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Fighting cancer with immunotherapy: Signaling molecule causes regression of blood vessels

Immunotherapy with T-cells offers great hope to people suffering from cancer. Some initial successes have already been made in treating blood cancer, but treating solid tumors remains a major challenge. The signaling molecule interferon gamma, which is produced by T-cells, plays a key role in the therapy. It cuts off the blood supply to tumors, as a new study reveals.

A microscopic image of tumor tissue under the influence of TNF (left) and IFN- ? (right). Red blood cells are pictured in a magenta color. TNF bursts the blood vessels and releases large amounts of blood cells, whereas IFN-? lets vessels retreat.
Credit: Christian Friese / MDC

Immunotherapy with T-cells offers great hope to people suffering from cancer. Some initial successes have already been made in treating blood cancer, but treating solid tumors remains a major challenge. The signaling molecule interferon gamma, which is produced by T-cells, plays a key role in the therapy. It cuts off the blood supply to tumors, as a new study in the journal Nature reveals.

The immune system is the body’s most powerful weapon against diseases. So what if it were possible to use the immune system to fight cancer? For a long time now, researchers have been trying to do just that — for example, by employing a special kind of immune cell called T-cells. They are „special mobile forces“ that — after undergoing training — patrol the body, and can seek out and kill cancer cells. This strategy has been successful in initial clinical trials — but mostly just in the treatment of cancers that do not form tumors, such as blood cancer.

Good at fighting blood cancer, but not so effective against solid tumors

Large solid tumors, on the other hand, sometimes pose big problems for T-cells. Though adept at targeting cancer cells swimming in the bloodstream, they have difficulty attacking compact tumors. The tumor weakens the aggressors through the delivery of inhibiting signals.

The scientists working with Dr. Thomas Kammertöns, Prof. Thomas Blankenstein, Prof. Hans Schreiber and Christian Friese are searching for solutions with their research team at Charité — Universitätsmedizin Berlin, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute of Health (BIH) and the Einstein Foundation.

In a study published in the journal Nature, they investigated how the signaling molecules of T-cells affect the immediate tumor environment, which includes the connective tissue as well as the blood vessels that supply the tumor.

T-cells produce not only tumor necrosis factor (TNF) but also the molecule interferon gamma (IFN-γ). Until now, however, there has been little understanding about how IFN-γ really works. „We knew that IFN-γ attacks cancer cells via the tumor microenvironment,“ says Kammertöns. „We now wanted to find out exactly which cells are targeted by the signaling molecules.“

Blood vessel regression is induced

The researchers generated genetically modified mice and used a clinically relevant cancer model. This included animals in which only blood vessel cells were susceptible to the signaling molecule.

In this mouse model IFN-γ pruned back the blood vessels in the tumors, thus shutting down the supply of oxygen and nutrients and killing the tumors. The researchers were able to observe this process microscopically in living mice in fine detail. They found that the blood vessel cells alone responded to the signaling molecule. When the researchers targeted other types of cells with IFN-γ, the tumors continued their growth.

These findings provided an explanation for the molecule’s powerful properties, which were already well known. „IFN-γ is one of the most important weapons in the T-cells‘ arsenal,“ says Thomas Kammertöns.

Thomas Blankenstein, lead investigator of the study, says: „The two together — IFN-γ and tumor necrosis factor — are a powerful team. TNF bursts tumor blood vessels, thus opening up the tissue, while IFN-γ cuts off the blood supply and keeps the tumor at bay over the long term.“

Optimizing T-cell therapy

The study offered the researchers clues on how to improve T-cell therapy for solid cancer tumors. Thomas Blankenstein explains: „We want to understand exactly how T-cells target tumors. Destroying a tumor’s infrastructure is probably more effective than killing individual cancer cells.“

„Our findings are significant beyond tumor therapy,“ says Thomas Kammertöns. „Interestingly, the mechanism used by IFN-γ to eliminate solid tumors resembles the physiological regression of blood vessels during development. It also disrupts wound healing.“

„IFN-γ might also affect the formation of new blood vessels after strokes or heart attacks. That’s why we want to find out more about the molecular processes behind all of this.“


Story Source:

Materials provided by Max Delbrück Center for Molecular Medicine in the Helmholtz Association. Note: Content may be edited for style and length.


