Primary source: Lancet Oncology

Source reference:

Boyd N, et al “Breast tissue composition and other risk factors for breast cancer in young women: a cross-sectional study” Lancet Oncol 2009; DOI: 10.1016/S1470-2045(09)70078-6.

RIDGEWOOD, N.J., April 30 — The addition of cetuximab (Erbitux) to standard chemotherapy for non-small-cell lung cancer prolonged survival and can now be regarded as a first-line treatment option, researchers said.

• Explain to interested patients that the addition of cetuximab to their chemotherapy regimen may prolong their survival, but only for a short time.
• Note that they also may experience additional side effects, including a rash and diarrhea.

Among 1,125 chemotherapy-naive adult patients, those receiving chemotherapy plus cetuximab survived for a median of 11 months, compared with a median of 10 months for those receiving chemotherapy alone (hazard ratio for death 0.871; CI 0.762 to 0.996, P=0.044), Robert Pirker, M.D., of the Medical University of Vienna, and colleagues reported in the May 2 issue of The Lancet.

A monoclonal antibody, cetuximab targets the epidermal growth factor receptor (EGFR) and has shown efficacy as adjunctive therapy in treatment of metastatic colon cancer and squamous cell cancer of the head and neck.

Because the drug also showed an increased response rate and improved survival in a randomized phase II trial in patients with EGFR-expressing non-small-cell lung cancer, Dr. Pirker and colleagues undertook the open-label FLEX (First-Line ErbituX in lung cancer) trial, with the aim of showing prolonged overall survival time.

The chemotherapy regimen consisted of an intravenous infusion of cisplatin 80 mg/m² on day one and an intravenous infusion of vinorelbine, 25 mg/m² on days one and eight of every three-week cycle for up to six cycles.

A total of 557 patients were assigned to also receive intravenous infusions of cetuximab, in a starting dose of 400 mg/m² over two hours on day 1 and from day 8 at a dose of 250 mg/m² over one hour per week.

Median follow-up time was 24 months; 47% of the cetuximab patients were alive at one year compared with 42% of those who received chemotherapy alone.

Cetuximab also was associated with an increase in survival in a number of subgroups, including white patients, who had a hazard ratio for death of 0.803 (95% CI 0.694 to 0.928, P=0.003) and whose median survival time was 11 months, compared with nine months with chemotherapy alone.

Survival benefits also were seen with all histological subtypes, the investigators reported.

The median survival time was 12 months for patients with adenocarcinomas receiving cetuximab plus chemotherapy and 10 months in those receiving chemotherapy alone.

For those with squamous cell carcinomas, survival times for the cetuximab and chemotherapy groups were 10 and 9 months, respectively.

The combination also was better than chemotherapy alone in terms of overall response rates, which were 36% in the cetuximab group and 29% in the chemotherapy group (P=0.010).

Complete responses were seen in 2% and 1% of the cetuximab and chemotherapy groups, and partial responses were seen in 35% and 28%, although progression-free survival was not different, being a median of five months for both groups.

There were no differences in quality of life between the two groups, but the anti-EGFR antibody-associated adverse events of an acne-like skin rash, diarrhea, and infusion reactions were more common among the cetuximab patients.

“Cetuximab added to platinum-based chemotherapy can be regarded as a new standard first-line treatment option for patients with EGFR-expressing advanced non-small-cell lung cancer,” the investigators concluded.

In an accompanying editorial, Roy S. Herbst, M.D., of the M.D. Anderson Cancer Center in Houston, and Fred R. Hirsch, M.D., of the University of Colorado in Denver, stated that a positive survival trial in lung cancer is “a major advance.”

“This survival result is noteworthy,” they wrote, because it contrasts with negative studies that used tyrosine kinase inhibitors of the epidermal growth factor receptor such as erlotinib and gefitinib.

The specificity, pharmacology, and mechanism of action for an antibody to this receptor probably account for the drug’s efficacy in this setting, they noted.

