathyFromEngland

Additions:
~*Researchers Reveal Biological Properties Of Exciting New Class Of Potential Anti-Cancer Drugs

*Targeting Tumors The Natural Way

Targeting Tumors The Natural Way
29 Mar 2007
By mimicking Nature's way of distinguishing one type of cell from another, University of Wisconsin-Madison scientists now report they can more effectively seek out and kill cancer cells while sparing healthy ones.
The new tumor targeting strategy, presented today (March 25) at the annual national meeting of the American Chemical Society, cleverly harnesses one of the body's natural antibodies and immune responses. "The killing agent we chose is already in us," says UW-Madison chemistry professor Laura Kiessling, who led the work with postdoctoral researcher Coby Carlson. "It's just not usually directed toward tumor cells."
In a series of cell-based experiments, the researchers' system recognized and killed only those cells displaying high levels of receptors known as integrins. These molecules, which tend to bedeck the surfaces of cancer cells and tumor vasculature in large numbers, have become important targets in cancer research.
In contrast, an established tumor-homing agent linked to the cell toxin doxorubicin destroyed cells even when they expressed very little integrin, indicating this strategy has the potential to kill cancerous and healthy cells indiscriminately.
"This study suggests that the cell recognition mode we used can direct an endogenous immune response to destroy cancer cells selectively," says Kiessling. "We think this could lead to a new class of therapeutic agents not only for cancer but also for other diseases involving harmful cells."
Cancer cells typically display higher levels of certain receptors on their surfaces than do normal cells, a fact that allows scientists to pinpoint tumor cells lurking among the body's scores of cell types. A popular approach employs a cell-binding agent, such as a monoclonal antibody, that is powerfully attracted to the target receptor and holds fast to any cell displaying it.
Although this strategy has benefits, it's not natural, says Kiessling. Cell recognition in living systems instead involves binding agents that attach only weakly to any single target receptor, and thus stick to cells only when several receptors are displayed together. These weak "multivalent" interactions cut down on cases of mistaken identity, because if the agent contacts the wrong cell type, it can be easily displaced.
The team got the idea to mimic this process from efforts to transplant pig organs into primates. The surfaces of most mammalian and bacterial cells express large amounts of a carbohydrate, called alpha-Gal in scientific shorthand, while the cells of humans and other higher primates do not. What humans and primates do produce in abundance is an antibody against the carbohydrate, called anti-Gal.
When scientists tried transplanting pig organs into primates, the anti-Gal antibodies bound to the alpha-Gal on the organ's cells, unleashing a potent immune response that caused immediate organ rejection. But true to natural cell recognition, the immune response occurs only when clusters of many alpha-Gal molecules are present for anti-Gal to bind with.
Armed with this knowledge, Kiessling's group modified an agent known to bind tightly to integrin and tethered it to alpha-Gal. When they mixed this molecule with cells displaying high levels of integrin, the agent, by attaching to the receptor, decorated the cells with large amounts of alpha-Gal. In cell cultures containing human serum, the alpha-Gal then elicited the cell-destroying immune reaction.
In cells with low concentrations of integrin, the agent still bound, but the resulting levels of alpha-Gal weren't sufficient to elicit the immune response, and the cells survived. The same wasn't true if the cell-binding agent delivered doxorubicin to cells instead: They were killed regardless of the amount of integrin they carried.
Because target receptors on cancer cells usually reside on healthy cells, too - albeit in lower numbers - therapies aimed at these receptors are always expected to have debilitating side effects. That's why Kiessling's approach holds such promise.
"What we've shown is that you don't need a receptor that's found solely on tumor cells," she says. "You just need one that's found in significantly higher numbers on cancerous cells than on normal ones."
http://www.medilexicon.com/medicalnews.php?newsid=66117∞

Deletions:
~*Researchers Reveal Biological Properties Of Exciting New Class Of Potential Anti-Cancer Drugs

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Edited on 2007-03-28 12:35:19 by KathyFromEngland

Additions:
~*Chemist Aims To Flush Away Tumours

*Researchers Reveal Biological Properties Of Exciting New Class Of Potential Anti-Cancer Drugs

Researchers Reveal Biological Properties Of Exciting New Class Of Potential Anti-Cancer Drugs
27 Mar 2007
New research published by scientists from The Institute of Cancer Research, funded by Cancer Research UK and the Wellcome Trust, reveals for the first time the biological properties of a promising new class of synthetic potential anti-cancer drugs.
The compounds are from a new group of inhibitors known as HSP90 (Heat Shock Protein 90) inhibitors. HSP90 is a key cellular protein that has been shown to be a particularly appealing target for anti-cancer drugs as its inhibition causes the breakdown of multiple cancer causing proteins. Previous HSP90 research has demonstrated that these inhibitors could be developed into effective treatments for a range of cancers including: prostate, breast, colon, ovarian and skin.
The research, published in the journal Cancer Research*, provides the first detailed description of the lead compound - CCT018159 - a 3,4 diaryl pyrazole resorcinol HSP90 inhibitor discovered by the team. These molecules work by binding into a key region of the HSP90 protein in place of an ATP (Adenosine Triphosphate) molecule. CCT018159 is particularly exciting as it delivers a multi-pronged attack on cancer cells, causing them to 'commit suicide' and also preventing the spread of the cancer cells and the formation of new tumour blood vessels (angiogenesis).
Professor Paul Workman of the Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research says: "This research is still in the early stage but HSP90 inhibitors continue to be a really exciting group of potential new drugs. Their real strength lies in the fact that they target so many different aspects of the cancer cell machinery at the same time. This gives a very powerful anti-cancer effect and makes it difficult for tumours to develop resistance. We are delighted with the progress that has been made so far and we look forward to taking these therapies to the next stage."
http://www.medilexicon.com/medicalnews.php?newsid=66042∞

Deletions:
~*Chemist Aims To Flush Away Tumours

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Edited on 2007-03-23 12:58:16 by KathyFromEngland

Additions:
~*Taking Away Cbl-b Improves Antitumor Immune Responses

*Chemist Aims To Flush Away Tumours

Chemist Aims To Flush Away Tumours
23 Mar 2007
A researcher from the University of Bradford has been awarded a grant to investigate a way of flushing out cancerous tumours in the body with no potentially harmful side-effects.
Dr Klaus Pors, a Medicinal Chemist based at the University's Institute of Cancer Therapeutics, has been awarded ?96,474 by Yorkshire Cancer Research to develop a medicine that is harmless to the body but will help to eradicate tumours by using the cancer cell to convert a drug from something inactive to a powerful cell-killing agent.
The research centres on a group of proteins found in all humans called Cytochromes P450 (CYPs), which are most commonly found in the liver. They form part of the body's immune system and their job is to metabolise compounds in the liver and other filter organs, making these compounds more 'polar' and enabling harmful substances to be excreted out of the body via the urinary system.
Whilst there are 57 known types of CYPs, some are known to be more highly present in cancer cells compared to the surrounding normal tissue. Dr Pors aims to exploit them by essentially hijacking the CYPs in the tumour to produce an agent that is highly damaging to the cancer cell DNA whilst leaving normal healthy cells alone.
Dr Pors will be using the grant to employ a post-doctoral researcher to help develop these novel tumour-selective agents. He said: "A major obstacle in the treatment of cancer is the lack of selective killing of cancer cells. Clinicians currently use chemotherapeutic agents which generally damage normal tissues and lead to severe side-effects.
"It is envisaged that an agent would be administered to patients that produces no side-effects commonly associated with current therapies, but when reaching the tumour will be converted to an ultra-potent agent that causes the demise of the tumour.
"I'm delighted that Yorkshire Cancer Research has funded our work here, using money raised in the region for research in the region but more importantly, if our work is successful, patients all over the world could benefit from such highly targeted anti-cancer drugs that in principle will cause no harmful side-effects."
Dr Pors and a team of researchers have spent the last 15 months analysing samples taken from cancer patients in Bradford and Leeds in order to get to this stage. If the lab-based work is successful, he hopes to move to Phase 1 Clinical Trials within five years.
BRADFORD UNIVERSITY
Bradford
West Yorkshire
BD7 1DP
http://www.bradford.ac.uk∞
http://www.medilexicon.com/medicalnews.php?newsid=65879∞

Deletions:
~*Taking Away Cbl-b Improves Antitumor Immune Responses

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Edited on 2007-03-23 09:30:31 by KathyFromEngland

Additions:
~*ImmuneRegen BioSciences Announces Promising Data On Homspera Suggesting Potential As A Co-Therapeutic Agent

*Taking Away Cbl-b Improves Antitumor Immune Responses

Taking Away Cbl-b Improves Antitumor Immune Responses
20 Mar 2007
Many researchers are developing ways in which to harness the immune response to treat patients with cancer. However, many results have not been as successful as hoped, largely because tumors develop ways in which to suppress the immune system. For example, before immune cells known as CD8+ T cells can destroy tumors cells they must receive signals through 2 receptors on their cell surface and many tumors do not express the molecules that trigger the second signal, through CD28.
In a study that appears online in advance of publication in the April print issue of the Journal of Clinical Investigation, Hua Gu and colleagues show that mouse CD8+ T cells lacking a protein known as Cbl-b can respond in vitro without receiving a signal through CD28. In vivo, when mice lacking Cbl-b were transplanted with tumors they rejected the tumors rapidly, whereas normal mice did not. In addition, if mice that spontaneously develop tumors were engineered to lack Cbl-b the incidence of spontaneous tumor development was markedly decreased. Although these data indicate that ablation of Cbl-b can enhance antitumor immune responses, further studies are needed to determine the short- and long-term impact of Cbl-b ablation before these observations can be translated into the clinic for the treatment of individuals with cancer.
http://www.medilexicon.com/medicalnews.php?newsid=65412∞

