Leiomyosarcoma Direct Research Foundation - LMSdr

News

This page contains brief updates, occasional News highlights and
other developments that might be of interest to the LMS community.

If you would like to contribute information to the LMS Community
via this page, please contact us

Also available soon: our LMSdr Newsletter.

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A Novice's Gleanings: Reports on LMS Tissue Sample Repository and LMS Microarray Study

. . . Dr. Cheng-Han Lee, pathologist . . . Dr. John Brooks is Chair of Pathology at Pennsylvania Hospital . . . Read More

Presentation on Osteoporosis
and Bone Health

. . . Dr. Gina D'Amato, a medical oncologist . . . talked about osteoporosis and bone health . . . Read More

Excellence in Care Award

. . . Dr. Gina D’Amato honored with 2006 Excellence in Care Award given by LMSdr . . . Read More

Leiomyosarcoma Direct Research
awards the first grant.

. . . LMSdr approves a Research Grant to further the work of Dr. Matt Van de Rijn at Stanford University . . . Read More

An artistic way of spreading
the word about LMS can be seen
at Moffitt Cancer Center.

. . . One of the LMS Quilts recently went on display at Moffitt Cancer Center in Tampa, Florida. . . Read More

Important Follow-Up Interviews
for the LMS microarray project
at Stanford University.

. . . “This is a very important part of the study,” states Dr. Cheng-Han Lee. . . Read More

Dr. Matt Van de Rijn has sent us
the following update on the
LMS microarray project at Stanford University.

. . . We are happy to announce that we have finished processing all freshly frozen tumor tissues. . . Read More

Presentation on Osteoporosis and Bone Health for Cancer Patients

June 15, 2007
Moffitt Cancer Center in Tampa, FL.

Dr. Gina D'Amato, a medical oncologist in the sarcoma program, talked about osteoporosis and bone health for cancer patients on June 15 at the Moffitt Cancer Center in Tampa.

Chemotherapy and other cancer treatments can increase the risk of osteoporosis for both men and women.

The presentation was held in the Stabile Research Building. Merck, maker of Fosamax, provided calcium-rich refreshments. For more information, message the event organizer at Lucy.Gonzalez-Barr@moffitt.org or call 813-745-2963.

2006 Excellence in Care Award

By Suzie Siegel

     Doctors guided Gina Z. D'Amato into a darkened room. Then the lights came on, revealing a lavish party crowded with her bosses, staff and parents.
     The surprise party honored her for winning the first Excellence in Care Award given by the LMSarcoma Direct Research Foundation.
     "It's a special award because the foundation recognizes, not only research, but patient care," said Dr. D'Amato, of the H. Lee Moffitt Cancer Center and Research Institute in Tampa.
     She lauded the foundation for giving research grants. "We're obviously not getting enough money from the government, and we need outside resources."
     People can donate to the foundation in order to nominate and vote for professionals who give excellent care.
     "Although I nominated you for this award, others added their voice," I told Dr. D'Amato, who is my "primary" oncologist. "This award 'symbolizes our deepest thanks for your dedication.' It also honors your colleagues who share your values.
     Gina has developed a reputation for patient care and advocacy. LMSers who have never met you don't hesitate to recommend you to new patients."
     The doctors at Moffitt work for the University of South Florida. Dr. D'Amato, an assistant professor, is well-respected and internationally known in sarcoma.
     "She speaks around the country on emerging treatment for sarcomas," according to the Moffitt Web site. "Her research interests include basic science research in PI3k/Akt/mTOR inhibition of sarcomas and early phase clinical trials involving novel anticancer agents for sarcomas."

     Dr. D'Amato received her undergraduate and medical degrees at the University of Miami in Coral Gables, Florida. She completed her internal medicine residency at the University of Miami/Jackson Memorial Hospital and a medical oncology/hematology fellowship at Moffitt.
     Dr. Douglas Letson, division chief, recounted how he had invited her to be the first medical oncologist in the sarcoma program. She asked who would mentor her, and he said he would. He laughed, pointing out that he's a surgeon.
     Once, they were out on business and her cell phone rang. She took the call, explaining it was a patient, he said. It's unusual for doctors to give their cell-phone numbers to patients and even more unusual to interrupt business with their boss.
     Dr. Letson also praised Dr. D'Amato for helping Moffitt join SARC (Sarcoma Alliance for Research through Collaboration). He noted that Moffitt is running many more clinical trials in sarcoma these days.
     Dr. D'Amato mentored Dr. Samuel Agresta, who then joined the program as a medical oncologist. He also was nominated for the excellence-in-caring award.
     Other nominees were: Drs. David Jablons and Michael Mann of the University of California Medical School-San Francisco; Dr. Arthur Staddon and RN Denise Smith from the Joan Karnell Cancer Center at the Pennsylvania Hospital in Philadelphia; and Dr. Charles Forscher of Cedars Sinai Medical Center in Los Angeles.
     Patient volunteers, nurses and other medical professionals, and administrative staff who make it possible for doctors to spend time with patients attended the reception at Moffitt.

