Such a new collaboration was recently established with Dr. Dina Lev at the Department of Cancer Biology at the MD Anderson Cancer Center in Houston Texas. The contact person from iCureASPS for this collaboration is Dr. Nancy Landfish who serves as iCureASPS Medical Affairs Director.

Recently, a member in the iCureASPS community has donated the first 5,000 dollars to support Dr. Dina Lev’s research who recently published a scientific paper: “Angiogenesis-promoting gene patterns in Alveolar Soft Part Sarcoma”. Dr. Dina Lev conducts research on the highly vascular (angiogenic) nature of ASPS because she believes that this is an important factor driving ASPS metastasis. Her laboratory evaluates gene expression of ASPS frozen samples to identify candidate genes possibly contributing to ASPS angiogenesis. Next she would like to study the importance of these genes and gene products in ASPS metastasis and their possible regulation by the ASPL-TFE3 fusion gene. Lev’s studies may potentially result in better understanding of ASPS progression, and would lead to identification of targets for the development of novel therapeutics.

The specific aims of Dr. Dina Lev are:

1) to create an annotated paraffin and frozen tissue bank for ASPS.

2) to collaborate with other scientists with an interest in ASPS research, with the aim of expanding the available bioresources.

3) to study the expression and function of potential angiogenic factors in ASPS.

4) to investigate the effect of the ASPL-TFE3 fusion gene on the expression of the studied angiogenic factors.

If you are interested to support this research of Dr. Lev, please write to Dr. Nancy Landfish at: Nancy.Landfish@HCAhealthcare.com

______________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

While efforts are made in few medical centers to develop a convenient ASPS model system, there is currently no ASPS cell line or an animal model for studying mechanisms of drug therapy on ASPS. Therefore, for his initial research on ASPS, Dr. Mark Pines performed studies on: (1) tumor samples that were donated by ASPS patients and (2) on a renal (kidney) tumor cell line derived from a patient, which contains the same genetic translocation as ASPS (ASPL-TFE3).

iCureASPS is very proud to be a supporter of Dr. Mark Pines in his efforts to understand the oncogenic nature of ASPS and in his efforts to develop a novel therapy for this disease.

Additional resources on Halofuginone (click on the links to learn more):

Halofuginone - U.S. National Institutes of Health: 
1. Halofuginone Hydrobromide in treating patients with progressive advanced solid tumors
2. Topical Halofuginone Hydrobromide in treating patients with HIV-Related Kaposi’s Sarcoma

Halofuginone – other resources:

3. Inhibition of fibroblast to myofibroblast transition by halofuginone contributes to the chemotherapy-mediated antitumoral effect
4. Halofuginone receives FDA orphan drug status for Scleroderma
5. Halofuginone to treat fibrosis in chronic graft-versus-host disease and scleroderma

______________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

Lazar and colleagues analyze expression of genes, which are known to modulate angiogenesis. Angiogenesis is the process involving the growth of new blood vessels to supply blood to organs and in the context of cancer, to malignant tumors. In his study Lazar finds that at least 18 of these genes are uniquely over expressed in ASPS. Lazar uses bioinformatics analyses to show that at least five of these genes contain regulatory elements that may directly be induced by the ASPL-TFE3 fusion protein, the translocation product of ASPS (ASPL-TFE3 fusion protein). The induction of these genes will then activate angiogenesis. Lazar’s study further suggests that cure for ASPS may be achieved by therapies that inhibit angiogenesis. The material for this study comes from 33 ASPS tumor samples from patients who were treated at the MD Anderson between the years 1986 to 2005. This last point indicates the importance of tumor samples for research on ASPS.

Vistica and colleagues describe the development of a new tool (antibody-based diagnostic detection) that easily discriminates between the two forms of Alveolar Soft Part Sarcoma: ASPS Type I and ASPS Type II. ASPS is characterized by a chromosomal translocation of two chromosomes: X and 17. This translocation forms the ASPL-TFE3 fusion transcript (see above). One of two different ASPL-TFE3 fusion transcripts is found in ASPS tumors, producing type 1 or type 2 fusion proteins. Currently it is not known if the prognosis of patients with ASPS type 1 is different from those with ASPS type 2. This diagnostic tool by Vistica enables detection of the ASPL-TFE3 fusion proteins and the discrimination between the two ASPS types.