Deletions:
~*ImmuneRegen BioSciences Announces Promising Data On Homspera Suggesting Potential As A Co-Therapeutic Agent

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Edited on 2007-03-21 10:52:13 by KathyFromEngland

Additions:
ImmuneRegen BioSciences, a wholly owned subsidiary of IR BioSciences Holdings, Inc. (OTC Bulletin Board: IRBO), announced today that data obtained by the Company on its Substance P analog, Homspera, suggests that the compound has potential value as a co-therapeutic agent or vaccine adjuvant. Studies performed in animal models of influenza and acute radiation syndrome have revealed the potential capability of Homspera to enhance the action of approved antiviral medications as well as to provide adjunctive impact on antitumor radiation therapy.
Studies in cell culture have revealed elevations in components of the innate immune system that are consistent with Toll-like Receptor activation, a postulated mechanism by which vaccine adjuvants accomplish their immunosensitization. Additionally, the anti-anthrax activity reported by Homspera is similarly consistent with activation of components of innateimmunity that have been reported to have anti-anthrax activity, such as defensins. "While these results from the use of Homspera are preliminary, we believe that upcoming studies in non-human primates may provide confirmation that Homspera could play an important role, in conjunction with other therapies, in improving treatment outcomes in influenza and cancer, two large- market opportunities," said ImmuneRegen's CEO Michael Wilhelm. "With the pharmaceutical and biotechnology industries increasingly focused on adjunctive therapies, we are committed to accelerating development of this promising compound."

Deletions:
ImmuneRegen BioSciences, a wholly owned subsidiary of IR BioSciences Holdings, Inc. (OTC Bulletin Board: IRBO), announced today that data obtained by the Company on its Substance P analog, Homspera, suggests that the compound has potential value as a co-therapeutic agent or vaccine adjuvant. Studies performed in animal models of influenza and acute radiation syndrome have revealed the potential capability of Homspera to enhance the action of approved antiviral medications as well as to provide adjunctive impact on antitumor radiation therapy.
Studies in cell culture have revealed elevations in components of the innate immune system that are consistent with Toll-like Receptor activation, a postulated mechanism by which vaccine adjuvants accomplish their immunosensitization. Additionally, the anti-anthrax activity reported by Homspera is similarly consistent with activation of components of innateimmunity that have been reported to have anti-anthrax activity, such as defensins. "While these results from the use of Homspera are preliminary, we believe that upcoming studies in non-human primates may provide confirmation that Homspera could play an important role, in conjunction with other therapies, in improving treatment outcomes in influenza and cancer, two large- market opportunities," said ImmuneRegen's CEO Michael Wilhelm. "With the pharmaceutical and biotechnology industries increasingly focused on adjunctive therapies, we are committed to accelerating development of this promising compound."

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Edited on 2007-03-21 10:49:17 by KathyFromEngland

Additions:
~*Toward Powerful New Anticancer Drugs With New Ways Of Targeting Tumors

*ImmuneRegen BioSciences Announces Promising Data On Homspera Suggesting Potential As A Co-Therapeutic Agent

ImmuneRegen BioSciences Announces Promising Data On Homspera Suggesting Potential As A Co-Therapeutic Agent
21 Mar 2007
ImmuneRegen BioSciences, a wholly owned subsidiary of IR BioSciences Holdings, Inc. (OTC Bulletin Board: IRBO), announced today that data obtained by the Company on its Substance P analog, Homspera, suggests that the compound has potential value as a co-therapeutic agent or vaccine adjuvant. Studies performed in animal models of influenza and acute radiation syndrome have revealed the potential capability of Homspera to enhance the action of approved antiviral medications as well as to provide adjunctive impact on antitumor radiation therapy.
Studies performed in the cotton rat model of influenza at Virion Systems, Inc. (VSI, a Maryland biotechnology corporation) have revealed the ability of Homspera to diminish the impact of influenza virus infection on animal weight loss and temperature. In addition, viral titers were found to be decreased up to 90% in lungs and nose of treated animals.
The Company believes that, in conjunction with a neuraminidase inhibitor such as oseltamivir (Tamiflu(R), Roche Pharmaceuticals), Homspera might be an effective adjuvant therapeutic by decreasing the number of viruses at which this enzyme would need to be inhibited.
Potential also exists for Homspera to be used as an adjuvant therapy for cancer patients, as treatment often includes radiation following chemotherapy, in an attempt to kill more of the cancer cells. Survival data from gamma- irradiated mice studies and mechanistic studies in cell culture have shown indications of hematopoietic stem cell replenishment of circulating leukocytes and platelets, which could be of value in radiation-treated cancer patients.
Studies in cell culture have revealed elevations in components of the innate immune system that are consistent with Toll-like Receptor activation, a postulated mechanism by which vaccine adjuvants accomplish their immunosensitization. Additionally, the anti-anthrax activity reported by Homspera is similarly consistent with activation of components of innateimmunity that have been reported to have anti-anthrax activity, such as defensins. "While these results from the use of Homspera are preliminary, we believe that upcoming studies in non-human primates may provide confirmation that Homspera could play an important role, in conjunction with other therapies, in improving treatment outcomes in influenza and cancer, two large- market opportunities," said ImmuneRegen's CEO Michael Wilhelm. "With the pharmaceutical and biotechnology industries increasingly focused on adjunctive therapies, we are committed to accelerating development of this promising compound."
Since the identification of a single therapeutic with both immunoadjuvant capabilities plus the ability to enhance maturation and mobility of stem cells might be of significant therapeutic significance, the Company plans future studies to explore this opportunity in more detail.
http://www.medilexicon.com/medicalnews.php?newsid=65681∞

Deletions:
~*Toward Powerful New Anticancer Drugs With New Ways Of Targeting Tumors

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Edited on 2007-03-02 00:25:32 by KathyFromEngland

Additions:
In the article, C&EN associate editor Lisa Jarvis explains that the new compounds may circumvent the long-standing problem of drug resistance, in which anti-cancer drugs gradually loose their effectiveness. The drugs focus on a new target in the war against cancer - a substance called heat shock protein 90 (Hsp90). Heat shock proteins are most active when the cell is exposed to elevated temperatures, infection, inflammation, toxins and other stresses that can cause a protein to unfold. Like housekeepers, heat shock proteins help those proteins - including mutated, cancer-causing proteins - get back into their proper shape.
When Hsp90's effects are blocked in cancer cells, those cancer-causing proteins cannot survive, potentially stopping the disease in its track. When Hsp90's effects are blocked in cancer cells, damaged proteins accumulate, and the cell dies. Jarvis explains that cancer cells, with their horribly mutated proteins, seem to be especially dependent on Hsp90, and more vulnerable than other body cells when Hsp90's effects are blocked. The article describes how new discoveries have changed heat shock proteins from laboratory curiosities into some of today's most promising targets for developing new drugs.

Deletions:
In the article, C&EN associate editor Lisa Jarvis explains that the new compounds may circumvent the long-standing problem of drug resistance, in which anti-cancer drugs gradually loose their effectiveness. The drugs focus on a new target in the war against cancer - a substance called heat shock protein 90 (Hsp90). Heat shock proteins are most active when the cell is exposed to elevated temperatures, infection, inflammation, toxins and other stresses that can cause a protein to unfold. Like housekeepers, heat shock proteins help those proteins - including mutated, cancer-causing proteins - get back into their proper shape.
When Hsp90's effects are blocked in cancer cells, those cancer-causing proteins cannot survive, potentially stopping the disease in its track. When Hsp90's effects are blocked in cancer cells, damaged proteins accumulate, and the cell dies. Jarvis explains that cancer cells, with their horribly mutated proteins, seem to be especially dependent on Hsp90, and more vulnerable than other body cells when Hsp90's effects are blocked. The article describes how new discoveries have changed heat shock proteins from laboratory curiosities into some of today's most promising targets for developing new drugs.

