GastroIntestinal / Gastroenterology News

The somatostatin analog octreotide LAR (SandostatinR LARR) can retard tumor progression in patients with metastatic neuroendocrine midgut tumors, according to interim results of a phase IIIb trial reported here at the American Society of Clinical Oncology’s 2009 Gastrointestinal Cancers Symposium.

The study, conducted at 18 cancer centers in Germany, found that octreotide LAR was associated with a 66 percent reduction in the risk of disease progression compared with placebo after six months of treatment (p=0.000072).

“Octreotide LAR should be considered the standard of care in patients with newly diagnosed, functionally active or inactive, well-differentiated metastatic midgut neuroendocrine tumors and a low hepatic tumor load,” Rudolf Arnold, MD, with Philipps University in Marburg , Germany, said.

Dr. Arnold was the principal investigator of the trial, known as PROMID (Placebo-Controlled Prospective Randomized Study on the Antiproliferative Efficacy of Octreotide LAR in Patients with Metastatic Neuroendocrine Midgut Tumors).

He noted at a news conference that the standard treatment option for patients with metastatic midgut neuroendocrine tumors, a rare gastrointestinal tumor, is surgery. Additional options include hepatic embolization in the event of liver metastases or radioligand therapy. However, both approaches are associated with significant side effects, he added.

The trial included 85 treatment-na??ve patients with histologically confirmed locally inoperable or metastasized well-differentiated neuroendocrine tumors and a Karnofsky index greater than 60.

About 70 percent of patients had surgery before enrolling in the trial to remove the primary tumor, while the remainder had more advanced, inoperable disease. Eighty six percent had liver metastases.

Participants were randomized to octreotide LAR 30 mg i.m. every four weeks or placebo i.m. every four weeks for 18 months or until CT- or MRI-documented tumor progression or death.

The primary endpoint was median time to tumor progression.

After six months of treatment, tumor progression was reduced in 69% of octreotide LAR-treated patients and 39% of placebo-treated patients, Dr. Arnold said.

The median time to tumor progression was 14.3 months in the octreotide LAR group and six months in the placebo group (HR=0.34, p=0.000072).

Importantly, octreotide LAR’s favorable effect was observed in patients with either functioning (hormone-secreting) or non-functioning (non-secreting) neuroendocrine tumors.

Patients who derived the most benefit were newly diagnosed patients who had a tumor load that was less than or equal to 10%, Dr. Arnold observed.

Because most patients enrolled in the trial are still alive, it is not yet possible to ascertain an overall survival benefit, he added.

The side effects related to octreotide LAR were in line with those reported in earlier studies of the drug in patients with neuroendroine tumors and included diarrhea, fatigue, fever, and bile stones. Five patients dropped out of the trial because of side effects.

“Overall, our results support the use of octreotide LAR for patients after cytoreductive surgery who have few remaining metastases,” Dr. Arnold said.

The PROMID trial is the first placebo-controlled study to test octreotide LAR for the treatment of malignant neuroendocrine tumors.

Octreotide has been used to treat the clinical syndromes associated with neuroendocrine tumors. Octreotide also substantially reduces and in many cases normalizes growth hormone and/or insulin-like growth (IGF) factor-1 levels in patients with acromegaly.

(Octreotide belongs to Novartis)

Jill Stein
Jill Stein is a Paris-based freelance medical writer.
jillstein03(at)gmail

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Attending general surgeons at Beth Israel Deaconess Medical Center (BIDMC) will be required to prove basic motor skills outside an operating room before performing laparoscopic surgery on patients.

CRICO/RMF, the Harvard medical community’s professional liability insurer, will offer “Fundamentals in Laparoscopic Surgery” (FLS) as a refresher course in January 2008. As an incentive for this voluntary program, CRICO/RMF is providing a one-time patient safety incentive to attending general surgeons who demonstrate successful completion of the FLS exam.

“We enthusiastically endorse the efforts of the general surgeons in their quest to improve and maintain their skills in laparoscopic surgery,” said Robert Hanscom, Vice President of Loss Prevention and Patient Safety. “We are grateful for the opportunity to fund this important effort for surgeons.”

In an unprecedented requirement, all BIDMC general surgeons will need FLS certification to obtain privileges in laparoscopy. This requirement for certification for privileging at BIDMC is the first time surgeons in the United States will be required to demonstrate motor skills, according to Daniel B. Jones, MD, FACS, BIDMC’s Chief of Minimally Invasive Surgery.

