MediWound Recommended for Approval in Europe
Congratulations to Gal Cohen (CEO) and Lior Rosenberg (CMO) and our friends and colleagues at MediWound for the EMA recommendation for approval. Target Health began its collaboration with MediWound in 2001 with our good friends Ronit Koren and Marian Gorecki. Target e*CRF® was used in the Phase II program and for the EMA Phase III pivotal trial, which means that Target e*CRF was used in 4 regulatory approvals in 2012 (3 US and 1 EMA); 2 of the approvals came out of Israel.
“The European Medicines Agency (EMA) has recommended approval of third degree burn treatment NexoBrid, developed by MediWound Ltd. This is a major achievement for the company, as this is the first time the EU has approved a treatment that consists of an enzyme-based debriding agent for the removal of necrotic tissue from severe burn wounds, instead of surgical intervention. NexoBrid is a gel made of a mixture of enzymes which are extracted from the stem of the pineapple plant. It should be applied topically to a clean burn wound to remove the eschar (the dried-out, thick, leathery, black necrotic tissue that covers severe burn wounds) four hours after the burn. The quick removal of the eschar greatly shortens the recovery time from severe burns. NexoBrid also reduces the risk of infection of the burn as it includes disinfectants. Four hours after the gel is smeared on the burn, it can be wiped off, exposing the burned area, and thus enabling doctors to determine subsequent treatment. Teva Pharmaceutical Industries Ltd. has an option to acquire control of MediWound and a marketing agreement with it.“
For more information about Target Health contact Warren Pearlson ( 212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Sanofi Halves Price of Cancer Drug Zaltrap
If cancer is detected, it will be “staged,“ a process of finding out how far the cancer has spread. While tumor size may not correlate with the stage of cancer, staging enables physicians to determine what type of treatment to provide.
Stage 0 — Cancer is only in the innermost lining of the colon or rectum.
Stage I — Cancer has not spread beyond the inner wall of the colon or rectum.
Stage II — Cancer has spread into the muscle layer of the colon or rectum.
Stage III — Cancer has spread to one or more lymph nodes in the area.
Stage IV — Cancer has spread to other parts of the body, such as the liver, lung, or bones.
The French drugmaker Sanofi said, in the beginning of October 2012, that the results of a late-stage study of its Zaltrap drug showed a “statistically significant improvement in overall survival“ in patients with colon cancer. The detailed results of the Phase III study of the drug used in conjunction with 1) ___ were published in the October edition of the Journal of Clinical Oncology. Zaltrap, also known as aflibercept, is a so-called anti-angiogenic agent, designed to starve tumors of blood.
Then, in an unusual move, Sanofi SA (formerly Sanofi-Aventis) said that it would effectively cut in half the price of their new cancer drug after a leading cancer center said it would not use the drug because it was too 2) ___. The move could be a sign of resistance to increases in the prices of cancer drugs, some of which cost more than $100,000 a year and increase survival by a few 3) ___.
Zaltrap came to market in August at a price of about $11,000 a month. Soon after, Memorial Sloan-Kettering Cancer Center in New York decided not to use the drug, saying it was twice as expensive but no more effective than a similar medicine, 4) ___ from Genentech. Both drugs improved median survival by 1.4 months. Three doctors at Sloan-Kettering publicized the cancer center’s decision last month in an Op-Ed article in The New York Times.
“Ignoring the cost of care is no longer tenable,“ they wrote. “Soaring spending has presented the medical community with a new obligation. When choosing treatments for 5) ___, we have to consider the financial strains they may cause alongside the benefits they may deliver.“
Sanofi argued that the 6) ___ they had set was very similar to that of Avastin. This past week, in reconsideration, Sanofi stated that they recognize that there was some market resistance to the perceived relative price of Zaltrap in the U.S. they were taking immediate action across the U.S. oncology community to reduce the net cost of Zaltrap. Sanofi said it would not change the official price for Zaltrap but would offer discounts of about 50%. Zaltrap, which is given intravenously, is not bought directly by patients but is sold to 7) ___ or hospitals, which administer it. The cost is then reimbursed by Medicare or private insurers. Patients could be liable for a co-payment.