Journal Reference:

  1. Thomas Kammertoens, Christian Friese, Ainhoa Arina, Christian Idel, Dana Briesemeister, Michael Rothe, Andranik Ivanov, Anna Szymborska, Giannino Patone, Severine Kunz, Daniel Sommermeyer, Boris Engels, Matthias Leisegang, Ana Textor, Hans Joerg Fehling, Marcus Fruttiger, Michael Lohoff, Andreas Herrmann, Hua Yu, Ralph Weichselbaum, Wolfgang Uckert, Norbert Hübner, Holger Gerhardt, Dieter Beule, Hans Schreiber, Thomas Blankenstein. Tumour ischaemia by interferon-γ resembles physiological blood vessel regression. Nature, 2017; DOI: 10.1038/nature22311

Max Delbrück Center for Molecular Medicine in the Helmholtz Association. „Fighting cancer with immunotherapy: Signaling molecule causes regression of blood vessels.“ ScienceDaily. ScienceDaily, 26 April 2017. <www.sciencedaily.com/releases/2017/04/170426131018.htm>

Quelle: Fighting cancer with immunotherapy: Signaling molecule causes regression of blood vessels

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Tests To Help With Breast Cancer Treatment Decisions

Herzlichen Dank an The Breast Cancer Authority!

When you’ve just received a diagnosis of breast cancer, you are faced with many different treatment options. Your mind is in a whirl with fear, confusion, and disbelief. While none of these feelings help decision making, there are some tests that can help: Oncotype DX and Mammaprint. 

These tests are genomic tests that analyze the activity of specific genes in the breast tumor. They can help you determine if your risk of breast cancer coming back is high or low, which can help you in making a decision about whether to have chemotherapy, radiation, or other therapies to reduce risk after surgery.

There are two main types of tests – Oncotype DX and Mammaprint.

Oncotype Dx has two tests for breast cancer – one for Ductal Carcinoma in situ (DCIS) – Oncotype DX DCIS and one for invasive breast cancer – Oncotype DX.  Mammaprint has one test for invasive breast cancer. Let’s look at these in greater detail.

What are genomic tests?

Genomic tests look at specific genes in your individual tumor and try to determine what is driving its growth. This is different from genetic tests which look at your inherited risk or predisposition for cancer. Genomic tests provide information that can help tailor your treatment plan to you as an individual. They are a type of personalized medicine. This is really important, because not all breast cancers are the same and, in fact, some breast cancers might have more in common with a prostate cancer than they do with another type of breast cancer. One size treatment definitely does not fit all.

Oncotype DX DCIS

This test is only for people diagnosed with DCIS or, as it is often called, “stage zero” breast cancer. In addition to general information such as tumor size, margins, and grade, Oncotype DX DCIS helps determine the likelihood of DCIS recurring or invasive breast cancer occurring within the next 10 years.

It examines a sample of the tumor tissue that has already been removed during the lumpectomy for DCIS. By looking at the expression of 21 different genes in the tumor, it provides a DCIS score of between 0-100. The lower the score, the lower the risk of recurrence. Two scores are given, one to determine the risk of recurrence of DCIS and another for the risk of occurrence of an invasive breast cancer.

Knowing the DCIS score can help you decide whether to have radiation treatment  following the lumpectomy. If your risk of recurrence is low, then maybe you can spare yourself further treatment and the possible side effects that go with it.

To be eligible for Oncotype DX DCIS, you need to have recently been diagnosed with DCIS and had lumpectomy surgery. The decision should be made in discussion with your doctor/oncologist.

In the US, insurance might cover the cost of this test; the testing company will help you determine if this is the case and provide information to your insurers, as necessary. In the UK, these tests can be conducted under the NHS or privately.

Many oncologists are now familiar with these tests for invasive breast cancer; sadly, the Oncotype DX DCIS test does not appear to be known by all oncologists, so it’s good for you to be proactive and start the discussion. Here is a link to the validation work done on the test that you can forward to your oncologist, and further links are given at the bottom of this post:

Clinical validation of oncotype DX DCIS

I definitely think it is worth having a discussion with your oncologist, sharing the references as necessary, and if you don’t get anywhere with the oncologist, talk to your family doctor or surgeon.