The editorialists pointed out that the treatment could be particularly beneficial in patients with squamous cell carcinoma who are not candidates for bevacizumab, and it could also be tried in earlier, more potentially curative settings with radiation or surgery.

They concluded that further biomarker studies will be needed to determine which patients can benefit most, and that the development of new targeted therapies will require this “more personalized approach to cancer.”

The study was sponsored by Merck KGaA. Two of the investigators are full-time employees of Merck KGaA, and several of the investigators reported relationships with Merck KGaA and with multiple other pharmaceutical companies.

Primary source: The Lancet

Source reference:
Pirker R, et al “Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomized phase III trial” Lancet 2009; 373: 1525-31.

Additional source: The Lancet

Source reference:
Herbst RS, Hirsch FR “Patient selection criteria and the FLEX study” Lancet 2009; 373: 1497-98.

RIDGEWOOD, N.J., April 30 — Treatment with erythropoiesis-stimulating agents (ESAs) in patients with cancer was associated with worse mortality during active treatment and with poorer overall survival, a large meta-analysis revealed.

• Explain to interested patients that treatment of anemia with erythropoiesis-stimulating agents may improve their quality of life by reducing anemia and fatigue, but their survival may be shortened.
• Note that they also may be at increased risk for thromboembolic events and tumor growth.

ESA-treated patients had an estimated 17% increased mortality (combined HR 1.17 95% CI 1.06 to 1.30, P=0.003) as well as worsened overall survival (combined HR 1.06; 95% CI 1.00 to 1.12, P=0.046), Julia Bohlius, M.D., M.Sc.P.H., of the University of Bern in Switzerland, and colleagues reported in the May 2 issue of The Lancet.

These agents, including epoetin alfa (Epogen, Procrit), epoetin beta (NeoRecormon), and darbepoetin alfa (Aranesp) are used to treat anemia in patients with cancer.

The drugs increase hemoglobin concentrations, reduce the need for red blood cell transfusions, and can potentially improve quality of life, but they also increase the risk of thromboembolic events and may stimulate tumor growth, the researchers noted.

Safety of the agents has been discussed in a number of hearings conducted by the Food and Drug Administration and the European Medicines Agency, and their effect on survival has been uncertain.

Previous studies that sought to address these concerns were literature-based meta-analyses of aggregated results with heterogeneous mortality endpoints.

In contrast, this meta-analysis was based on individual data from 13,933 patients in 53 randomized controlled trials, including those done by independent investigators and ESA manufacturers.

Analysis of individual patient data permitted consideration of prognostic factors at the patient level, and allowed investigation of subgroups of interest and modification of effects by patient and study characteristics, the researchers said.

It also allowed the definition of uniform survival endpoints and analyses of mortality during active study periods as well as of overall survival based on the longest available follow-up, they explained.

Mortality during the active study period was defined as death from any cause between the date of randomization and 28 days after the end of the study phase, and overall survival was defined as death from any cause between the date of randomization and the last available follow-up.

Median age at randomization was 61 years for patients receiving ESAs and 60 years for controls. Median hemoglobin concentrations at baseline were 106 g/L in ESA patients and 108 g/L in controls.

The planned epoetin doses ranged from 21,000 IU to 63,000 IU per week; planned doses for darbepoetin were from 100 mcg to 157.5 mcg per week.

In assessment of mortality during the active study period, median follow-up of ESA patients was 3.7 months and that of control patients was 3.9 months.

In assessment of overall patient survival, the median follow-up of ESA patients was 6.2 months and that of control patients was 8.3 months, for a combined hazard ratio of 1.06 (95% CI 1.00 to 1.12, P=0.046).

Patients were given chemotherapy in 38 of the trials, with 5,676 patients being randomized to ESA and 4,765 to control. A 10% increase in mortality was seen in ESA patients undergoing chemotherapy, the researchers reported.

In the chemotherapy trials, assessment of mortality during the active study period found that the median follow-up of ESA patients was 4.1 months and that of controls was 4.3 months, for a combined hazard ratio of 1.10 (95% CI 0.98 to 1.24, P=0.12).

