Ostomyland's Wicked Wiki: Articles about new Colorectal Cancer drugs, treatment methods, research etc.

Most recent edit on 2007-11-23 13:46:16 by KathyFromEngland

Additions:
~*Phase II Study Of Therapeutic Vaccine Shows Efficacy In Patients With Metastatic Colorectal Cancer

*Fighting Colorectal And Breast Cancer With Newly Identified Enzyme

Fighting Colorectal And Breast Cancer With Newly Identified Enzyme
Article Date: 02 Nov 2007 - 3:00 PDT
Researchers at the Virginia Commonwealth University Massey Cancer Center have identified the enzyme sphingosine kinase 2 as a possible new therapeutic target to improve the efficacy of chemotherapy for colon and breast cancer.
In the Nov. 1 issue of the journal Cancer Research, researchers examined human colon and breast cancer cells and established a role of sphingosine kinase 2 (SphK2), an enzyme that forms the potent lipid mediator sphingosine-1-phosphate in the death of cancer cells mediated by the chemotherapeutic drug, doxorubicin.
Doxorubicin is able to kill cancer cells by working with p53, one of the most protective anti-cancer proteins in the human body. However, doxorubicin also relies on p53- independent mechanisms to induce death in colon and breast cancer cells.
"Understanding how doxorubicin kills in a p53-independent manner is a major goal of cancer researchers because most cancer cells have mutated p53," said lead author Sarah Spiegel, Ph.D., chair and professor in the VCU Department of Biochemistry and Molecular Biology and co-leader of the cancer center's cancer cell biology program.
According to Spiegel, the study demonstrated that SphK2 is important for p53-independent induction of expression of p21, a cyclin-dependent kinase inhibitor. This p21 regulates the cell cycle, and apoptosis or programmed cell suicide, mediated by doxorubicin. Human colon and breast cancer cells were killed more efficiently by doxorubicin when SphK2 was removed from the cells.
"Therefore, the findings suggest that SphK2 influences the balance between cytostasis, and apoptosis of human cancer cells," Spiegel said. Cytostasis refers to the stoppage of cellular growth and multiplication.
Spiegel said that cell death was induced by doxorubicin and decreased p21.
Spiegel, who is internationally recognized for her pioneering work on new lipid mediators that regulate cell growth and cell death, and her colleagues, first discovered the role of sphingosine-1-phosphate in cell growth regulation nearly a decade ago. Spiegel and her team are continuing this work to better understand the functions of these enzymes.
http://www.medicalnewstoday.com/articles/87494.php∞

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~*Phase II Study Of Therapeutic Vaccine Shows Efficacy In Patients With Metastatic Colorectal Cancer

Edited on 2007-11-23 13:14:37 by KathyFromEngland

Additions:
~*Phase II Study Of Therapeutic Vaccine Shows Efficacy In Patients With Metastatic Colorectal Cancer

Phase II Study Of Therapeutic Vaccine Shows Efficacy In Patients With Metastatic Colorectal Cancer
Article Date: 03 Aug 2007 - 1:00 PDT
A therapeutic cancer vaccine has shown effectiveness when given alongside chemotherapy to patients with metastatic colorectal cancer in a phase II trial, according to researchers at Oxford BioMedica (UK) Ltd. The study found that six of the 17 metastatic colorectal cancer patients in the study showed tumor shrinkage, classified as complete or partial responses following independent expert review.
The study, reported in the August 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, was designed to demonstrate the safety and immunogenicity of the vaccine, called modified vaccinia Ankara-encoding 5T4 (TroVax?), when used alongside standard chemotherapy. The research was funded by Oxford BioMedica which is developing the vaccine in partnership with Sanofi-Aventis.
Unlike preventative vaccines, such as the human papillomavirus vaccine to prevent cervical cancer, TroVax is a therapeutic vaccine, designed to stimulate the immune systems of patients who already have cancer. The vaccine consists of an attenuated (non-disease causing) version of the vaccinia virus modified to deliver the gene for 5T4, a protein found in many tumors.
"The idea is that the modified virus enters cells, produces the tumor protein and stimulates the immune system," said lead study author Richard Harrop, Ph.D., vice president of clinical immunology at Oxford BioMedica. "To give a vaccine alongside chemotherapy might seem counterintuitive, since chemotherapy can weaken the immune system, but our study shows that TroVax could be complementary to standard chemotherapy, enhancing the immune response to tumors."
The target of this immuno-therapy approach is a tumor antigen called 5T4, a protein embedded within the membrane of cancer cells. The protein is rarely found in normal tissues, but is produced at high levels by a wide range of human cancers, including colorectal, renal, gastric and ovarian. The production of 5T4 has been associated with cancer metastasis and poor prognosis for patients.
"Typically, the immune system doesn't pay attention to this molecule, so by producing 5T4 artificially in combination with the 'danger signals' associated with a viral infection, we are demanding that the immune system take notice," Harrop said. "TroVax causes cells at the injection site to produce 5T4 in a way which agitates the immune system into producing antibodies and killer T cells. It is hoped that these two components of the immune system then migrate to tumors and kill them without harming any normal tissues."
"In essence, it's like turning up your stereo in the hopes that it will attract the police to your neighbor's rowdy party," Harrop said.
Harrop and his colleagues administered the vaccine to 17 patients with metastatic colorectal cancer just before, during and after the patients were treated with the standard chemotherapy regimen FOLFOX which consists of the agents: 5-fluorouracil, folinic acid and oxaliplatin.
Through the course of the study, the researchers monitored the patients for an immune response to 5T4. Eleven of the 17 patients who received the complete course of vaccinations (six injections) mounted strong immune responses to the 5T4 tumor protein. Of these 11 patients, six exhibited significant shrinkage of their tumors and one patient no longer had any detectable tumors. Researchers noted no complications stemming from TroVax vaccination or any other evidence that would call into question the safety of the vaccine.
While the study was not designed to prove that patients survived longer than would normally be expected, the researchers noted that, on average, the overall median survival was 68 weeks in all 17 vaccinated patients and 118 weeks in the 11 patients who received all six vaccinations.
According to Harrop, the researchers are currently testing the vaccine in a phase III trial in renal cancer patients in the U.S. and Europe and Sanofi Aventis is planning a phase III study in colorectal cancer.
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.
http://www.aacr.org∞
http://www.medicalnewstoday.com/articles/78551.php∞

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~*Pfizer Initiates Phase 3 Trial To Study Sunitinib Malate In Patients With Metastatic Colorectal Cancer

Edited on 2007-11-23 13:09:57 by KathyFromEngland

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~*In First Line Treatment Of Metastatic Colorectal Cancer Erbitux Demonstrates Consistent Efficacy

*Pfizer Initiates Phase 3 Trial To Study Sunitinib Malate In Patients With Metastatic Colorectal Cancer

Sunitinib malate is a multi-kinase inhibitor which works by inhibiting angiogenesis, the process by which tumors acquire blood vessels bringing oxygen and nutrients needed for growth, and proliferation, the process by which cells multiply.
Phase I Study in Metastatic Colorectal Cancer
New data presented this week from an ongoing, open-label Phase I trial of 16 previously untreated mCRC patients randomized to three distinct dosing regimens, determined the maximum tolerated dose (MTD) for sunitinib malate of four weeks on treatment followed by two weeks off (4/2) in combination with FOLFIRI was 37.5 mg/day. This regimen appeared to be active and generally well-tolerated in patients who have received no prior treatment for metastatic disease. Of the 10 patients who received this dosing regimen, four patients experienced partial response to date and stable disease has been observed in six patients. Treatment emergent grade 3 adverse events for patients on the sunitinib malate 37.5 mg/day 4/2 regimen were one case of respiratory tract infection and two cases of neutropenia without fever.
"Despite progress in recent years, colorectal cancer remains a hard-to-treat cancer for which new options are sorely needed," said Alfredo Carrato MD, PhD, Elche University Hospital and lead investigator on the sunitinib malate multi-national Phase III trial in mCRC. "These data support further research of sunitinib malate in metastatic colorectal cancer, in an effort to potentially expand the range of therapies available to physicians and patients."
For more information about sunitinib malate trials currently open and enrolling, please visit http://www.ClinicalTrials.gov∞ or http://www.suntrials.com∞ or call Pfizer Oncology's toll-free number at 001-646-277-4066.
Disclosure Notice: The information contained in this release is as of June 27, 2007. Pfizer assumes no obligation to update any forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about various products in development, including their potential benefits, that involves substantial risks and uncertainties. Such risks and uncertainties include, among other things, the uncertainties inherent in research and development; decisions by regulatory authorities regarding whether and when to approve any drug applications that may be filed for any such products in development as well as their decisions regarding labeling and other matters that could affect their availability or commercial potential; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2006 and in its reports on Form 10-Q and Form 8-K.
http://www.pfizer.com∞

Deletions:
~*In First Line Treatment Of Metastatic Colorectal Cancer Erbitux Demonstrates Consistent Efficacy

Edited on 2007-11-23 13:01:51 by KathyFromEngland

Additions:
~*Improving Colorectal Cancer Treatment

*In First Line Treatment Of Metastatic Colorectal Cancer Erbitux Demonstrates Consistent Efficacy