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Edited on 2007-03-02 00:21:21 by KathyFromEngland

Additions:
~*A New Target In The War On Cancer

*Toward Powerful New Anticancer Drugs With New Ways Of Targeting Tumors

Toward Powerful New Anticancer Drugs With New Ways Of Targeting Tumors
The search for new anticancer drugs has led scientists in Pittsburgh to synthesize a compound that works in a different way than existing agents and is so potent that minute levels of 10 parts per trillion block the growth of tumor cells in laboratory experiments. Kazunori Koide and colleagues describe the compound as one of the most potent of all anticancer agents in a report scheduled for the March 7 issue of the Journal of the American Chemical Society.
The parent compound, FR901464, inhibited the growth of cancer cells implanted into laboratory mice. Because of structural similarity between FR901464 and their analogue, called meayamycin, the Koide group is cautiously optimistic that meayamycin also will be effective against tumors in mice. The amount that the Koide employed against cancer cells is equivalent to 10 seconds in 32,000 years or one packet of sugar (5 grams) in a coffee cup the size of 400 Olympic-size pools.
In the article, researchers explain that existing chemotherapy medications work by targeting only a handful of vulnerable spots in a tumor, such as the DNA or hormone receptors. That limited range of targets has led scientists to seek new generations of medications that work in different ways.
ARTICLE #4
"Total Synthesis, Fragmentation Studies, and Antitumor/Antiproliferative Activities of FR901464 and Its Low Picomolar Analogue"
CONTACT:
Kazunori Koide, Ph.D.
University of Pittsburgh
Pittsburgh, Pennsylvania 15260
http://www.medilexicon.com/medicalnews.php?newsid=63884∞

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~*A New Target In The War On Cancer

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Edited on 2007-03-01 17:47:06 by KathyFromEngland

Additions:
~*Researchers Wake Up Viruses Inside Tumors To Image And Then Destroy Cancers

*A New Target In The War On Cancer

A New Target In The War On Cancer
A new family of potential anti-cancer drugs is quietly causing excitement in the pharmaceutical industry as early data from clinical trials shows promising responses in patients, according to an article in Chemical & Engineering News (C&EN), the ACS' weekly newsmagazine.
In the article, C&EN associate editor Lisa Jarvis explains that the new compounds may circumvent the long-standing problem of drug resistance, in which anti-cancer drugs gradually loose their effectiveness. The drugs focus on a new target in the war against cancer - a substance called heat shock protein 90 (Hsp90). Heat shock proteins are most active when the cell is exposed to elevated temperatures, infection, inflammation, toxins and other stresses that can cause a protein to unfold. Like housekeepers, heat shock proteins help those proteins - including mutated, cancer-causing proteins - get back into their proper shape.
When Hsp90's effects are blocked in cancer cells, those cancer-causing proteins cannot survive, potentially stopping the disease in its track. When Hsp90's effects are blocked in cancer cells, damaged proteins accumulate, and the cell dies. Jarvis explains that cancer cells, with their horribly mutated proteins, seem to be especially dependent on Hsp90, and more vulnerable than other body cells when Hsp90's effects are blocked. The article describes how new discoveries have changed heat shock proteins from laboratory curiosities into some of today's most promising targets for developing new drugs.
http://www.medilexicon.com/medicalnews.php?newsid=63886∞

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~*Researchers Wake Up Viruses Inside Tumors To Image And Then Destroy Cancers

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Edited on 2007-03-01 17:28:42 by KathyFromEngland

Additions:
~*Success Of Electrical Treatment For Tumor Removal Shown By Hebrew University, U.S. Researchers

*Researchers Wake Up Viruses Inside Tumors To Image And Then Destroy Cancers

Researchers Wake Up Viruses Inside Tumors To Image And Then Destroy Cancers
01 Mar 2007
Researchers have found a way to activate Epstein-Barr viruses inside tumors as a way to identify patients whose infection can then be manipulated to destroy their tumors. They say this strategy could offer a novel way of treating many cancers associated with Epstein-Barr, including at least four different types of lymphoma and nasopharyngeal and gastric cancers.
In the March 1 issue of Clinical Cancer Research, a team of radiologists and oncologists from Johns Hopkins Medical Institutions describe how they used two agents already on the market - one of which is the multiple myeloma drug Velcade - to light up tumor viruses on a gamma camera. The technique is the first in the new field of in vivo molecular-genetic imaging that doesn't require transfecting tumors with a "reporter" gene, the scientists say.
"The beauty of this is that you don't have to introduce any reporter genes into the tumor because they are already there," says radiologist Martin G. Pomper, M.D., Ph.D. "This is the only example we know of where it is possible to image activated endogenous gene expression without having to transfect cells."
A variety of blood and solid cancers are more likely to occur in people who have been infected with the Epstein-Barr virus (EBV), but not everyone with these cancers has such infections. For those who do, researchers, such as Hopkins oncologist and co-author Richard F. Ambinder, M.D., Ph.D., have been working on ways to activate the reproductive, or "lytic" cycle, within the virus to make it replicate within the tumor cell. When enough viral particles are produced, the tumor will burst, releasing the virus. In animal experiments, this experimental therapy, called lytic induction therapy, results in tumor death.
As the first step in this study, researchers screened a wide variety of drugs to see if any of them could reawaken the virus. They were fortunate in that one of the genes that is expressed upon viral lytic induction is EBV's thymidine kinase (EBV-TK), an enzyme that helps the virus begin to reproduce. This kinase is of interest because researchers know its "sister" kinase, the one produced by the herpes simplex virus, can be imaged by an injected radiolabeled chemical (FIAU), which can then be imaged using a gamma camera.
"To perform molecular-genetic imaging, we have always had to infect cells with active herpes simplex virus so that they can replicate, express TK, and only then could we use the FIAU tracer to make the cells light up," Pomper says. "So we were hoping to find a way to turn latent Epstein-Barr virus on in these cancers, and use the thymidine kinase it then produces to enable us to see the virus-associated tumors with radiolabeled FIAU."
The researchers screened 2,700 agents until they hit upon Velcade, a targeted chemotherapy drug already approved for use in multiple myeloma. "We were both surprised and lucky," he says. "Velcade is a proteasome inhibitor, but it also induces the lytic cycle thereby activating the TK in the Epstein-Barr virus. Once the TK is activated, we can image the tumors."
To test their findings, the researchers used mice carrying human Burkitt's lymphoma, a cancer often associated with Epstein-Barr viral infection. Tumors glowed in mice given Velcade followed by an injection of FIAU, but not in mice that weren't given Velcade. Mice whose Burkitt's lymphoma did not contain Epstein-Barr virus also did not respond to either Velcade or FIAU, according to researchers.
"Velcade woke up the virus in the tumors, which increased viral load by 12-fold, all the while cranking out TK," Pomper says. "An injection of FIAU made it easy to image the tumors with virus in them."
The method is highly sensitive, he says: as few as five percent of the cells within the tumor mass needed to be induced into the lytic cycle in order to be detected.
Not only can FIAU light up the tumors, it can also potentially kill them, Pomper says. For imaging purposes, FIAU can carry a radionuclide that emits a low energy gamma photon, but it can also be engineered to carry therapeutic radionuclides, which are lethal to cells in which TK is activated.
Results of this study suggests that this strategy could be applied to other viruses associated with tumors, and that other drugs may potentially be used to activate these viruses, Pomper says. "Velcade is only one of an array of new, as well as older agents, that can induce lytic infection, and a particular agent could be tailored for use in a specific patient through imaging," he says.
The study was funded by the National Cancer Institute.
http://www.medilexicon.com/medicalnews.php?newsid=64268∞

Deletions:
~*Success Of Electrical Treatment For Tumor Removal Shown By Hebrew University, U.S. Researchers

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Edited on 2007-02-17 15:38:28 by KathyFromEngland

Additions:
~*Jefferson Scientists Find Guardian Gene's Choices Crucial To Stopping Cancer Process

*Success Of Electrical Treatment For Tumor Removal Shown By Hebrew University, U.S. Researchers

Success Of Electrical Treatment For Tumor Removal Shown By Hebrew University, U.S. Researchers
17 Feb 2007
A potential breakthrough in minimally invasive surgical removal of tumors has been demonstrated using an innovative technique involving microsecond electrical pulses that can punch permanent nanoscale holes in the membranes of targeted cells without harming adjacent healthy tissue.
The technique, known as irreversible electroporation (IRE), was developed by a research team headed by Boris Rubinsky, currently on leave as professor of bioengineering and mechanical engineering at the University of California, Berkeley, and now head of the Center for Biomedical Engineering in the Service of Humanity and Society at the Hebrew University of Jerusalem. The success of a large-scale study on pigs who were treated using the technique is described in the February issue of the journal Technology in Cancer Research and Treatment.
"I've been working in this area of minimally invasive surgery for 30 years now," said Rubinsky, lead author of the paper in the journal. "I truly think that this will be viewed as one of the most important advances in the treatment of tumors in years. I am very excited about the potential of this technique. It may have tremendous applications in many areas of medicine and surgery."
Rubinsky co-authored the paper with Dr. Gary Onik, director of surgical imaging at Florida Hospital Celebration Health. They founded the Oncobionic Company two years ago to commercialize IRE. Oncobionic is in the process of being sold to AngioDynamics, a New York-based manufacturer of medical devices for minimally invasive surgery.
It was first reported in the early 1970s that the application to cells of very fast electrical pulses �" in the microsecond and millisecond range �" creates an electrical field that causes nanoscale pores to open in the cell membrane (electroporation). But research since then has mainly focused on reversible electroporation, which uses voltages low enough to temporarily increase the cell membrane's permeability. The holes in the cell membrane created by reversible electroporation close up shortly after treatment, allowing the cell to survive.
"This concept of reversible electroporation really caught on in modern biotechnology, especially over the last decade," said Rubinsky. "It is used primarily to help get genes and drugs into cells (but is not effective in killing "target" cells directly). The field of irreversible electroporation was pretty much forgotten."
Irreversible electroporation uses electrical pulses that are slightly longer and stronger than reversible electroporation. With IRE, the holes in the cell membrane do not reseal, causing the cell to die. IRE utilizes a range of electrical current that causes permanent damage to cell membranes without generating heat and thermal damage.
The advantage to this, say the researchers, is that IRE overcomes the limitations of current minimally invasive surgical techniques that use extreme heat, such as hyperthermia or radiofrequency, or extreme cold, such as cryosurgery, to destroy tumorous cells. They point out that this type of temperature damage to cells also causes structural damage to proteins and the surrounding connective tissue. For liver cancer, for example, the bile duct is at risk for damage. For prostate cancer, the urethra and surrounding nerve tissue is often affected.
Irreversible electroporation, on the other hand, acts just on the targeted cell membrane, leaving collagen fibers and other vascular tissue structures intact. The researchers said that leaving the tissue's "scaffolding" in place in this manner allows healthy cells to regrow far more quickly than if everything in the region were destroyed.
In the new study, the researchers set out to demonstrate that the IRE technique could produce reliable and predictable results in a large animal model. They performed the IRE surgical technique on 14 healthy female pigs under general anesthesia, using the same procedures as if the patients were human.
They showed that selected cell membranes were destroyed, while untargeted adjacent tissue healed remarkably quickly. Although the tissue chosen for destruction in this study was healthy, the researchers found in a prior cell culture study that IRE effectively kills human liver cancer tissue.
A further chronic drawback of heat or cryo (cold) treatments for cancer is the difficulty in treating cells that are immediately adjacent to the blood vessels. Because blood maintains a relatively stable temperature, it actually transfers heat or cold away from a treatment area in an attempt to return the region to a normal temperature range. That means some cancerous cells might actually survive treatment.
"That counts for a lot of failures when treating liver cancers," said Onik. "With IRE, you can destroy cancerous cells right next to the blood vessels. It's a more complete treatment. In my clinical experience, this is about as good as it gets. We've been using other techniques for a long time. This provides significant improvements over other treatments."
"While we are obviously very excited about this advance in tumor removal, we are still in the early stages of our learning curve," Onik cautioned. "There is always the potential for unexpected results."
The IRE technology was cleared for human use by the U.S. Food and Drug Administration in November 2006. Onik is scheduled to begin human clinical trials for IRE this summer.
http://www.medilexicon.com/medicalnews.php?newsid=63303∞