Assessment of overall survival in the chemotherapy trials found a median follow-up of 6.7 months in the ESA arm and 8.4 months in the control arm, for a combined hazard ratio of 1.04 (95% CI 0.97 to 1.11, P=0.263).

The investigators noted that they found little evidence for an interaction between ESA treatment, baseline hemoglobin concentration, planned ESA doses, and mortality, although patients whose baseline hematocrit was low had an increased risk of death compared with other subgroups.

“Low hematocrits might be a marker for advanced cancer and increased vulnerability to the detrimental effects of erythropoiesis-stimulating drugs,” they suggested.

The investigators also observed that patients with previous thromboembolic events seemed to be protected from an ESA-associated increase in mortality, explaining that prophylactic anticoagulation during cancer treatment might have been protective against thrombogenic effects.

Debate continues as to whether these agents are safer in patients undergoing chemotherapy than in those undergoing other treatments such as radiation, the researchers said.

They suggested that patients not undergoing myelosuppressive anticancer treatment are more likely to achieve higher hemoglobin concentrations and might therefore be at greater risk of thromboembolic events and impairments in tumor control.

They concluded that in clinical practice the increased risks of these agents should be balanced against potential benefits and that consideration should be given to the individual patient’s clinical circumstances and preferences.

They also said that more data are needed on quality of life and tumor progression, and that further research should focus on the cellular and molecular mechanisms and pathways involved.

Several of the study investigators disclosed relationships with manufacturers of ESAs including Amgen, Johnson & Johnson, and Hoffmann-La Roche.

Primary source: The Lancet

Source reference:
Bohlius J, et al “Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials” Lancet 2009; 373: 1532-42.

New data from several studies evaluating new techniques for early diagnosis and treatment of lung cancer are being presented at the first European Multidisciplinary Conference on Thoracic Oncology (EMCTO) in Lugano, Switzerland (1-3 May 2009).

“Lung cancer is the leading cause of cancer deaths worldwide and also in Europe. One of the reasons for this is that symptoms of lung cancer are very often lacking or occur only late in the course of the disease,” said Prof Rudolf M. Huber from the University of Munich in Germany.

“The prognosis of lung cancer patients is very dependent on how advanced their disease is. In stage I for example, where the tumour has not yet spread, 5-year-survival rates are about 70%; whereas in stage IV, where it has metastasised to other parts of the body, survival is about 1%. Even for patients with locally advanced tumours, survival over 5 years is only about 10%. Therefore every effort should be undertaken to diagnose early in the course of the disease.”

“Developing better tools for distinguishing between lung cancer and other lung diseases will help us offer greater hope for patients,” added Prof Huber.

In one study presented at the conference, Italian researchers compare two computed tomography techniques for diagnosing indeterminate lung lesions, finding that a form of single-photon emission computed tomography could offer an alternative method in situations where positron emission tomography is not available.

In another abstract, UK scientists report that a new approach to diagnosis that ensures a patient has had a chest CT scan before they attend a clinic has the potential to reduce the time between their first abnormal chest X-ray and final diagnosis.

Also during the conference, Greek investigators suggest that they may have found a new factor that will help indicate a patient’s prognosis at the time of diagnosis. Their work indicates that the expression of specific cell surface molecules on tumour cells correlates with clinical parameters. The results “could comprise a promising prognostic factor in lung carcinomas, thus presenting exciting possibilities for the future.”

Source
European Society for Medical Oncology

Varian Medical Systems is introducing a new brachytherapy applicator set which is hoped to increase treatment precision and aid comfort for patients suffering from bronchial cancer. The Centering Intraluminal Applicator set is being made available for use with Varian’s GammaMed™ and VariSource™ brachytherapy afterloaders.

The Centering Intraluminal Applicator set has been designed for treatment of the trachea, main bronchus and esophagus. The special design of the 3-centering catheter enables a centered position of the source in the lumen of the trachea or the bronchus while maintaining a channel for air to pass and for the patient to breathe. The three centering baskets can be partly or totally extended enabling an individual adaptation to the patient’s anatomy.