     In addition to Drs. Letson and Agresta, physicians in attendance included:
          Dr. Vernon Sondak, division chief of the cutaneous program and director of surgical education. Dr. Sondak also specializes in sarcoma and knew the founders of the LMS list at www.acor.org. In his clinic, he always wears his purple LMS wristband.
          Dr. Jonathan Zager, a surgeon in both sarcoma and the cutaneous program. I gave him my purple wristband.
          Dr. Marilyn Bui, a sarcoma pathologist who also is scientific director of Moffitt's Analytic Microscopy Core Facility. She wishes all LMS patients would rely on pathologists experienced in sarcoma.
          Dr. Clifford Schold, physician-in-chief for Moffitt, chief academic officer, an executive vice president, and chair of the department of interdisciplinary oncology. He agreed that patient care is integral to research. Patients are more likely to participate in clinical trials and support research if they trust their doctors will provide good care.

     Jack Pledger, director of the Moffitt Research Institute, recalled how Dr. Judah Folkman, the father of anti-angiogenesis research, spent time talking to LMS patient and RN Joan Connor and me. Dr. Folkman had come to Moffitt to receive an award, and Joan had flown down from Port Republic, N.J., to hear him.
     Pledger noted that he has a research interest in sarcoma. His other titles include: deputy director; executive vice president of the Moffitt Cancer Center; director of basic science; and director of the National Functional Genomics Center.
     Representatives of the pharmaceutical company Biogen Idec had decorated the room with bouquets of red Gerbera daisies and tulips as well as silver and gold helium balloons, which were later given to patients in the hospital. Biogen provided champagne with strawberries, a rich chocolate cake, and many other delectables. The foundation's Web site was projected on the wall.
     Perhaps the best testimony comes from Al Meller, of Chattanooga, Tenn. In an email, he recalled how Dr. D'Amato took him and his late wife, Judy, on a tour of her research facilities, "talking about the research she was doing, introducing us to some of the technicians, and showing us the equipment, etc."
     Al recalled other good memories about Judy's care from May to December 2005. "The two I will mention involve the beginning and the end.
     The beginning was the very first meeting when Judy and Dr. D'Amato met to discuss her possible admittance into the clinical trial of AP23573. While Judy still felt quite well, her situation was rapidly deteriorating after being dismissed by M.D. Anderson, and she didn't meet all the criteria for admittance into the trial.
     Dr. D'Amato exhibited such a caring, friendly and confident attitude, and still held out hope for the trial or other potential treatments. Her hopes were backed up by action. She went to bat for Judy and obtained the necessary clearance. A move we both were very grateful for and remained so.
     At the end, while the clinical trial was successful for Judy, she succumbed to a combination of organ failures due to other causes. But the one aspect that I shall always remember is the friendly, caring, compassion Dr. D'Amato showed to Judy and I in the final days even after Judy had been placed in an end of life coma and was no longer under Dr. D'Amato's care.

Daily, she would still come and stand by Judy's bedside and then visit with me. I have every confidence that helped Judy in her transition. I know her advice to me to seek counseling was helpful. I did so and it opened doors for me to start at new life - which I have. But those six months that we experienced Dr. D'Amato's care will always hold a very special place in my heart. I know they did in Judy's.
Thank you, Dr. D'Amato!"

Click here to see more pictures.

A Novice's Gleanings
Reports on LMS Tissue Sample Repository and LMS Microarray Study

Notes from gloria schwartz – Hugfest April 2007

Dr. Cheng-Han Lee, pathologist, studied under Dr. Matt Van de Rijn who initiated the LMS Microarray Study at Standford University. Dr. Lee now practices in Vancouver and continues to collaborate with Dr Matt on our LMS study.

Dr. John Brooks is Chair of Pathology at Pennsylvania Hospital with expertise in LMS and is a member of the Sarcoma Foundation of America. He is founder and Director of the new Repository for LMS tissue samples at Pennsylvania Hospital in Philadelphia.