Deletions:
~*Jefferson Scientists Find Guardian Gene's Choices Crucial To Stopping Cancer Process

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Edited on 2007-01-11 03:18:36 by KathyFromEngland

Additions:
According to Steven McMahon, Ph.D., associate professor of cancer biology at Jefferson Medical College, who led the work, the p53 gene's - or rather its protein's - ability to direct a damaged cell to either stop growing or commit suicide depends on turning on separate groups of target genes. He and his co-workers have found that after a cell's DNA is damaged, the p53 protein's ability to bind to the DNA can be affected. Two enzymes, hMOF and TIP60, can chemically alter an amino acid, lysine 120, at the binding site, in turn influencing p53's decision on which target genes to turn on. The alteration can short-circuit p53's ability to cause the damaged cell to commit suicide, though it can still stop cell growth, suggesting that this change may help explain a mechanism behind p53's choice. They report their findings in the journal Molecular Cell.
"It's been known that p53 can induce cell cycle arrest or apoptosis (programmed cell death) as a way of eliminating developing cancer cells in response to cell damage, but no one has known how the choice is made," says Dr. McMahon. "This work narrows how the decision is made."
The findings could have implications for future drug development strategies. "Most chemotherapy strategies are aimed at getting cancer cells to die," Dr. McMahon says. "Figuring out what pathways p53 uses to cause that versus cell cycle arrest is important. It looks like this new modification that we have identified helps p53 make that decision."
"p53 is such an important player in the cancerous process - it's nearly always mutated or inactivated in cancer - that continuing to understand more about how it works will likely have significant implications for cancer research," says Dr. McMahon. "We wouldlike to understand the interplay between this newly identified pathway and others involved in p53 and cancer.

Deletions:
According to Steven McMahon, Ph.D., associate professor of cancer biology at Jefferson Medical College, who led the work, the p53 gene's - or rather its protein's - ability to direct a damaged cell to either stop growing or commit suicide depends on turning on separate groups of target genes. He and his co-workers have found that after a cell's DNA is damaged, the p53 protein's ability to bind to the DNA can be affected. Two enzymes, hMOF and TIP60, can chemically alter an amino acid, lysine 120, at the binding site, in turn influencing p53's decision on which target genes to turn on. The alteration can short-circuit p53's ability to cause the damaged cell to commit suicide, though it can still stop cell growth, suggesting that this change may help explain a mechanism behind p53's choice. They report their findings in the journal Molecular Cell.
"It's been known that p53 can induce cell cycle arrest or apoptosis (programmed cell death) as a way of eliminating developing cancer cells in response to cell damage, but no one has known how the choice is made," says Dr. McMahon. "This work narrows how the decision is made."
The findings could have implications for future drug development strategies. "Most chemotherapy strategies are aimed at getting cancer cells to die," Dr. McMahon says. "Figuring out what pathways p53 uses to cause that versus cell cycle arrest is important. It looks like this new modification that we have identified helps p53 make that decision."
"p53 is such an important player in the cancerous process - it's nearly always mutated or inactivated in cancer - that continuing to understand more about how it works will likely have significant implications for cancer research," says Dr. McMahon. "We wouldlike to understand the interplay between this newly identified pathway and others involved in p53 and cancer.

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Edited on 2007-01-11 03:16:25 by KathyFromEngland

Additions:
~*Turning Green Gunk To Anti-Cancer Gold

*Jefferson Scientists Find Guardian Gene's Choices Crucial To Stopping Cancer Process

Jefferson Scientists Find Guardian Gene's Choices Crucial To Stopping Cancer Process
Scientists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have uncovered a novel pathway by which the anti-cancer gene p53 springs into action, protecting a damaged cell from becoming cancer. The gene can either halt the cell's growth or send it spiraling toward certain death. How this choice is made, the researchers say, could have implications for future strategies in chemotherapy drug development.
According to Steven McMahon, Ph.D., associate professor of cancer biology at Jefferson Medical College, who led the work, the p53 gene's - or rather its protein's - ability to direct a damaged cell to either stop growing or commit suicide depends on turning on separate groups of target genes. He and his co-workers have found that after a cell's DNA is damaged, the p53 protein's ability to bind to the DNA can be affected. Two enzymes, hMOF and TIP60, can chemically alter an amino acid, lysine 120, at the binding site, in turn influencing p53's decision on which target genes to turn on. The alteration can short-circuit p53's ability to cause the damaged cell to commit suicide, though it can still stop cell growth, suggesting that this change may help explain a mechanism behind p53's choice. They report their findings in the journal Molecular Cell.
"It's been known that p53 can induce cell cycle arrest or apoptosis (programmed cell death) as a way of eliminating developing cancer cells in response to cell damage, but no one has known how the choice is made," says Dr. McMahon. "This work narrows how the decision is made."
The findings could have implications for future drug development strategies. "Most chemotherapy strategies are aimed at getting cancer cells to die," Dr. McMahon says. "Figuring out what pathways p53 uses to cause that versus cell cycle arrest is important. It looks like this new modification that we have identified helps p53 make that decision."
"p53 is such an important player in the cancerous process - it's nearly always mutated or inactivated in cancer - that continuing to understand more about how it works will likely have significant implications for cancer research," says Dr. McMahon. "We wouldlike to understand the interplay between this newly identified pathway and others involved in p53 and cancer.
"Since p53 can make this decision, this might give some insight into which function of p53 is more important in which tissues," says co-author Stephen Sykes, a Ph.D. candidate at the University of Pennsylvania. "For example, K120 (lysine 120) mutations cause tumors in the prostate, but are not so much involved in causing immune system cancers such as lymphomas. That could suggest that p53's potential to cause cell death could be more important in certain tissues than in others. In the future, if someone could develop therapies that could specifically activate p53's potential to drive programmed cell death versus the cell cycle arrest potential, it might influence how a doctor might choose to treat a certain type of cancer.
"This may potentially enable the development of a cancer drug that would stimulate the enzymes to promote this modification driving p53 to apoptosis."
http://www.medilexicon.com/medicalnews.php?newsid=60395∞

Deletions:
~*Turning Green Gunk To Anti-Cancer Gold

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Oldest known version of this page was edited on 2007-01-11 03:06:50 by KathyFromEngland []

Articles about new cancer drugs, treatment methods etc.

New Results Indicating Harmful Effects Of Cortisone Drugs In The Treatment Of Solid Tumors

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08 May 2006

The results will now have to be verified for humans in controlled prospective studies. Subsequently, it will have to be decided whether the treatment guidelines for a number of solid tumors need to be modified. Until then, it is strictly advised not to terminate ongoing therapies with cortisone drugs without consulting the doctor in charge.

Cortisone drugs used in cancer treatment cause programmed cell death, or apoptosis, in transformed cells of the hematopoietic system. In addition, the drugs lessen side effects such as nausea and vomiting and protect against edema formation as well as allergies to specific chemotherapy drugs. At the same time, glucocorticoids protect normal body tissue against harmful side effects of the tumor. These facts have given the drugs a good reputation. The recommendations for cancers of the blood have so far also been applied to the treatment of carcinomas by leading oncological organizations. However, sufficient controlled studies have not yet been performed for this area of application.

In a diversified investigation of cells from over a dozen types of cancer including tumors of the lung, breast, Prostate , Colon, pancreas, and nerve tissue, Ingrid Herr and clinicians of Heidelberg University Hospital have now confirmed a suspicion that arose back in mid-2003. Jointly with colleagues from Ulm and Heidelberg, Herr had shown at the time that cell lines from cervical and lung cancers respond significantly less well to drug treatment or irradiation when glucocorticoids are given at the same time. The researchers put this down to a change in the apoptosis program. For reasons that are not yet known, substances of the steroid hormone group block programmed cell death in solid tumors, while inducing apoptosis in malignant blood cells.