“This new applicator set helps clinicians to optimize the dose distribution thanks to its ability to center the source at the middle of the bronchial lumen,” says Claudia Andres-Zindler, brachytherapy applicator product manager. “Crucially, it also allows the patient to breathe unaided during treatment.”

The Centering Intraluminal Applicator set uses a Seldinger guide wire technique to allow for easy implant guidance and a radiopaque x-ray marker line over the full length of the centering catheter and through the centering baskets allows an easy identification using either fluoroscopic or x-ray images.

High dose rate brachytherapy involves placing the radioactive source inside or next to the area requiring treatment. Varian Medical Systems, the world leader in radiotherapy, supplies a wide range of brachytherapy afterloaders and applicator sets to hospitals and cancer clinics throughout the world. More information on the Centering Intraluminal Applicator set can be obtained from www.varian.com

Source
Varian Medical Systems, Inc.

Antigenics Inc. (NASDAQ: AGEN) announced that Oncophage® (vitespen) has been granted orphan drug status for the treatment of glioma (brain cancer) by the US Food and Drug Administration (FDA). In March, the European Medicines Agency (EMEA) granted a similar designation for Oncophage.

“Glioma is such an aggressive and challenging cancer that when patients are diagnosed with recurrence of this life threatening disease, they rarely live beyond six months,” said Andrew T. Parsa, MD, PhD, associate professor in the department of neurological surgery at the University of California, San Francisco, and lead investigator of a Phase 2 trial evaluating Oncophage in glioma. “Given the poor survival rates, the medical community needs new treatment options, and I am hopeful of the potential for Oncophage to significantly improve clinical outcomes in this patient population.”

As announced in November 2008, final data from a Phase 1, investigator-sponsored trial conducted at the Brain Tumor Research Center at the University of California, San Francisco, showed that Oncophage vaccination following brain cancer surgery increased overall median survival to approximately 10.5 months, with four patients surviving beyond 12 months and one patient surviving almost 2.5 years. This is compared to a historical median survival of only 6.5 months postsurgery. Phase 2 results are expected to be presented later this year.

Orphan Drug Designation in the United States

In the United States, the Orphan Drug Act provides for the orphan drug designation, which aims to encourage the development of drugs involved in the diagnosis, prevention or treatment of a medical condition affecting fewer than 200,000 people in the country. Orphan drug designation entitles Antigenics to seven years of market exclusivity for Oncophage in the treatment of glioma patients in the event of market approval for this indication. Additional incentives for orphan drug development include tax credits related to development expenses, reduction in FDA user fees and FDA assistance in clinical trial design.

About Oncophage

In April 2008, Oncophage was approved in Russia for the adjuvant treatment of kidney cancer patients at intermediate-risk for disease recurrence. In October 2008, Antigenics submitted a marketing authorization application to the EMEA requesting conditional approval for Oncophage in earlier-stage, localized renal cell carcinoma.

Derived from each individual’s tumor, Oncophage contains the ‘antigenic fingerprint’ of the patient’s particular cancer and is designed to reprogram the body’s immune system to target only cancer cells bearing this fingerprint. Oncophage is intended to leave healthy tissue unaffected and limit the debilitating side effects typically associated with traditional cancer treatments such as chemotherapy and radiation therapy. Oncophage has been studied in Phase 3 clinical trials for the treatment of kidney cancer and metastatic melanoma and is currently being investigated in a Phase 2 trial in recurrent glioma.

Oncophage has also received fast track and orphan drug designations from the U.S. Food and Drug Administration for both kidney cancer and metastatic melanoma.

In April 2009, the World Vaccine Congress named Oncophage the best therapeutic vaccine.

About Brain Tumors

Glioma is the most common type of brain tumor and is currently a fatal disease impairing areas such as thinking, personality and movement. The National Cancer Institute estimates that about 19,000 cases are diagnosed every year in the United States and, according to historical estimates, the median survival of patients with previously treated glioma is typically three to six months.