Both were both very complimentary of the fine work we as an LMS community are doing. Recognition was given to Iqbal Ahmed, Sharon Anderson and Suzanne Kurtz for their work initiating the project & obtaining the tumor samples and to Ricki Gero who is volunteering to help Dr. Brooks.

DR. BROOKS - Repository for LMS Tissue Samples

Getting the Tissue Samples
These LMS tissue samples will be available for LMS research. Once the blocks are collected at Pennsylvania Hospital, he will notify the Sarcoma Research Community and SARC (consortium of Sarcoma oncologists) as well as the Cancer Tissue Block organization. When a researcher requests samples, he will send only a thin slice- not the entire sample, ensuring ample supple for other researchers. (Sending one slice is possible because of the set-up of the Repository- whereas a hospital has to send the entire block and then have it returned.)

Having the blocks in one place with all the proper patient documentation will not only accelerate research efforts but will also provide a safe place for the samples (paraffin blocks and fresh-frozen tissues). He assured us that obtaining one sample from the hospital will not exhaust our tumor block supply. Only one of the blocks is sent to the Repository. Often LMS tumors are large enough for many blocks so there will be sufficient supply that remains at your hospital. Needle biopsies- small samples, are not routine for LMS.

Dr. Matt Van der Rijn of Stanford, who is doing microarray research (see below) on the samples we have already sent to Stanford University, is getting ready to send the 1^st 100 samples to Dr. Brooks for the Repository.

Scientific Advisory Board
Dr. Brooks will develop a Scientific Advisory Board to screen proposals for research.

Tissue MicroArray - TMS
Dr. Brooks will evaluate Diagnostic (Dx) and Prognostic (Px) markers in Soft Tissue Sarcomas. Gene chips array differ in that it color codes high expression and low expression of genes one case at a time.

TMA is the reverse – it uses plugs from our blocks to analyze proteins which antibodies can target and to do cyto-analysis.

LMS information
LMS is 15% of Soft Tissue Sarcomas (STS). There are 14,000 cases a year. LMS has very bizarre looking cells- "cytogenics"

Slides were displayed indicating the differences in cancer cell formation for different sarcoma types. Dr. Brooks pointed out that LMS looks similar to MFH. This may have indications for some relationship between the two or possibly for related treatments.

LMS frequently shows a loss of chromosome10 and 13q.

LMS incidence according to SEER data from 1978 to present: LMS was 23.9% in their data base; 1/4 of all STS if add lungs, uterus.
-- 7% uterus
-- for women 40% of LMS uterine
-- more prevalent in black women

LMS Genome Analysis
-- 2,200 genes altered or abnormal in LMS in 25 altered chromosomes
-- There are more defective copies in high grade tumors, meaning high grade gains a lot of DNA - 4 or 5 copies while low grade tumors show losses 2x as great.

(Dr Lee: the defective genes that allow the cancer cells to proliferate create many copies of themselves while the genes that stop tumor growth- suppressor genes, decreased in their number of copies from the normal 2 to 1 or to 0.)

Inferior Vena Cava LMS- over 80% women. It looks like uterine LMS. The composition of the muscle is the same type- (if I understood this correctly.)

Hypoxia-genes If a tumor can live in a low oxygen environment, it is more difficult to attack it. Therefore, if a tumor has hypoxia genes, the tumor can survive. Vaccines may be helpful and might indicate the appropriate chemo or treatment.

Mifeprestone - an anti-progesterone
Some feel ULMS has high progesterone. A study showed good results with low grade ULMS. However, there WAS growth in high grade ULMS; 80% of ULMS is high grade.

Response to questions:
1 - Mitotic Rate:
Low rate is 1 or 2 or 3 per 10
High rate is 20 per 10

2 - Primary versus metastasis
Preceding therapy, most stay the same. If a tumor is high grade, mets will be high grade.
However, if a tumor was low grade many years ago and it reoccurs, it can change to high grade. Some post therapy tumors can reduce in rate indicating therapy is successful

Dr. LEE - LMS Microarray Study

LMS is very complex. This is part of the reason nothing definitive has been identified yet. The approach to studying it has to be multifaceted.

HOW GENES CONTROL CELLS:
-- DNA is the architect - drawing a copy of the master blueprint.
-- RNA is the copy that DNA makes.
-- Protein is then produced by the RNA. (RNA translates its copy into a protein)
-- MiRNA (Micro RNA) is a new concept – the researcher who identified how it plays into cell and cancer growth alterations just received the Nobel Prize.

Onco-gene / oncoprotein can lead to malignant growth as it leads cells astray. (The bad guys.)

Tumor Suppressor genes keep cells in check.