Oncotype DX and Mammaprint

Both Oncotype DX and Mammaprint are genomic tests suitable for early stage invasive breast cancer. They both predict the benefit of chemotherapy or other types of treatment, as well as the likelihood of 10 year recurrence.

They are similar tests but have some differences, as outlined below:

Comparison of oncotype DX and mammaprint for invasive breast cancer

Looking at this table can help determine if you are eligible for either of these tests.

As with Oncotype DX DCIS, some insurance companies in the US will pay for these tests whereas some don’t include them in coverage. Both testing companies offer financial assistance or guidance, so it’s worth calling them to discuss if you are interested and want to check coverage. In the UK, these tests can be conducted under the NHS or privately.

These tests are important because some of the cancer treatments, like chemotherapy, can have many side effects and are hard to get through. If there is little to no benefit in these treatments for you as an individual, then these genomic tests give you the confidence to not have a treatment that has greater potential for risk than for benefit.

Obviously the decision of further treatment is based on more than just these results. It involves detailed discussion with your oncologist, but also personal consideration of what you want and how you feel. Remember, you can take your time over treatment decisions. You might feel rushed, but take adequate time until you feel comfortable that you are making the right personal decision. These tests can go a long way in giving you confidence in your decision, but it is still a personal choice that needs to be right for you as an individual based on your mind and spirit, as well as your body.

Here are links to each of these three tests for more information

Patient information on Oncotype DX DCIS

Oncologist information on Oncotype DX DCIS

Patient information on Oncotype DX

Oncologist information on Oncotype DX

Patient information on Mammaprint

Oncologist information on Mammaprint

Let me know if you’ve had any of these tests and how they helped you.

Ruth BaillieRuth Baillie is originally from the UK and now lives most of the year in Northern California. She holds two Master’s degrees, one in Personalized Nutrition (distinction), and another in Health Psychology. She is a Registered Nutritional Therapist, Certified Professional Cancer Coach, and Cancer Guide, and has undertaken considerable post-graduate studies in integrative naturopathic oncology. She is the author of “Choices in mind-body medicine for cancer patients in Sonoma County, California” and her research has been published in peer-reviewed journals.

 

Tests To Help With Breast Cancer Treatment Decisions


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Herantis Pharma’s clinical study with Lymfactin advances to high dose level

Herantis Pharma’s clinical study with Lymfactin advances to high dose level

Herantis Pharma Plc
Company release 6 March 2017 at 10:00 am

Herantis Pharma Plc’s („Herantis“) clinical study with the company’s innovative gene therapy investigational product Lymfactin® for the treatment of secondary lymphedema has advanced to highest planned dose level owing to good reported safety. A Data Monitoring Committee of independent experts recommended proceeding to high dose treatments after assessing safety data on the previously treated patients. Following the recommendation, the first high dose treatment has already been administered.

 „We are naturally very happy for the safety of Lymfactin® in the first treatments“, comments Pekka Simula, Herantis‘ CEO. „This is the first clinical study in the world to apply gene therapy for repairing damages of the lymphatic system. Safety of the patients is our #1 priority so we want to move ahead carefully. We are thrilled to announce this milestone by coincidence on March 6: World Lymphedema Day!“

„Collaboration with the participating university hospitals in this study has been excellent“, adds Katarina Jääskeläinen, Herantis‘ Project Manager for the clinical study. „Secondary lymphedema is a disfiguring, disabling disease that severely impacts the quality of life of patients. We hope our Lymfactin® will significantly improve the quality of life of patients in the future.“

The Phase 1 clinical study continues recruiting patients with breast cancer associated lymphedema at three university hospitals in Finland: In Helsinki, Tampere, and Turku. The study intends to recruit at most 18 patients by the end of 2017.

World Lymphedema Day

March 6 was officially recognized World Lymphedema Day since 2015 by e.g. the U.S. Senate. It is celebrated around the world largely thanks to the patient advocacy group Lymphatic Education & Research Network (LE&RN) to increase lymphedema awareness.

About breast-cancer associated lymphedema

Approximately 20% of breast cancer patients who undergo axillary lymph node dissection develop secondary lymphedema, a chronic, progressive, disabling and disfiguring disease that severely affects quality of life. Symptoms include a chronic swelling of an upper limb, thickening and hardening of skin, loss of mobility and flexibility, pain, and susceptibility to secondary infections. Secondary lymphedema is currently treated with compression garments, special massage, and exercises. While these therapies may relief the symptoms in some patients they do not cure lymphedema, which is caused by damage to the lymphatic system. There are currently no approved medicines for the treatment of this condition.

