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

I am very pleased to announce that this year Cure Alveolar Soft Part Sarcoma International and Team ASPS raised a total of $42,160. All donations are transferred to support ASPS research in the laboratories of Dr. Glenn Dranoff and Dr. Massimo Loda at the Dana Farber Cancer Institute. Dr. Glenn Dranoff, who developed the GVAX clinical trial for ASPS patients, continues his studies to develop better cancer vaccine approaches. Dr. Massimo Loda does research that aims to identify new targets for therapy through the analysis of ASPS tissue samples.

I would like to extend my thanks to Team ASPS 2009, our donors, friends, family members, and to the ASPS community, for helping us in our fight to find a cure! Photos from the Team ASPS PMC 2009 bike ride below are courtesy of David Eisenberg. See more in the Facebook group dedicated to Team ASPS.

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

Cediranib is being developed by AstraZeneca as a possible anti-cancer chemotherapeutic agent for oral administration.

National Institutes of Health website has a list of 65 Cediranib clinical trials. Some of these studies are recruiting new patients. One of these studies, which was opened on 18 July 2009, recruits Alveolar Soft Part Sarcoma Patients: “Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma”. Currently, this is one of the most promising known treatments for ASPS.

You can read encouraging comments about Cediranib from ASPS patients using the drug since September 2007 in the appropriate section of our forum.

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

In the past six years, we have worked hand in hand with the Dana-Farber Cancer Institute. The results of that work are the first “Cancer Vaccine” Clinical Trial to treat ASPS.  The trial opened in November 2005 and following that the ARQ197 clinical trial opened as well.

I am asking you to help and sponsor Team ASPS and directly support the current efforts to find a cure for Alveolar Soft Part Sarcoma.

We welcome online donations through the pmc.org website: http://www.pmc.org/.  Click on the “e-gifts” link on the upper left side of the website page. Then use the code YL0002 as the eGift ID number.
 
We thank you for your support.
 
Together we will find the cure!

Best Wishes,

Yosef Landesman

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

Here are few words from Katie Nemgar, AJ’s friend and one of the fundraiser organizers:

“Thank you to everyone who assisted us in the ongoing battle against Alveolar Soft Part Sarcoma. The Knockin’ Down ASPS Committee is extremely happy to announce that we raised over $19,000!  We can’t thank each of you enough for your support! The majority of the money that was raised will be sent to the Dana Farber Cancer Institute towards ASPS research, more specifically to the research of Dr. Glenn Dranoff.  The remainder of the money will go to the Salisbury family as they pay off some of AJ’s hospital bills.

Although AJ was unable to physically attend our event, we know that he was there in spirit.  He would have been proud to see everyone come together to spread the word and work toward finding a cure for ASPS.  We think of AJ often and he is dearly missed.  We are grateful to have had the opportunity to know such a genuine person.

We have decided to make Knockin’ Down ASPS an annual event in memory of our good friend.  As the year moves along and plans come to fruition, you will be notified of upcoming information regarding next year’s event.  Our hope is that everyone who participated this year will be able to join us next year!  Once again, thank you to everyone who is helping us in Knockin’ Down ASPS!”

To read more about AJ, and the fundraiser, visit http://www.KnockinDownASPS.com/.

______________________________________________________

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

For the first time, a team of researchers, among them Dr. David Vistica, reported their success in the establishment of a stable Alveolar Soft Part Sarcoma cell line for the first time. The origin of this cell line is from a lymph node metastasis which was donated by a female patient. Very importantly, the cell line was carefully tested and was found to maintain the characteristics of the original ASPS tumor for over three years.

This cell line will facilitate investigations into the biology of ASPS, and aid in the pre-clinical identification of new ASPS therapeutics. Here below is the abstract of the poster:

Establishment and characterization of ASPS-1, a novel cell line derived from metastatic alveolar soft part sarcoma

Investigation into the biology of Alveolar Soft Part Sarcoma (ASPS) and preclinical evaluation of potential ASPS therapeutics have been severely hampered by the lack of both in vitro and in vivo models of this soft tissue sarcoma. Recently we have described an in vivo xenograft model of ASPS in sex-matched NOD.SCID\NCr mice. This model, established from a lymph node metastasis from a female patient, has maintained characteristics consistent with those of the original ASPS tumor for over 3 years. Characteristics studied include: (1) tumor histology and staining with Periodic Acid Schiff/Diastase, (2) the presence of the ASPL-TFE3 type 1 fusion transcript, (3) nuclear staining with antibodies to the ASPL-TFE3 type 1 fusion protein, (4) maintenance of the t(X;17)(p11;q25) translocation characteristic of ASPS, (5) stable expression of signature ASPS gene transcripts and finally, the development and maintenance of a functional vascular network, a hallmark of ASPS. Utilizing this ASPS xenografted tumor we have successfully developed the first cell line of this rare pediatric sarcoma. Organoid nests consisting of 15-25 ASPS cells were isolated from ASPS xenograft tumors by capture on 70 um filters and plated in vitro. Following attachment to the substratum, these nests deposited small aggregates of ASPS cells. Over a period of 1.5 years, these cells were expanded and monitored for the following: ASPL-TFE3 type 1 fusion transcript, the t(X;17)(p11;q25) translocation and expression of up regulated ASPS transcripts involved in angiogenesis (ANGPTL2, HIF1 alpha, MDK, MET,VEGF, TIMP-2) , cell proliferation (PRL, PCSK1, IGFBP1), metastasis (ADAM9) as well as the transcription factor BHLHB3 and the muscle specific transcripts TRIM63 and ITGB1BP3. This ASPS cell line forms colonies in soft agar and retains the ability to produce highly vascularized ASPS tumors in NOD.SCID\NCr mice. Immunohistochemistry of selected ASPS markers on these tumors indicated similarity to those of the original patient tumor as well as to xenografted ASPS tumors. This ASPS cell line will facilitate investigation into the biology of ASPS and aid in the pre-clinical identification of new ASPS therapeutics.