Does this effect occur only in individual malignant tumors or is this a general mechanism? To answer this question, the Heidelberg researchers analyzed more than 150 tissue samples of representative cancers using common cell lines, freshly isolated tumor tissue cells and tumors that had been transplanted into mice. They found out that over 85 percent of tumors studied develop a resistance and, thus, become less sensitive to numerous tested anticancer drugs and radiation when steroid hormones are given at the same time. The effect was observed for various common glucocorticoids and at very low levels and lasted for quite some time even after a single dose. In addition, tumors appear to grow faster under these conditions.

Ingrid Herr recently published these results in five individual publications. The scientist has now compared these to data from other research projects and provided a summary in an article in the specialist journal Lancet Oncology. It turned out that over 50 years ago researchers had already observed increased metastasis in breast cancer patients who received cortisone drugs. Elevated levels of endogenous glucocorticoids, which often occur in patients with renal cell carcinoma, were found to correlate with a worsening prognosis. Patients with brain metastases of a primary lung tumor responded less well to cancer treatment when they received steroid hormones at the same time. These are alarming results. On the other hand, a retrospective study showed no negative effects of cortisone drugs on the survival of ovarian cancer patients. However, the results of a further patient study indicate that systemic treatment with steroid hormones also appears to increase the risk of skin cancer or lymphoma. Researchers presume that the development of therapy resistance and the increased tendency to metastasize of solid tumors under glucocorticoid treatment may be caused not only by inhibition of apoptosis, but also by a weakening of the immune system.

However, scientists emphasize that it is too early to condemn glucocorticoid therapy altogether, since it also has many positive effects in cancer treatment. It is necessary to verify the assumptions reached from investigations with cell lines and animals in controlled prospective studies. This is the topic of ongoing research projects.
http://www.medilexicon.com/medicalnews.php?newsid=42912∞

Update On Cancer Drug Candidate CYT997 - For Tumor Types Including Breast, Prostate And Colon, As Well As Some Leukemias

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26 Jun 2006

Cytopia Ltd (ASX:CYT) is pleased to provide an update on the progress of its Phase I trial for the cancer drug candidate CYT997.

CYT997 is an orally available vascular targeting and cytotoxic agent that has proven effective in animal models of a wide range of tumour types including breast, Prostate and Colon, as well as some leukemias.

In March 2005, Cytopia successfully lodged an Investigational New Drug (IND) Application for CYT997 with the Food and Drug Administration of the United States (FDA) and in July 2005 commenced a Phase I dose escalation study in cancer patients at the Royal Brisbane and Women's Hospital (RBWH). The trial is under the direction of medical oncologists, Drs Jason Lickliter and Paul Vasey.

The clinical study is designed to determine the safety and tolerability, dose-limiting toxicities and maximum tolerated dose of CYT997 when given as a 24-hour intravenous infusion every three weeks. Eligible trial participants are cancer patients with advanced solid tumours who have failed one or more first-line therapies or for whom no standard therapy exists. Pharmacokinetic and biological activity data is also being collected.

The dose levels of CYT997 administered to date have been well tolerated by patients and no dose limiting toxicities (DLTs) have yet been identified. To date, sixteen patients have received a total of 46 doses of CYT997 across six incremental dose levels.

Dose escalation will continue until two or more patients within a dose level exhibit a DLT. The maximum tolerated dose will then be determined in accordance with the approved clinical trial protocol. While the company cannot be certain when dose-limiting toxicities will be identified, Cytopia anticipates that the trial will continue in the third quarter of 2006.

Regulatory oversight for the trial continues to be provided by the institutional Human Research Ethics Committees and the FDA.

Oral applications of CYT997

The company will apply later this year to various regulatory authorities to conduct a Phase I clinical trial investigating the oral administration of CYT997. Subject to regulatory approval, this clinical trial will commence at a site in Australia in late 2006. This clinical trial will have similar objectives to the current intravenous trial, including the determination of safety and tolerability of CYT997 when given by mouth.

The company is currently finalising formal preclinical toxicity studies for oral administration which will form the basis of the clinical trial regulatory submission.

Efficacy studies

The company is currently concluding planning for future Phase II studies for CYT997, including the application of the compound in highly-vascular cancers with poor prognosis such as hepatoma. Advancement of the compound into Phase II efficacy studies is necessarily contingent upon the findings of the Phase I clinical trials programme and regulatory approval, however the company intends to commence a Phase II trial shortly after the conclusion of each of the Phase I programmes.

Commercial Ready Grant

In December 2005 Cytopia was awarded an AusIndustry grant of $3 million over three years to assist in the clinical development of CYT997. The grant will provide matching funds for the Phase I oral trial and initial efficacy studies of CYT997 as a monotherapy and potentially in combination with a front-line cytotoxic drug.

About Cytopia

Cytopia Ltd is an Australian biotechnology company focused on the discovery and development of new drugs to treat cancer, immune disorders and cardiovascular diseases. Cytopia conducts its research and development via subsidiaries based in Melbourne and New York and specialises in discovering new molecules that can inhibit enzymes known as kinases, an exciting new class of drugs.

http://www.cytopia.com.au∞
http://www.medilexicon.com/medicalnews.php?newsid=45891∞

New Biotechnology Discovered - Should Help Solve The Puzzles Of Cancer, Alzheimer's, Atherosclerosis And Infectious Diseases

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04 May 2006

Researchers at UC Santa Barbara have developed a new biotechnology that enables scientists to identify and engineer protease substrates, giving them the means of crafting pharmaceuticals to outsmart disease. Their work, authored by Patrick Daugherty, an assistant professor of Chemical Engineering, and Kevin Boulware, a PhD candidate, are published online today in the Proceedings of the National Academy of Sciences.

Proteases (or peptidases) are encoded by about two percent of genes in the human genome and play key roles in nearly all diseases. They act as "molecular scissors" by attaching to specific sequences contained within other proteins, called substrates, and cutting them in specific locations. For example, proteases are responsible for digesting food, for determining the proper time for cells to die, and for removing damaged proteins from the body.

But the substrates for most proteases are unknown, and this has limited researchers' ability to facilitate or thwart protease action. By identifying substrates, scientists gain the ability to regulate protein function, creating the capacity to speed up, slow down or eliminate particular protease actions. Daugherty's approach also makes it easier to measure protease action and thus develop pharmaceuticals that control protease activity.

Daugherty and Boulware developed a general combinatorial approach to identify optimal substrates of proteases, using quantitative kinetic screening of cellular libraries of peptide substrates (CLiPS). The results suggest that CLiPS will be broadly useful for characterizing proteases and developing optimal substrates for therapeutic applications.

Of the roughly 1,000 proteases in the human genome, only about ten percent of the targets have been identified, but Daugherty believes that scientists will identify nearly all of them in the next five to ten years. "This technology will give us a scalable tool that will allow us to effectively tackle this challenge," he says.
http://www.medilexicon.com/medicalnews.php?newsid=42587∞

From Vomiting To Vaccination: Food Poisoning Bug Used To Deliver Cancer Vaccine

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26 Jun 2006

By clever design, researchers have devised a way for the bacterium Salmonella typhimurium - often associated with food poisoning - to safely and effectively deliver a vaccine against cancer.

Certain molecules on the surface of cancer cells are either unique or more abundant than those found on non-cancerous cells. These molecules, or antigens, can stimulate the immune system to mount an immune response against the tumor. It is hoped that when a vaccine containing cancer-specific antigens is administered to cancer patients, these antigens will trigger an immune response that targets cancer cells without harming normal cells. Although many cancer vaccine strategies have resulted in measurable immune responses when tested, tumor remission has been observed in only a minority of patients. The identification of new cancer antigens, delivery formulations and vectors is sorely needed.

Since disease-causing bacteria are well equipped to stimulate the immune system, researchers have started to examine the suitability of bacteria that have been genetically manipulated to strip them of their disease-causing ability as delivery vehicles for cancer vaccines. One such bacterium is Salmonella typhimurium, often the culprit in food poisoning in humans. In a study appearing online on June 22 in advance of print publication in the July issue of the Journal of Clinical Investigation, Sacha Gnjatic and colleagues from the Ludwig Institute for Cancer Research constructed an avirulent strain of Salmonella typhimurium endowed with the capacity to deliver the known tumor cell antigen NY-ESO-1. This approach was able to elicit NY-ESO-1-specific CD8+ and CD4+ T cells from lymphocytes taken from cancer patients. Oral delivery of this vaccine to mice resulted in the regression of established NY-ESO-1-expressing tumors. The results of the study suggest that delivery of a cancer vaccine using the Salmonella typhimurium-based delivery system is a promising novel strategy for cancer vaccine development.
http://www.medilexicon.com/medicalnews.php?newsid=45813∞

Cephalon's Fentanyl Effervescent Buccal Tablet Reduces Intensity Of Breakthrough Pain In Cancer Patients

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05 May 2006

Results of a Phase 3 clinical trial demonstrate positive results with a fentanyl effervescent buccal tablet (FEBT) in all measures of pain control assessed in a chronic cancer pain population. The Cephalon, Inc. (Nasdaq: CEPH) data were reported in a platform presentation at the annual meeting of the American Pain Society (APS). FEBT utilizes a new delivery technology designed to produce a more rapid and efficient absorption of medicine. The medication is designed to help patients with a common, yet undertreated, component of chronic pain called breakthrough pain, which is characterized by its fast onset.

"Helping patients get better control of their pain requires that clinicians adequately address breakthrough pain," said Donald Taylor, M.D., of Comprehensive Pain Care PC in Marietta, Ga., a study investigator. "For breakthrough pain, you need a medication that comes closer to matching the rapid onset of the pain episodes and has a relatively short duration of action. Based on the results of the Phase 3 clinical trials, FEBT appears to have that profile."