______________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

One week prior to the PMC bike ride, iCureASPS hosted a private reception to honor Team ASPS riders and researchers from the Dana Farber Cancer Institute.

iCureASPS would like to thank the riders of Team ASPS 2007: David Eisenberg (captain of Team ASPS), Adam Eisenberg, Benji Eisenberg, Sara Eisenberg, Eugenie Gore, Ynbal Landesman, Hila Landesman, Yosef Landesman, Tim Schuettge and Katya Tsaioun. We thank our donors, good friends, family members and the ASPS community for supporting iCureASPS efforts to find a cure.

Photos below are courtesy of David Eisenberg and are copyright protected by Flickr.

Click here to see more photos from the event!

______________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

Tel: 310-633 8400, 310-633 8419
From the site of “Premiere Oncology”:

“A Phase 2 Study of ARQ 197 in Patients with Microphthalmia Transciption Factor Assciated Tumors.

The purpose of this study is to determine the overall response rate in patients with unresectable locally advanced or metastatic alveolar soft parts sarcoma, clear cell sarcoma or translocation associated renal cell carcinoma. Since this study will allow patients over 13 years of age, it will also be evaluating the safety of ARQ 197 in adolescent and young adult patients with MiT tumors. Patients will be followed for the effect of the drug in terms of side effects, how it affects their disease, and pharmacokinetic testing. Pharmacokinetics (PKs) is a method to determine the levels of a drug in the blood and see how the body absorbs, distributes, metabolizes and eliminates it. This is done by frequent blood draws on key days during the first 4 weeks of treatment.

ARQ 197 is an oral drug in the family of targeted therapies. It is a c-Met inhibitor and is not approved by the FDA. In this study, it is an investigational drug.”

For direct link to “Premiere Oncology” website please click here.

______________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

1. Resection - by a standard open lung surgery (by a thoracotomy or sternotomy approach) or VATS (video-assisted thoracic surgery). It is a challenging task and not always technically feasible, each case is different due to the size, number and location of the metastases and only thoracic surgeon will be able to say based on a CT scan if a given case is resectable. To be eligible for a resection lungs have to be the only active metastatic organ with the primary tumor resected and other metastases successfully treated before.

2. Ablation - a local treatment done percutaneously by an interventional radiologist using one of the less invasive methods (cryoablation, radiofrequency ablation or LITT) or by non-invasive methods (stereotactic radiosurgery (SRS) or tomotherapy).Previously, we reviewed the use of stereotactic radiosurgery (SRS) here.

Now, we will discuss laser assisted surgery for the removal of multiple lung metastases in a surgical procedure. Open lung surgery (by a thoracotomy or sternotomy approach) is a gold standard if the goal is to resect all lung metastases. Lung metastases smaller than 2 mm often cannot be seen on the CT scan. Open surgery allows the surgeon to visually inspect the lungs, as well as palpate (explore by touch) the lung tissue. An experienced surgeon can find a metastasis as small as 0.5-1 mm by this method. Traditionally, lung metastases are removed by ”wedge” or “lobe resection”. In that type of surgery, tumor (or tumors) are removed from the lung by stapling and clamping devices. Due to the geometric straight lines and angles of the stapler, the removal of lung metastases by this method results in a considerable loss of healthy lung tissue. Loss of a large amount of lung tissue can ultimately lead to a decrease in lung function. Another downside of this technique is the limitation of the location - there has to be an open edge to use a stapler. This means that tissue is removed in the shape of a pizza slice. If the metastases are centrally located or deep seated they are not accessible for this surgical tool. Hence, metastatic disease to the lungs is considered to be unresectable unless a whole lobe or a lung is being removed. ASPS is often a very disseminated disease, with all of the lobes affected. In this case, resection is not feasible using the conventional stapler assisted method. In some cases, complete resection can still be done by a new technique - laser assisted resection. To use this technique, the surgeon employs a special medical laser. The advantages of this tool are a high degree of precision and an ability to resect deep seated and centrally located metastases without critical loss of lung parenchyma. Using the laser, the surgeon can follow along the contour of the metastasis and remove it, thereby sparing much of the healthy lung tissue and its function. This may be crucial for patients with multiple metastases. It provides the patient with a better quality of life and allows repeated surgery, if needed.

Dr. Axel Rolle, from the Department of Thoracic and Vascular Surgery, Coswig (Dresden), Germany has been working on this laser technique since 1988, developing therapeutic laser technology for the resection of lung tissue (parenchyma). Lung parenchyma contains 80% water, and is of very low density (lots of air chambers). Therefore, in order for the laser to work in this type of tissue, it must have excellent cutting properties, and be able to control bleeding easily (coagulation). The first lasers in use were based on 1064nm wavelength laser. Dr. Rolle has developed and is using since the late 90-ties a longer wavelength laser of 1318nm, which is emitted from Nd:YAG. He found that this laser has both better precision when cutting, preserving the tissue around the metastasis, and improved bleeding control. Dr. Rolle has published these findings demonstrating the clinical benefit of this technique (Rolle et al 2006 (1)). This procedure is an unique opportunity to remove maximal tumor load from the lungs in a parenchyma-saving and lobe-sparing approach.