Authors:  Susan Kenney, David T. Vistica, Luke Stockwin, Sandra Burkett, Melinda Hollingshead, Suzanne Borgel, David Schrump, Robert Shoemaker. NCI-Frederick, Frederick, MD, National Cancer Institute, Bethesda, MD

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

1. Involved in angiogenesis: ANGPTL2, HIF-1 alpha, MDK, c-MET, VEGF, TIMP-2.
2. Involved in cell proliferation: PRL, IGFBP1, NTSR2, PCSK1
3. Involved in metastasis: ADAM9, ECM1, POSTN
4. Involved in steroid biosynthesis: CYP17A1, STS.

So far, the cell origin of ASPS was not clear. The study identifies the muscle-restricted gene expression as ITGB1, BP3/MIBP, MYF5, MYF6 and TRIM63. This strengthens the hypothesis that the primary ASPS tumor develops from muscle cell progenitor.

The full paper, including all genes found to be expressed in ASPS, is available here.
______________________________________________________

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

Team AVEO represents the biotechnology company AVEO Pharmaceuticals in the Pan Massachusetts Challenge (PMC). This year was the first year that Team AVEO restricted their donations for ASPS research, and the fifth year in a row for Team ASPS. Some of our riders rode 90 miles and others rode 150 miles. The total sum collected by Team AVEO and Team ASPS was $27,003 and $32,090, respectively.

The total donation of $59,093 will support work done by two lead researchers at the DFCI: Dr. Andrew Wagner, a principal investigator in the ARQ197 clinical trial, and Dr. Massimo Loda, who aims to identify new targets for therapy through the analysis of ASPS tissue samples.

iCureASPS would like to extend its thanks from the ASPS community to Team AVEO, Team ASPS 2008, our donors, friends, and family members, for helping us in our fight to find a cure for our loved ones.

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

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

Dr. Lev published a study on angiogenesis-promoting genes in Alveolar Soft Part Sarcoma, in December 2007.  Dr. Lev is also co-author in a study on the activation of the insulin growth factor receptor 1R (IGFR1) in ASPS, which was recently reported at the 2008 meeting of the American Association for Cancer Research (AACR).

The contact person from iCureASPS for this collaboration is Dr. Nancy Landfish, who serves as the iCureASPS Medical Affairs Director.

Here is a summary of Dr. Lev’s research goals on Alveolar Soft Part Sarcoma:

The sarcoma research laboratory at MD Anderson Cancer Center is focused on the comprehensive multidisciplinary study of soft tissue sarcomas. One major area of interest is alveolar soft part sarcoma (ASPS). The rarity of these tumors and the lack of bioresources such as human tissues, cell lines, and animal models impedes intensive research in this field and thus enhanced molecular understanding as it relates to tumor inception and progression. Our major goals are to assemble and develop these needed bio-resources. Utilizing the MD Anderson Cancer Center tissue bank we were able to assemble an ASPS specific tissue microarray (TMA), which will potentially aid us in identifying the expression of genes and proteins of interest.  ASPS are highly metastatic; their metastatic propensity is possibly secondary to their enhanced angiogenicity and vascularity. We have recently utilized the ASPS TMA to evaluate the expression of multiple angiogenic factors and other molecular targets; data stemming from these studies will hopefully be submitted for publication in recent months. 

Our Research Aims:
1)  To expand our annotated paraffin and frozen tissue bank for ASPS
2)  To collaborate with other scientists with an interest in ASPS research
3)  To study the expression and function of angiogenic factors in ASPS and evaluate their potential as therapeutic targets 
4)  To evaluate the effect of the TFE3 fusion gene on the expression of the studied angiogenic factors

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

“My son participated in the GVAX trial in 2006. His story appeared on this web-site about a year and a half ago. He is a clear cell sarcoma patient. His primary tumor diagnosis, at the left upper thigh was found in 2002. Later in 2006, 2 adjacent lymph nodes and 3 lungs mets were identified. In addition, a questionable fourth lung met was also seen in his lung. The two lymph nodes were resected in 2006 and were used to prepare his cancer vaccine in the GVAX clinical trial. He had 13 injections of the cancer vaccine and no other treatment except for surgeries to remove the primary tumor and mets. Following the GVAX trial, one of his lung mets in the size of 4mm disappeared, one met in the size of 6 mm was resected and one 3 mm met has not being changed in size since then.
My son’s last scans were done in August 2008 and I’m pleased to report that the radiology report reads that there is no evidence of additional metastatic disease.
 
I know that “Argonaut” has shared Anthony’s success story of the GVAX clinical trial on the iCureASPS Forum: (Anthony - 32 months without growth) Like “Argonaut” also I am grateful that our both sons are experiencing a good outcome.
 
My speculation is that the cancer vaccine GVAX was in fact effective at least in our two cases and that intact immune system could be one of important factors to achieve a positive vaccine outcome. I know that this is “Argonaut’s” theory and since I have benefited by reading his son’s experience, I wanted to let him know that there is someone out there experiencing the same good news. Granted, a slightly different disease but the participation in the same GVAX trial puts us in the same group.
 
I hope we can explore the science behind what happened rather than just being grateful. Hopefully this information can and will be used to create better outcomes for all. ”

______________________________________________________

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