In First Line Treatment Of Metastatic Colorectal Cancer Erbitux Demonstrates Consistent Efficacy
Article Date: 03 Jul 2007 - 1:00 PDT
The first European presentation of key Erbitux? (cetuximab) data at the 9th World Congress of Gastrointestinal Cancers (WCGIC) reinforces the consistent efficacy of Erbitux in the first-line treatment of metastatic colorectal cancer (mCRC). The key Erbitux studies presented - involving more than 70 centres across Europe - represent best practice in clinical trials management and collaboration.
Two key studies presented at the meeting, validate the role of Erbitux as an effective first-line treatment in mCRC patients, when used in conjunction with two different types of chemotherapy treatment. The CRYSTALa trial, a phase III study of Erbitux plus FOLFIRI (irinotecan-based therapy) compared with FOLFIRI alone, met the primary endpoint of significantly increasing median duration of progression-free survival in patients with previously untreated mCRC. This randomized, controlled trial studied almost 1,200 patients and demonstrated a 15% reduction (hazard ratio: 0.085) in the risk of metastatic colorectal cancer growing or spreading compared to the control arm, which was statistically significant (p=0.0479). In addition, one year after trial therapy initiation, 34% of patients in the Erbitux arm had not progressed vs 23% of patients in the control arm.
The study also achieved its secondary endpoint of significantly increasing response rate (tumor shrinkage by 50% or more) (47% in the Erbitux plus FOLFIRI group compared to 39% in the FOLFIRI alone group). Furthermore, in a subgroup analysis of patients who had liver limited disease (patients who had liver metastases only), the positive effect of the addition of Erbitux was even more pronounced, resulting in a PFS of 11.4 months with Erbitux vs. 9.2 months in the control arm and a 36% reduction in the risk of metastatic colorectal cancer growing or spreading. The number of complete resections of the metastases in the subgroup who had liver metastases only was more than double with Erbitux plus FOLFIRI vs. control arm (9.8% versus 4.5%). The number of complete resections in the overall population was three times higher in the Erbitux plus FOLFIRI arm.
"These results indicate that we have a new first-line treatment option for metastatic colorectal cancer," said Eric Van Cutsem, MD, PhD, a professor at University Hospital Gasthuisberg in Leuven, Belgium, and lead author of the study. "These findings are remarkable because they point towards the potential for this combination to provide a cure for those patients who were able to undergo a complete resection."
The CRYSTAL results were supported by the findings of the OPUSb study. Erbitux plus FOLFOX (oxaliplatin-based therapy) was compared with FOLFOX alone to measure overall response rate (tumor shrinkage by 50% or more). Response rate was found to be 46% in the Erbitux arm compared with 36% in the oxaliplatin-only arm. The safety profile of Erbitux in combination with chemotherapy was manageable and consistent with the current safety information.
Commenting on the studies, Carsten Bokemeyer, MD, PhD and lead author for the OPUS study from the University Hospital Hamburg, Germany, says: "Overall, these first-line studies demonstrate that, when added to current standard chemotherapy, Erbitux significantly increases response and resection rates, which in turn, significantly increases the chance of cure for mCRC patients."
As well as first-line use, a number of studies presented at WCGIC reinforce the versatility of Erbitux in treating a broad range of patients with mCRC. Data from the phase III EPICc study, which compared Erbitux plus irinotecan with irinotecan alone in mCRC patients who had failed first-line treatment with oxaliplatin-based chemotherapy, showed that progression-free survival, response rate and health-related quality of life was significantly improved in the Erbitux arm. A new retrospective European study (Bouchahda et al) on the use of Erbitux in elderly patients with extensively pre-treated mCRC demonstrated that the combination of Erbitux with irinotecan-based therapy resulted in good activity and acceptable tolerability comparable to that of the non-elderly population.
Commenting on the data for an important subgroup of the CRYSTAL trial, which had liver limited disease, Dr Wolfgang Wein, Senior Executive Vice President, Oncology, Merck Serono - a division of Merck KGaA, Darmstadt, Germany said "We are delighted with the results presented at WCGIC. Besides the significant outcomes for the overall population in the CRYSTAL trial we were able to define the patients with the greatest benefit. In patients with metastases limited to the liver 10% of patients had a complete resection of the tumor, which means hope for cure. This was possible because Erbitux significantly increased the tumor response rate".
More than 370,000 people develop colorectal cancer in Europe every year, accounting for 13% of the total cancer burden and around 200,000 deaths.1 Approximately 25% of patients present with metastatic disease.2 Five-year survival rates for patients with mCRC are as low as 5%.3
http://www.medicalnewstoday.com/articles/75760.php∞

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~*Improving Colorectal Cancer Treatment

Edited on 2007-11-23 13:00:24 by KathyFromEngland

Additions:
~*Treatment Developed Which Slows The Growth Of Colon And Liver Cancers

*Improving Colorectal Cancer Treatment

Improving Colorectal Cancer Treatment
Article Date: 29 Jun 2007 - 1:00 PDT
Researchers have provided new information about a protein responsible for colorectal cancer and the target of a potential drug against this cancer.
Called clusterin, this protein has been linked to the development of tumor cells and resistance to cancer therapy, but how it works is not well understood. Pending questions include how this protein is expressed in normal and cancer cells, how it helps cancer cells escape ionizing radiation and chemotherapy, and which patients will benefit from treatment with a drug targeting clusterin.
Claus Lindbjerg Andersen, Torben Falck Orntoft, and colleagues discovered that clusterin is not expressed in normal cells, while in 25 percent of colorectal tumors, the cancer cells contained clusterin. They also showed that the protein is actually made by the cancer cells themselves. These new findings should help improve current therapies against colorectal cancer, especially for patients with tumors producing clusterin, the scientists concluded.
http://www.medicalnewstoday.com/articles/75500.php∞

Deletions:
~*Treatment Developed Which Slows The Growth Of Colon And Liver Cancers

Edited on 2007-11-23 12:58:02 by KathyFromEngland

Additions:
~*Pfizer Initiates Phase 3 Trial To Study Sunitinib Malate In Patients With Metastatic Colorectal Cancer

*Treatment Developed Which Slows The Growth Of Colon And Liver Cancers

Treatment Developed Which Slows The Growth Of Colon And Liver Cancers
Article Date: 24 Jun 2007 - 15:00 PDT
Leire Garc?a Navarro, a researcher at the School of Pharmacy of the University of Navarra, has developed a new treatment which slows the growth of colon and liver cancers.
This discovery is the principal result of her doctoral dissertation, entitled "Lipo-Polymeric Vectors for the Transfer of DNA in Cancer Cells of the Colon", which was subsidized by the Basque Government. In order to carry out the study, this scientist of the Department of Pharmacy and Pharmaceutical Technology used genetic therapy with non-viral vectors for transferring genetic material to the cancerous cells. With this technique, we can assure the therapeutic function of the drug in a wide variety of tissues. In addition, we can apply the treatment repeatedly, since it does not generate immunity, as occurs with viral vectors.
With the objective of improving the effectiveness of this methodology, the specialist worked on designing non-viral systems which act directly upon the liver and the colon. In this manner, she prepared, optimized and evaluated, in vitro and in vivo, a new pharmaceutical format called 'lipopolyplex.' This compound aids the genetic material in penetrating into the damaged cells, and allows drug release in tumorous organs. 500,000 deaths per year
Experimentation with the new drug in mice has shown that it slows tumor growth with respect to those animals subjected to other procedures. This diminishing of the cancerogenous area is possible, according to the scientist, thanks to the stimulation of the immune system, since the introduction of the correct gene in the diseased body can cause it to repair itself and destroy the tumor.
In addition, the researcher of the University of Navarra noted that colon cancer alone causes more than 500,000 deaths per year in the West, and currently the only effective treatment is surgery. Despite this treatment, noted the researcher, between 40 and 60% of colon cancer patients die, and for this reason it is important that we seek out treatment based on genetic therapy.
http://www.medicalnewstoday.com/articles/74904.php∞

Deletions:
~*Pfizer Initiates Phase 3 Trial To Study Sunitinib Malate In Patients With Metastatic Colorectal Cancer

Edited on 2007-11-23 07:35:16 by KathyFromEngland

Additions:
~*Colon Cancer Proteins Show Promise For Blood Test

*Pfizer Initiates Phase 3 Trial To Study Sunitinib Malate In Patients With Metastatic Colorectal Cancer

Pfizer Initiates Phase 3 Trial To Study Sunitinib Malate In Patients With Metastatic Colorectal Cancer
Article Date: 06 Jul 2007 - 1:00 PDT
Pfizer announced recently the initiation of a Phase III clinical trial to evaluate the safety and efficacy of sunitinib malate, in combination with a standard chemotherapy regimen, in patients with metastatic colorectal cancer (mCRC) - cancer originating in the colon that has spread to other parts of the body. In addition, new data from a Phase I study being presented this week at the World Congress on Gastrointestinal Cancer (WCGC) in Barcelona showed that sunitinib malate is active and generally well-tolerated in combination with a standard chemotherapy regimen, FOLFIRI, in previously untreated patients with mCRC. These data support further evaluation of sunitinib malate in mCRC in a Phase III program.
"We are encouraged by these data which add to a growing body of research demonstrating the activity and tolerability of sunitinib malate in numerous cancers," said Charles Baum, MD PhD, head of oncology development at Pfizer. "Based on these early findings presented this week, Pfizer is committed to continued exploration of sunitinib malate in the treatment of advanced colorectal cancer through a global Phase III program."
Sunitinib Malate Phase III Trial in Colorectal Cancer
A multi-national Phase III study is currently open and enrolling in Europe, Canada, Asia and South America and will include more than 700 patients to evaluate the safety and efficacy of sunitinib malate combined with FOLFIRI, a standard chemotherapy regimen used in mCRC comprised of fluorouracil (5-FU), folinic acid (leucovorin), and irinotecan, compared with FOLFIRI plus placebo, in the first-line treatment of patients with mCRC.
Sunitinib malate is a multi-kinase inhibitor which works by inhibiting angiogenesis, the process by which tumors acquire blood vessels bringing oxygen and nutrients needed for growth, and proliferation, the process by which cells multiply.
http://www.medicalnewstoday.com/articles/76036.php∞

Deletions:
~*Colon Cancer Proteins Show Promise For Blood Test

Edited on 2007-11-23 07:25:54 by KathyFromEngland

Additions:
~*Scientists Develop New Drugs To Fight Colon And Breast Cancer More Effectively

*Colon Cancer Proteins Show Promise For Blood Test

Colon Cancer Proteins Show Promise For Blood Test
Article Date: 16 Jun 2007 - 1:00 PDT
Searching for less invasive screening tests for cancer, Johns Hopkins scientists have discovered proteins present in blood that accurately identify colon cancer and precancerous polyps.
Initial studies of the proteins, CCSA-3 and CCSA-4, suggest they could be used to develop a blood test to identify at-risk individuals.
"The reality is that many people are not getting regular screening colonoscopies," says cancer researcher Robert Getzenberg, Ph.D. "So, ideally we'd like to identify those with some molecular for the disease and really need them."
Current screening guidelines for healthy people call for a baseline colonoscopy - colonic cleansing, fasting and heavy sedation followed by the insertion of a flexible, optical-scanning scope through the rectum into the colon -- at age 50, followed by re-screening at least every five to 10 years. Colonoscopy is not foolproof; cancers can develop between screenings.
First discovered by Getzenberg and colleagues at the University of Pittsburgh through a protein scan, the two blood-dwelling proteins are thought to be remnants of cellular debris castoff from dead cancer cells. Although the proteins' roles are not entirely clear, the Johns Hopkins scientists say they are part of the scaffolding that supports structures within a cell's control center, the nucleus.
Alteration of such nuclear scaffolding is a hallmark of cancer cells that is easily detectable under the microscope as a misshapen and discolored nucleus. That led Getzenberg to the notion that "there must be something at the molecular level that would form a molecular flag for cancer via a blood test."
To find the flag, Getzenberg's team drew blood samples from 107 apparently healthy individuals the day before their scheduled colonoscopies, and from 28 colorectal cancer patients.
Using a particular concentration of scaffold-proteins as a marker for disease, the Johns Hopkins team - which did not know the colonoscopy results in advance -- were 100 percent accurate in identifying the 28 existing cancers. Using the same protein markers, investigators also correctly identified 51 of 53 individuals (96.2 percent) with normal colons and 14 of 18 (77.8 percent) people with advanced precancerous polyps, which Getzenberg says are the most important to detect through routine screening.
When researchers combined samples, they correctly identified 42 of 46 (91.3 percent) containing both cancers and advanced precancerous polyps. Protein levels were accurate in correctly assessing additional blood samples from 125 people with benign conditions and other cancers.
"These proteins seem very good at separating normal samples from cancerous ones and identifying other groups with pre-cancers at high risk for disease as well," says Getzenberg, who is a professor of urology and director of research at Johns Hopkins' Brady Urological Institute. Results are published in the June 15 issue of Cancer Research.
The researchers are planning larger studies at several hospitals over the next several months. It may take several years to complete the full range of testing.
Getzenberg says that storing and processing the samples are among the major hurdles in biomarker development, a field that spans ongoing research on many cancers and various body fluids. "It is difficult to get many facilities to adhere to precise storage and processing conditions important for keeping proteins stable," he says. "Different conditions could create incorrect results." Researchers also differ in the type of biomarkers they seek, with some looking for proteins, like Getzenberg, and others searching for DNA components.
Getzenberg and the University of Pittsburgh hold a patent for the technology described above, which is licensed to Onconome Inc. Funding for the study described in this article was provided by Onconome Inc. and the National Cancer Institute. Under a licensing agreement between Onconome Inc. and University of Pittsburgh, Getzenberg is entitled to a share of royalty received by the University on sales of products described in this article. Getzenberg also is a paid consultant to Onconome Inc. which has a licensing agreement with The Johns Hopkins University covering CCSA-3 and -4 related technologies. The terms of this arrangement are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.
Additional authors are Eddy S. Leman, Grant W. Cannon, Lori J. Sokoll, and Daniel W. Chan at Johns Hopkins; and Robert E. Schoen and Joel L. Weissfeld at the University of Pittsburgh Cancer Institute.
http://www.hopkinskimmelcancercenter.org∞
http://www.urology.jhu.edu/∞
http://www.jhmi.edu∞
http://www.medicalnewstoday.com/articles/74295.php∞