About Lymfactin®

Lymfactin® is a gene therapy expressing the growth factor VEGF-C specific to the development of lymphatic vessels. Based on preclinical studies Lymfactin® triggers the growth of new functional lymphatic vasculature in the damaged area and thus repairs the underlying cause of secondary lymphedema. Lymfactin®, patented by Herantis, is based on the internationally renowned scientific research of academy professor Kari Alitalo and his research group, a national centre of excellence at the University of Helsinki. Herantis also holds patents for a combination therapy, which may expand the use of Lymfactin® in other lymphedemas. See our introductory video on Lymfactin®: http://herantis.com/media/videos/

About Herantis Pharma Plc

Herantis Pharma Plc is an innovative drug development company focused on regenerative medicine and unmet clinical needs. Our first-in-class assets are based on globally leading scientific research in their fields: CDNF for disease modification in neurodegenerative diseases, primarily Parkinson’s and ALS; and Lymfactin® for breast cancer associated lymphedema, with potential also in primary lymphedema. The shares of Herantis are listed on the First North Finland marketplace run by Nasdaq Helsinki Ltd.

Distribution:

Nasdaq Helsinki
Main media
http://www.herantis.com

https://globenewswire.com/news-release/2017/03/06/931689/0/en/Herantis-Pharma-s-clinical-study-with-Lymfactin-advances-to-high-dose-level.html?utm_content=buffer4533b&utm_medium=social&utm_source

 

LE&RN Symposium Real-time Visualization of Lymph Movement

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https://livestream.com/LymphaticRF/Aldrich

Thanks for all the fantastic work you are doing Lymphatic Education & Research Network !


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Primäre Lymphödeme-Hereditary Lymphedema – NORD (National Organization for Rare Disorders)

Quelle: Hereditary Lymphedema – NORD (National Organization for Rare Disorders)

Hereditary Lymphedema

NORD gratefully acknowledges Joseph L. Feldman, MD, Senior Clinician Educator, Pritzker School of Medicine University of Chicago; Director, Lymphedema Treatment Center, NorthShore University Health System, for assistance in the preparation of this report.

Synonyms of Hereditary Lymphedema

  • primary lymphedema

Subdivisions of Hereditary Lymphedema

  • congenital hereditary lymphedema
  • hereditary lymphedema, type I
  • lymphedema-distichiasis
  • lymphedema praecox
  • lymphedema tarda
  • Milroy disease
  • Nonne-Milroy disease

General Discussion

Hereditary lymphedema is a genetic developmental disorder affecting the lymphatic system. It is characterized by swelling (edema) of certain parts of the body. The lymphatic system is a circulatory network of vessels, ducts, and nodes that filter and distribute certain protein-rich fluid (lymph) and blood cells throughout the body. In hereditary lymphedema, lymphatic fluid collects in the subcutaneous tissues under the epidermis due to obstruction, malformation, or underdevelopment (hypoplasia) of various lymphatic vessels. There are three forms of hereditary lymphedema: congenital hereditary lymphedema or Milroy disease; lymphedema praecox or Meige disease; and lymphedema tarda. Symptoms include swelling (lymphedema) and thickening and hardening of the skin in affected areas. In most cases, hereditary lymphedema is inherited as an autosomal dominant trait. Lymphedema may be classified as primary or secondary. Hereditary lymphedema is also known as primary lymphedema. Secondary lymphedema occurs because of damage to the lymphatic system from surgery, radiation therapy, trauma or infection (e.g. filariasis). Lipedema is a symmetrical accumulation of subcutaneous fat, most often in the legs. Lipedema occurs almost exclusively in females. Tenderness and bruising are also common. Typically, the feet are not swollen and thickening of the skin of the toes (Stemmer’s sign).  Lipedema is frequently misdiagnosed as lymphedema.