The investigational, sugar-free fentanyl tablet is placed between the upper cheek and the gum, where an effervescent reaction helps the active ingredient, fentanyl, dissolve and enhances the rate and extent of absorption. If approved by the U.S. Food and Drug Administration (FDA), FEBT would be the first oral buccal tablet developed specifically for the treatment of breakthrough pain in cancer patients.

The double-blind, placebo-controlled, randomized trial evaluated FEBT in chronic pain patients with cancer-related breakthrough pain. Thirty U.S. sites enrolled 123 patients with cancer who were already receiving various around-the-clock opioid medications for persistent pain, and had one to four episodes of breakthrough pain a day that were controlled with a short-acting oral opioid. After the initial dose titration phase, 72 patients completed a double-blind phase in which they were randomly assigned to one of 18 predefined dosing regimens that would expose each individual patient to both FEBT and placebo during the course of the study. Patients had the option to use their prior supplemental opioid for any breakthrough pain episode that did not respond within 30 minutes of FEBT or placebo administration.

Key study findings, include:

-- FEBT produced clinically significant decreases in pain intensity after administration . analgesic effect was apparent at the first time-point measured, 15 minutes after administration, and was sustained throughout the one-hour assessment.

-- There was significantly more pain relief reported with FEBT than placebo.

-- Mean global medication performance ratings - a measure of patient satisfaction - were higher for FEBT compared to placebo at all points of evaluation.

-- Study patients were twice as likely to require supplemental opioid medications for episodes of breakthrough pain when using the placebo dose than after receiving FEBT.

-- Adverse events associated with FEBT in the clinical trial were typical of those seen with opioids and in cancer populations being treated with chemotherapy, including nausea (22%), dizziness (22%), and headache (15%). Two patients withdrew from the study because of adverse events at the site of tablet placement.

"Cephalon was the first company to clinically study breakthrough pain, and we are developing additional treatment approaches for this often debilitating chronic pain condition," said Dr. Paul Blake, Executive Vice President, Worldwide Medical and Regulatory Operations at Cephalon. "The data presented today at APS were pivotal to Cephalon's FDA submission last fall for the review of FEBT as a safe and effective treatment for breakthrough pain in opioid tolerant patients with cancer."

Clinical trials of FEBT also are underway with patients who are treated with opioids and who experience breakthrough pain associated with a range of chronic pain conditions, including chronic back and neuropathic pain. More information about these studies is available at
http://www.clinicaltrials.gov∞.

Breakthrough Pain and its Impact

Approximately 50 million Americans suffer from chronic pain each year. Chronic pain consists of two components: persistent pain, pain that is continuous throughout the day, and breakthrough pain, transitory flares of moderate-to-severe pain in a person whose persistent pain is otherwise controlled. Breakthrough pain often goes unrecognized and inadequately treated, yet it affects large numbers of Americans who live with chronic pain. Breakthrough pain can reach peak intensity in as little as three minutes and typically lasts for 30 to 60 minutes. It may occur during a specific activity, spontaneously with no apparent cause, or when the dose of the persistent pain medicine wears off.

An estimated 64 percent of all cancer patients treated for persistent pain - and up to 74 percent of patients treated for persistent pain from other conditions such as low back pain, diabetic neuropathy, and osteoarthritis - will experience breakthrough pain. The costs of breakthrough pain episodes are high for individuals, families, and society, with resulting economic impact seen in increased medical expenditures and decreased work productivity.
http://www.medilexicon.com/medicalnews.php?newsid=42814∞

Cancer Treatments That Target Just The Cancerous Cells

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12 Apr 2006

Conventional cancer treatments are generally effective in wiping out tumor cells, but in the process they also may kill healthy cells. Researchers are focusing their efforts now on treatments that can target just the cancerous cells, without harming healthy tissue in their midst. These new types of drugs are known as targeted therapies, and physicians are studying their effectiveness and possible side effects in a variety of different types of cancer.

Several targeted therapies are being studied alone and in combination to treat a variety of cancer types. In particular, cancerous brain tumors can be more difficult to treat than other cancers, and oncologists are developing therapies that target these cells to improve patients' survival. Researchers also are gaining a better understanding of the molecular differences between cancerous and healthy cells, improving current treatment and survival rates, according to studies presented today at the 97th Annual Meeting of the American Association for Cancer Research.

NF-kB as a Therapeutic Target in Malignant Gliomas: Abstract No. 1506

Researchers from the National Cancer Institute in Bethesda, Md., have found they may be able to successfully treat brain tumor cells with a new targeted therapy that inhibits the activity of a cell protein called nuclear factor-Kappa B (NF-kB).

The drug, called bortezomib or (Velcade?) - when used alone or in combination with other cancer treatments - represents a potential new way to treat malignant glioma, a particularly stubborn and aggressive brain tumor.

"Targeting the NF-kB pathway either alone or in combination with other chemotherapy agents, is an effective anti-glioma treatment," said Ai-Min Hui, M.D., Ph.D., research fellow at the NCI and the lead investigator of the study.

In their study, the NCI researchers set out to determine the role of NF-kB in reversing the apoptotic (or programmed cell death) effect of selective estrogen receptor modulators (SERMs) in brain cancer, as well as potential therapies that can be used either alone or in combination to block the protein. High levels of NF-kB are activated and present in transplanted glioma cells and glioma tumor samples, but not in normal brain tissue cells.

SERMs have shown some value in inducing cell death in brain cancers by a previously unknown method. They are designed to deliver the benefits of estrogen without its negative side effects, although gliomas do not generally express the estrogen receptor. However, previous studies have shown that NF-kB protects glioma cells from breaking down, therefore reversing the effect of SERM therapies.

Researchers looked at 203 glioma samples and determined that NF-?B was activated. They also noticed that the level of activation was related to the grade of the tumor, suggesting that NF-?B is related to tumor progression. Treatment with bortezomib suppressed both unregulated and signal-oriented activation in NF-kB by inhibiting the breakdown of IkB-alpha. IkB-alpha is one of a series of inhibitory proteins that controls the activation of NF-kB, preventing it from binding to DNA in the nucleus. Bortezomib not only stops the degradation of IkB-alpha, it also suppresses the activation of NF-kB, thus stopping cell growth.

"By interfering with the function of IkB-alpha proteins, bortezomib was shown to induce glioma cell degradation and enhance anti-cancer effects of SERMs," said Ai-Min Hui, M.D., Ph.D., research fellow at the National Cancer Institute and lead investigator on this trial.

"New studies looking at the combined use of bortezomib and high-dose tamoxifen may provide a viable treatment option for patients with recurrent, high grade malignant gliomas," he said.

Malignant gliomas are one of the most common brain tumors, accounting for more than half of the 18,000 primary cancerous brain tumors diagnosed annually in the United States, and are the fourth most common cause of cancer death in patients aged 15 to 44.

Standard treatment for patients diagnosed with brain cancer is surgery followed by radiation, sometimes with added chemotherapy. However, current therapies are considered inadequate to fight this deadly disease and researchers have been trying to identify new targets and develop new agents with different mechanisms of action to help increase patients' survival.

PTEN-Loss Mediated Herceptin (trastuzumab) Resistance and Targeting the PI3K Pathway as a Counteracting Strategy: Abstract No. IS-445

Researchers from The University of Texas M. D. Anderson Cancer Center, Houston, have identified why some women with Her-2 positive breast cancer, an aggressive form of the disease, do not respond to the drug trastuzumab (Herceptin?) or may actually develop a resistance to the treatment.

The investigators discovered that a combination of trastuzumab and a new kinase inhibitor, PI3K, may work together to increase these patients' chances of survival.

Trastuzumab treats women with metastatic breast cancer whose tumors overproduce the ErbB2 gene. The overproduction of the ErbB2 gene, also called Her-2/neu, leads to aggressive breast cancer and poorer patient survival. ErbB2 is part of a family of genes called epidermal growth factor receptors (EGFR) that stimulate cell growth and division. Trastuzumab has shown outstanding efficacy for patients with high levels of the ErbB2 gene.

Approximately one-third of patients who possess the ErbB2 gene will respond to trastuzumab therapy, but the treatment is sometimes combined with other chemotherapy agents to make it more effective.

Still other patients develop resistance to the therapy over time.

In this study, researchers found that loss of PTEN can lead to resistance of trastuzumab. The PTEN gene (phosphatase and tensin homolog deleted on chromosome ten) acts as a tumor suppressor gene, helping to regulate the cycle of cell division by keeping cells from growing and dividing uncontrollably or too rapidly, and ultimately forming tumors. Normally, the PTEN enzyme acts as part of a chemical pathway that signals cells to stop dividing and causes cells to undergo apoptosis.

However, reduced levels of PTEN contribute to trastuzumab resistance, both in vivo (humans and mice) and in vitro (culture). Patients with PTEN-deficient breast cancer have poorer outcomes and response to trastuzumab therapy when compared to those with normal PTEN levels.

The researchers then examined the role played by phosphoinositide 3-kinase (PI3K) pathway inhibitors to reverse PTEN-reduction-mediated trastuzumab resistance. PI3K regulates several key signals that initiate cell processes frequently disrupted by carcinogenesis, a process by which normal cells are transformed into cancer cells.

Seven PI3K pathway inhibitors, either currently in use or under development in clinical trials, were examined. One inhibitor used in combination with trastuzumab successfully inhibited cell growth, and a second, when used with trastuzumab, sensitized the therapeutic effects of the drug. Researchers said the next step is to conduct a phase I/II study looking at these combinations in patients who did not respond to traztuzumab as a first-line therapy.