Deletions:
~*Scientists Develop New Drugs To Fight Colon And Breast Cancer More Effectively

Edited on 2007-06-30 02:11:57 by KathyFromEngland [Restored to Original Version by Kathy]

Additions:
~*Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) + Oxaliplatin) And For Avastin
Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) + Oxaliplatin) And For Avastin
Evidence for this theory has been mounting for the past year. On January 10, 2007, Dr. Sheila Fraser of St. James's University Hospital in Leeds, U.K. delivered a paper at the Society of Academic & Research Surgery Conference in Cambridge, U.K., in which she described a test tube experiment further supporting this claim. Fraser's presentation, titled "Reovirus as a Potentially Immunogenic as well as Cytotoxic Therapy for Metastatic Colorectal Cancer," reported how cells taken from a colorectal cancer liver metastases were more susceptible to death many weeks after treatment with reovirus, and long after the virus had cleared the patient's system. These cells, when cultured in the laboratory, also appeared to be vulnerable to re-infection with reovirus. Moreover, Dr. Fraser noted that dendritic cells, which prime the immune system against cancer, were activated by exposure to the reovirus.
"We understand how the reovirus replicates within and kills cancer cells," explains Dr. Matt Coffey, Chief Scientific Officer at Oncolytics, "but we also observed that tumors sometimes continue to shrink long after the virus is gone." Immunologic work now suggests that reovirus exposure is "educating" the immune system to recognize and kill the same cancer cells that were attacked by reovirus. "If you can teach the immune system to recognize cancer cells," says Coffey, "it may be possible to fight off the disease for much longer than we originally anticipated."
Late in 2006, another collaborator, Dr. Alan Melcher of the Cancer Research UK Clinical Centre in Leeds, hypothesized that reovirus activation of dendritic cells, which are key to early detection of infection (through the innate immune response), may "instruct" cells belonging to the adaptive immune response, namely natural killer cells and T cells, to attack the tumor even after the virus no longer remains in the body. That poster was presented at the European National Societies of Immunology Meeting in Paris.
Interestingly, another study conducted in 2006 at the Mayo Clinic suggested that momentarily suppressing the immune system allows the virus to continue replicating, leading to increased cancer cell killing. This in turn leads to the creation of more tumor antigens (the elements that educate the immune system), thereby increasing the vaccinating effect of the virus and perhaps improving the efficacy of oncolytic virus therapy.
"The apparent dual mechanism of action for oncolytic viruses will need to be tested further, both in patients and in the laboratory. If the effects turn out to be genuine, the implications for long-term survival from many types of cancer could be significant," says Coffey. Researchers believe that therapies working simultaneously, but through different mechanisms, may overcome the resistance to treatment that is typically seen in cancer. In addition, this double attack on cancer could point to new treatment regimens based on conventional therapies like radiation and chemotherapy with biological agents.
http://www.medilexicon.com/medicalnews.php?newsid=62587∞
Tequila raw ingredient being developed into drug-carrier that targets colon diseases
CHICAGO, March 27
Compounds derived from the blue agave, a fruit used to make tequila, shows promise in early laboratory studies as a natural, more effective way to deliver drugs to the colon than conventional drug-carriers, according to chemists at the University of Guadalajara in Mexico. The development could lead to improved treatments for ulcerative colitis, irritable bowel syndrome, cancer, Crohn?s disease and other colon diseases, they say.
Drug delivery to the colon is an ongoing challenge to physicians. Many drugs are destroyed by stomach acids before they?ve had a chance to reach the intestine, where they usually are absorbed. Researchers have tried to circumvent this problem by inserting the drugs into carrier molecules that resist breakdown in the stomach but have had difficulty finding a suitable carrier compound.
The tequila compounds, a class of polysaccharides known as fructans, were developed by the scientists in Mexico into tiny microspheres that are capable of carrying existing drugs that are used to treat colon diseases. Because the compounds resist destruction in the stomach, they could allow more of the drugs to reach the colon intact and improve their effectiveness, the researchers say. Their study was presented today at the 233rd national meeting of the American Chemical Society.
?This study shows that the agave fruit is good for more than just tequila. It also has medicinal value,? says study leader Guillermo Toriz, Ph.D., an assistant professor at the university. ?Agave fructan is the ideal natural carrier of drugs for the colon.?
Researchers have known for some time that fructans, which are polymers of fructose, are resistant to acid degradation and theorized that they might be a useful drug delivery vehicle. But only a few plant sources, such as agave, contain fructans in large amounts. The agave fruit is 80 percent fructans by weight when ripe, the researchers say.
Toriz and his associates extracted fructans from the blue agave, the base ingredient of tequila. They chemically modified the fructan compound to allow drugs to be encapsulated, making the drugs resistant to degradation in the digestive system.
The researchers then prepared microspheres of the compounds and filled them with ibuprofen as a model of drug delivery to the colon. In laboratory tests, the ibuprofen-filled microspheres were exposed to hydrochloric acid for an hour and appeared physically intact upon subsequent microscopic examination, the scientists say.
Topiz and his research group currently are working on improving the durability of the fructans and plan animal studies in the future. If further studies show promise, human studies of the agave microspheres are anticipated. Funding for the study was provided by the Mexican National Science and Technology Council.
http://www.eurekalert.org/pub_releases/2007-03/acs-tri031207.php∞
Tequila Raw Ingredient Being Developed Into Drug-carrier That Targets Colon Diseases
31 Mar 2007
Compounds derived from the blue agave, a fruit used to make tequila, shows promise in early laboratory studies as a natural, more effective way to deliver drugs to the colon than conventional drug-carriers, according to chemists at the University of Guadalajara in Mexico. The development could lead to improved treatments for ulcerative colitis, irritable bowel syndrome, cancer, Crohn's disease and other colon diseases, they say.
Drug delivery to the colon is an ongoing challenge to physicians. Many drugs are destroyed by stomach acids before they've had a chance to reach the intestine, where they usually are absorbed. Researchers have tried to circumvent this problem by inserting the drugs into carrier molecules that resist breakdown in the stomach but have had difficulty finding a suitable carrier compound.
The tequila compounds, a class of polysaccharides known as fructans, were developed by the scientists in Mexico into tiny microspheres that are capable of carrying existing drugs that are used to treat colon diseases. Because the compounds resist destruction in the stomach, they could allow more of the drugs to reach the colon intact and improve their effectiveness, the researchers say. Their study was presented today at the 233rd national meeting of the American Chemical Society.
"This study shows that the agave fruit is good for more than just tequila. It also has medicinal value," says study leader Guillermo Toriz, Ph.D., an assistant professor at the university. "Agave fructan is the ideal natural carrier of drugs for the colon."
Researchers have known for some time that fructans, which are polymers of fructose, are resistant to acid degradation and theorized that they might be a useful drug delivery vehicle. But only a few plant sources, such as agave, contain fructans in large amounts. The agave fruit is 80 percent fructans by weight when ripe, the researchers say.
Toriz and his associates extracted fructans from the blue agave, the base ingredient of tequila. They chemically modified the fructan compound to allow drugs to be encapsulated, making the drugs resistant to degradation in the digestive system.
The researchers then prepared microspheres of the compounds and filled them with ibuprofen as a model of drug delivery to the colon. In laboratory tests, the ibuprofen-filled microspheres were exposed to hydrochloric acid for an hour and appeared physically intact upon subsequent microscopic examination, the scientists say.
Topiz and his research group currently are working on improving the durability of the fructans and plan animal studies in the future. If further studies show promise, human studies of the agave microspheres are anticipated. Funding for the study was provided by the Mexican National Science and Technology Council.
http://www.medilexicon.com/medicalnews.php?newsid=66392∞
Nuvelo Receives FDA Fast Track Status For rNAPc2 In Both First- And Second-Line Treatment Of Metastatic Colorectal Cancer
29 Mar 2007
Nuvelo, Inc. (Nasdaq: NUVO) today announced that it has been granted two separate fast track designations by the U.S. Food and Drug Administration (FDA) for its product candidate, rNAPc2. The first fast track designation is for first-line treatment of metastatic colorectal cancer (mCRC) to improve progression-free survival and overall survival when added to Avastin(R)-containing 5- flurourocil (5-FU)-based chemotherapy regimens. The other is for second-line treatment of mCRC to improve progression-free survival and overall survival when added to 5-FU-based chemotherapy regimens. Fast track designation, which was mandated by the FDA Modernization Act of 1997, can potentially facilitate development and expedited review of Biologics License Applications (BLA). Fast track designation is reserved for new drugs that demonstrate the potential to address an unmet medical need and are intended for the treatment of a serious or life-threatening condition.
rNAPc2 is currently being studied in a Phase 2 clinical trial in subjects with mCRC, which accounted for approximately 55,000 colorectal cancer deaths in 2006. The primary objectives of this trial are to determine the safety and efficacy of twice-weekly, subcutaneous rNAPc2 for the second-line treatment of mCRC in combination with select 5-FU-based chemotherapy regimens.
"Given the magnitude of mCRC related deaths, there is a need for additional safe and effective treatments that prevent metastasis and prolong survival," said Michael Levy, M.D., executive vice president of research and development for Nuvelo. "We are pleased that the FDA has granted us fast track designation and are committed to developing rNAPc2 to further understand its potential to help this underserved patient population."
http://www.medilexicon.com/medicalnews.php?newsid=66347∞
Suicide Gene Therapy Kills Bowel Cancer Cells
25 May 2007
An innovative type of gene therapy has for the first time succeeded in making bowel cancer cells commit suicide, according to a report in Cancer Research* this week.
The therapy, developed by Cancer Research UK-funded scientists at The Institute of Cancer Research, combines cutting-edge techniques to target tumour cells. Known as GDEPT (Gene-Directed Enzyme Prodrug Therapy), the treatment uses a virus to attack cancer cells.
But the researchers have added an extra gene to the virus. The virus is programmed to switch on the gene only if it reaches a tumour. When the gene is switched on, the virus produces a protein that activates an otherwise harmless 'prodrug', given separately.
Because this drug is only activated in tumours, it selectively kills only cancer cells. In normal tissue, the drug remains inactive, so healthy cells are not affected.
This is the first time such a therapy has proved successful at killing bowel cancer cells, albeit only in the laboratory. Cancer Research UK and The Institute of Cancer Research are supporting the development of the therapy, and hope to take it into early clinical trials in the future.
Lead researcher, Professor Caroline Springer of The Institute's Cancer Research UK Centre for Cancer Therapeutics, said: "We have developed a smart method to selectively target cancer cells. Normal cells are spared because the virus doesn't produce the protein that activates the drug unless it is inside a tumour.
"The beauty of our approach is that the cancer cells are made to commit suicide both by the virus and the activated drug �" the two work in tandem. And once activated, the drug has the added bonus of causing the virus to produce more of the activating protein, which activates more of the drug, and so on. It's the first time we've seen a 'positive feedback loop' like this in a GDEPT therapy."
The drug damages DNA inside the cancer cells to the point where the cells stop functioning. They have no choice but to shut down and die.
Another benefit of the therapy is that it doesn't just kill only the cancer cells infected by the virus.
"We also see a significant 'bystander effect'," added Prof Springer. "This means the cells killed by the virus or the drug release signals into the tumour that tell neighbouring cancer cells to die too."
In lab experiments, mice with bowel tumours that received the therapy lived twice as long as those that did not. The researchers suggest their technique could one day be used as a treatment for advanced bowel cancer that doesn't respond to standard chemotherapy.
Professor John Toy, medical director of Cancer Research UK, said: "GDEPT therapy has been in development for several years. But this study shows the technique - always a smart therapy - is becoming ever more sophisticated. For the first time it has been shown to be effective at killing bowel cancer cells in a laboratory model of human colon cancer. This is another stride towards the possible use of GDEPT for cancer patients."
* Cancer Research, Vol 67 Issue 10
GDEPT: an oncolytic adenovirus is injected into the bloodstream. The virus's DNA contains an added gene for CPG2 (Carboxypeptidase G2) but the gene is controlled so that it is only translated in the presence of telomerase, an enzyme found in many cancers but much less so in normal tissue. When the virus reaches a tumour that is producing telomerase, the gene is translated and the virus produces the protein CPG2.
Meanwhile a "prodrug" is injected. A prodrug is an inactive form of a drug. In this case the prodrug, called ZD2767P, is activated by CPG2 - hence it is only activated in regions of the body where the virus is producing CPG2, i.e. in tumours.
http://www.medilexicon.com/medicalnews.php?newsid=72020∞
Poniard Pharmaceuticals Announces Promising Data From Interim Safety Analysis Of Phase 1 Trials Of Picoplatin In Colorectal And Prostate Cancers
02 Jun 2007
Poniard Pharmaceuticals, Inc. (Nasdaq: PARD), a biopharmaceutical company focused on oncology, today announced promising results from an interim safety analysis of two Phase 1 dose-escalating trials of picoplatin, a new generation platinum for the potential first-line treatment of metastatic colorectal cancer (CRC) and metastatic hormone-refractory prostate cancer (HRPC). Initial safety data from the Phase 1 trial in CRC demonstrated that picoplatin can be safely administered with fluorouracil and leucovorin, and initial safety data from the Phase 1 trial in HRPC demonstrated that picoplatin can be safely combined with the dose of docetaxel (Taxotere(R)) used in current practice for HRPC.
The data were included in abstracts published in the 2007 American Society of Clinical Oncology (ASCO) Annual Meeting Proceedings.
-- Abstract #14510. Gladkov Jr O, Manikhas G, Biakhov M, Tjulandin S, Karlin D. Phase 1 study of picoplatin in combination with 5- fluorouracil and leucovorin as initial therapy in subjects with metastatic colorectal cancer.
-- Abstract #15546. Roman L, Karlov P, Kaprin A, Gladkov Jr O, Breitz H. Phase 1 study of picoplatin and docetaxel with prednisone in patients with chemotherapy-na?ve metastatic hormone refractory prostate cancer.
"Our new data indicate that picoplatin can be safely combined with established cancer therapeutics. In 66 patients treated up to 10 months, we have observed reversible myelosuppression that is non-cumulative and has not led to any treatment-related mortality," said Jerry McMahon, Ph.D., chairman and CEO of Poniard. "These Phase 1 studies have explored different doses of picoplatin and different dosing schedules either in combination with docetaxel for prostate cancer or with 5-fluorouracil and leucovorin for colorectal cancer. We anticipate that the Phase 2 trials for both indications will begin in the third quarter of 2007, shortly after the maximum tolerated doses have been defined."
He added, "In the Phase 1 colorectal cancer study, only three patients have experienced grade 1 neuropathy to date. There has been no neuropathy greater than grade 1 in all patients treated, including four patients who have received a cumulative picoplatin dose of greater than 900 mg/m2. The objective of our planned Phase 2 trial is to confirm the neuropathy-sparing properties of picoplatin given once every two weeks in a randomized trial compared to oxaliplatin and to enable a Phase 3 clinical trial to show superior safety and efficacy of FOLPI (picoplatin combined with fluorouracil and leucovorin) compared to FOLFOX (oxaliplatin combined with fluorouracil and leucovorin). The goal of our planned Phase 2 study in prostate cancer is to generate proof-of-concept data demonstrating that picoplatin has improved efficacy with docetaxel and to enable future picoplatin combination studies with taxanes for prostate and other cancer indications."
http://www.medilexicon.com/medicalnews.php?newsid=72878∞
Scientists Develop New Drugs To Fight Colon And Breast Cancer More Effectively
04 Jun 2007
The doctoral thesis 'Potencial terapeutico de nuevos farmacos antitumorales. Estudio sobre lineas celulares epiteliales' (Therapeutic Potential of New Antitumor Drugs. A Study on Epithelial Cell Lines) has allowed for the development of six new drugs to fight colon and breast cancer more effectively than other currently used drugs. The study was conducted at the Department of Human Anatomy and Embryology at the University of Granada (Universidad de Granada [http://www.ugr.es]∞) by Octavio Caba P?rez, member of the research group "Avances en Biomedicina" (Progress in Biomedicine), under the direction of professors Antonia Ar?nega, Juan Antonio Marchal and Fernando Rodr?guez.
The importance of this study, in which researchers from the Department of Pharmaceutical and Organic Chemistry have also collaborated, is that it enabled the identification of a total of six antitumor compounds similar to 5-fluorouracil (5-FU), one of the most widely-used drugs nowadays to fight colon and breast cancer. These compounds are more effective against malignant cells (those which are cancerous) and less toxic against benign cells (those which are unnecessarily destroyed or harmed with treatments such as chemotherapy).
As Caba P?rez points out, the current method used to fight tumors "produces several 'collateral damages'. A drug can be very effective against breast cancer, but it can also affect the rest of the benign epithelial tissue. As everybody knows, current treatments for cancer destroy a large number of unaffected cells in addition to affected cells," says Caba P?rez.
In this study researchers analyzed more than 150 drugs aimed at reducing the toxicity of the 5-FU against the benign cells, thus avoiding the reproduction of new carcinomas or other side effects. "We discarded compounds until we finally found six which have shown to be better than currently used drugs," says Caba P?rez.
Research on cell lines
So far, the study has been conducted on cell lines, and not on patients, using a new technique called "Microarrays" or "DNA Chips", which enables the identification of the effects produced by drugs on each gene the lowest and most specific level that Medicine can deal with.
"Our research," says Caba P?rez, "has been conducted with absolute precision with the aim of obtaining the lowest possible concentration of drug producing the most significant effect on cancerous cells". Therefore, this study has shown the importance of the presence of some toxic compounds like chlorine, flourine or uracil in drugs. This presence is one of the variables used to develop new antitumor drugs.
Part of the results of this study (which has been possible thanks to cooperation between the UGR [http://www.ugr.es∞] and the company VILPOMAS) have been published in the January 1 issue of the international journal "Tetrahedron". The remainder of the results will be published in various international journals on Biomedicine.
UNIVERSITY OF GRANADA - COMMUNICATIONS DEPARTMENT
Secretariado de Comunicaci?n - Universidad de Granada
Hospital Real - Cuesta del Hospicio s/n
http://www.ugr.es∞
http://www.medilexicon.com/medicalnews.php?newsid=72984∞