Dr. Leonard B. Saltz, chief of gastrointestinal oncology at Sloan-Kettering and one of the authors of the Op-Ed article, said that the discounts could give doctors and hospitals an incentive to use Zaltrap because they could profit from the difference between the discounted price they pay for the drug and the higher price at which they are reimbursed by 8) ___.
Zaltrap, developed by Sanofi and Regeneron Pharmaceuticals, was approved by the FDA in August for use as a second-line treatment for 9) ___ cancer, meaning after an initial regimen had stopped working. Like Avastin, Zaltrap impedes the formation of blood vessels that nourish cancer cells.
ANSWERS: 1) chemotherapy; 2) expensive; 3) months; 4) Avastin; 5) patients; 6) price; 7) doctors; 8) insurers; 9) colorectal
Benoit B. Mandelbrot (1924-2010)
Benoit B. Mandelbrot, a wandering visionary — Photo: Louis Fabian Bachrach
Benoit B. Mandelbrot (1924-2010) had the kind of beautiful, buzzing mind that made even gifted fellow scientists feel shabby around the edges. Mandelbrot is said to have revitalized visual geometry and coined the term “fractal“ to refer to a new class of mathematical shapes that uncannily mimic the irregularities found in nature. He prized roughness and complication. “Think of color, pitch, loudness, heaviness and hotness,“ he once said. “Each is the topic of a branch of physics.“ He dedicated his life to studying roughness and irregularity through geometry, applying what he learned to biology, physics, finance and many other fields.
He was never easy to pin down. He hopscotched so frequently among disciplines and institutions – I.B.M., Yale, Harvard – that in his new memoir, “The Fractalist,“ he rather plaintively asks, “So where do I really belong?“ The answer is: nearly everywhere.
Mandelbrot was born in Warsaw to a middle-class Lithuanian Jewish family that prized intellectual achievement. His mother was a dentist; his father worked in the clothing business. Both loved knowledge and ideas, and their relatives included many fiercely brainy men. “I grew up,“ Mandelbrot writes, “in what may be called a house of mathematics.“
The family fled to Paris in 1936, in time to escape Hitler’s advances. Once in Paris, he was mentored by a brilliant mathematician uncle. Family members split up – Mandelbrot and his brother lived for a while in various parts of France – to avoid the Nazis until France was liberated. Back in school, he learned he was, as he puts it, “a taupin, linguistically an extreme form of the American ?nerd.’“ He also discovered that he had what he calls a “freakish gift“ for solving complex mathematical problems by reducing them to familiar geometric shapes in his mind. He compared the disparate shapes that filled his head to a well-populated zoo. He studied at the prestigious Ecole Polytechnique in Paris, and later at the California Institute of Technology, Princeton and M.I.T. At M.I.T. he got to know the young Noam Chomsky and debated going into linguistics.
Mandelbrot ultimately settled at I.B.M., an association that lasted 35 years. He took frequent leaves, teaching at many colleges, including Yale, where he was a professor for 17 years. His work on fractals was inspired, in no small part, by his childhood love of maps; he began to think about creating “random coastlines from a simple formula,“ as he put it. The arrival of computer graphics greatly aided his quest. He ultimately described what became known as the Mandelbrot set, famous, he writes, for being “the most complex object in mathematics,“ and inspired decades of trippy graphic representations.
Beautiful minds don’t always write beautiful books. Life isn’t fair that way. But “The Fractalist“ evokes the kinds of deceptively simple questions Mandelbrot asked – “What shape is a mountain, a coastline, a river or a dividing line between two river watersheds?“ – and the profound answers he supplied.
Just published: Graphic: “The Fractalist; Memoir of a Scientific Maverick“/Benoit B. Mandelbrot
In 1975, Mandelbrot coined the term fractal to describe cosmological structures he was studying, and published his ideas in Les objets fractals, forme, hasard et dimension (1975; an English translation Fractals: Form, Chance and Dimension was published in 1977) Mandelbrot developed here ideas from the article Deux types fondamentaux de distribution statistique (1938; an English translation Two Basic Types of Statistical Distribution) of Czech geographer, demographer and statistician Jarom?r Korcak (1895-1989).