Signs & Symptoms

The main symptom associated with hereditary lymphedema is swelling (edema) or puffiness in different parts of the body because of the accumulation of protein-rich fluid (lymph) in the soft layers of tissue under the epidermis (lymphedema). Swelling frequently occurs in one or both legs, but may also be present in the trunk, face, genitalia and arms. When lymphedema develops in the legs, swelling is usually most noticeable in the foot and ankle but may also be present in the calf and thigh.. In some cases, swelling may cause tightness, discomfort and unusual tingling sensations (paresthesias) in the affected areas. The affected area heals poorly even after minor trauma (e.g., cut or insect bite). The skin of the affected area may become abnormally dry, thickened or scaly skin (hyperkeratosis) resulting in a “woody” texture.

Hereditary lymphedema type IA (Milroy’s disease) is characterized by swelling (edema) that is present at or shortly after birth (congenital). In rare cases, edema may develop later in life. The legs are most often affected. The extent and location of edema varies greatly from case to case even among individuals in the same family. In some cases the genitals may also be affected. Additional complications sometimes associated with hereditary lymphedema type I include upslanting toenails, small warty growths on the affected areas (papillomatosis), abnormally large or prominent leg veins, and, in males, urethral abnormalities and the development of a fluid-filled sac along the spermatic cord of the scrotum (hydrocele).

Hereditary lymphedema type II (Meige disease, lymphedema praecox) develops around puberty or shortly thereafter in most individuals. This is the most common type of primary lymphedema. In addition to lymphedema of the legs, other areas of the body such as the arms, face and larynx may be affected. Some individuals may develop yellow nails.

Lymphedema tarda is defined as primary lymphedema occurring after the age of 35. The legs are most often affected, but the arms and other areas may be affected as well.

Hereditary lymphedema may progress and, in some cases, may improve over time. Obesity makes management of lymphedema more difficult. Affected individuals with lymphedema are at risk for developing infections including bacterial infection of the skin and underlying tissue (cellulitis) or infection of the lymphatic vessels (lymphangitis). These infections are characterized by areas of warm, painful and reddened skin. Red skin “streaks” may also develop in the infected area. Increased edema is common. A general feeling of ill health (malaise), fever, chills, and/or headaches may also occur. If left untreated, cellulitis can lead to septicemia, skin abscesses, areas of ulceration, and/or tissue damage (necrosis). Cellulitis is more common in males than females. Athlete’s foot (Tinea pedis) can cause cracks in the interdigital skin, bacterial invasion and cellulitis.

In rare cases of persistent lymphedema, additional complications may develop including fluid (e.g., chyle) accumulation body cavities such as the thorax (chylothorax) and abdomen (chylous ascities). Chyle is a fat-laden cloudy fluid that is absorbed during digestion by the lymphatic vessels located around the intestine. Chyle normally flows through lymphatic vessels into the upper chest (thoracic duct) and is then deposited into veins, where it mixes with blood. In some people with hereditary lymphedema, the lymphatic vessels may rupture or become blocked (obstructed), causing chyle to accumulate in the chest cavity (chylothorax). A patient with primary chylous ascites needs to be on a no-fat diet supplemented with medium chair triglycerides and vitamins. Addition of a diuretic such as Spironolactone has been reported to be a valuable adjunct to dietary control.

Affected individuals may also be at a greater risk than the general population for developing a malignancy at the affected site. These malignancies include angiosarcoma. Angiosarcomas are cancerous tumors that develop from blood or lymphatic vessels. They may occur in any area of the body. A specific type of angiosarcoma is known as lymphagiosarcoma, or Stewart-Treves syndrome. This cancerous tumor may rarely develop in longstanding cases of primary or secondary lymphedema. Angiosarcoma occurs in the lymphedematous extremity but can spread to the adjacent trunk and lungs.

Causes

Many researchers believe that hereditary lymphedema may result from changes (mutations) in one of the different disease genes (genetic heterogeneity). Most cases of hereditary lymphedema type IA and type II are inherited as autosomal dominant traits. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

Investigators have determined that some cases of hereditary lymphedema type IA (Milroy’s disease) occur because of mutation in the FLT4 gene which encodes of the vascular endothelial growth factor receptor 3 (VEGFR-3) gene located on the long arm (q) on chromosome 5 (5q35.3). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 5q35.3” refers to band 35.3 on the long arm of chromosome 5. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Investigators have determined that some cases of hereditary lymphedema type II (Meige disease) occur because of mutations of the ‘forkhead’ family transcription factor (FOXC2) gene located on the long arm (q) of chromosome 16 (16q24.3).