Categories

CategoryCancer

Deletions:
~*Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) Oxaliplatin) And For Avastin
Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) Oxaliplatin) And For Avastin
Evidence for this theory has been mounting for the past year. On January 10, 2007, Dr. Sheila Fraser of St. James's University Hospital in Leeds, U.K. delivered a paper at the Society of Academic

Edited on 2007-06-29 21:42:11 by JtpQu9

Additions:
~*Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) Oxaliplatin) And For Avastin
Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) Oxaliplatin) And For Avastin
Evidence for this theory has been mounting for the past year. On January 10, 2007, Dr. Sheila Fraser of St. James's University Hospital in Leeds, U.K. delivered a paper at the Society of Academic

Deletions:
~*Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) + Oxaliplatin) And For Avastin
Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) + Oxaliplatin) And For Avastin
Evidence for this theory has been mounting for the past year. On January 10, 2007, Dr. Sheila Fraser of St. James's University Hospital in Leeds, U.K. delivered a paper at the Society of Academic & Research Surgery Conference in Cambridge, U.K., in which she described a test tube experiment further supporting this claim. Fraser's presentation, titled "Reovirus as a Potentially Immunogenic as well as Cytotoxic Therapy for Metastatic Colorectal Cancer," reported how cells taken from a colorectal cancer liver metastases were more susceptible to death many weeks after treatment with reovirus, and long after the virus had cleared the patient's system. These cells, when cultured in the laboratory, also appeared to be vulnerable to re-infection with reovirus. Moreover, Dr. Fraser noted that dendritic cells, which prime the immune system against cancer, were activated by exposure to the reovirus.
"We understand how the reovirus replicates within and kills cancer cells," explains Dr. Matt Coffey, Chief Scientific Officer at Oncolytics, "but we also observed that tumors sometimes continue to shrink long after the virus is gone." Immunologic work now suggests that reovirus exposure is "educating" the immune system to recognize and kill the same cancer cells that were attacked by reovirus. "If you can teach the immune system to recognize cancer cells," says Coffey, "it may be possible to fight off the disease for much longer than we originally anticipated."
Late in 2006, another collaborator, Dr. Alan Melcher of the Cancer Research UK Clinical Centre in Leeds, hypothesized that reovirus activation of dendritic cells, which are key to early detection of infection (through the innate immune response), may "instruct" cells belonging to the adaptive immune response, namely natural killer cells and T cells, to attack the tumor even after the virus no longer remains in the body. That poster was presented at the European National Societies of Immunology Meeting in Paris.
Interestingly, another study conducted in 2006 at the Mayo Clinic suggested that momentarily suppressing the immune system allows the virus to continue replicating, leading to increased cancer cell killing. This in turn leads to the creation of more tumor antigens (the elements that educate the immune system), thereby increasing the vaccinating effect of the virus and perhaps improving the efficacy of oncolytic virus therapy.
"The apparent dual mechanism of action for oncolytic viruses will need to be tested further, both in patients and in the laboratory. If the effects turn out to be genuine, the implications for long-term survival from many types of cancer could be significant," says Coffey. Researchers believe that therapies working simultaneously, but through different mechanisms, may overcome the resistance to treatment that is typically seen in cancer. In addition, this double attack on cancer could point to new treatment regimens based on conventional therapies like radiation and chemotherapy with biological agents.
http://www.medilexicon.com/medicalnews.php?newsid=62587∞
Tequila raw ingredient being developed into drug-carrier that targets colon diseases
CHICAGO, March 27
Compounds derived from the blue agave, a fruit used to make tequila, shows promise in early laboratory studies as a natural, more effective way to deliver drugs to the colon than conventional drug-carriers, according to chemists at the University of Guadalajara in Mexico. The development could lead to improved treatments for ulcerative colitis, irritable bowel syndrome, cancer, Crohn?s disease and other colon diseases, they say.
Drug delivery to the colon is an ongoing challenge to physicians. Many drugs are destroyed by stomach acids before they?ve had a chance to reach the intestine, where they usually are absorbed. Researchers have tried to circumvent this problem by inserting the drugs into carrier molecules that resist breakdown in the stomach but have had difficulty finding a suitable carrier compound.
The tequila compounds, a class of polysaccharides known as fructans, were developed by the scientists in Mexico into tiny microspheres that are capable of carrying existing drugs that are used to treat colon diseases. Because the compounds resist destruction in the stomach, they could allow more of the drugs to reach the colon intact and improve their effectiveness, the researchers say. Their study was presented today at the 233rd national meeting of the American Chemical Society.
?This study shows that the agave fruit is good for more than just tequila. It also has medicinal value,? says study leader Guillermo Toriz, Ph.D., an assistant professor at the university. ?Agave fructan is the ideal natural carrier of drugs for the colon.?
Researchers have known for some time that fructans, which are polymers of fructose, are resistant to acid degradation and theorized that they might be a useful drug delivery vehicle. But only a few plant sources, such as agave, contain fructans in large amounts. The agave fruit is 80 percent fructans by weight when ripe, the researchers say.
Toriz and his associates extracted fructans from the blue agave, the base ingredient of tequila. They chemically modified the fructan compound to allow drugs to be encapsulated, making the drugs resistant to degradation in the digestive system.
The researchers then prepared microspheres of the compounds and filled them with ibuprofen as a model of drug delivery to the colon. In laboratory tests, the ibuprofen-filled microspheres were exposed to hydrochloric acid for an hour and appeared physically intact upon subsequent microscopic examination, the scientists say.
Topiz and his research group currently are working on improving the durability of the fructans and plan animal studies in the future. If further studies show promise, human studies of the agave microspheres are anticipated. Funding for the study was provided by the Mexican National Science and Technology Council.
http://www.eurekalert.org/pub_releases/2007-03/acs-tri031207.php∞
Tequila Raw Ingredient Being Developed Into Drug-carrier That Targets Colon Diseases
31 Mar 2007
Compounds derived from the blue agave, a fruit used to make tequila, shows promise in early laboratory studies as a natural, more effective way to deliver drugs to the colon than conventional drug-carriers, according to chemists at the University of Guadalajara in Mexico. The development could lead to improved treatments for ulcerative colitis, irritable bowel syndrome, cancer, Crohn's disease and other colon diseases, they say.
Drug delivery to the colon is an ongoing challenge to physicians. Many drugs are destroyed by stomach acids before they've had a chance to reach the intestine, where they usually are absorbed. Researchers have tried to circumvent this problem by inserting the drugs into carrier molecules that resist breakdown in the stomach but have had difficulty finding a suitable carrier compound.
The tequila compounds, a class of polysaccharides known as fructans, were developed by the scientists in Mexico into tiny microspheres that are capable of carrying existing drugs that are used to treat colon diseases. Because the compounds resist destruction in the stomach, they could allow more of the drugs to reach the colon intact and improve their effectiveness, the researchers say. Their study was presented today at the 233rd national meeting of the American Chemical Society.
"This study shows that the agave fruit is good for more than just tequila. It also has medicinal value," says study leader Guillermo Toriz, Ph.D., an assistant professor at the university. "Agave fructan is the ideal natural carrier of drugs for the colon."
Researchers have known for some time that fructans, which are polymers of fructose, are resistant to acid degradation and theorized that they might be a useful drug delivery vehicle. But only a few plant sources, such as agave, contain fructans in large amounts. The agave fruit is 80 percent fructans by weight when ripe, the researchers say.
Toriz and his associates extracted fructans from the blue agave, the base ingredient of tequila. They chemically modified the fructan compound to allow drugs to be encapsulated, making the drugs resistant to degradation in the digestive system.
The researchers then prepared microspheres of the compounds and filled them with ibuprofen as a model of drug delivery to the colon. In laboratory tests, the ibuprofen-filled microspheres were exposed to hydrochloric acid for an hour and appeared physically intact upon subsequent microscopic examination, the scientists say.
Topiz and his research group currently are working on improving the durability of the fructans and plan animal studies in the future. If further studies show promise, human studies of the agave microspheres are anticipated. Funding for the study was provided by the Mexican National Science and Technology Council.
http://www.medilexicon.com/medicalnews.php?newsid=66392∞
Nuvelo Receives FDA Fast Track Status For rNAPc2 In Both First- And Second-Line Treatment Of Metastatic Colorectal Cancer
29 Mar 2007
Nuvelo, Inc. (Nasdaq: NUVO) today announced that it has been granted two separate fast track designations by the U.S. Food and Drug Administration (FDA) for its product candidate, rNAPc2. The first fast track designation is for first-line treatment of metastatic colorectal cancer (mCRC) to improve progression-free survival and overall survival when added to Avastin(R)-containing 5- flurourocil (5-FU)-based chemotherapy regimens. The other is for second-line treatment of mCRC to improve progression-free survival and overall survival when added to 5-FU-based chemotherapy regimens. Fast track designation, which was mandated by the FDA Modernization Act of 1997, can potentially facilitate development and expedited review of Biologics License Applications (BLA). Fast track designation is reserved for new drugs that demonstrate the potential to address an unmet medical need and are intended for the treatment of a serious or life-threatening condition.