Laparoscopy or ‘Band-aid surgery” distends the abdomen with carbon dioxide gas. Ports the diameter of a pencil have an air seal that permits long instruments to be inserted into the abdomen without losing air. The technique of several small cuts allows patients to experience less pain, shorter hospitalization and faster recovery.

Most surgeons who trained before 1990 had no formal training. Passing the FLS exam (flsprogram) raises the bar by allowing the surgeon to show they have the skill to safely perform basic laparoscopic surgery.

“If we can ask bus drivers to pass an eye test, shouldn’t you be able to ask your surgeon to pass a skills test?” said Jones. “This requirement simply puts all surgeons on the same footing as their colleagues in terms of their skills on such basic techniques as tying knots.”

Surgeons will be tested, using a trainer box, on their proficiency to suture, cut in a circle and move objects from one location to another. In addition, an online written exam ensures cognitive knowledge of laparoscopy. The Carl J Shapiro Simulation and Skills Center (bidmc.harvard.edu/sasc) serves as the regional FLS testing site for New England.

All surgeons who complete the course successfully will receive continuing medical education credits through the Society of American Gastrointestinal and Endoscopic Surgeons and the American College of Surgeons. The FLS Patient Safety Incentive Program has been made available to all attending general surgeons insured by CRICO. Details can be viewed at rmf.harvard.edu/fls.

“I know that the program provides participants with the basic skills they should have as laparoscopic surgeons,” said Jones. “When I did it myself, I found the course serves as a refresher on rare complications and events that I may not have seen but could see in the future.” Jones predicts that FLS will become a new minimal standard for all surgeons offering basic laparoscopy to patients.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School, and consistently ranks among the top four in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox.

For more information, visit bidmc.harvard.edu.

CRICO/RMF is the patient safety and medical malpractice company owned by and serving the Harvard medical community since 1976.

For more information, visit Harvard Medical School, or
Fundamentals of Laparoscopic Surgery (FLS). Continue reading →

“The recent signing of a license agreement between the CSIRO/Australian Capital Ventures Limited joint venture and Austgrains Pty Ltd has paved the way for large scale commercial crops of BARLEYmax® – unique grain developed by CSIRO using conventional plant breeding techniques,” says the Director of the CSIRO Food Futures Flagship, Dr Bruce Lee.

“It contains more than twice the amount of insoluble and soluble fibre found in wheat or oats, as well as resistant starch, which helps promote healthy digestive bacteria,” Dr Lee says.

Austgrains’ Managing Director, Warren Hannam, says the unique nutritional characteristics of BARLEYmax are a valuable addition to the range of healthy food ingredients available in Australia.

“Austgrains specialises in supplying grain and functional food ingredients to the food manufacturing industry, making BARLEYmax a perfect fit for our company,” he says.

Austgrains Pty Ltd is a private company associated with publicly listed Washington H Soul Pattinson and Company Limited and its group of companies, producing and marketing specialty ingredients such as the Nu Soya range of soy products and omega-3 oils.

BARLEYmax Business Manager, CSIRO’s Geoff Ball, says clinical testing by CSIRO Human Nutrition has shown that products made with BARLEYmax – such as breakfast cereals, muffins and breads – have a low Glycaemic Index and strong bowel health attributes.

“Further testing showed BARLEYmax has excellent processing properties and foods made with the new grain have a naturally sweet, slightly nutty taste,” Mr Ball says. “With large volumes to be produced soon by Austgrains, healthy foods made with BARLEYmax are likely to be on Australian breakfast tables in the near future.”

Source: Geoff Ball

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Response Genetics, Inc. (Nasdaq:RGDX), a company focused on the development and sale of molecular diagnostic tests for cancer, announced the availability of its ResponseDX: Gastric™ genetic test panel, a proprietary PCR-based diagnostic test. By analyzing the expression of genes that correlate with response to commonly used chemotherapy agents, physicians can better tailor treatment for their patients with gastric cancer and gastroesophageal (GE) junction cancer. Approximately 37,000 people diagnosed with cancer each year in the U.S. may benefit from ResponseDX: Gastric™ testing. This newest ResponseDX™ test is available nationwide through the company’s national sales force.