In a recent scientific publication, Dr. Rolle reported the results of a study, which aimed to define the role of his new 1318-nm Nd:YAG laser, in order to preserve lung tissue for patients with multiple lung metastases (Rolle et al 2006 (2)). During the period of that study: January 1996 to December 2003, a total of 328 cancer patients were treated with the new 1318 nm Nd:YAG laser system. A total of 3267 lung nodules were resected by the laser (an average of 10 tumors per patient (range 2-124). Despite the unusually high number of the resected metastases due to the most difficult cases being referred for his surgery the lobectomy rate was only 7 %.
Dr. Rolle concludes -

“This new 1318-nm Nd:YAG laser facilitates complete resection of multiple bilateral centrally located metastases and thus is lobe sparing. Outcomes are better when metastases are removed completely from the lung for long-term survival than those patients who had incomplete resection”.

Dr. Rolle contact information at the Center for Pneumology and Thoracic and Vascular Surgery, Academic Teaching Hospital of Dresden University:

Dr. Rolle
Fachkrankenhaus Coswig GmbH
Neucoswigerstr. 21
01640 Coswig
Germany

Phone: 0049 (0)3523 - 65 102
Fax: 0049 (0)3523 - 65 103
E-mail: prof.rolle@fachkrankenhaus-coswig.de

Dr. Rolle’s website: http://www.lungenmetastasen.info/Index_englisch.htm

More information about laser surgery:

1. Dr. Rolle performed laser assisted resections on at least two ASPS patients with very multiple lung metastases. You can read one first hand experience at this link.

2. Laser Lung surgery website created by a sarcoma patient: http://www.geocities.com/laserlungsurgery/

3. Read more about laser resection at the National Cancer Institute website: http://www.cancer.gov/cancertopics/factsheet/Therapy/lasers
__________________________

Yosef Landesman, Ph.D. (in cooperation with Olga Tkatcheva and Ivan Goroun)
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

Camilla’s Story:
In 1983 I was diagnosed with metastatic Alveolar Soft Part Sarcoma. I had a large tumor in my right inner thigh, 25 metastatic tumors in my right lung and approximately 30 metastatic tumors in my left lung. I started immediately an aggressive treatment, which included 4 surgeries to remove the primary and the metastatic ASPS tumors from my body. Then I had 2 1/2 years of chemotherapy.

Twenty four years have passed since I was diagnosed and 20 years since my last chemotherapy treatment. I am currently living a healthy, cancer free life in Portland OR , and I am an ER nurse. 

In 1997, despite all the toxic chemotherapy, I had a beautiful son. I am truly lucky.

Camilla 

Our team ride July 15 was dedicated to the 2007 Team Sarcoma Initiative (SEE OUR TEAM PHOTO BELOW). Team Sarcoma is an internationally coordinated set of events to raise awareness of sarcoma and funds to support sarcoma research, clinical trials, and patient and family services. Our 50 mile ride was one of over 50 “Team Sarcoma Events”, which took place in 13 countries and 21 states in the USA, July 14-21 2007.

Please click the following link to see a short presentation about Sarcoma: A Forgotten Cancer.

Please click the link below to read about the various Team Sarcoma Initiative: 2007 Team Sarcoma Initiative Events.

  ______________________________________________________  

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

I would like to share with you an e-mail from a parent whose child, a clear cell sarcoma patient participated in the GVAX clinical trial. I hope that this e-mail will encourage other patients on that trial to tell us about their own experience in this trial. For comments and further discussion please click on: Forum, Dana Farber Cancer Vaccine Clinical Trial (GVAX).

“I have been a reader of the iCureASPS website since its inception. Thank you so much for the hard work and efforts. My child was diagnosed five years ago with Clear Cell Sarcoma (CCS) and he was selected to participate in the GVAX cancer vaccine trial at the Dana Farber in Boston.

He was diagnosed in 2002. His primary tumor of 3.5 cm was located in the left upper thigh. At that time signs of tumor spread were not evident except for one 2mm lung nodule that could be scar tissue from past unrelated sickness. Surgery to remove the primary tumor was the only treatment option which was recommended for him.