Source
Antigenics Inc.

Advaxis, Inc. (OTCBB: ADXS) Phase 1 clinical study of the therapeutic cancer vaccine ADSX11-001 (formerly Lovaxin C) has been accepted for publication in the peer reviewed journal Vaccine and the abstract is available for review on PubMed (Maciag, Radulovic & Rothman; The First Clinical Use Of A Live-Attenuated Listeria Monocytogenes Vaccine: A Phase I Safety Study of Lm-LLO-E7 in Patients With Advanced Carcinoma of The Cervix.).

Vaccine specializes in scientific publications pertaining to vaccines and vaccination.

The article discusses the treatment of groups of five (5) patients who received two (2) doses of ADXS11-001 at one (1) of three (3) doses, 1.0 x 109, 3.30 x 109 or 1.0 x 1010 cfu (bacteria) as IV infusions. All fifteen (15) treated patients received ampicillin beginning at five (5) days after each infusion. This trial was designed to assess the safety of ADXS11-001 in a population with recurrent, metastatic cervix cancer who had failed cytotoxic therapy comprised of radiotherapy, chemotherapy or both.

The agent was found to be administered safely with side effects consisting of a flu-like syndrome comprised of fever, nausea, chills, headache, myalgia, etc. This response is common to many immunotherapies and is believed to result from the release of chemical mediators of immunity called cytokines. Cytokine release characterizes what is termed an “innate” immune response. Very strong innate immunity can be associated with hypotension, and this was observed at the highest dose tested, resulting in no further dose escalation. All side effects, including hypotension, were resolved with symptomatic treatment and did not require the administration of antibiotics, except for two (2) cases of fever that persisted at seventy-two (72) hours and, per the protocol, ampicillin was given to these patients at that time. These fevers remitted upon antibiotic administration and both of these patients are still alive. Although not designed to assess efficacy, response and survival data was collected.

The median survival of cervix cancer patients who fail first line cytotoxic therapy, according to work conducted by the Gynecologic Oncology Group of the National Cancer Institute, is 180 days. The median survival in this trial was 347 days.

Historically, one (1) year survival in this disease is approximately 5%. In this study, one (1) year survival was 53%. Four (4) of the thirteen (13) patients evaluable for efficacy (30%) experienced tumor reductions. One (1) patient experienced a greater than 30% reduction of her tumor burden which is the criterion for a partial response. This patient received additional chemotherapy and surgery subsequent to ADXS11-001 and became tumor free for over sixteen (16) months, and is still alive at 903 days. The two (2) patients who experienced fever requiring antibiotics are alive at 804 and 935 days.

ADXS11-001 was safely administered in clinical use in a severely debilitated terminal cervix cancer population. Some indications of efficacy were observed, however the small number of treated patients does not allow for conclusions regarding efficacy to be made at this time.

About the ADXS11-001 Immunotherapy

Advaxis™ technology platform uses modified Listeria monocytogenes to deliver a tumor-specific antigen fusion protein. Pre-clinically, bioengineered attenuated Listeria that secrete Advaxis™ proprietary fusion protein have the ability to generate a robust immune response, break immune tolerance to cancer and produce an unusually strong and effective multi-level therapeutic immune response to existing cancer and other diseases. ADXS11-001 is a therapeutic vaccine, like Dendreon’s (NGM: DNDN) Provenge that treats active cancer, but at much lower cost, because it is not formulated for a specific patient.

Advaxis™ Listeria-based technology is based on over a decade worth of work by Dr. Yvonne Paterson in her laboratory at the University of Pennsylvania. The Company’s proprietary antigen fusion protein technology stimulates innate immunity i.e., both arms of the adaptive cellular immune system, suppresses regulatory T-cells that inhibit many vaccines in the function of activated tumor-killing cells in addition to other anti-tumor effects.

For further information on ADXS11-001, please visit: http://www.advaxis.com/lc.htm.

About Advaxis, Inc.