While on secondment as Visiting Professor at Harvard University in 1979, Mandelbrot began to study fractals called Julia sets that were invariant under certain transformations of the complex plane. Building on previous work by Gaston Julia and Pierre Fatou, Mandelbrot used a computer to plot images of the Julia sets of the formula z2 – u. While investigating how the topology of these Julia sets depended on the complex parameter u he studied the Mandelbrot set fractal that is now named after him. (Note that the Mandelbrot set is now usually defined in terms of the formula z2 + c, so Mandelbrot’s early plots in terms of the earlier parameter ? are left-right mirror images of more recent plots in terms of the parameter c.)
In 1982, Mandelbrot expanded and updated his ideas in The Fractal Geometry of Nature. This influential work brought fractals into the mainstream of professional and popular mathematics, as well as silencing critics, who had dismissed fractals as “program artifacts“. Mandelbrot left IBM in 1987, after 35 years and 12 days, when IBM decided to end pure research in his division He joined the Department of Mathematics at Yale, and obtained his first tenured post in 1999, at the age of 75. At the time of his retirement in 2005, he was Sterling Professor of Mathematical Sciences. His awards include the Wolf Prize for Physics in 1993, the Lewis Fry Richardson Prize of the European Geophysical Society in 2000, the Japan Prize in 2003, and the Einstein Lectureship of the American Mathematical Society in 2006.
The small asteroid 27500 Mandelbrot was named in his honor. In November 1990, he was made a Knight in the French Legion of Honor. Mandelbrot emphasized the use of fractals as realistic and useful models of many “rough“ phenomena in the real world. Natural fractals include the shapes of mountains, coastlines and river basins; the structures of plants, blood vessels and lungs; the clustering of galaxies; and Brownian motion. Fractals are found in human pursuits, such as music, painting, architecture, and stock market prices. Mandelbrot believed that fractals, far from being unnatural, were in many ways more intuitive and natural than the artificially smooth objects of traditional Euclidean geometry: Clouds are not spheres, mountains are not cones, coastlines are not circles, and bark is not smooth, nor does lightning travel in a straight line.
Chris Anderson, curator of TED conferences, described Mandelbrot as “an icon who changed how we see the world.“ Former French President Nicolas Sarkozy said Mandelbrot had “a powerful, original mind that never shied away from innovating and shattering preconceived notions“. Sarkozy also added, “His work, developed entirely outside mainstream research, led to modern information theory.“ Mandelbrot’s obituary in The Economist points out his fame as “celebrity beyond the academy“ and lauds him as the “father of fractal geometry.“
Mandelbrot died in a hospice in Cambridge, Massachusetts, on 14 October 2010 from pancreatic cancer, at the age of 85. Reacting to news of his death, mathematician Heinz-Otto Peitgen said “if we talk about impact inside mathematics, and applications in the sciences, he is one of the most important figures of the last 50 years.“
First Gene Therapy Study in Human Salivary Gland Shows Promise
Aquaporin-1 encodes a protein that naturally forms pore-like water channels in the membranes of cells to help move fluid, such as occurs when salivary gland cells secrete saliva into the mouth.
Although sometimes overlooked, salivary glands present an ideal target for gene therapy. They are easily accessible and, once a gene is introduced, it has no obvious escape route into the bloodstream, where it can have unintended consequences. If treatment proves safe and effective, it could help cancer survivors with chronic dry mouth
According to an article published online in the Proceedings of the National Academy of Sciences (5 November 2012), the first-ever safety, or Phase I, clinical study of gene therapy in a human salivary gland has been performed and demonstrated that gene therapy can be performed safely in the human salivary gland. The study also showed that the transferred gene, Aquaporin-1, has great potential to help head and neck cancer survivors who battle with chronic dry mouth. These initial results clear the way for additional gene therapy studies in the salivary glands.