rNAPc2 is currently being studied in a Phase 2 clinical trial in subjects with mCRC, which accounted for approximately 55,000 colorectal cancer deaths in 2006. The primary objectives of this trial are to determine the safety and efficacy of twice-weekly, subcutaneous rNAPc2 for the second-line treatment of mCRC in combination with select 5-FU-based chemotherapy regimens.
"Given the magnitude of mCRC related deaths, there is a need for additional safe and effective treatments that prevent metastasis and prolong survival," said Michael Levy, M.D., executive vice president of research and development for Nuvelo. "We are pleased that the FDA has granted us fast track designation and are committed to developing rNAPc2 to further understand its potential to help this underserved patient population."
http://www.medilexicon.com/medicalnews.php?newsid=66347∞
Suicide Gene Therapy Kills Bowel Cancer Cells
25 May 2007
An innovative type of gene therapy has for the first time succeeded in making bowel cancer cells commit suicide, according to a report in Cancer Research* this week.
The therapy, developed by Cancer Research UK-funded scientists at The Institute of Cancer Research, combines cutting-edge techniques to target tumour cells. Known as GDEPT (Gene-Directed Enzyme Prodrug Therapy), the treatment uses a virus to attack cancer cells.
But the researchers have added an extra gene to the virus. The virus is programmed to switch on the gene only if it reaches a tumour. When the gene is switched on, the virus produces a protein that activates an otherwise harmless 'prodrug', given separately.
Because this drug is only activated in tumours, it selectively kills only cancer cells. In normal tissue, the drug remains inactive, so healthy cells are not affected.
This is the first time such a therapy has proved successful at killing bowel cancer cells, albeit only in the laboratory. Cancer Research UK and The Institute of Cancer Research are supporting the development of the therapy, and hope to take it into early clinical trials in the future.
Lead researcher, Professor Caroline Springer of The Institute's Cancer Research UK Centre for Cancer Therapeutics, said: "We have developed a smart method to selectively target cancer cells. Normal cells are spared because the virus doesn't produce the protein that activates the drug unless it is inside a tumour.
"The beauty of our approach is that the cancer cells are made to commit suicide both by the virus and the activated drug �" the two work in tandem. And once activated, the drug has the added bonus of causing the virus to produce more of the activating protein, which activates more of the drug, and so on. It's the first time we've seen a 'positive feedback loop' like this in a GDEPT therapy."
The drug damages DNA inside the cancer cells to the point where the cells stop functioning. They have no choice but to shut down and die.
Another benefit of the therapy is that it doesn't just kill only the cancer cells infected by the virus.
"We also see a significant 'bystander effect'," added Prof Springer. "This means the cells killed by the virus or the drug release signals into the tumour that tell neighbouring cancer cells to die too."
In lab experiments, mice with bowel tumours that received the therapy lived twice as long as those that did not. The researchers suggest their technique could one day be used as a treatment for advanced bowel cancer that doesn't respond to standard chemotherapy.
Professor John Toy, medical director of Cancer Research UK, said: "GDEPT therapy has been in development for several years. But this study shows the technique - always a smart therapy - is becoming ever more sophisticated. For the first time it has been shown to be effective at killing bowel cancer cells in a laboratory model of human colon cancer. This is another stride towards the possible use of GDEPT for cancer patients."
* Cancer Research, Vol 67 Issue 10
GDEPT: an oncolytic adenovirus is injected into the bloodstream. The virus's DNA contains an added gene for CPG2 (Carboxypeptidase G2) but the gene is controlled so that it is only translated in the presence of telomerase, an enzyme found in many cancers but much less so in normal tissue. When the virus reaches a tumour that is producing telomerase, the gene is translated and the virus produces the protein CPG2.
Meanwhile a "prodrug" is injected. A prodrug is an inactive form of a drug. In this case the prodrug, called ZD2767P, is activated by CPG2 - hence it is only activated in regions of the body where the virus is producing CPG2, i.e. in tumours.
http://www.medilexicon.com/medicalnews.php?newsid=72020∞
Poniard Pharmaceuticals Announces Promising Data From Interim Safety Analysis Of Phase 1 Trials Of Picoplatin In Colorectal And Prostate Cancers
02 Jun 2007
Poniard Pharmaceuticals, Inc. (Nasdaq: PARD), a biopharmaceutical company focused on oncology, today announced promising results from an interim safety analysis of two Phase 1 dose-escalating trials of picoplatin, a new generation platinum for the potential first-line treatment of metastatic colorectal cancer (CRC) and metastatic hormone-refractory prostate cancer (HRPC). Initial safety data from the Phase 1 trial in CRC demonstrated that picoplatin can be safely administered with fluorouracil and leucovorin, and initial safety data from the Phase 1 trial in HRPC demonstrated that picoplatin can be safely combined with the dose of docetaxel (Taxotere(R)) used in current practice for HRPC.
The data were included in abstracts published in the 2007 American Society of Clinical Oncology (ASCO) Annual Meeting Proceedings.
-- Abstract #14510. Gladkov Jr O, Manikhas G, Biakhov M, Tjulandin S, Karlin D. Phase 1 study of picoplatin in combination with 5- fluorouracil and leucovorin as initial therapy in subjects with metastatic colorectal cancer.
-- Abstract #15546. Roman L, Karlov P, Kaprin A, Gladkov Jr O, Breitz H. Phase 1 study of picoplatin and docetaxel with prednisone in patients with chemotherapy-na?ve metastatic hormone refractory prostate cancer.
"Our new data indicate that picoplatin can be safely combined with established cancer therapeutics. In 66 patients treated up to 10 months, we have observed reversible myelosuppression that is non-cumulative and has not led to any treatment-related mortality," said Jerry McMahon, Ph.D., chairman and CEO of Poniard. "These Phase 1 studies have explored different doses of picoplatin and different dosing schedules either in combination with docetaxel for prostate cancer or with 5-fluorouracil and leucovorin for colorectal cancer. We anticipate that the Phase 2 trials for both indications will begin in the third quarter of 2007, shortly after the maximum tolerated doses have been defined."
He added, "In the Phase 1 colorectal cancer study, only three patients have experienced grade 1 neuropathy to date. There has been no neuropathy greater than grade 1 in all patients treated, including four patients who have received a cumulative picoplatin dose of greater than 900 mg/m2. The objective of our planned Phase 2 trial is to confirm the neuropathy-sparing properties of picoplatin given once every two weeks in a randomized trial compared to oxaliplatin and to enable a Phase 3 clinical trial to show superior safety and efficacy of FOLPI (picoplatin combined with fluorouracil and leucovorin) compared to FOLFOX (oxaliplatin combined with fluorouracil and leucovorin). The goal of our planned Phase 2 study in prostate cancer is to generate proof-of-concept data demonstrating that picoplatin has improved efficacy with docetaxel and to enable future picoplatin combination studies with taxanes for prostate and other cancer indications."
http://www.medilexicon.com/medicalnews.php?newsid=72878∞
Scientists Develop New Drugs To Fight Colon And Breast Cancer More Effectively
04 Jun 2007
The doctoral thesis 'Potencial terapeutico de nuevos farmacos antitumorales. Estudio sobre lineas celulares epiteliales' (Therapeutic Potential of New Antitumor Drugs. A Study on Epithelial Cell Lines) has allowed for the development of six new drugs to fight colon and breast cancer more effectively than other currently used drugs. The study was conducted at the Department of Human Anatomy and Embryology at the University of Granada (Universidad de Granada [http://www.ugr.es]∞) by Octavio Caba P?rez, member of the research group "Avances en Biomedicina" (Progress in Biomedicine), under the direction of professors Antonia Ar?nega, Juan Antonio Marchal and Fernando Rodr?guez.
The importance of this study, in which researchers from the Department of Pharmaceutical and Organic Chemistry have also collaborated, is that it enabled the identification of a total of six antitumor compounds similar to 5-fluorouracil (5-FU), one of the most widely-used drugs nowadays to fight colon and breast cancer. These compounds are more effective against malignant cells (those which are cancerous) and less toxic against benign cells (those which are unnecessarily destroyed or harmed with treatments such as chemotherapy).
As Caba P?rez points out, the current method used to fight tumors "produces several 'collateral damages'. A drug can be very effective against breast cancer, but it can also affect the rest of the benign epithelial tissue. As everybody knows, current treatments for cancer destroy a large number of unaffected cells in addition to affected cells," says Caba P?rez.
In this study researchers analyzed more than 150 drugs aimed at reducing the toxicity of the 5-FU against the benign cells, thus avoiding the reproduction of new carcinomas or other side effects. "We discarded compounds until we finally found six which have shown to be better than currently used drugs," says Caba P?rez.
Research on cell lines
So far, the study has been conducted on cell lines, and not on patients, using a new technique called "Microarrays" or "DNA Chips", which enables the identification of the effects produced by drugs on each gene the lowest and most specific level that Medicine can deal with.
"Our research," says Caba P?rez, "has been conducted with absolute precision with the aim of obtaining the lowest possible concentration of drug producing the most significant effect on cancerous cells". Therefore, this study has shown the importance of the presence of some toxic compounds like chlorine, flourine or uracil in drugs. This presence is one of the variables used to develop new antitumor drugs.
Part of the results of this study (which has been possible thanks to cooperation between the UGR [http://www.ugr.es∞] and the company VILPOMAS) have been published in the January 1 issue of the international journal "Tetrahedron". The remainder of the results will be published in various international journals on Biomedicine.
UNIVERSITY OF GRANADA - COMMUNICATIONS DEPARTMENT
Secretariado de Comunicaci?n - Universidad de Granada
Hospital Real - Cuesta del Hospicio s/n
http://www.ugr.es∞
http://www.medilexicon.com/medicalnews.php?newsid=72984∞