Affected Populations

Hereditary lymphedema affects females more often than males. The estimated prevalence of these disorders is 1 in 6,000 individuals within the general population. Hereditary lymphedema type II (Meige syndrome) is the most common form accounting for approximately 80 percent of cases. The prevalence of hereditary lymphedema type I (Milroy disease) is unknown. Approximately 200 cases have been reported in the medical literature.

Diagnosis

The diagnosis of hereditary lymphedema may be confirmed by a thorough clinical evaluation and a variety of specialized imaging tests including lymphoscintigraphy, ultrasound, and magnetic resonance imaging (MRI). During lymphoscintigraphy, a radioactively labeled colloid substance is injected intradermally into either the hands or feet. The time required for the tracer to be transported from the point of injection to the regional lymph nodes is recorded. In congenital lymphedema, the tracer may move sluggishly or not move from the site of injection. During an ultrasound, reflected sound waves create an image of the developing fetus. An ultrasound is used to rule out other conditions. A Doppler ultrasound can evaluate venous conditions such as varicose veins and venous blood clots. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. An MRI is used to detect findings characteristic of hereditary lymphedema including swelling (edema), a mass surrounded by a sac containing lymph fluid (lymphocele), and the formation of fibrous tissue (fibrosis).

Standard Therapies

Treatment

No gene therapy for hereditary lymphedema is currently available. There is no FDA approved medication to treat lymphedema. Lymphedema risk reduction practices should be followed to reduce complications such as infection and an increase in swelling. Treatment is aimed at reducing swelling and preventing infection. Complete decongestive therapy (CDT) is a form of treatment in which specialized manual techniques (manual lymph drainage) is combined with multilayered compression bandaging, meticulous skin care, exercise, and the use of well-fitted compression garments.. Decongestive and conditioning exercises are important components of CDT. Patients and their parents/caregivers should be counseled on the importance of adhering to lymphedema management recommendations to prevent progression the lymphedema. Antibiotics can be used to treat infections such as cellulitis or as a preventive (prophylactic) measure in individuals with recurrent infections. Athlete’s foot can be treated with antifungal topical medications.

Various surgical techniques have been used to treat individuals with hereditary lymphedema including the surgical joining of small lymphatic vessels to nearby small veins (microsurgical anastomosis) has had some limited success in people with lymphedema. The goal of this surgery is to reduce swelling by creating new pathways for lymphatic fluid flow and “rechanneling” this flow into the venous system. According to the medical literature, these therapies have had only limited effectiveness. Reducing operations are available to remove excess fibrotic tissue in cases of severe lymphedema. Continued use of compression garments is necessary after reducing surgery. Liposuction has not been found to be effective in primary lymphedema.

Individuals with hereditary lymphedema should avoid long periods of immobility with legs in a dependent position. Affected individuals should also take special care to avoid wounds in any affected area because of a reduced resistance to infection. Certain medications such as calcium channel blocking drugs and non-steroidal anti-inflammatory drugs may worsen swelling in the legs and the benefits and risks need to be discussed with the patient’s physician. Excessive salt intake can cause fluid retention.

Genetic counseling will benefit people with hereditary lymphedema and their families. Rehabilitation therapy may be necessary in cases where extreme lymphedema impairs daily activities.

 

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com.

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

Botanicals such as the Benzopyrones and Saponins (e.g., horse chestnut seed extract) as well as the trace element Selenium have been advocated by some as adjunctive treatments for lymphedema.

Benzopyrones, a group of substances such as coumarin, hydroxethylrutin and flavinoid derivatives, have been used for the treatment of individuals with hereditary lymphedema. These drugs breakdown proteins found in lymph and may stimulation lymph flow thereby reducing lymph accumulation and subsequent swelling. However, the effectiveness of such medications is unproven and under debate. Hepatotoxicity has been reports in up to 6% of the patients taking coumarin. More research is necessary to determine the long-term effectiveness and safety of benzopyrone therapy in individuals with hereditary lymphedema.

Occasionally, drugs that promote fluid mobilization (i.e., diuretics) have been used for people with lymphedema. These medications increase urinary output and may help to reduce swelling in some affected individuals. However, diuretics have not been proven successful in reducing the swelling in primary lymphedema but may be beneficial in patients with mixed origin edema, e.g., phlebolymphedema. The prolonged use of diuretics for the treatment of hereditary lymphedema should be carefully directed by a physician as these medications may have several long-term side effects.