“You cannot imagine how fulfilling it is to jot down an idea on a napkin in 1991 and then see it enter a clinical trial and help people.,“ said Bruce Baum, D.M.D., Ph.D., lead author on the study and recently retired NIDCR scientist who spent the last 21 years moving gene therapy in the salivary glands from the research bench to the clinic. “Can a scientist ask for anything better?“
Baum’s interest in helping head and neck cancer survivors dates to the early 1980s. While attending to patients in the NIDCR’s Dry Mouth Clinic, Baum encountered numerous people with head and neck cancer who had received radiation therapy to shrink their tumors. The radiation, while effective in treating cancer, had inadvertently damaged nearby salivary glands, compromising their ability to secrete saliva into the mouth.
Baum said he was thoroughly frustrated at the time because he had no effective moisture-restoring treatments to offer most patients. They had beaten cancer, but the radiation had left them with a permanent parched sensation in their mouths that diminished their quality of life and often led to chronic oral problems, such as difficulty swallowing, inflammation, infection, bad breath, and pain.
In the early 1990s, as the first gene-therapy studies entered research clinics, Baum saw an opportunity to make a difference. An initial napkin sketch of the procedure and 15 years of research later, Baum and his colleagues had assembled a compelling scientific case in animal studies that the transferred Aquaporin-1 gene, once expressed, will create new water channels in the impermeable salivary gland cells and allow water to flow through them. After rigorous reviews by NIH and the U. S. Food and Drug Administration, the Phase I protocol was launched and the first patients treated in 2008.
In the clinical trial, 11 head and neck cancer survivors were given a single-dose injection of the Aquaporin-1 gene directly into one of their two parotid salivary glands, the largest of the major salivary glands. The gene was packaged in a disabled, non-replicating adenovirus, the cause of the common cold when intact but incapable of causing a cold in this case. As is standard in gene therapy studies, the virus served as the vector, or Trojan horse, to deliver the gene into the cells lining the salivary gland. Results showed that five participants had increased levels of saliva secretion, as well as a renewed sense of moisture and lubrication in their mouths, within the study’s first 42 days. Of the six who didn’t benefit from gene therapy, none had serious side effects. The most common side effect was a transient and relatively minor immune response against the disabled adenovirus.
Novel Genes May Drive Rare, Aggressive Form of Uterine Cancer
Cancer of the uterine lining, or endometrium, is the most commonly diagnosed gynecological malignancy in the United States. Also called endometrial cancer, it is diagnosed in about 47,000 American women and leads to about 8,000 deaths each year. Each of its three major subtypes — endometrioid, serous and clear-cell — is caused by a different constellation of genetic alterations and has a different prognosis. Endometrioid tumors make up about 80% of diagnosed tumors. Surgery often is a complete cure for women with the endometrioid subtype, since these cases are often diagnosed at an early stage. Compared to other subtypes, the 2 to 10% of uterine cancers that comprise the serous subtype do not respond well to therapies. The five-year survival rate for serous endometrial cancer is 45%, compared to 65% for clear-cell and 91% for endometrioid subtypes. Serous and clear-cell endometrial tumor subtypes are clinically aggressive and quickly advance beyond the uterus.
According to a study published online in Nature Genetics (28 October 2012), several genes have been identified that are linked to one of the most lethal forms of uterine cancer, serous endometrial cancer. The study describes how three of the genes found in the study are frequently altered in the disease, suggesting that the genes drive the development of tumors.
To determine which genes are altered in serous endometrial cancer, the authors undertook a comprehensive genomic study of tumors by sequencing their exomes, the critical 1 to 2% of the genome that codes for proteins. The authors focused on the rarer, more aggressive forms of endometrial cancer. They began their study by examining serous tumor tissue and matched normal tissue from 13 patients. National Cancer Institute and Massachusetts General Hospital pathologists processed the 26 tissue samples, which subsequently underwent whole-exome sequencing at the NIH Intramural Sequencing Center.
