Your $ Making Progress on LMS

From Sharon Anderson Hi Steve, Please share the attached research article with family and friends who contributed to Rebecca's fundraising efforts. Her contributions funded the mice studies, which had dramatic results. We can't thank everyone enough. L, Sharon I can't attach the article but can include the following: Press Release from Stanford on CD47 Antibody and LMS discovery http://www.eurekalert.org/pub_releases/2012-03/sumc-sas032112.php Single antibody shrinks variety of human tumors transplanted into mice, Stanford study shows STANFORD, Calif. — Human tumors transplanted into laboratory mice disappeared or shrank when scientists treated the animals with a single antibody, according to a new study from the Stanford University School of Medicine. The antibody works by masking a protein flag on cancer cells that protects them from macrophages and other cells in the immune system. The scientists achieved the findings with human breast, ovarian, colon, bladder, brain, liver and prostate cancer samples. It is the first antibody treatment shown to be broadly effective against a variety of human solid tumors, and the dramatic response — including some overt cures in the laboratory animals — has the investigators eager to begin phase-1 and -2 human clinical trials within the next two years. "Blocking this 'don't-eat-me' signal inhibits the growth in mice of nearly every human cancer we tested, with minimal toxicity," said professor of pathology Irving Weissman, MD, who also directs Stanford's Institute of Stem Cell Biology and Regenerative Medicine and the Ludwig Center for Cancer Stem Cell Research at Stanford. "This shows conclusively that this protein, CD47, is a legitimate and promising target for human cancer therapy." The antibody treatment also significantly inhibited the ability of the tumors to metastasize throughout the animals' bodies. "This is exciting work and will surely trigger a worldwide wave of research designed to convert this strategy into useful therapies," said Robert Weinberg, PhD, a professor of biology at the Whitehead Institute for Biomedical Research in Massachusetts who was not involved in the research. "Mobilizing the immune system to attack solid tumors has been a longstanding goal of many cancer researchers for decades." The research will be published online March 26 in the Proceedings of the National Academy of Sciences. Weissman, who is the Virginia & D.K. Ludwig Professor for Clinical Investigation in Cancer Research at Stanford and a member of the Stanford Cancer Institute, is the senior author of the research. Postdoctoral scholars Stephen Willingham, PhD, and Jens-Peter Volkmer, MD, are the co-first authors of the study. Previous work in Weissman's lab has shown that CD47 is normally expressed on the surfaces of circulating blood stem cells to protect them from immune cells called macrophages. Macrophages patrol the body looking for signs of trouble in the form of invaders or rogue cells, but they sometimes latch onto the wrong targets. CD47 prompts them to release cells they've grabbed by mistake. Weissman and his colleagues also showed previously that some types of cancer cells — particularly those of blood cancers such as leukemia and lymphoma — have figured out a way to game the system and use this "don't-eat-me signal" to their advantage by expressing CD47 on their own surfaces. In 2010, they found that blocking CD47 with a specific antibody (plus adding another to further stimulate the macrophages' killing instinct) can cure some cases of human non-Hodgkin's lymphoma in mice. But it wasn't known until now how widespread or clinically important the phenomenon would be in human solid tumors. In the current study, Willingham and Volkmer collected surgical samples of a variety of human tumors, including ovarian, breast, colon, bladder, brain, liver and prostate. To do so, they enlisted the help of clinical experts from across the School of Medicine, including those specializing in oncology, urology, obstetrics and gynecology, radiation oncology, neurosurgery, hematology, pathology, otolaryngology and hepatology. They showed that nearly every human cancer cell they examined expressed CD47 — usually at higher levels (on average, about three times more) than did non-cancerous cells. Furthermore, people whose cancer cells express a lot of CD47 tend to have shorter life spans than people with similar cancers that express less CD47. This suggests