The primary cancer growth can develop secondary changes which make it hard to target. This can happen at DNA, RNA, Protein or MiRNA levels.

On Microarray slide from our LMS samples: 1 - ErbB2- Brightness of color shows gene aberrations. Red indicates too many copies - causing tumor growth Green indicates too few copies - does not placing cell growth in check.

2 - Typical slide with 49 samples ( they appear as tiny plugs similar to the end of a small pencil eraser) which creates 40,000 points of information, with red and green highlighted where intense activity.

GENE MICRO ARRAY/GENE EXPRESSION
1. Slide of 51 fresh frozen tissue samples from 46 patients: 15 ULMS, 35 other. Analysis indicated that these particular 51 seem to have 2 groups of higher level kinase genes, a type of protein that activates other proteins. Pharmaceuticals are very interested in kinases — in seeking ways to inhibit them /attack the function of these proteins. (Dr. Brook's Tissue Microarray will be used to correlate with Dr Matt's studies on these types of issues.)

2. They also looked at DNA: how the gene expresses itself in these LMS samples – i.e. the number of copies DNA makes of itself. A slide showed DNA: Red indicates too many copies Green a decrease in copies. As each chromosome has 2 copies, RED indicates more than 2 copies (they will often see 12 or 24) while GREEN indicates less than 2 (1 or 0)

Police Oncogene - If see 1 or 0 copies it indicates the tumor cell has eliminated the Suppressor Gene allowing the tumor to grow.

Chromosomes are given an address-
-- 13q is one region of study. It seems implicated in some LMS.
-- RB1 (Rentino Blastoma gene) is a tumor suppressor gene showing up as green in several cases. It was deleted in 90% of LMS samples they studied. (Young people with Rentino Blastoma are prone to developing Sarcomas and LMS later in life)
-- P53 also showed up as green for some LMS and other cancers like breast cancer. The aim would be to restore it. Question: Does positive reaction to ET743 indicate aberrant P53? Dr. Brooks: We don't yet know. The company producing ET743 is now researching this issue)

MiRNA binds before it can be translated preventing it from becoming a protein. Matt has done micro array analysis of MiRNA, also.

PROTEINS
They are also looking at Proteins/Protein Expression (the final product), through TMA – tissue microarray studies. Protein expression examples are VEGF, CD 68.

MACROPHAGES
Between spindle cells they have identified lots of inflammatory cells. Found in significant numbers in LMS are high levels of MACROPHAGES markers – VEGF, CDs, etc. High levels have been found to be poor prognostic indicators for breast and other cancers. They can facilitate the invasion of a tumor cell to build a highway of blood vessels [angiogenesis]. Macrophages are known to work with cancer cells to facilitate their growth and metastasis. In breast cancer it has been shown to deliver oxygen nutrients to the tumor and increase angiogenesis.

Therefore Dr. Matt saw need to move toward tissue analysis (TMA).

Matt has done tissue microarray for 300 cases (samples). 126 primary tumors from 100 different hospitals across the US and Canada. Most are female, average age 51. 50% ULMS. Average tumor size 9. cm. Majority are high grade. None had received therapy. All have followed up data. (Dr. Lee noted Sharon called every single one)

Their study used an anti-body against macrophage CD 163 + (increased copies – showing up red). Tumors with more macrophages will do worse. This proved a statistically significantly better indicator than current Sarcoma guidelines. More studies are planned with samples from Vancouver. Goal is to attack macrophages to decrease tumor growth it is felt macrophages work to enhance cancer tumor growth.

MODELS FOR STUDY
When they use a disease model they want to make sure it reflects the actual disease, that is represents the biology of LMS tumors. They use cell lines. They have been working with Dr. Jonathan Fletcher at Brigham Young in Boston. They looked at his LMS cell lines He has 4.

Early step is looking for a good model. Then they will move to study it in culture dish or put it into an animal model Macrophage markers need to confirm the above information.

Question-
Will taking anti-inflammatories help curtail the macrophages? Answer: Goal to find what is the key in inflammation reaction as some inflammation can suppress cancer and some can increase it

About SAMPLES- the best is fresh frozen, if you can line this up before surgery. The paraffin used in paraffin blocks does affect the DNA a bit but is still very effective.

LMSarcoma Direct Research awards grant to further Leiomyosarcoma Research.