Categories

CategoryCancer

Edited on 2007-06-16 10:44:21 by KathyFromEngland

Additions:
~*Poniard Pharmaceuticals Announces Promising Data From Interim Safety Analysis Of Phase 1 Trials Of Picoplatin In Colorectal And Prostate Cancers

*Scientists Develop New Drugs To Fight Colon And Breast Cancer More Effectively

Scientists Develop New Drugs To Fight Colon And Breast Cancer More Effectively
04 Jun 2007
The doctoral thesis 'Potencial terapeutico de nuevos farmacos antitumorales. Estudio sobre lineas celulares epiteliales' (Therapeutic Potential of New Antitumor Drugs. A Study on Epithelial Cell Lines) has allowed for the development of six new drugs to fight colon and breast cancer more effectively than other currently used drugs. The study was conducted at the Department of Human Anatomy and Embryology at the University of Granada (Universidad de Granada [http://www.ugr.es]∞) by Octavio Caba P?rez, member of the research group "Avances en Biomedicina" (Progress in Biomedicine), under the direction of professors Antonia Ar?nega, Juan Antonio Marchal and Fernando Rodr?guez.
The importance of this study, in which researchers from the Department of Pharmaceutical and Organic Chemistry have also collaborated, is that it enabled the identification of a total of six antitumor compounds similar to 5-fluorouracil (5-FU), one of the most widely-used drugs nowadays to fight colon and breast cancer. These compounds are more effective against malignant cells (those which are cancerous) and less toxic against benign cells (those which are unnecessarily destroyed or harmed with treatments such as chemotherapy).
As Caba P?rez points out, the current method used to fight tumors "produces several 'collateral damages'. A drug can be very effective against breast cancer, but it can also affect the rest of the benign epithelial tissue. As everybody knows, current treatments for cancer destroy a large number of unaffected cells in addition to affected cells," says Caba P?rez.
In this study researchers analyzed more than 150 drugs aimed at reducing the toxicity of the 5-FU against the benign cells, thus avoiding the reproduction of new carcinomas or other side effects. "We discarded compounds until we finally found six which have shown to be better than currently used drugs," says Caba P?rez.
Research on cell lines
So far, the study has been conducted on cell lines, and not on patients, using a new technique called "Microarrays" or "DNA Chips", which enables the identification of the effects produced by drugs on each gene the lowest and most specific level that Medicine can deal with.
"Our research," says Caba P?rez, "has been conducted with absolute precision with the aim of obtaining the lowest possible concentration of drug producing the most significant effect on cancerous cells". Therefore, this study has shown the importance of the presence of some toxic compounds like chlorine, flourine or uracil in drugs. This presence is one of the variables used to develop new antitumor drugs.
Part of the results of this study (which has been possible thanks to cooperation between the UGR [http://www.ugr.es∞] and the company VILPOMAS) have been published in the January 1 issue of the international journal "Tetrahedron". The remainder of the results will be published in various international journals on Biomedicine.
UNIVERSITY OF GRANADA - COMMUNICATIONS DEPARTMENT
Secretariado de Comunicaci?n - Universidad de Granada
Hospital Real - Cuesta del Hospicio s/n
http://www.ugr.es∞
http://www.medilexicon.com/medicalnews.php?newsid=72984∞

Deletions:
~*Poniard Pharmaceuticals Announces Promising Data From Interim Safety Analysis Of Phase 1 Trials Of Picoplatin In Colorectal And Prostate Cancers

Edited on 2007-06-16 10:39:57 by KathyFromEngland

Additions:
~*Suicide Gene Therapy Kills Bowel Cancer Cells

*Poniard Pharmaceuticals Announces Promising Data From Interim Safety Analysis Of Phase 1 Trials Of Picoplatin In Colorectal And Prostate Cancers

Poniard Pharmaceuticals Announces Promising Data From Interim Safety Analysis Of Phase 1 Trials Of Picoplatin In Colorectal And Prostate Cancers
02 Jun 2007
Poniard Pharmaceuticals, Inc. (Nasdaq: PARD), a biopharmaceutical company focused on oncology, today announced promising results from an interim safety analysis of two Phase 1 dose-escalating trials of picoplatin, a new generation platinum for the potential first-line treatment of metastatic colorectal cancer (CRC) and metastatic hormone-refractory prostate cancer (HRPC). Initial safety data from the Phase 1 trial in CRC demonstrated that picoplatin can be safely administered with fluorouracil and leucovorin, and initial safety data from the Phase 1 trial in HRPC demonstrated that picoplatin can be safely combined with the dose of docetaxel (Taxotere(R)) used in current practice for HRPC.
The data were included in abstracts published in the 2007 American Society of Clinical Oncology (ASCO) Annual Meeting Proceedings.
-- Abstract #14510. Gladkov Jr O, Manikhas G, Biakhov M, Tjulandin S, Karlin D. Phase 1 study of picoplatin in combination with 5- fluorouracil and leucovorin as initial therapy in subjects with metastatic colorectal cancer.
-- Abstract #15546. Roman L, Karlov P, Kaprin A, Gladkov Jr O, Breitz H. Phase 1 study of picoplatin and docetaxel with prednisone in patients with chemotherapy-na?ve metastatic hormone refractory prostate cancer.
"Our new data indicate that picoplatin can be safely combined with established cancer therapeutics. In 66 patients treated up to 10 months, we have observed reversible myelosuppression that is non-cumulative and has not led to any treatment-related mortality," said Jerry McMahon, Ph.D., chairman and CEO of Poniard. "These Phase 1 studies have explored different doses of picoplatin and different dosing schedules either in combination with docetaxel for prostate cancer or with 5-fluorouracil and leucovorin for colorectal cancer. We anticipate that the Phase 2 trials for both indications will begin in the third quarter of 2007, shortly after the maximum tolerated doses have been defined."
He added, "In the Phase 1 colorectal cancer study, only three patients have experienced grade 1 neuropathy to date. There has been no neuropathy greater than grade 1 in all patients treated, including four patients who have received a cumulative picoplatin dose of greater than 900 mg/m2. The objective of our planned Phase 2 trial is to confirm the neuropathy-sparing properties of picoplatin given once every two weeks in a randomized trial compared to oxaliplatin and to enable a Phase 3 clinical trial to show superior safety and efficacy of FOLPI (picoplatin combined with fluorouracil and leucovorin) compared to FOLFOX (oxaliplatin combined with fluorouracil and leucovorin). The goal of our planned Phase 2 study in prostate cancer is to generate proof-of-concept data demonstrating that picoplatin has improved efficacy with docetaxel and to enable future picoplatin combination studies with taxanes for prostate and other cancer indications."
http://www.medilexicon.com/medicalnews.php?newsid=72878∞

Deletions:
~*Suicide Gene Therapy Kills Bowel Cancer Cells

Edited on 2007-06-16 10:31:24 by KathyFromEngland

Additions:
~*Nuvelo Receives FDA Fast Track Status For rNAPc2 In Both First- And Second-Line Treatment Of Metastatic Colorectal Cancer