that an analysis of the levels of CD47 expression in some types of tumors could be a valuable prognostic tool for patients and their doctors. Willingham and Volkmer then implanted the different human tumor cells into matching locations in the bodies of mice — breast cancer tumors into the mammary fat pads, and ovarian cancer tumors into the abdomen, for example. Once the tumors were well-established (after two weeks or more), they treated the animals with the anti-CD47 antibody. The researchers saw that most of the established tumors begin to shrink and even, in some cases, disappear within weeks of treatment with the antibody. In one case, antibody treatment cured five mice injected with the same human breast cancer cells. When the tumor was gone, the treatment was discontinued; the mice were monitored for four months with no signs of recurrence. "These results indicate that anti-CD47 antibodies can dramatically inhibit the growth of human solid tumors by blocking the ability of CD47 to transmit the 'don't-eat-me' signal to macrophages," concluded the authors. "If the tumor was highly aggressive," said Weissman, "the antibody also blocked metastasis. It's becoming very clear that, in order for a cancer to survive in the body, it has to find some way to evade the cells of the innate immune system." The innate immune system is the body's first line of defense against pathogens like bacteria and viruses. Unlike the adaptive immunity conferred by antibodies and T cells that recognize and battle specific molecules, cells of the innate immune system, like macrophages, respond non-specifically to a variety of threats. The researchers' approach didn't work in every animal, though. A set of mice with breast cancer cells from a one human patient experienced no benefit from antibody treatment. "There's certainly more to learn," said Weissman. "We need to learn more about the relationship between macrophages and tumor cells, and how to draw more macrophages to the tumors." He suggested that reducing the size of a tumor with surgery or radiotherapy before antibody treatment could make the treatment more effective. Another option, he added, would be to use a second antibody in addition to CD47 that would further stimulate the ability of the macrophages or other immune cells to kill the cancer cells. While treatment modifications may be beneficial, the findings about the effect of the single antibody are promising in their own right and set the stage for advancing the research. "We believe these results show that we should move forward quickly but cautiously into human clinical trials for many types of solid tumors," Weissman said. [Continue article at the above link] Below is summary of the work on LMS by Dr. Matt van de Rijn at Stanford. This is incredible news and the next stage will be a clinical trial to test this vaccine in humans. Sharon .................................................................................. Protein blocking frees macrophages to attack LMS tumors Leiomyosarcoma (LMS) is a rare and aggressive cancer that affects smooth muscle cells such as those found in the uterus and soft tissues throughout the body. Previous studies have linked poor clinicals outcomes of the disease with the presence of immune system cells known as tumor associated macrophages (TAMs), suggesting that TAMs promote LMS tumors. Badreddin Edris et al. (pp. 6656–6661) investigated a technique that interferes with the mechanism that hides cancerous LMS cells from the immune system and turns the presence of TAMs against LMS tumors. The authors used antibodies against CD47, a protein that inhibits the process known as phagocytos is , whereby macrophages engulf and ingest dis eas ed cells . In trials with two human cell lines interfering with CD47 increased phagocytosis in vitro, according to the authors. To evaluate the technique in vivo, the authors transplanted LMS cells into mice and after 6 weeks treated randomized animals for 1 week with a humanized anti-CD47 antibody. After treatment, the authors found that the test subjects exhibited striking decreases in the size of primary tumors and the number of metastatic sites. The findings suggest that therapies with anti-CD47 antibodies can potentially both reduce tumor size and inhibit LMS metastasis, according to the authors. — T.J. Reprinted from Proceedings of the National Academy of Sciences www.pnas.org doi: 10.1073/iti1712109 PNAS April 24, 2012 vol. 109 no. 17 6355-6356