“ResponseDX™ tests offer physicians and their patients an objective way to chart a course of therapy during a very stressful time – the period between diagnosis and the start of treatment,” said Kathleen Danenberg, CEO and president of Response Genetics, Inc. “By personalizing care based on a tumor’s genetic makeup-as opposed to the “one-size-fits-all” approach that has been the standard until now-patients can receive the drug most likely to benefit their unique situation.”

ResponseDX: Gastric™ tests quantitatively analyze three genes: excision repair cross-complementing factor 1 (ERCC1), thymidylate synthase (TS) and human epidermal growth factor receptor 2 (HER2). ERCC1 gene expression is a molecular marker shown to correlate with sensitivity to platinum-based drugs such as cisplatin, carboplatin and oxaliplatin; TS gene expression is a biomarker for sensitivity to the drug 5- fluorouracil (5-FU), an inhibitor of DNA replication and a component of the combination 5-fluorouracil-folinic acid- oxaliplatin (FOLFOX); and HER2 is a marker for sensitivity to trastuzumab, which was recently shown to have activity in gastric cancer.1

Data from Response Genetics-sponsored studies and others show that in order for gastric cancer patients to derive the maximum benefit from FOLFOX therapy, expression of both ERCC1 and TS genes must be at specific levels. However, if either marker is below a specific threshold, other therapies are available as alternative options (e.g., FOLFIRI)2,3,4.

About ResponseDX™ Tests

Response Genetics has developed PCR-based genetic tests – ResponseDX tests- to help physicians make more informed therapeutic treatment decisions for patients with non-small cell lung cancer (NSCLC), gastric cancer and colorectal cancer. The proprietary ResponseDX™ panels include four key genes: excision repair cross-complementing factor 1 (ERCC1), thymidylate synthase (TS), human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor expression (EGFR). These test panels also include the analysis of EGFR gene mutations in NSCLC and K-ras (KRAS) gene mutations in colorectal cancer. Using ResponseDX™ testing, clinicians may make better treatment decisions by adopting a cost-effective panel approach.

Response Genetics’ KRAS mutation analysis provides some of the fastest turnaround times in the industry and accurate results on the smallest biopsies – which benefits patients because, in many cases, no tissue samples other than the pre-treatment diagnostic biopsy will be required for the biomarker analysis. All tests use technology developed by Response Genetics to isolate RNA from formalin-fixed, paraffin-embedded (FFPE) archived tissue for quantitative RT-PCR analysis of gene expression and analyzed in RGI’s CLIA-certified laboratory.

1. Van Cutsem E, et al. Efficacy results from the ToGA trial: a Phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC). Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract LBA4509.

2. Shirota Y., et al. ERCC1 and Thymidylate Synthase mRNA Levels Predict Survival for Colorectal Cancer Patients Receiving Combination Oxaliplatin and Fluorouracil Chemotherapy. J Clin Oncol. Dec 1 2001:4298-4304.
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According to the
American Society for Gastrointestinal Endoscopy (ASGE), colonoscopy remains
the most effective screening option for colorectal cancer. Colonoscopy is
widely accepted as the best method for colon cancer screening because it
allows the trained physician to thoroughly evaluate the entire colon.
Colonoscopy has a high detection rate for polyps, including small lesions,
and the ability to remove them immediately during the procedure, rather
than scheduling a second exam. Biopsies can also be taken of any abnormal
areas at the same time as the screening or diagnostic test.

“Although there have been recent studies showing improvements in other
colon cancer screening modalities, colonoscopy is the most effective
because it is both diagnostic and therapeutic. Not only does it allow us to
see the entire colon and identify polyps of all sizes, but it also allows
us to remove polyps during the same exam, before they turn into cancer,”
said Mark Pochapin, MD, spokesperson for the ASGE. “Many colorectal cancer
deaths can be prevented through proper detection. If you are over 50 or
have a family history of colorectal cancer, talk to your doctor about
getting screened today.”

Earlier this year, the American Cancer Society announced drops in
cancer deaths, which were attributed to earlier detection and improved
treatment. The biggest decrease occurred in colorectal cancer deaths.

A 2006 study by Yale researchers found that, as Medicare coverage for
colorectal cancer screening expanded, so did colonoscopies and with that,
early cancer detection rates. The key variable in survival statistics among
cancers, including colorectal, is early detection and prevention. These
findings support ASGE’s position that colonoscopy is the most effective
screening and prevention method.