Research Grant: $40,000.
LMSarcoma Direct Research awards grant to further Leiomyosarcoma Research.
Awarded to Dr. Matt van de Rijn at Stanford University.
December 2006

LMSdr is pleased to announce that we have approved a Research Grant of $40,000 to further the work of Dr. Matt Van de Rijn at Stanford University. This Grant will help in the total funding package that will allow Dr. van de Rijn to hire a technician who will be trained in the techniques of tissue microarray and help the LMS microarray project move forward without interruption. This funding will also help pay for equipment and chemicals needed in the project. To learn more about Dr. van de Rijn's project, you may visit his website at http://med.stanford.edu/labs/vanderijn.

This Research Grant and the future research grants that will be awarded by the foundation are made possible by the many patients, families and friends of Leiomyosarcoma Direct Research who have dedicated their time, efforts and contributions to help as we search for the cure to Leiomyosarcoma. To all of you the whole LMS community owes a debt of gratitude.

Sincerely,
Suzanne Kurtz, Executive Director

LMS Quilt on display at Moffitt Cancer Center, Tampa Florida.

LMS Quilt on display at Moffitt Cancer Center, Tampa Florida.
June, 2006

Many LMS patients, caregivers, and loved ones have worked for years putting together patchwork quilts. Each frame tells its own story, through words or pictures, about a struggle to survive, a bittersweet memory of a lost loved one, or a hope for the future.

One of the LMS Quilts recently went on display at Moffitt Cancer Center in Tampa, Florida. Among the attendees were LMS survivor Suzie Siegel (see photo #1) and Doctors Gina D'Amato and Vernon Sondak (see photo #2).

Our Thanks to Moffitt for supplying these photos.

Dr. Matt Van de Rijn has sent us the following update
on the LMS microarray project at Stanford University.

Leiomyosarcoma Research Updates from Stanford University
May 14, 2006

Our current focus in the study of leiomyosarcoma is to understand the genetic and the molecular changes that occur in leiomyosarcoma in comparison to benign smooth muscle tumor and non-neoplastic smooth muscle. We have with the invaluable help of patient groups obtained many fresh frozen and parafilm embedded tumor tissues. We are happy to announce that we have finished processing all freshly frozen tumor tissues from more than 80 cases of leiomyosarcoma and 22 cases of benign smooth muscle tumor and tissues on the Stanford gene array (gene chip). Gene array study is an extremely powerful technique that enables us to simultaneously examine the expression levels of more than 42,000 gene fragments on one slide/array. Having an understanding of the expression levels of all genes present in the malignant cells of leiomyosarcoma will hopefully allow us to identify genes that are involved in the malignant transformation of leiomyosarcoma and may lead to the development of better diagnostic makers, prognostic markers and potentially even targeted therapy. The next phase of our study is to analyze the large dataset (102 cases × 42,000 gene data points = 4,284.000 total data points) generated by the gene expression study. We hope that the results from our ongoing analysis of this large database will provide us with important biologic insights about leiomyosarcoma in the coming year. In addition to our gene expression study using the fresh frozen tissue, we are also in the final phase of paraffin embedded tumor tissue (tissue block) collection. These paraffin embedded tissue blocks will be used to make a tissue microarray that can contain several hundreds of cases of leiomyosarcoma on a single slide. This will allow us to for instance examine for the presence or absence of a particular therapeutic target on hundreds of cases of leiomyosarcoma in one experiment. In a few months, we will begin the construction of the leiomyosarcoma tissue microarray that will consist of more than 500 cases of leiomyosarcoma collected from US, Canada and Europe. In parallel and with the help of members of the leiomyosarcoma patient organizations, we hope to update the clinical follow-up on most of these cases. We believe that this will be the largest series of leiomyosarcoma assembled and it will serve as a tremendously valuable testing tool to rapidly validate the clinical utility of any potential diagnostic, prognostic or therapeutic marker that may emerge from our ongoing gene expression analysis or from any future studies.

Important Follow-Up Interviews for the LMS microarray project at Stanford University.

Leiomyosarcoma Research Updates from Stanford University
June, 2006

If you participated in the LMS Microarray Study by Dr. Matt van de Rijn at Stanford University, expect an email or phone call in the next few weeks. Sharon Anderson, a member of LMSarcoma Direct Research, will be helping collect missing information and updating previously given information from each of the 253 participants who sent their paraffin block tissue samples to this study. “This is a very important part of the study,” states Dr. Cheng-Han Lee, assistant researcher with Dr. van de Rijn. The researchers intend to also collect follow-up information in two more years. If you have new contact information or questions, please email Sharon Anderson at Sharon@lmsdr.org. To read about the LMS Microarray Study which was started in 2004, you can visit www.LMSRA.org. To view photos of Sharon and Dr. Cheng-Han Lee, click here.