With the exome data in hand, the authors filtered through millions of data points to locate alterations, or mutations. They disqualified from the analysis any mutation found in a tumor and its matched healthy tissue, looking expressly for mutations that occurred exclusively in the tumor cells. They also eliminated one of the 13 tumors from analysis because its exome had hundreds more unique mutations than any other tumor. The study detected more than 500 somatic mutations within the remaining 12 tumors. The study next looked for genes that were mutated in more than one of the tumors. An alteration that occurs in more than one tumor is more likely to be relevant to the development of the cancer than a unique alteration. The authors felt confident that alterations in nine genes could be driver genes in serous endometrial cancer. Three of the nine genes had previously been recognized by researchers in the cancer genetics field as a cause of serous endometrial cancer. To get a clearer picture of driver gene status among the other six genes, the authors sequenced each gene in 40 additional serous endometrial tumors. They discovered that three of the six genes – CHD4, FBXW7 and SPOP – are altered at a statistically high frequency in serous endometrial cancer.
The team also found that this set of three genes is mutated in 40% of the serous endometrial cancer tumors and in 15 to 26% of the other endometrial cancer subtypes. Probing still further, the authors looked for the same genes highlighted by their exome sequencing study within databases that organize genes according to their biological function. They found an enrichment of genes involved in chromatin remodeling, the dynamic process by which the contents of the cell nucleus, including DNA, are packaged and modified. Chromatin remodeling enables tightly packaged DNA to be accessed for the expression of genes. Intriguingly, CHD4 was one of the genes that formed the chromatin-remodeling cluster.
The authors also noted frequent mutations in genes that regulate a process known as ubiquitin-mediated protein degradation. The process targets unneeded proteins for destruction, and thus prevents them from accumulating within the cell. Left to accumulate, some of the target proteins are known to drive cancer formation. FBXW7 and SPOP are both known to play a role in binding to the unneeded proteins and targeting them for destruction. Many of the FBXW7 gene mutations that were identified are known in other cancers to be driver mutations that prevent the FBXW7 protein from binding to its target protein. The authors believes that altered SPOP may behave the same way. The current findings build on the team’s 2011 study that showed for the first time that alterations in the PIK3R1 gene occur in all subtypes of endometrial cancer and are most frequent in the more common endometrioid subtype.
New Mechanism of Action for Class of Chemotherapy Drugs
In recent years, drugs classified as PARP inhibitors have been shown to be promising anticancer agents for breast and ovarian cancer. Members of the PARP family of proteins are involved in a number of critical cellular processes, including DNA damage repair and programmed cell death. Prior to this study, PARP inhibitors were thought to work primarily by blocking PARP enzyme activity, thus preventing the repair of DNA damage and ultimately causing cell death. The PARP family of proteins in humans includes PARP1 and PARP2, which are DNA binding and repair proteins. When activated by DNA damage, these proteins recruit other proteins that do the actual work of repairing DNA. Under normal conditions, PARP1 and PARP2 are released from DNA once the repair process is underway.
According to a study published online in Cancer Research (1 November 2012), a significant new mechanism of action has been discovered for PARP inhibitors. In this study, the authors established that PARP inhibitors have an additional mode of action: localizing PARP proteins at sites of DNA damage, which has relevance to their anti-tumor activity. The trapped PARP protein-DNA complexes are highly toxic to cells because they block DNA replication. When the authors tested three PARP inhibitors for their differential ability to trap PARP proteins on damaged DNA, they found that the trapping potency of the inhibitors varied widely. The study showed that when bound to PARP inhibitors, PARP1 and PARP2 become trapped on DNA. The authors showed that trapped PARP-DNA complexes are more toxic to cells than the unrepaired single-strand DNA breaks that accumulate in the absence of PARP activity, indicating that PARP inhibitors act as PARP poisons.
In collaboration with James Doroshow, M.D., deputy director for clinical and translational research at NCI, the investigators used PARP assays (ways of measuring PARP activity in cells and tissues) to compare three PARP inhibitor compounds that are currently in clinical testing: MK-4827, olaparib, and veliparib. The authors found that the three PARP inhibitors differed in their ability to inhibit PARP enzyme activity, with olaparib being the most potent inhibitor, followed by veliparib and then MK-4827. However, in terms of toxicity, MK-4827 was the most potent, followed by olaparib and then veliparib. Moreover, PARP1 complexes with MK-4827 and olaparib were shown to be more tightly bound to DNA than complexes with veliparib.