Colorectal cancer is the third most commonly diagnosed cancer in men
and women and the second leading cause of cancer-related deaths in the
United States, killing nearly 56,000 people each year. Many of those deaths
could be prevented with earlier detection. The five-year relative survival
rate for people whose colorectal cancer is treated in an early stage is
greater than 90 percent. Unfortunately, only 39 percent of colorectal
cancers are found at that early stage. Once the cancer has spread to nearby
organs or lymph nodes, the five-year relative survival rate decreases
dramatically.

ASGE screening guidelines recommend that, beginning at age 50,
asymptomatic men and women at average risk for developing colorectal cancer
should have a colonoscopy every 10 years. People with risk factors, such as
a family history of colon cancer, should begin earlier. Patients are
advised to discuss their risk factors with their physician to determine
when to begin routine colorectal cancer screening and how often they should
be screened.

Colorectal cancer can be present in people without symptoms, known
family history, or predisposing conditions, such as inflammatory bowel
disease.

The following symptoms, however, might indicate colorectal cancer:

— Change in bowel habits

— Diarrhea or constipation

— Narrower than normal stools

— Unexplained weight loss

— Constant tiredness

— Blood in the stool

— Feeling that the bowel does not empty completely

— Abdominal discomfort-gas, bloating, fullness, cramps

— Unexplained anemia

To ensure the best possible patient outcomes, ASGE has taken a
leadership role in developing quality measures for endoscopic procedures
such as colonoscopy. Establishing quality indicators, such as appropriate
withdrawal time and detection rates, is a major step toward providing
patients the highest quality endoscopic care. ASGE’s “Quality Indicators
for Colonoscopy,” a section in the “Quality Indicators for Gastrointestinal
Endoscopic Procedures” supplement published in the April 2006 issue of
Gastrointestinal Endoscopy, can be found online at
asge/PublicationsProductsIndex.aspx?id=352.

For more information about colorectal cancer screening or to find a
qualified physician, visit ASGE’s colorectal cancer awareness Web site at
screen4coloncancer.

About the American Society for Gastrointestinal Endoscopy

Founded in 1941, the mission of the American Society for
Gastrointestinal Endoscopy is to be the leader in advancing patient care
and digestive health by promoting excellence in gastrointestinal endoscopy.
ASGE, with more than 10,000 physician members worldwide, promotes the
highest standards for endoscopic training and practice, fosters endoscopic
research, recognizes distinguished contributions to endoscopy, and is the
foremost resource for endoscopic education. Visit asge and
screen4coloncancer for more information.

About Endoscopy

Endoscopy is performed by specially-trained physicians called
endoscopists using the most current technology to diagnose and treat
diseases of the gastrointestinal tract. Using flexible, thin tubes called
endoscopes, endoscopists are able to access the human digestive tract
without incisions via natural orifices. Endoscopes are designed with
high-intensity lighting and fitted with precision devices that allow
viewing and treatment of the gastrointestinal system. In many cases,
screening or treatment of conditions can be delivered via the endoscope
without the need for further sedation, treatment or hospital stay.

American Society for Gastrointestinal Endoscopy
screen4coloncancer Continue reading →

GlaxoSmithKline (NYSE: GSK) announced that the Food and Drug Administration (FDA) has determined that U.S. healthcare practitioners can resume the use of Rotarix® (Rotavirus Vaccine, Live, Oral), effective immediately. This action supersedes the FDA’s recommendation from March 22, 2010 and reflects the agency’s assessment that the presence of porcine circovirus type 1 (PCV-1) in the vaccine poses no safety risk.

The FDA stated that the benefits of rotavirus vaccination are substantial, and include prevention of death in some parts of the world and hospitalization for severe rotavirus disease in the United States. The FDA further concluded that these benefits outweigh the risk, which is theoretical.

Barbara Howe, MD, Vice President, Director, North American Vaccine Development, GlaxoSmithKline stated: “We appreciate the swift and thorough review conducted by both the FDA and an expert advisory committee into the recent findings related to PCV-1 and the benefit/risk profile of Rotarix. We will continue to work with the FDA and other regulatory authorities on next steps as we maintain our commitment to helping protect infants from rotavirus disease in the U.S. and around the world.”

About PCV-1

Porcine circovirus 1 (PCV-1) is a small circular virus composed of a single strand of DNA. According to scientific literature, PCV-1 is a common virus that has been found in pork products. This is consistent with the body of literature that has not shown any evidence of PCV-1 infection in humans, or any other animals, including pigs.