Based in North Brunswick, New Jersey, Advaxis is developing proprietary Listeria monocytogenes (Lm) cancer vaccines based on technology developed by Dr. Yvonne Paterson, professor of microbiology at the University of Pennsylvania and chairperson of Advaxis’ scientific advisory board. Advaxis is developing attenuated live Lm vaccines that deliver engineered tumor antigens, which stimulate multiple simultaneous immunological mechanisms to fight cancer.

For further information on the Company, please visit: http://www.advaxis.com.

Forward-Looking Statements

Certain statements contained in this press release are forward-looking statements that involve risks and uncertainties. The statements contained herein that are not purely historical are forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements deal with the Company’s current plans, intentions, beliefs and expectations and statements of future economic performance. Forward-looking statements involve known and unknown risks and uncertainties that may cause the Company’s actual results in future periods to differ materially from what is currently anticipated. Factors that could cause or contribute to such differences include those discussed from time to time in reports filed by the Company with the Securities and Exchange Commission. The Company cannot guarantee its future results, levels of activity, performance or achievements.

Source
Advaxis, Inc.

Tigris Pharmaceuticals, Inc., a privately held drug development company, announced that dosing has started in a Phase I clinical trial of GGTI-2418. GGTI-2418 is a synthetic peptidomimetic inhibitor of geranylgeranyltransferase I (GGTase I) that induces apoptosis by downregulating several pivotal oncogenic and tumor survival pathways.

The Phase I study is led by Dr. Peter O’Dwyer, Professor of Medicine at the University of Pennsylvania School of Medicine and Program Leader of the Experimental Therapeutics Program at the Abramson Cancer Center of the University of Pennsylvania, and by Dr. Gabriela Chiorean, Assistant Professor of Medicine at the Indiana University School of Medicine and a physician/researcher with the Indiana University Melvin and Bren Simon Cancer Center.

“This is the first geranylgeranyltransferase inhibitor to move to clinical phase studies,” stated Edmundo Muniz, M.D., Ph.D., President and Chief Executive Officer of Tigris. “Initiation of this Phase I study of GGTI-2418 in these two top Phase I cancer research centers is a significant step in the development of this first-in-class molecule to treat cancer in many different tumor types.”

“We are excited to participate in the first study of this novel agent,” commented Dr. Chiorean. “The development of a molecule to inhibit the geranylgeranyltransferase pathway would be a significant advancement in cancer treatment.”

The primary objective of the Company’s Phase I trial with GGTI-2418 is to determine its safety, tolerability, and recommended Phase II dose. Patients with metastatic solid tumors for which standard treatments have failed, or for whom standard therapies are not available, will be evaluated. The number of patients to be enrolled will depend on the number of patient cohorts investigated until dose-limiting toxicity is reached.

Tigris in-licensed the exclusive worldwide rights to GGTI-2418 from Yale University and the University of South Florida. Said M. Sebti, Ph.D., Director of the Drug Discovery Program at the Moffitt Cancer Center and Andrew Hamilton, Ph.D., Professor of Chemistry at Yale University were the co-inventors of GGTI-2418.

About GGTI-2418

GGTI-2418 is a synthetic peptidomimetic inhibitor of GGTase I that appears to induce apoptosis by downregulating several pivotal oncogenic and tumor survival pathways. GGTase I catalyzes the lipid posttranslational modification which is required for the function of Rho GTPases (frequently found aberrantly activated in human cancer). GGTase I inhibitors block Rho function in cancer cells and induce a G1 phase cell cycle arrest by a mechanism involving induction of the CDK inhibitors p21waf and p27kip, CDK2 and CDK4 inhibition and hypophoshorylation of the tumor suppressor Rb. GGTase I inhibitors also induce apoptosis by a mechanism involving downregulation of the expression of survivin and suppression of the activation of PI3K/Akt.

About Tigris Pharmaceuticals, Inc.