These findings suggest that there may be two classes of PARP inhibitors, catalytic inhibitors that act mainly to inhibit PARP enzyme activity and do not trap PARP proteins on DNA, and dual inhibitors that both block PARP enzyme activity and act as PARP poison.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area
FDA Approves Xeljanz for Rheumatoid Arthritis
Rheumatoid arthritis (RA) is an autoimmune disease, in which the body’s immune system mistakenly attacks healthy tissue leading to inflammation of the joints and surrounding tissues. According to the Centers for Disease Control and Prevention, RA affects an estimated 1.5 million Americans.
The FDA has approved Xeljanz (tofacitinib) to treat adults with moderately to severely active (RA) who have had an inadequate response to, or who are intolerant of, methotrexate. Xeljanz, a pill taken twice daily, works by blocking molecules called “Janus kinases,“ which are important in the joint inflammation of RA.
Xeljanz is being approved ahead of the product’s prescription drug user fee goal date of 21 November 2012, the date the agency was scheduled to complete review of the drug application.
The safety and effectiveness of Xeljanz were evaluated in seven clinical trials in adult patients with moderately to severely active RA. In all of the trials, patients treated with Xeljanz experienced improvement in clinical response and physical functioning compared to patients treated with placebo. The use of Xeljanz was associated with an increased risk of serious infections, including opportunistic infections (infections that occur primarily when the immune system is suppressed), tuberculosis, cancers and lymphoma. Xeljanz carries a Boxed Warning regarding these safety risks. Xeljanz treatment is also associated with increases in cholesterol and liver enzyme tests and decreases in blood counts.
The FDA approved Xeljanz with a Risk Evaluation and Mitigation Strategy (REMS), which consists of a Medication Guide advising patients about important safety information and a communication plan to inform health care providers about the serious risks associated with Xeljanz. To study the long-term effects of Xeljanz on heart disease, cancer, and serious infections, the FDA is requiring a postmarketing study that will evaluate two doses of Xeljanz and include a group of patients on another approved treatment to serve as a comparison.
The most common adverse reactions in clinical trials were upper respiratory tract infections, headache, diarrhea, and inflammation of the nasal passage and the upper part of the pharynx.
Xeljanz is marketed by New York-based Pfizer Inc.
Beef Stroganoff a la Hensby
We are gratified to know that our subscribers (now over 4,500) are enjoying the Target Healthy Eating section of the weekly newsletter. Everyone is invited to interact with it, as they choose (send letters, photos, comments, recipes, articles, jokes, etc).
The recipe below, is an international effort. The original one, sent in French by our colleague and gourmet part-time chef, Chris Hensby, living in Saint-Germain-en-Laye, suburb of Paris, was translated by Adam Harris of Target Health Inc. and handed back to Joyce Hays of Target Health Inc., who prepared it this past Wednesday night and sampled it with Jules Mitchel, also of Target Health Inc.
We are honored to present to you, a French recipe, the original Christopher Hensby French recipe and a slightly altered Joyce Hays version, greatly enjoyed on Wednesday night.
First prepare the onions and mushrooms
Add the beef and Creme fraiche (or sour cream) — smack your lips
Voila! Boeuf Stroganoff a la Hensby
Boeuf Stroganoff a la Hensby
- 2 oignions couper finement.
- 500 a 600 g de champignon de Paris couper en tranche de 2 a 3 mm.
- Sel et poivre
- 50ml de Cognac ou Armagnac
- 100 ml de bouillon de boeuf
- 2CS Creme fraiche 5%
- 1CS soit de moutard de Dijon ou de prefrrence a la ancienne.
- 2 a 3 CS Paprika en poudre.
- 3CS huile d’olive
- 3CS Beurre demi-sel.