About Rotarix®

Rotarix is a two-dose, orally-administered vaccine that offers protection against rotavirus to infants and children. More than 69 million doses of the vaccine have been distributed globally, with 2.5 million in the United States.

In the U.S., Rotarix is indicated for the prevention of rotavirus gastroenteritis caused by G1 and non-G1 types (G3, G4, and G9). It is approved for use in infants 6 weeks to 24 weeks of age.

The safety profile of Rotarix is based on extensive clinical data from the largest vaccine clinical trial program conducted by GSK, enrolling more than 90,000 participants in Europe, Latin America, Asia, Africa, and the U.S.

Important Safety Information Based on the Rotarix US Prescribing Information

– In clinical studies, common adverse events were fussiness/irritability, cough/runny nose, fever, loss of appetite, and vomiting.

– Contraindications include a history of any of the following: Hypersensitivity to any component of the vaccine including latex rubber (contained in the oral applicator), uncorrected congenital malformation of the gastrointestinal tract, or Severe Combined Immunodeficiency Disease (SCID).

– Administration in infants suffering from acute diarrhea or vomiting should be delayed.

– Safety and effectiveness in infants with chronic gastrointestinal disorders, or with known primary or secondary immunodeficiencies, have not been evaluated.

– Vaccination may not provide 100% protection to all recipients.

About Rotavirus

Rotavirus is the leading cause of severe gastroenteritis among children below five years of age and a major disease burden in developing countries. It is estimated that more than half a million children die of rotavirus gastroenteritis each year, a child a minute worldwide. Of these deaths, 90% occur in Asia and Africa. More than 100,000 deaths each year occur in India and sub-Saharan Africa and 35,000 in China. It is predicted that rotavirus vaccination could prevent more than 2 million rotavirus deaths globally over the next decade.

Globally, 25% to 55% of all children under the age of five hospitalized with diarrhoea or acute gastroenteritis are infected with rotavirus.

Before rotavirus vaccination was introduced in the U.S., each year an estimated 2.7 million children younger than five years of age experienced rotavirus disease, resulting in hundreds of thousands of emergency room visits and more than 55,000 hospitalisations.

GlaxoSmithKline Biologicals

GlaxoSmithKline Biologicals (GSK Biologicals), GlaxoSmithKline’s vaccines business, is one of the world’s leading vaccine companies and a leader in innovation. The company is active in the fields of vaccine research, development and production with over 30 vaccines approved for marketing and 20 more in development.

GlaxoSmithKline one of the world’s leading research-based pharmaceutical and healthcare companies is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

Cautionary statement regarding forward-looking statements

Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK’ s operations are described under ‘Risk Factors’ in the ‘Business Review’ in the company’ s Annual Report on Form 20-F for 2009.

Source: GlaxoSmithKline

View drug information on Rotarix. Continue reading →

Stress can change the balance of bacteria that naturally live in the gut, according to research published this month in the journal Brain, Behavior, and Immunity.

“These bacteria affect immune function, and may help explain why stress dysregulates the immune response,” said lead researcher Michael Bailey.

Exposure to stress led to changes in composition, diversity and number of gut microorganisms, according to scientists from The Ohio State University. The bacterial communities in the intestine became less diverse, and had greater numbers of potentially harmful bacteria, such as Clostridium.

“These changes can have profound implications for physiological function”, explained Dr Bailey. “When we reduced the number of bacteria in the intestines using antibiotics, we found that some of the effects of stress on the immune system were prevented”, he added. “This suggests that not only does stress change the bacteria levels in the gut, but that these alterations can, in turn, impact our immunity.”

“This is the first evidence that the gut microorganisms may play a role in innate immunological stress responses,” said Monika Fleshner, Professor of Integrative Physiology at the University of Colorado, Boulder. “The study reveals the dynamic interactions between multiple physiological systems including the intestinal microbiota and the immune system.”

Because gut bacteria have been linked to diseases like inflammatory bowel disease, and even to asthma, a future goal of the study is to determine whether alterations of gut bacteria is the reason why these diseases tend to be worse during periods of pressure.

The research was conducted with colleagues from the Texas Tech University Health Sciences Center and the Research and Testing Laboratories, and was funded by the National Institute of Health.