Tigris Pharmaceuticals, Inc. is a privately held biopharmaceutical company that develops therapeutic technologies, using a translational research approach, for use in oncology and other areas of unmet medical need. Tigris’ mission is to efficiently move its existing and future technologies through the various stages of clinical development in order to meet patients’ needs for safe and effective treatments of human illnesses.

This news release contains forward-looking statements that involve risks and uncertainties that could cause our actual results and experiences to differ materially from anticipated results and expectations expressed in such forward-looking statement. These forward-looking statements include, without limitation, statements regarding the mechanism of action of GGTI-2418, its potential advantages, its potential for use in treating cancer, as well as the timing, progress and anticipated results of the clinical development and regulatory processes concerning GGTI-2418. These statements are based on our current beliefs and expectations as to such future outcomes, and are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. Factors that might cause such a material difference include, among others, risks that the results of clinical trials will not support our claims or beliefs concerning the effectiveness of GGTI-2418, our ability to finance our development of GGTI-2418, regulatory risks, and our reliance on third party researchers and other collaborators. We assume no obligation to update these statements, except as required by law.

Source: Tigris Pharmaceuticals, Inc

With equipment readily available to health officials and businesses, a Purdue University researcher has found a way to detect trace amounts of melamine in infant formula.

Using infrared lasers and light spectroscopy methods, Lisa Mauer, an associate professor of food science, was able to detect melamine in baby formula at one part per million in about five minutes or less. Melamine, a synthetic chemical used in plastics and other products, has been found in baby formula and other milk-based products imported from China. High doses of melamine were associated with cancer in some animals, and it is especially dangerous for infants, according to the Centers for Disease Control and Prevention.

“We have found detection methods that are inexpensive and do not require a lot of the product or time for sampling,” said Mauer, whose paper on the testing method was published in the early online version of The Journal of Agricultural and Food Chemistry. “Any company could do this itself. Police agencies, state departments of health and many colleges have this type of equipment.”

Mauer obtained unadulterated samples of powdered formula and measured the samples using near- and mid-infrared spectroscopy techniques. Infrared laser beams reflected off the sample and toward a detector, which calculated how much of the laser’s energy was absorbed by the sample and created an absorbance spectrum that was unique to the sample.

The same data were collected for pure melamine. When the formula was mixed with melamine and analyzed, the new spectrum was compared to that of the unadulterated formula, showing the concentration of melamine in the sample.

“The melamine structure is very different than the formula, so you can see differences in the spectrum,” Mauer said. “Because they are so different, we can detect down to one part per million of melamine.”

Federal guidelines allow for only one part per million of melamine in infant formula and up to two and a half parts per million in other products. Having an inexpensive and quick test would make it easier to test imported or domestically made products for melamine.

“If someone wanted to build a calibration model to detect melamine in their products, all they’d have to do is collect the spectrum of their product, add known quantities of melamine to their product, then collect those spectra and compare them,” Mauer said. “Thumbprint analysis is basically the same thing. We can’t see the differences with our own eyes, but software programs can.”

Mauer and her four graduate students found the melamine detection process after she received a new software program that she wanted the students to become familiar with. Mauer challenged them to use spectroscopy to detect melamine, thinking they might be able to do so at high concentrations.

After successful tries at higher concentrations, Mauer and the students kept lowering the concentration of melamine until they reached one part per million.

Writer: Brian Wallheimer

ABSTRACT

Melamine Detection in Infant Formula Powder Using Near- and Mid-Infrared Spectroscopy

Lisa J. Mauer, Alona A. Chernyshova, Ashley Hiatt, Amanda Deering and Reeta Davis

Near- and mid-infrared spectroscopy methods (NIR, FTIR-ATR, FTIR-DRIFT) were evaluated for the detection and quantification of melamine in infant formula powder. Partial least-squares (PLS) models were established for correlating spectral data to melamine concentration: R2 > 0.99, RMSECV e 0.9, and RPD g 12. Factorization analysis of spectra was able to differentiate unadulterated infant formula powder from samples containing 1 ppm melamine with no misclassifications, a confidence level of 99.99%, and selectivity > 2. These nondestructive methods require little or no sample preparation. The NIR method has an assay time of 1 min, and a 2 min total time to detection. The FTIR methods require up to 5 min for melamine detection. Therefore, NIR and FTIR methods enable rapid detection of 1 ppm melamine in infant formula powder.