- 600 g de filet du boeuf ou de boeuf bon qualite/prix couper en morceaux de 4 a 5 cm de longueur par 1cm de largeur par 0.5 cm de profondeur.
- Dans un poele ajuter 1CS du beurre et 1 CS huile d’olive, chauffe, rajoute les champignons et fiat dore. Ajouter le cognac / armagnac et chauffe fortement / flambee pendant 10 a 20 secondes.
- Rajouter la creme fraiche et bien melange et garde tiede.
- Mettez l’oignon dans un autre poele avec 1CS du beurre et 1 CS huile d’olive et chauffer jusqu’a ils sont mou.
- Transfere aux champignons et nettoyer le poele.
- Rajouter le paprika (soit 3CS ou 2CS paprika plus 1CS de moutarde au choix), le bouillon de boeuf et chauffer doucement.
- Dans l’autre poele, mettez 1CS du beurre et huile d’olive dans et bien chauffe.
- Saisonnier le viande avec sel et poivre et rajouter au poele bien chaud, tourner et dore sure tous les cotes.
- Rajouter a l’autre poele et fait la cuisson pendant environ 10 minute ( plus long si la viande et plus dur que le filet de b?uf ou on prefere qu’il soit bien cuit).
- On peut varier la dose de paprika et la dose et choix de moutard pour changer le gout.
Boeuf Stroganoff a la Hensby (the American version)
- 2 onions finely chopped.
- 1 pound mushrooms (I used shitake) cut every 2 to 3 mm.
- Salt and pepper
- 50 ml or 1 3/4 oz Cognac or Armagnac
- 100 ml or 3 1/2 oz (almost 1/2 cup) beef stock
- 2 tablespoons Creme fraiche 5%
- 1 tablespoon Dijon mustard
- 2 to 3 tablespoons Paprika powder
- 3 tablespoons olive oil
- 3 tablespoons salted butter (I substituted olive oil)
- 600 g or 1.31 lbs. (21 oz.) fillet of good quality beef cut into small cubes about 4 to 5 cm (1.5 to 2 inches) long. (I used fillet mignon)
- Wide egg noodles made in advance (I used Shirataki soy wide noodles)
- In a skillet add 1 tablespoon of butter and 1 tablespoon olive oil, heat, add the mushrooms and brown. Add the cognac / armagnac, heat on high for 10 to 20 seconds.
- Add the creme fraiche, mix well and keep warm.
- Put the onion in another pan with 1 tablespoon butter and 1 tablespoon olive oil and heat until soft.
- Add the mushrooms to the onions and clean the remaining pan.
- Add the paprika (either 3 tablespoons paprika or 2 tablespoons paprika plus 1 tablespoon mustard), beef broth and heat gently.
- In the clean pan, put 1 tablespoon butter and olive oil and heat well.
- Season meat with salt and pepper and add to the hot pan, brown on both sides.
- Add to the other pan with the mushrooms and continue cooking for about 10 minutes. (Longer if the meat is tougher or you prefer it well done).
- You can vary the amount of paprika and mustard according to taste.
- You are going to want to sop up the gravy with some bread or rolls.
Serve this delicious Stroganoff over the egg noodles with warm bread or rolls, so you can sop up the gravy, your favorite simple tossed salad and a glorious full-bodied red wine (Merlot, French, naturally) that envelopes you like a hug or a warm fleece throw. Let the winter winds howl, with this menu you are assured of peace and harmony and a delicious experience, with your best friend.
Cheers! Pour your favorite Merlot
Cheers! New adventure with Guigal Chateau D’Ampuis Cote Rotie 2004
A Peek at the gorgeous Paris suburb of Saint-Germain-en-Laye
The Terrace at Saint-Germain, Spring, 1875 by Alfred Sisley. The Walters Art Museum.
Saint-Germain-en-Laye, founded in 1020, is one of the most elegant and beautiful suburbs of Paris. It has always been an important historical location for royalty, for Napoleon during the French Revolution, and for the French underground during World War II. St Germain en Laye was the German Army Headquarters during the occupation from 1940 to 1944. As a consequence, the city became an active center of the French Resistance.
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