BUT – in February of 2006, the cancer was found growing in two lymph nodes. In addition to the 2mm lung nodule that remained unchanged, three new nodules were found as well. Their dimensions were of 6mm, 4mm and 3mm. My child never had radiation or chemotherapy. The doctors thought that he was an “ideal” candidate for the GVAX cancer vaccine clinical trial because his immune system was intact. The doctors used the two affected lymph nodes for the preparation of the cancer vaccine.

I am very glad to report that today after 13 GVAX injections since February 2006 the 4mm lung tumor disappeared. The 3mm tumor remains unchanged and no new tumors have been discovered. The 6mm lung nodule was removed in August 2006, six months into the clinical trial. Analysis of that tumor showed T-cell infiltration, which may indicate an enhanced immune response against the tumor.

The GVAX injections caused no side effects except for redness around the injection site that would last for about a week after each injection followed by some itching. The next scans for my child will be taken in November 07. Thank you so much for the hard work you’ve done. I would like also to say that I find the doctors at Dana Farber wonderful people.”

___________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com

Here is a progress report on those projects.

1. The GVAX clinical trial – Opened on January 2006, the first cancer vaccine trial for ASPS is still open and continues to recruit more patients. This tumor vaccine is tailored for each patient based on his/her own tumor. The GVAX technology was developed by Glenn Dranoff, M.D., Director of the Human Gene Transfer Laboratory Core, Dana-Farber Cancer Institute, Co-Leader Cancer Vaccine Center, Department of Medical Oncology, Dana-Farber, Harvard Medical School. In the current trial, Dr. Dranoff incorporates experience that he accumulated over 10 years of cancer vaccine studies in patients with metastatic melanoma and lung cancer. This clinical trial is led by Dr. Glenn Dranoff, Dr. Steve Hodi, and Dr. John Goldberg.

2. The creation of an Alveolar Soft Part Sarcoma tumor transplant in mice (NEW PROJECT) – Many new cancer therapies are developed and tested in clinical trials. How could one predict the efficacy of a drug against ASPS? The goal of this project is to grow ASPS tumor fragments in mice. The resulting ASPS tumors can then be propagated in more mice and used as a preclinical model to test candidate drugs.
This project is led by Massimo Loda, M.D., Professor of Pathology, Harvard Medical School, Dana Farber Cancer Institute. In his lab, Dr. Ewa Sicinska, Dr. Carmen Priolo and Dr. Joseph Brito make up the team working on this project. We encourage ASPS patients who are operated at the Dana Farber to donate their fresh tumors to the Massimo lab. More material obtained means better chances for successful transplant lines.

3. Identification of Kinase Inhibitors that target ASPS (New PROJECT) – During the last few years, much progress on understanding the biology of ASPS was made through studies that were done in the laboratory of David Fisher MD, PhD, Director Melanoma Program in Medical Oncology & Division of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute, Children’s Hospital Boston, Harvard Medical School, in collaboration with John Goldberg, MD, Fellow in Pediatric Hematology/Oncology Dana-Farber Cancer Institute, Children’s Hospital Boston. In this study Dr. Fisher and Dr. Goldberg will try to identify “weak links” in ASPS that can be targeted by kinase inhibitors.

Following is a message from Dr. Fisher and Dr. Goldberg to the iCureASPS community:

“Dear iCureASPS and supporters,

We at the Dana-Farber Cancer Institute would like to express our gratitude for your support of our efforts to find a cure for alveolar soft part sarcoma, and we applaud your participation in the Pan Mass Challenge. We share your goal of bringing laboratory based findings into clinical trials as rapidly as possible for this insidious cancer. Over the coming year, our efforts will focus on targeting specific molecular switches that research has demonstrated to be potential weak points in ASPS. The first action will be to initiate a specific clinical trial with a biotechnology company to treat ASPS with a targeted kinase inhibitor. While there is no guarantee that any one targeted agent will help ASPS, we are working with many companies to insure that no stone goes unturned in our quest for a cure and that no weapon is left behind in this effort. These trials will involve both treating the patient and learning as much as possible from them to improve the future protocols. Both laboratory and clinical research are heavily resource dependent, but our patients need new therapies and science is pointing the way to many promising options. Of course, we will continue to monitor the progress of patients who received study vaccine on DFCI 05-115 (The GVAX clinical trial), which is an ongoing project here. We will also continue our efforts to find new targets in these cancers in the laboratory through the analysis of upregulated genes and activated proteins.

Best,

John M. Goldberg, MD
David E. Fisher, MD, PhD”

__________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com