Sources: Elsevier, AlphaGalileo Foundation. Continue reading →

After announcing that all fresh spinach suspected of containing E. coli had been recalled across the USA, FDA officials said it was safe to eat again. Dr. David Acheson, Chief Medical Officer, Center for Food Safety and Applied Nutrition, FDA, said spinach is now as safe to eat as it was before the outbreak started.

Acheson added that all the affected spinach had originated from Natural Selection Foods, San Juan Bautista, California.

All Natural Selection Foods fresh spinach products with consume-by-dates of August 17 to October 1 have been recalled. The company says it is taking measures to improve safety inspections.

Natural Selection Foods is willing to pay toward the medical costs of people who became ill with E. coli poisoning during this outbreak.

The source of the contamination has still eluded investigators – there is a chance they may never know, say officials.

Spinach and E. coli Outbreak (FDA)

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Raven
biotechnologies, inc., a privately held company focused on the development
of monoclonal antibody therapeutics (MAbs) for cancer, announced it
is continuing to enroll new patients in the maximum tolerated dose cohort
expansion segment of its Phase 1/2a trial for patients with cancers of the
gastrointestinal tract that express the RAAG12 antigen.

RAAG12 is a glycotope (sugar structure) that is widely found on the
surface of tumor cells of many kinds of cancer, particularly cancers of the
gastrointestinal tract (adenocarcinomas of gastroesophageal, pancreatic and
colorectal origin). RAV12, Raven’s lead clinical monoclonal antibody drug
candidate, targets the RAAG12 antigen.

This segment of the trial will yield additional information about the
safety of the drug and define the pharmacokinetics of the antibody.

The appropriate dose and schedule of RAV12 was chosen in a
dose-escalation segment of the Phase 1/2a trial that involved 33 patients.
This trial revealed that a fractionated dosing regimen provided an improved
safety profile for the antibody. Raven is now enrolling patients in a
second segment of the trial in which all patients are receiving the
recommended dose and schedule of drug. Information from the Phase 1/2a
trial will be supporting the dosing in a Phase 2 study in pancreatic
cancer, the next clinical trial scheduled for RAV12.

The trial is being conducted at five institutions in the United States:
The Sarah Cannon Cancer Center in Nashville, TN; The Fox Chase Cancer
Center in Philadelphia, PA; Premiere Oncology in Santa Monica, CA;
Georgetown University Medical Center in Washington, DC; and The University
of Miami Medical Center in Miami, FL.

About RAV12

RAV12 is a novel, chimeric monoclonal antibody that is directed against
a primate-specific glycotope (sugar structure) that is widely displayed on
the surfaces of tumor cells, particularly those of gastrointestinal origin
(gastroesophageal, pancreatic, and colorectal cancers). Preclinical studies
have demonstrated that RAV12 may kill tumor cells in a number of ways:
first, the antibody is directly cytotoxic to a human colon cancer cell line
in vitro through induction of oncotic cell death, a form of cell death
characterized by cell and organelle swelling and loss of membrane
integrity; second, the antibody mediates antibody-dependent cellular
cytotoxicity; third, the antibody mediates complement dependent cell
killing; and finally, the antibody alters cellular signaling required for
cell survival. RAV12 is highly efficacious in human colon, gastric, and
pancreatic tumor xenograft models in vivo and has been found to be well
tolerated in repeat dose primate toxicology studies.

About GI Cancers

Adenocarcinomas are malignant tumors of the epithelial cells that line
glands or viscera. They typically spread by way of the circulatory or
lymphatic systems and are poorly treated after metastatic spread. More than
90 percent of colon, stomach and pancreatic tumor specimens express the
RAV12 defined antigen, RAAG12. Adenocarcinomas arising elsewhere, such as
breast, endometrial, ovarian, lung and prostate, display the antigen at
lower frequency.

About Raven

Raven biotechnologies, inc. (ravenbio) is a privately
held biotechnology company focused on the development of monoclonal
antibody therapeutics for treating cancer. Raven’s lead product candidate,
RAV12, targets adenocarcinomas and is in clinical development for the
treatment of gastrointestinal and other cancers. Raven’s discovery process
simultaneously identifies cell-surface drug targets and the antibody
therapeutics to regulate them. Our focus on biological function allows us
to rapidly identify novel target antigens and therapeutic candidates in
their native configuration in the intact cell membrane. Our integrated
approach is based on proprietary methods for optimizing the production of
MAbs targeting cell-surface proteins, including the use of human
tissue-specific progenitor and tumor stem cell lines developed at Raven.