"PTEN seems to be a very sensitive and specific predictor to trastuzumab-based therapy and data suggest that activation of PTEN is a novel mechanism underlying the anti-tumor activity of trastuzumab.

Combination therapy may provide more effective therapeutic regimens, allowing more patients to benefit from trastuzumab," said Dihua Yu, M.D., Ph.D., professor in the department of surgical oncology and director of research in the Surgery Division, The University of Texas M. D. Anderson Cancer Center.

A Novel, Potent and Selective IGF-1R Small Molecule Inhibitor Blocks Activation of IGF-1R Signaling in Vitro and Inhibits IGF-1R Dependent Tumor Growth in Vivo: Abstract No. LB-281

Researchers from OSI
Pharmaceuticals have identified a new small molecule inhibitor that may stop the growth of colon cancer. In this study, investigators discovered and tested an IGF-1R inhibitor, referred to as Compound 1.*

Compound 1 was shown to hinder the signaling response of IGF-1R -- specifically blocking the activation of two downstream pathways, stopping tumor cell growth and survival. The study also showed that the colon cancer tumors respond to the drug because they produce and are dependent on the growth-promoting effects of IGF-II.

"We are very encouraged by the results seen in our pre-clinical IGF-1R inhibitor program. The most important finding of our study was that, when administered orally, our IGF-1R inhibitor prevented the growth of human colon cancer tumors in mice," said Jonathan A. Pachter, Ph.D., senior director of cancer biology, OSI Pharmaceuticals, Long Island, N.Y. Insulin-like growth factor 1 receptor (IGF-1R) is a cellular protein with a molecular structure similar to that of the receptor for insulin, a hormone that regulates the amount of glucose sugar in the blood. The IGF-1R has been shown to play roles in tumor cell growth and the inhibition of cell death. There are two circulating proteins (or ligands) that activate the IGF-1R (IGF-I and IGF-II). The excess production of IGF-II is thought to encourage tumor growth.

Certain tumors, including colorectal, non-small cell lung, ovarian and some cancers in children, drive their own growth and survival through the overproduction of IGF-II. This IGF-II activates the IGF-1R on the surface of cancer cells to stimulate tumor growth, making IGF-1R an important treatment target for many human cancers.

"This small molecule represents a potent and selective IGF-1R kinase inhibitor that could be effective in the treatment of IGF-II driven human cancers," said Dr. Pachter.

A variety of approaches to block IGF-1R signaling have been used to cause cell death in a broad range of cancers, both in cell cultures and live models. Through the use of structure-based design, OSI Pharmaceuticals has been able to identify small molecules that selectively block the ability of IGF-1R to increase cell growth.

Another major challenge in the development of IGF-1R inhibitors is to avoid blocking the closely related insulin receptor that regulates glucose levels in the blood. Results from the study showed that in addition to diminishing or halting tumor growth in human cancer cells transferred to live test animals, OSI's IGF-1R inhibitor showed no substantial rise in blood sugar.
http://www.medilexicon.com/medicalnews.php?newsid=41332∞

Reviving Shelved Anti-cancer Drugs

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08 May 2006

A seam of untapped anti-cancer drugs is set to be mined by Cancer Research UK through a new initiative that will see the charity team up with some of the world's biggest pharmaceutical and biotechnology companies.

Clinical Development Partnerships (CDP) is a joint initiative between Cancer Research UK and Cancer Research Technology, the charity's development and commercialisation arm. It aims to increase the number of successful new treatments for cancer by taking undeveloped anti-cancer agents from industry and putting them into clinical trials.

The initiative is targeted at leading pharmaceutical and biotechnology companies who have a large pool of molecules that may have anti-cancer properties. However, these companies have to prioritise which agents they take into clinical development - this leaves potentially effective treatments on pharmaceutical companies' shelves.

CDP will take promising but ?deprioritised' anti-cancer drugs into early stage clinical trials through Cancer Research UK's highly experienced Drug Development Office. Effectively the charity will ?borrow' a drug from a company and conduct early clinical trials at no cost to the company. If the drug looks promising, the company retains the option to develop and market the drug, but with the charity receiving a share of any revenues.

Harpal Kumar, chief executive of Cancer Research Technology and chief operating officer of Cancer Research UK, said: ?Cancer Research UK has set an ambitious target to double its drug development activity over the next five years and we are seizing an opportunity to seek out new treatments that otherwise might not get developed.?

There are many reasons why potential treatments do not make it to market. Science has progressed so rapidly in recent years that there are more compounds available than commercial resources to investigate them. And because drug development is so time-consuming and expensive - a new anti-cancer drug can take in excess of 10 years and ?500 million to develop - anything that doesn't look extremely promising is not developed by a pharmaceutical company.

Harpal Kumar added: ?The drug companies have these potential treatments trapped in their pipelines and we have the expertise and capacity to release this potential. Their drug candidates coupled with our world-class network of trial centres and scientists, offers a perfect partnership to achieve the greatest impact in the global fight against cancer.?

Dr Richard Tiner, medical director of the Association of the British Pharmaceutical Industry, said: ?This is a simple, rapid and cost-effective way in which pharmaceutical companies can boost their product lines. Companies will retain intellectual property rights to their original molecules and first option to view the trial data, so should have no reservations about loaning these compounds to Cancer Research UK for further investigation.

?The pharmaceutical industry is aware that it can't develop all the potential treatments it would like to because of its huge pipelines, so this initiative offers companies a unique opportunity to maximise the value of their shelved assets and develop new treatments for the benefit of cancer patients.?

Professor Alex Markham, chief executive of Cancer Research UK, said: ?Making the leap from something that looks promising in the laboratory to testing it in patients is one of the most challenging steps in drug development.

?There is a real potential here for us to develop a raft of new anti-cancer drugs. This may include new medicines to tackle the rarer cancers - those that tend to be lower down a business' priority list because they are less profitable. Ultimately we want to increase the number of new treatments for all cancer patients.?
http://www.medilexicon.com/medicalnews.php?newsid=42908∞

Experiments With Fruit Quality Improvement Lead To New Approach For Halting Spread Of Cancer Cells

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07 Jul 2006

Experimental work aimed at improving the quality of fruit has led to the discovery by Hebrew University of Jerusalem agricultural researchers of a promising new avenue of drug treatment for halting the growth and spread of cancer cells in animals and humans.

Their approach has been shown to inhibit the malignant cells without affecting normal cells and without the severe side effects of traditional treatments such as radiation and chemotherapy. The strategy involves isolating the malignant tumor from its nutritional and oxygen supplies, thereby halting its growth and stopping metastases (spread of cancer cells to other parts of the body).

The work on the project was carried out at the Hebrew University Faculty of Agricultural, Food and Environmental Quality Sciences in Rehovot by Prof. Oded Shoseyov, Dr. Levava Roiz, Dr. Patricia Smirnoff and Dr. Betty Schwartz. Their discoveries were published recently in the journal Cancer of the American Cancer Society.

The approach of the Hebrew University researchers is based on the actions of actibind, a protein that is produced by the black mold Aspergillus niger and that is a well-known microorganism used in bio and food technology. In plants, actibind binds actin, a major component of the intracellular structure in plants, interfering with the plants' pollen tubes and halting cell growth.

While the Hebrew University researchers were initially interested in the activity of actibind in connection with a horticultural project aimed at improving the quality of peaches and nectarines, an actibind-like protein, RNaseT2, was also subsequently found to bind actin in human and animal migrating cells, such as the cells that are responsible for new blood vessel formation (angiogenesis) in tumors.

By blocking the blood supply to the tumors, actibind halted the ability of malignant cells to move through the blood stream to form new metastases. A further plus is that actibind is not toxic to normal cells, thereby significantly minimizing the risk of side effects.

In laboratory experiments using cell cultures that originated from human colon cancer, breast cancer and melanoma, increasing the level of actibind was found to reduce the ability of these cells to form tumorogenic colonies. Further experimentation, with a variety of animal models, showed that the increased actibind inhibited the growth of colon cancer-derived tumors, metastases and blood vessel formation. These promising discoveries were detailed in the Cancer article.

The results shown in working with actibind led to a further development in the researchers' project. During the completion of the human genome project, the gene encoding for RNaseT2, the human actibind-like protein, was found on chromosome 6. The Hebrew University team used genetic engineering procedures to produce a recombinant RNaseT2 protein that showed an impressive anti-cancer potential. These results have raised broad interest in international scientific meetings and in business circles.

The fungal actibind and the human RNaseT2 represent the basis for a new class of drugs that could be used as a front-line therapy in the fight against cancer, say the researchers.
http://www.medilexicon.com/medicalnews.php?newsid=46545∞

Flavonoid-rich Apples And Apple Products Exhibit Unique Way To Enhance Health

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04 Aug 2006

Apples have long been a symbol of health, and doctors encourage Americans to add more fruits and vegetables, including apples and apple products, to their daily diets. Now, researchers Dr. Eric Gershwin and Carl Keen at the University of California, Davis have discovered a new way in which flavonoid-rich apples and apple products protect cells from the type of damage that leads to heart disease and age-related cancers.

The current findings appeared in the May issue of Experimental Biology and Medicine.

"We discovered how the unique mix of nutrients found in apples and apple products can actually help improve health, starting at the cellular level," says Eric Gershwin, professor of medicine at the UC Davis School of Medicine.