*Suicide Gene Therapy Kills Bowel Cancer Cells

Suicide Gene Therapy Kills Bowel Cancer Cells
25 May 2007
An innovative type of gene therapy has for the first time succeeded in making bowel cancer cells commit suicide, according to a report in Cancer Research* this week.
The therapy, developed by Cancer Research UK-funded scientists at The Institute of Cancer Research, combines cutting-edge techniques to target tumour cells. Known as GDEPT (Gene-Directed Enzyme Prodrug Therapy), the treatment uses a virus to attack cancer cells.
But the researchers have added an extra gene to the virus. The virus is programmed to switch on the gene only if it reaches a tumour. When the gene is switched on, the virus produces a protein that activates an otherwise harmless 'prodrug', given separately.
Because this drug is only activated in tumours, it selectively kills only cancer cells. In normal tissue, the drug remains inactive, so healthy cells are not affected.
This is the first time such a therapy has proved successful at killing bowel cancer cells, albeit only in the laboratory. Cancer Research UK and The Institute of Cancer Research are supporting the development of the therapy, and hope to take it into early clinical trials in the future.
Lead researcher, Professor Caroline Springer of The Institute's Cancer Research UK Centre for Cancer Therapeutics, said: "We have developed a smart method to selectively target cancer cells. Normal cells are spared because the virus doesn't produce the protein that activates the drug unless it is inside a tumour.
"The beauty of our approach is that the cancer cells are made to commit suicide both by the virus and the activated drug �" the two work in tandem. And once activated, the drug has the added bonus of causing the virus to produce more of the activating protein, which activates more of the drug, and so on. It's the first time we've seen a 'positive feedback loop' like this in a GDEPT therapy."
The drug damages DNA inside the cancer cells to the point where the cells stop functioning. They have no choice but to shut down and die.
Another benefit of the therapy is that it doesn't just kill only the cancer cells infected by the virus.
"We also see a significant 'bystander effect'," added Prof Springer. "This means the cells killed by the virus or the drug release signals into the tumour that tell neighbouring cancer cells to die too."
In lab experiments, mice with bowel tumours that received the therapy lived twice as long as those that did not. The researchers suggest their technique could one day be used as a treatment for advanced bowel cancer that doesn't respond to standard chemotherapy.
Professor John Toy, medical director of Cancer Research UK, said: "GDEPT therapy has been in development for several years. But this study shows the technique - always a smart therapy - is becoming ever more sophisticated. For the first time it has been shown to be effective at killing bowel cancer cells in a laboratory model of human colon cancer. This is another stride towards the possible use of GDEPT for cancer patients."
* Cancer Research, Vol 67 Issue 10
GDEPT: an oncolytic adenovirus is injected into the bloodstream. The virus's DNA contains an added gene for CPG2 (Carboxypeptidase G2) but the gene is controlled so that it is only translated in the presence of telomerase, an enzyme found in many cancers but much less so in normal tissue. When the virus reaches a tumour that is producing telomerase, the gene is translated and the virus produces the protein CPG2.
Meanwhile a "prodrug" is injected. A prodrug is an inactive form of a drug. In this case the prodrug, called ZD2767P, is activated by CPG2 - hence it is only activated in regions of the body where the virus is producing CPG2, i.e. in tumours.
http://www.medilexicon.com/medicalnews.php?newsid=72020∞

Deletions:
~*Nuvelo Receives FDA Fast Track Status For rNAPc2 In Both First- And Second-Line Treatment Of Metastatic Colorectal Cancer

Edited on 2007-05-04 11:06:57 by KathyFromEngland

Additions:
~*Tequila Raw Ingredient Being Developed Into Drug-carrier That Targets Colon Diseases
Tequila Raw Ingredient Being Developed Into Drug-carrier That Targets Colon Diseases
31 Mar 2007
Compounds derived from the blue agave, a fruit used to make tequila, shows promise in early laboratory studies as a natural, more effective way to deliver drugs to the colon than conventional drug-carriers, according to chemists at the University of Guadalajara in Mexico. The development could lead to improved treatments for ulcerative colitis, irritable bowel syndrome, cancer, Crohn's disease and other colon diseases, they say.
Drug delivery to the colon is an ongoing challenge to physicians. Many drugs are destroyed by stomach acids before they've had a chance to reach the intestine, where they usually are absorbed. Researchers have tried to circumvent this problem by inserting the drugs into carrier molecules that resist breakdown in the stomach but have had difficulty finding a suitable carrier compound.
"This study shows that the agave fruit is good for more than just tequila. It also has medicinal value," says study leader Guillermo Toriz, Ph.D., an assistant professor at the university. "Agave fructan is the ideal natural carrier of drugs for the colon."
Topiz and his research group currently are working on improving the durability of the fructans and plan animal studies in the future. If further studies show promise, human studies of the agave microspheres are anticipated. Funding for the study was provided by the Mexican National Science and Technology Council.
http://www.medilexicon.com/medicalnews.php?newsid=66392∞

Edited on 2007-05-04 09:49:58 by KathyFromEngland

Additions:
~*Tequila raw ingredient being developed into drug-carrier that targets colon diseases
Tequila raw ingredient being developed into drug-carrier that targets colon diseases
CHICAGO, March 27
Compounds derived from the blue agave, a fruit used to make tequila, shows promise in early laboratory studies as a natural, more effective way to deliver drugs to the colon than conventional drug-carriers, according to chemists at the University of Guadalajara in Mexico. The development could lead to improved treatments for ulcerative colitis, irritable bowel syndrome, cancer, Crohn?s disease and other colon diseases, they say.
Drug delivery to the colon is an ongoing challenge to physicians. Many drugs are destroyed by stomach acids before they?ve had a chance to reach the intestine, where they usually are absorbed. Researchers have tried to circumvent this problem by inserting the drugs into carrier molecules that resist breakdown in the stomach but have had difficulty finding a suitable carrier compound.
The tequila compounds, a class of polysaccharides known as fructans, were developed by the scientists in Mexico into tiny microspheres that are capable of carrying existing drugs that are used to treat colon diseases. Because the compounds resist destruction in the stomach, they could allow more of the drugs to reach the colon intact and improve their effectiveness, the researchers say. Their study was presented today at the 233rd national meeting of the American Chemical Society.
?This study shows that the agave fruit is good for more than just tequila. It also has medicinal value,? says study leader Guillermo Toriz, Ph.D., an assistant professor at the university. ?Agave fructan is the ideal natural carrier of drugs for the colon.?
Researchers have known for some time that fructans, which are polymers of fructose, are resistant to acid degradation and theorized that they might be a useful drug delivery vehicle. But only a few plant sources, such as agave, contain fructans in large amounts. The agave fruit is 80 percent fructans by weight when ripe, the researchers say.
Toriz and his associates extracted fructans from the blue agave, the base ingredient of tequila. They chemically modified the fructan compound to allow drugs to be encapsulated, making the drugs resistant to degradation in the digestive system.
The researchers then prepared microspheres of the compounds and filled them with ibuprofen as a model of drug delivery to the colon. In laboratory tests, the ibuprofen-filled microspheres were exposed to hydrochloric acid for an hour and appeared physically intact upon subsequent microscopic examination, the scientists say.
Topiz and his research group currently are working on improving the durability of the fructans and plan animal studies in the future. If further studies show promise, human studies of the agave microspheres are anticipated. Funding for the study was provided by the Mexican National Science and Technology Council.
http://www.eurekalert.org/pub_releases/2007-03/acs-tri031207.php∞

Edited on 2007-04-23 11:26:11 by KathyFromEngland [Page restored by Kathy]

Additions:
~*Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) + Oxaliplatin) And For Avastin
Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) + Oxaliplatin) And For Avastin
Evidence for this theory has been mounting for the past year. On January 10, 2007, Dr. Sheila Fraser of St. James's University Hospital in Leeds, U.K. delivered a paper at the Society of Academic & Research Surgery Conference in Cambridge, U.K., in which she described a test tube experiment further supporting this claim. Fraser's presentation, titled "Reovirus as a Potentially Immunogenic as well as Cytotoxic Therapy for Metastatic Colorectal Cancer," reported how cells taken from a colorectal cancer liver metastases were more susceptible to death many weeks after treatment with reovirus, and long after the virus had cleared the patient's system. These cells, when cultured in the laboratory, also appeared to be vulnerable to re-infection with reovirus. Moreover, Dr. Fraser noted that dendritic cells, which prime the immune system against cancer, were activated by exposure to the reovirus.
"We understand how the reovirus replicates within and kills cancer cells," explains Dr. Matt Coffey, Chief Scientific Officer at Oncolytics, "but we also observed that tumors sometimes continue to shrink long after the virus is gone." Immunologic work now suggests that reovirus exposure is "educating" the immune system to recognize and kill the same cancer cells that were attacked by reovirus. "If you can teach the immune system to recognize cancer cells," says Coffey, "it may be possible to fight off the disease for much longer than we originally anticipated."
Late in 2006, another collaborator, Dr. Alan Melcher of the Cancer Research UK Clinical Centre in Leeds, hypothesized that reovirus activation of dendritic cells, which are key to early detection of infection (through the innate immune response), may "instruct" cells belonging to the adaptive immune response, namely natural killer cells and T cells, to attack the tumor even after the virus no longer remains in the body. That poster was presented at the European National Societies of Immunology Meeting in Paris.
Interestingly, another study conducted in 2006 at the Mayo Clinic suggested that momentarily suppressing the immune system allows the virus to continue replicating, leading to increased cancer cell killing. This in turn leads to the creation of more tumor antigens (the elements that educate the immune system), thereby increasing the vaccinating effect of the virus and perhaps improving the efficacy of oncolytic virus therapy.
"The apparent dual mechanism of action for oncolytic viruses will need to be tested further, both in patients and in the laboratory. If the effects turn out to be genuine, the implications for long-term survival from many types of cancer could be significant," says Coffey. Researchers believe that therapies working simultaneously, but through different mechanisms, may overcome the resistance to treatment that is typically seen in cancer. In addition, this double attack on cancer could point to new treatment regimens based on conventional therapies like radiation and chemotherapy with biological agents.
http://www.medilexicon.com/medicalnews.php?newsid=62587∞
Nuvelo Receives FDA Fast Track Status For rNAPc2 In Both First- And Second-Line Treatment Of Metastatic Colorectal Cancer
29 Mar 2007
Nuvelo, Inc. (Nasdaq: NUVO) today announced that it has been granted two separate fast track designations by the U.S. Food and Drug Administration (FDA) for its product candidate, rNAPc2. The first fast track designation is for first-line treatment of metastatic colorectal cancer (mCRC) to improve progression-free survival and overall survival when added to Avastin(R)-containing 5- flurourocil (5-FU)-based chemotherapy regimens. The other is for second-line treatment of mCRC to improve progression-free survival and overall survival when added to 5-FU-based chemotherapy regimens. Fast track designation, which was mandated by the FDA Modernization Act of 1997, can potentially facilitate development and expedited review of Biologics License Applications (BLA). Fast track designation is reserved for new drugs that demonstrate the potential to address an unmet medical need and are intended for the treatment of a serious or life-threatening condition.
rNAPc2 is currently being studied in a Phase 2 clinical trial in subjects with mCRC, which accounted for approximately 55,000 colorectal cancer deaths in 2006. The primary objectives of this trial are to determine the safety and efficacy of twice-weekly, subcutaneous rNAPc2 for the second-line treatment of mCRC in combination with select 5-FU-based chemotherapy regimens.
"Given the magnitude of mCRC related deaths, there is a need for additional safe and effective treatments that prevent metastasis and prolong survival," said Michael Levy, M.D., executive vice president of research and development for Nuvelo. "We are pleased that the FDA has granted us fast track designation and are committed to developing rNAPc2 to further understand its potential to help this underserved patient population."
http://www.medilexicon.com/medicalnews.php?newsid=66347∞

Categories

Edited on 2007-04-19 22:24:32 by Ph3N1m

Additions:
~*Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) Oxaliplatin) And For Avastin
Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) Oxaliplatin) And For Avastin
Evidence for this theory has been mounting for the past year. On January 10, 2007, Dr. Sheila Fraser of St. James's University Hospital in Leeds, U.K. delivered a paper at the Society of Academic