Contact for additional information about hereditary lymphedema:

Joseph L. Feldman, MD
Senior Clinician Educator
Pritzker School of Medicine
University of Chicago
Director, Lymphedema Treatment Center
NorthShore University HealthSystem

 


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Understanding Lymphedema – Lymphedema & Wound Care Session – LE&RN -David Zawieja PhD

Einen super interessanten Beitrag! Herzlichen Dank für die Bereitstellung.


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Retinoic acid may significantly prevent lymphedema development, experimental model suggests

Using newly updated mouse models, researchers demonstrated the impactful preventive properties of 9-cis retinoic acid against lymphedema. Currently, there is no cure for lymphedema, a swelling of the extremities that most commonly occurs after treatment for cancer.

Quelle: Retinoic acid may significantly prevent lymphedema development, experimental model suggests

 

A study conducted at the Keck School of Medicine of the University of Southern California (USC) showed that 9-cis retinoic acid (alitretinoin) could significantly prevent postsurgical lymphedema. Furthermore, the experiments were conducted with updated, easily reproducible mouse models that more accurately simulated lymphedema development in humans. The National Institutes of Health-funded study was published in the Annals of Surgery.

Lymphedema occurs when damaged lymph nodes are unable to drain properly, causing swelling and tissue buildup. Lymphedema affects 140 million individuals globally, including 5 million people in the United States whose lymphedema is related to cancer-related lymphadenectomy. As surgical developments continue to increase cancer survival rates, the prevalence of lymphedema is expected to rise. And with no known cure for post-surgical lymphedema, lymph node dysfunction can negatively impact long-term quality of life.

„Physically, lymphedema is both uncomfortable and inconvenient,“ said Alex Wong, MD, assistant professor of surgery at Keck School of Medicine and one of the co-corresponding authors of the study. „Some patients express frustration at things we take for granted, like getting dressed. And for many of them, the swollen and deformed extremity is an unwelcome reminder of the cancer they fought or are still fighting.“

To examine the effect of alitretinoin, the research team induced lymphedema by making a small incision in the hind legs of mice rather than the base of the tail, as previous studies had done. This updated model better simulated lymph node dysfunction in humans in that rodent tails are not subject to the effects of gravity to the same extent as human arms and legs. And more simply, humans do not have a tail.

„Developing a more effective model for lymphedema research is as much of an achievement from our research as illustrating the potential benefits of retinoic acid,“ said Young-Kwon Hong, PhD, associate professor of surgery at Keck School of Medicine and co-corresponding author of the study. Hong previously illustrated the potential benefits of alitretinoin on preventing lymphedema in petri-dish models before developing the mouse model.

After the hind paw incisions were repaired, the mice were divided into two groups. One group received daily injections of 9-cis retinoic acid, while the other received a vehicle solution as a control. The mice treated with the retinoic acid experienced less postsurgical edema and significantly less paw lymphedema compared to the control group. Moreover, the mice treated with the retinoic acid had much faster lymphatic drainage and increased lymphatic vessel density.

„Lymphatic drainage and maintenance of the integrity of the lymphatic vessels are two key factors in preventing lymphedema,“ Hong said. „9-cis retinoic acid’s ability to accomplish both makes it a promising treatment option.“

Alitretinoin is already approved by the Food and Drug Administration for the treatment of skin lesions in acquired immune deficiency syndrome-related Kaposi’s sarcoma and eczema. If further studies prove fruitful, Wong hopes to establish a clinical trial for alitretinoin as a preventive measure against lymphedema.

„Our immediate next step is to experiment with timing,“ Wong said. „Currently, physicians watch and wait for lymphedema, but our study suggests that treatment at the time of surgery may be a more effective course.“


Story Source:

Materials provided by Keck Medicine of USC. Note: Content may be edited for style and length.


Journal Reference:

  1. Athanasios Bramos, David Perrault, Sara Yang, Eunson Jung, Young Kwon Hong, Alex K. Wong. Prevention of Postsurgical Lymphedema by 9-cis Retinoic Acid. Annals of Surgery, 2016; 264 (2): 353 DOI: 10.1097/SLA.0000000000001525