According to the researchers, proper communication between cells in the body is vital to every aspect of life. But when that communication is disrupted in some fashion, cells can be damaged or even die, leading to various disease states. In this case, Gershwin and his colleagues found that the distinctive combination of nutrients in apples and apple products is able to protect cells from destruction by fighting off damage caused by unwelcome intruders in the body.

"It's almost like having a spam filter on your computer; the good emails get through and the bad emails get stopped," remarks Gershwin. "Here, the apple components we observed acted like the spam filter."

Earlier studies have shown that components in apples and apple products known as flavonoids work as antioxidants, taking up free oxygen radicals that can cause damage to DNA. The UC Davis study takes that research further by looking beyond the beneficial antioxidant effects that apples and apple products provide to recognizing the ability of flavonoids to promote the cellular communication and filter the harmful effects of unwanted intruders.

In the current study, Gershwin and his colleagues exposed human cells to an extract of an apple mash made from different apple varieties. The researchers revealed that the apple extract was able to protect the cells from the normally lethal damage by interfering with the pathway that would otherwise damage or kill cells in the body. This damage could have lead to an increased risk of heart disease and certain cancers, if it was without the assistance of apples and apple products.

"This research on apples and apple products has helped us discover a new frontier that extends beyond what we have known for a long time - that apples and apple products can contribute to better health," says Gershwin. He adds that further research will help identify additional mechanisms by which the nutrients in apples and apple products can be protective against disease.
http://www.medilexicon.com/medicalnews.php?newsid=48789∞

Safety And Effectiveness Of Therapeutic Virus That Fights Cancer Enhanced By Mayo Clinic Researchers

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05 Aug 2006

Mayo Clinic researchers working with colleagues in Germany have devised a much-needed multilevel safety feature for viruses used to treat cancer. In the process of making cancer-killing viruses more specific to cancer tumor cells, they report having improved the therapeutic effectiveness of viruses. They did this by engineering a modified measles virus that turns on only in the presence of secretions specific to malignant cancer cells.

In effect, the Mayo Clinic virus makeover uses proteins secreted by cancer cells as the unique key to the virus' ignition. Their report on the topic appears in the August edition of Cancer Research (http://cancerres.aacrjournals.org/)∞.

The investigation was performed in laboratory mice that were transplanted with a human cancer. The process is still experimental -- and thus, years away from clinical use in humans. However, the Mayo results may be immediately useful in designing improved cancer treatments for humans. "Our work shows that oncolytic measles virus particle activation can be made dependent on substances secreted by cancer cells, and this enhances safety," explains Roberto Cattaneo, Ph.D., lead researcher on the Mayo team. "By doing this, our study broadens the safeguarding strategies possible to tightly restrict the targeted virus to cancer cells."

Significance of the Mayo Clinic Research
The Mayo researchers say their contribution is a key advance because it provides a method of designing a therapeutic virus that is safe, stable and that reliably targets and kills cancer cells. Importantly, it appears to greatly reduce the possibility that the virus would erroneously turn on and harm the patient by causing unintended infection.

As such, the Mayo innovation of the cancer-activated virus is a helpful safety advance for the promising experimental field of "oncolytic virotherapy." The phrase refers to the natural ability of certain viruses to kill cancer cells. It's a promising approach that has been known for nearly a century -- but constrained by safety concerns. Measles virus is one example of an oncolytic virus. For example, the live attenuated Edmonston measles vaccine strain can reduce or eliminate human lymphoma, myeloma, ovarian cancer and glioma tumors that are transplanted into laboratory mice.

Enhanced Safety and Effectiveness
The success of oncolytic virotherapy depends on restriction of viral growth to cancer cells --and only cancer cells -- to prevent unintended rogue infections elsewhere in the healthy body. The Mayo cancer-activated virus adds one more layer to a multiple safeguard system, so it now consists of three levels. The resulting enhanced security system now works at the level of:

* activation of the virus particle

* receptor recognition necessary for the virus to enter a cancer cell

* ability of the virus to multiply preferentially in cancer cells

These multiple safeguards are specific to and dependent on cancer cells -- and are therefore vital to fully transforming viruses into safe therapeutic agents.
http://www.medilexicon.com/medicalnews.php?newsid=48610∞

VioQuest Pharmaceuticals Doses First Patient In Phase I/IIa Clinical Trial With VQD-001 (Sodium Stibogluconate) For Treatment Of Solid Tumors

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27 Sep 2006

VioQuest Pharmaceuticals, Inc. (OTC Bulletin Board: VQPH), announced today that it has dosed the first patient in its Phase I/IIa clinical trial of VQD-001, Sodium Stibogluconate (SSG), for evaluation of solid tumors, at the MD Anderson Cancer Center. VQD-001 has shown in preclinical studies to specifically inhibit protein tyrosine phosphatases (PTPs), a family of enzymes believed to play a crucial role in solid tumor formation. PTPs are over-expressed in many advanced malignancies, including renal cancer and melanoma. Based on preclinical activity demonstrated in animal models, VQD-001 may represent a novel oncology therapeutic for halting solid tumor growth.

The MD Anderson trial is under the direction of principal investigator Luis Camacho, M.D., M.P.H., and is the first corporate-sponsored study of VQD- 001. Dr. Camacho is an Assistant Professor in the Phase I Program, Division of Cancer Medicine, whose research interests include cell signal inhibition and specific antibody mediated therapies.

The trial is a Phase I/IIa, open-label, dose escalation study to evaluate the safety, tolerability and pharmacokinetics of VQD-001 in combination with Interferon alpha-2b for patients with advanced malignancies.

Among the goals of this clinical trial is to find the highest tolerable dose of VQD-001 combined with Interferon alfa-2b in the treatment of patients with advanced cancer that have not responded to standard treatment or where there is no standard treatment for that type of cancer. The effectiveness and safety of this drug combination will also be studied.

Researchers also want to study the pharmacokinetics (PKs) of the treatment. PK testing is the study of what the body does to a drug over time, including how it is absorbed into the body, how it moves throughout the body, and how the body gets rid of the drug.

Dr. Camacho said, "I am most pleased to be leading this trial. VQD-001's long safety history gives us a real boost as we explore its anti-tumor activity in patients with advanced solid tumors. The pre-clinical animal models are very encouraging and our trial could shed light to a new family of anti-cancer compounds."

Dan Greenleaf, president and CEO of VioQuest, added, "The acceptance of our IND and the commencement of the trial for VQD-001 mark the achievement of another important clinical milestone for VioQuest. We are very excited about the potential of this compound and we look forward to further clinical progress in the months ahead."

There is an investigator-initiated Phase I/IIa study of VQD-001 in advanced malignancies currently in progress at the Cleveland Clinic Taussig Cancer Center, led by Ernest C. Borden, M.D., Director of Experimental Drug Discovery and Development, and Ronald Bukowski, M.D., Head of Experimental Therapeutics and Deputy Director of the Center. This trial is fully funded by the National Institutes of Health. VioQuest expects to report interim results from this trial during the first half of 2007.

About VQD-001: Sodium Stibogluconate (SSG)

VQD-001 is a clinical stage drug with a novel anti-tumor action that has potential as a treatment for cancer, either alone or in combination with other therapeutics. It has shown compelling preclinical activity, in multiple myeloma, malignant melanoma, bladder, and colon cancer cell lines. Investigators at the Cleveland Clinic Taussig Cancer Center found that VQD-001 inhibits specific protein tyrosine phosphatases (PTPases), which are over-expressed in certain cancers. This over-expression plays an integral role in tumor growth in certain cancers.
http://www.medilexicon.com/medicalnews.php?newsid=52758∞

Researchers Find Natural Anti-viral Enzyme Helps Keep Cancer Cells Alive

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09 Oct 2006

A molecule that cells normally use to fight viruses is also involved in keeping cancer cells alive, researchers at UT Southwestern Medical Center have discovered.

The anti-viral molecule, called TBK-1, was found to be essential for cancer cells to live, so blocking it might point to a treatment for fighting cancer, the researchers report in Cell.

"We got the surprise that this mechanism is involved in cancer cell survival, even though it's normally involved in immune response," said Dr. Michael White, associate professor of cell biology. "We found something a little bit different - an Achilles' heel of cancer cells that's apparently broadly conserved among many types of solid tumors."

Using cultured human cells, the researchers set out to study enzymes known to be involved in keeping cancer cells alive and proliferating. They soon narrowed the focus to one called RalB. This molecule is part of the Ras family of enzymes, which are mutated in 30 percent of all cancers and in 90 percent of pancreatic cancers.

The UT Southwestern scientists knew that RalB interacts with a protein complex called the exocyst, which helps small secretory packets in cells fuse to the cell membrane. The team isolated this complex, then chemically analyzed the proteins attached to it.

One protein they found on the exocyst, TBK-1, is known to be involved in cells' anti-viral response.

"There was nothing known about that mechanism to suggest how TBK-1 could drive cancer cell survival," Dr. White said.

The researchers found that TBK-1 is turned off in healthy cells unless the immune response is stimulated but was always active in the cancerous cells they studied. When they blocked the function of TBK-1 in both the cancerous and healthy cells, cancer cells died while healthy cells survived.

A German research team has studied clinical samples of tumors and found elevated levels of TBK-1, Dr. White said.

The TBK-1 action is part of an immune reaction called the "host defense response," which is distinct from the "adaptive" immune process, in which the body creates new antibodies against invading pathogens. A great deal is currently understood about how the adaptive immune system fights cancer and also helps create tissue environments permissive to cancer, Dr. White said, but a cancer-promoting role for the host defense response has not been previously seen.

It's a