Source:
Brian Wallheimer

Purdue University

To the News Service home page

Traditionally, cancer biologists have embraced a simple and direct model of the disease process: The tumor — the “seed” — was seen as bearing total responsibility for the spread of cancer to distant tissues — the “soil” in which the seed embedded itself, grew, and reproduced. The result was a seed-dominant model that determined the way doctors treated cancer, using strategies targeting the tumor seed but neglecting the role of the soil.

Recently, however, some researchers have been focusing on the permissive microenvironment, or the metastatic niche, that forms in particular tissues located far from the primary tumor, well before full metastasis takes hold.

“In cancer, it is metastatic disease that causes morbidity and mortality,” says Dr. David Lyden, co-author of an article in the April 2009 issue of Nature Reviews Cancer.

“At our lab, we’re developing a strategic approach to studying metastasis. Our goal is ultimately to be able to predict and pre-empt the process — early, if possible, but even in advanced metastasis,” adds Dr. Lyden, the Stavros S. Niarchos Associate Professor in Pediatric Cardiology, an investigator in the Division of Pediatric Hematology and Oncology, and associate professor of cell and development biology at Weill Cornell Medical College.

Led by Dr. Lyden, a team of researchers is looking at the molecular and cellular players that mediate changes at future sites of metastasis such as liver, lung, brain or bone, and thereby direct the migration patterns of tumor cells.

The group has zeroed in on several of these essential players, including bone marrow-derived cells and growth factors secreted by the tumor itself. These, Dr. Lyden explains, instruct the pre-metastatic niche to get ready for a long visit, one that will require comfortable accommodations for a rapidly growing population of permanent guests.

If the pre-metastatic niche does the tumor’s bidding and boosts production of inflammatory chemokines and fibronectin, among other cancer-friendly proteins, a secondary tumor has a good chance of forming — and thriving.

Dr. Lyden believes his lab’s discoveries could open doors leading to the development of new cancer treatments that target each step along the metastatic pathway. “We can envision a time in the not-too-distant future when we’ll be able to prevent metastasis through a new approach for early detection and treatment,” he says. “That’s why we’re studying the earliest changes in the pre-metastatic niche in such depth.

“At the same time,” he continues, “the challenge is to understand metastasis in its entirety by familiarizing ourselves with the shifting molecular and cellular microenvironment at each step along the way. The ramifications of this approach for cancer treatment, we believe, are inestimable.”

The Lyden lab at Weill Cornell was one of seven to be represented in the current issue of Nature Reviews, which is devoted exclusively to the subject of cancer metastasis in a special issue. In their article titled “The Metastatic Niche: Adapting the Foreign Soil,” Dr. Lyden and lead author Dr. Bethan Psaila, a Fulbright Fellow in the Lyden lab, summarize the discoveries and insights they’ve gleaned over the past decade.

“The ’seed and soil’ hypothesis is considered one of the most important among cancer biologists, but our lab — especially in collaboration with Dr. Rosandra Kaplan and the lab of Dr. Shahin Rafii — was actually first to address it in real terms,” Dr. Lyden says. “Now, many other labs are moving in this direction, and all of them are opening up highly promising new avenues for inquiry.”

Preventing and treating cancerous tumors will continue to be central to cancer treatment strategy, he adds. But soon, we may begin to see new strategies aimed at disarming the real killer: metastatic disease.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University’s medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in areas such as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, transplantation medicine, infectious disease, obesity, cancer, psychiatry and public health — and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries of the human body in health and sickness. In its commitment to global health and education, the Medical College has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson’s disease, the first indication of bone marrow’s critical role in tumor growth, and most recently, the world’s first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient.

Source: NewYork-Presbyterian Hospital

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