Deletions:
~*Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) + Oxaliplatin) And For Avastin
Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) + Oxaliplatin) And For Avastin
Evidence for this theory has been mounting for the past year. On January 10, 2007, Dr. Sheila Fraser of St. James's University Hospital in Leeds, U.K. delivered a paper at the Society of Academic & Research Surgery Conference in Cambridge, U.K., in which she described a test tube experiment further supporting this claim. Fraser's presentation, titled "Reovirus as a Potentially Immunogenic as well as Cytotoxic Therapy for Metastatic Colorectal Cancer," reported how cells taken from a colorectal cancer liver metastases were more susceptible to death many weeks after treatment with reovirus, and long after the virus had cleared the patient's system. These cells, when cultured in the laboratory, also appeared to be vulnerable to re-infection with reovirus. Moreover, Dr. Fraser noted that dendritic cells, which prime the immune system against cancer, were activated by exposure to the reovirus.
"We understand how the reovirus replicates within and kills cancer cells," explains Dr. Matt Coffey, Chief Scientific Officer at Oncolytics, "but we also observed that tumors sometimes continue to shrink long after the virus is gone." Immunologic work now suggests that reovirus exposure is "educating" the immune system to recognize and kill the same cancer cells that were attacked by reovirus. "If you can teach the immune system to recognize cancer cells," says Coffey, "it may be possible to fight off the disease for much longer than we originally anticipated."
Late in 2006, another collaborator, Dr. Alan Melcher of the Cancer Research UK Clinical Centre in Leeds, hypothesized that reovirus activation of dendritic cells, which are key to early detection of infection (through the innate immune response), may "instruct" cells belonging to the adaptive immune response, namely natural killer cells and T cells, to attack the tumor even after the virus no longer remains in the body. That poster was presented at the European National Societies of Immunology Meeting in Paris.
Interestingly, another study conducted in 2006 at the Mayo Clinic suggested that momentarily suppressing the immune system allows the virus to continue replicating, leading to increased cancer cell killing. This in turn leads to the creation of more tumor antigens (the elements that educate the immune system), thereby increasing the vaccinating effect of the virus and perhaps improving the efficacy of oncolytic virus therapy.
"The apparent dual mechanism of action for oncolytic viruses will need to be tested further, both in patients and in the laboratory. If the effects turn out to be genuine, the implications for long-term survival from many types of cancer could be significant," says Coffey. Researchers believe that therapies working simultaneously, but through different mechanisms, may overcome the resistance to treatment that is typically seen in cancer. In addition, this double attack on cancer could point to new treatment regimens based on conventional therapies like radiation and chemotherapy with biological agents.
http://www.medilexicon.com/medicalnews.php?newsid=62587∞
Nuvelo Receives FDA Fast Track Status For rNAPc2 In Both First- And Second-Line Treatment Of Metastatic Colorectal Cancer
29 Mar 2007
Nuvelo, Inc. (Nasdaq: NUVO) today announced that it has been granted two separate fast track designations by the U.S. Food and Drug Administration (FDA) for its product candidate, rNAPc2. The first fast track designation is for first-line treatment of metastatic colorectal cancer (mCRC) to improve progression-free survival and overall survival when added to Avastin(R)-containing 5- flurourocil (5-FU)-based chemotherapy regimens. The other is for second-line treatment of mCRC to improve progression-free survival and overall survival when added to 5-FU-based chemotherapy regimens. Fast track designation, which was mandated by the FDA Modernization Act of 1997, can potentially facilitate development and expedited review of Biologics License Applications (BLA). Fast track designation is reserved for new drugs that demonstrate the potential to address an unmet medical need and are intended for the treatment of a serious or life-threatening condition.
rNAPc2 is currently being studied in a Phase 2 clinical trial in subjects with mCRC, which accounted for approximately 55,000 colorectal cancer deaths in 2006. The primary objectives of this trial are to determine the safety and efficacy of twice-weekly, subcutaneous rNAPc2 for the second-line treatment of mCRC in combination with select 5-FU-based chemotherapy regimens.
"Given the magnitude of mCRC related deaths, there is a need for additional safe and effective treatments that prevent metastasis and prolong survival," said Michael Levy, M.D., executive vice president of research and development for Nuvelo. "We are pleased that the FDA has granted us fast track designation and are committed to developing rNAPc2 to further understand its potential to help this underserved patient population."
http://www.medilexicon.com/medicalnews.php?newsid=66347∞

Categories

CategoryCancer

Edited on 2007-03-29 07:34:49 by KathyFromEngland

Additions:
~*The Multi-Tasking Reovirus Kills Cancer Cells And Primes The Immune System

*Nuvelo Receives FDA Fast Track Status For rNAPc2 In Both First- And Second-Line Treatment Of Metastatic Colorectal Cancer

Nuvelo Receives FDA Fast Track Status For rNAPc2 In Both First- And Second-Line Treatment Of Metastatic Colorectal Cancer
29 Mar 2007
Nuvelo, Inc. (Nasdaq: NUVO) today announced that it has been granted two separate fast track designations by the U.S. Food and Drug Administration (FDA) for its product candidate, rNAPc2. The first fast track designation is for first-line treatment of metastatic colorectal cancer (mCRC) to improve progression-free survival and overall survival when added to Avastin(R)-containing 5- flurourocil (5-FU)-based chemotherapy regimens. The other is for second-line treatment of mCRC to improve progression-free survival and overall survival when added to 5-FU-based chemotherapy regimens. Fast track designation, which was mandated by the FDA Modernization Act of 1997, can potentially facilitate development and expedited review of Biologics License Applications (BLA). Fast track designation is reserved for new drugs that demonstrate the potential to address an unmet medical need and are intended for the treatment of a serious or life-threatening condition.
rNAPc2 is currently being studied in a Phase 2 clinical trial in subjects with mCRC, which accounted for approximately 55,000 colorectal cancer deaths in 2006. The primary objectives of this trial are to determine the safety and efficacy of twice-weekly, subcutaneous rNAPc2 for the second-line treatment of mCRC in combination with select 5-FU-based chemotherapy regimens.
"Given the magnitude of mCRC related deaths, there is a need for additional safe and effective treatments that prevent metastasis and prolong survival," said Michael Levy, M.D., executive vice president of research and development for Nuvelo. "We are pleased that the FDA has granted us fast track designation and are committed to developing rNAPc2 to further understand its potential to help this underserved patient population."
http://www.medilexicon.com/medicalnews.php?newsid=66347∞

Deletions:
~*The Multi-Tasking Reovirus Kills Cancer Cells And Primes The Immune System

Edited on 2007-02-11 08:45:14 by KathyFromEngland

Additions:
~*MClone Systems Incorporated And Bristol-Myers Squibb Announce Application In Japan For Use Of ERBITUX In Metastatic Colorectal Cancer

*The Multi-Tasking Reovirus Kills Cancer Cells And Primes The Immune System

Deletions:
~*MClone Systems Incorporated And Bristol-Myers Squibb Announce Application In Japan For Use Of ERBITUX In Metastatic Colorectal Cancer

Oldest known version of this page was edited on 2007-02-11 08:44:51 by KathyFromEngland []

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Articles about new Colorectal Cancer drugs, treatment methods, research etc.

Contents

*RNA Interference Stops Colon Cancer Spread In Mice
*Alcohol Consumption Habits May Threaten GI Health
*EntreMed Initiates Combination Phase 2 Clinical Trial With Panzem(R) NCD In Carcinoid Cancer
*Celecoxib May Help Prevent Colorectal Cancer In High Risk Patients, Studies Confirm
*Celebrex May Have Colon Cancer Protecting Qualities
*Blood Pressure Drugs Associated With Reduced Risk Of Esophageal, Pancreatic And Colon Cancers
*Callisto Announces Plan To Initiate A Single Agent Phase II Clinical Trial Of Atiprimod In Advanced Carcinoid Cancer Patients
*Metastatic Colorectal Cancer In Patients Who Have Failed Prior Chemotherapy - License Application For FDA Approval Of Panitumumab
*Targeted Therapies Showing Great Promise Against Colorectal Cancer
*Stool Testing Novel Technique For Detecting Colon Cancer
*3-D Imaging That Flies "through" And "around" Lung And Colon Cancer: Coming Soon
*Aspirin And Other NSAIDs May Not Reduce The Risk Of Colorectal Cancer In Long-term Smokers
*Large International Phase III Trial In Metastatic Colorectal Cancer Meets Primary Endpoints For XELOX (Xeloda(R) + Oxaliplatin) And For Avastin
*Soy And Fish Have Cancer Preventing Qualities
*Statin Use Not Associated With Colorectal Cancer Risk
*AstraZeneca Announces Recentin(R) As Global Trademark For Novel Cancer Treatment, AZD2171
*MClone Systems Incorporated And Bristol-Myers Squibb Announce Application In Japan For Use Of ERBITUX In Metastatic Colorectal Cancer

RNA Interference Stops Colon Cancer Spread In Mice

24 May 2006

Using one of the newest and most powerful tools of biomedical science, University of Texas Medical Branch at Galveston (UTMB) researchers have scored a dramatic success in the battle against colorectal cancer.

The scientists were the first to use what are known as "small interfering RNAs" to block the spread of human colorectal cancer cells implanted in laboratory mice. Small interfering RNAs (siRNAs), first described in 2001, are tiny bits of genetic material that can prevent the translation of genes into proteins -- including specific proteins involved in biochemical reactions that promote cancer and other diseases.

According to the federal Centers for Disease Control and Prevention, colorectal cancer is the country's second leading cancer killer. In 2002,
04 Apr 2006the most recent year for which statistics are available, 70,651 men and 68,883 women were diagnosed with the colorectal cancer in the United States; 28,471 men and 28,132 women died from the disease.

"What's exciting about this is that by using siRNAs we were able to selectively block components of the PI3K pathway, a biochemical pathway that is activated in a number of cancers, and suppress the spread of colon cancer in experimental animals," said UTMB professor of surgery B. Mark Evers, senior author of a paper on the research published in the June issue of Annals of Surgery. "Over the last couple of years people have talked a lot about cell-culture studies of siRNAs, but only a handful of labs have pushed it to animal models, which we need to do before going on to clinical trials."

To study the effects of siRNAs targeted against the PI3K pathway in mice, the researchers used a well-established technique in which human colorectal cancer cells were implanted into the spleens of genetically engineered immune-deficient "nude" mice. They then injected siRNAs designed to prevent the production of two specific PI3K proteins into the mice. The result was a major reduction in the spread of colorectal cancer to the liver.

Evers and the paper's other authors -- UTMB research fellows Piotr Rychahou and Lindsey Jackson and pathology professor Srinivasan Rajaraman -- also conducted a detailed analysis of the PI3K pathway's components and did experiments to determine how their siRNAs would affect colorectal cancer cell cultures. Scientists have already developed chemical inhibitors to attack the pathway (some of which are now in clinical trials), but toxic side effects limit their use.

"When we treat with siRNA and then follow the treatment with standard chemotherapeutic agents, we can markedly increase the rate at which cancer cells are killed," Evers said. "Since we have not seen any toxicity with these siRNAs in our mice, we think we can potentially also use them as a way to sensitize tumors and launch a combined attack that will allow us to achieve much better results with reduced side effects."

Jim Kelly
jpkelly@utmb.edu∞
University of Texas Medical Branch at Galveston
http://www.utmb.edu/∞
http://www.medilexicon.com/medicalnews.php?newsid=43954∞

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Articles about new Colorectal Cancer drugs, treatment methods, research etc.