To date Raven has identified multiple candidate therapeutic MAbs for
many cancer indications including lung, colon, pancreatic, prostate,
breast, brain, and ovarian cancer.

Raven biotechnologies, inc.
ravenbio Continue reading →

Two studies published in the current issue of Cell Transplantation (19:12) investigate frontiers of islet cell transplantation for treating diabetes. Researchers in Milan, Italy re-examine the role of bone marrow stem cells in diabetic therapy and islet cell regeneration and Canadian researchers offer improved strategies for optimizing pancreatic islet culture in vitro.

Both studies are in the current issue of Cell Transplantation, freely available on-line here.

New perspectives on role of bone marrow stem cells in islet transplantation

The role of bone marrow (BM)-derived stem cells in the islet cell regeneration process continues to evolve. A team of Italian researchers reports that employing BM-derived stem cells as “feeder tissue,” playing a protective role in supporting pancreatic islet repair for clinical use in treating diabetes, presents new therapeutic possibilities. Which cellular components of BM play the feeder role has not been clear.

“BM-derived cells have been found to differentiate into endothelial cells and their presence has been accompanied by a proliferation of recipient pancreatic cells that resulted in increased insulin production in the host pancreas,” said corresponding author Dr. Lorenzo Piemonti.

The researchers speculate that BM plays a role as feeder tissue by modulating, or enhancing, vascularization.

“We recently demonstrated that pancreatic mensenchymal stromal cells (MSCs) originate from bone marrow cells,” added Dr. Piemonti. “This suggests that there might be a ‘cross talk’ between bone marrow cells and the pancreas. Even more complex is the question of whether BM-pancreas cross talk plays a role in the pathogenesis of diabetes.”

For the researchers, the ‘easy availability’ of BM, and that BM may offer “the ideal microenvironment for islet survival,” suggest that exploring the possibility of using BM as the site for islet transplantation and they have started a clinical trial aimed at expanding on that idea.

“There is mounting evidence that BM and BM-derived stem cells can participate in the regeneration of pancreatic isolates,” concluded Dr. Piemonti. “Future studies should evaluate their effect for the prevention and cure of diabetes should it be verifiable that there is a cross talk between BM and the pancreas.”

Citation :
Ciceri, F.; Piemonti L. Bone Marrow And Pancreatic Islet: An Old Story With New Perspectives. Cell Transplant. 19(12): 1511-1522: 2010.

Improving pancreatic islet culture and preservation

Retrieving and preserving islet cells taken from nonliving donors for the purpose of islet cell transplantation to regenerate islet cells for patients suffering from diabetes is a current and successful practice. However, ensuring the integrity of the donor cells has been problematic.

“Following human islet isolation, apoptosis, or programmed cell death, occurs,” said Dr. Maryam Tabrizian, member of a McGill University (Canada) research team. “Studies have shown that islet isolation exposes islets to a variety of stresses, including loss of vasculature and eventual hypoxia. These factors must be controlled to avoid cell death and the optimization of islet culture must be assured to prolong the survival and functionality of the cells in vitro.”

According to the research team, nearly half of the islet mass is lost during donor surgery, preservation, transport and isolation, causing patients to undergo a second islet cell infusion. Better avenues of post-isolation culture, for up to two months duration, are needed, they said. This requires a better understanding of islet biology and the “basement membrane” of islet tissue. The researchers recommend combining many strategies supporting understanding of the need to maintain islet structural integrity and to provide a viable environment for islet preservation.

“Manipulation of the culture media, surface modified substrates, and the use of various techniques, such as encapsulation, embedding, scaffold and bioreactor approaches are among those strategies,” concluded the researchers.

“The survival of islets after isolation remains a significant limiting factor in the field of islet transplantation.” commented Dr. Rodolfo Alejandro, section editor for Cell Transplantation and Professor of Medicine at the University of Miami Miller School of Medicine. The prevention and repair of islet damage during isolation is of paramount importance. These two studies discuss novel approaches for this problem.

Citation:
Daoud, J.; Rosenberg, L.; Tabrizian, M. Pancreatic Islet Culture and Preservation Strategies: Advances, Challenges, and Future Outlook. Cell Transplant. 19(12):1523-1535; 2010.

Source:
David Eve

Cell Transplantation Center of Excellence for Aging and Brain Repair Continue reading →