Two Doctors' Tributes

Today (2/10/11), I received the following letter from Dr. Martha Tracy, Rebecca's oncologist, and e-mail from Matt van de Rijn, a pathologist working on LMS at Stanford:

Steve,

Rebecca was a woman of remarkable energy and courage. I have truly not met or worked with anyone with her ability to focus so clearly, broadly and consistently, on seeking additional opportunities for her care at the same time focusing on things like fundraising and family concerns at the same time...

Martha Tracy

Dear Mr. Cohen,

My sincere condolences with your loss. I apologize for being so late with this email but I wanted to request your permission to dedicate our next publication to the memory of Rebecca. It took much longer than I thought to get our manuscript ready for submission.

As you know her contributions to our research were immense, she is by far the greatest individual fundraiser for our work. I sincerely regret that I could not be present at any of the events she organized but it was wonderful to meet her here at Stanford when she visited with Sharon Anderson.

It would be an honor for me if you would allow me to add to the acknowledgement section of our soon to be submitted manuscript: “The authors dedicate this paper to the memory of Rebecca Cohen, LMS patient and fundraiser for LMS research.” Please let me know how you feel about this and whether you would like to discuss this further.

My best wishes,

Matt van de Rijn
Stanford University, Pathology

Rebecca's Memorial Service on YouTube

For those who missed Rebecca's Memorial Service or others who want to revisit or share it, Becca's Memorial Service is now on YouTube in three parts:


Video # 1
http://www.youtube.com/watch?v=TBNHYCF3FPQ

Video # 2
http://www.youtube.com/watch?v=f5fyLYSjyEQ

Video # 3
http://www.youtube.com/watch?v=cZwtRbdIc5A

Thanks,

Steve

New Memorial Location

The memorial will be held:
Sunday 1/16/11 2-4 pm
St. John's Church
2727 College Ave. (at Garber)
Berkeley, CA 94705

Obituary

Rebecca Roberts Cohen
May 11, 1958 - Nov. 18, 2010

Rebecca Bond Roberts Cohen, a lifelong Berkeley resident and physical education teacher, died peacefully at her home on November 18 after a three-year battle with cancer.

She taught physical education at Berkeley’s Berkwood Hedge School for 22 years, and adaptive physical education for the Mount Diablo Unified School District for five.

“Becca was a talented and dedicated physical education teacher who shared a passion for exercise and fitness with all of her students,” said Berkwood Hedge School director Jane Friedman. “She was part of the fabric of the Berkwood Hedge School community as a committed teacher, dedicated parent and loving friend.”

Roberts Cohen earned an adapted physical education specialist credential in 2007 after completing courses at Oakland’s Holy Names College and San Francisco State University, and a BS degree in physical education from Sonoma State in 1986.

In addition to teaching, Roberts Cohen created Sesame Chew Crispies, one of the first organic energy bars in the early ’90s, and was a licensed massage therapist. A gifted outdoor athlete, Roberts Cohen was an avid rock climber, scaling some of Yosemite’s most difficult peaks in the late ’70s. Just one and a half seasons after picking up cycling, she qualified for and competed in the1982 National Road Race as one of the top cyclists in Northern California. She became a competitive swimmer and rower after a knee injury sidelined her nascent bicycle career.

In September 2007, Roberts Cohen was diagnosed with Leiomyosarcoma (LMS), a rare form of uterine cancer. She helped produce three benefits that raised nearly $30,000 for Leiomyosarcoma Research.

Roberts Cohen is survived by her mother, Janet Roberts of Berkeley; father, Harry Roberts of Berkeley; two brothers, Carl Roberts of Portland and Norman Roberts of New York City; a daughter, Abigail Cohen; step daughter, Isabel Cohen of Oakland; husband, Steven Cohen; and a host of her friends and companions.

Donations may be made to:
LMSarcoma Direct Research or LMSdr
Post Office Box 52697, Tulsa, Oklahoma 74152
http://www.lmsdr.org/donatenow.php
or the donor’s choice of charities.

Memorial services will be held on Sunday, January 16 from 2-4 pm
St. John's Church
2727 College Ave. (at Garber)
Berkeley, CA 94705

San Francisco Chronicle 12/12/10

New Memorial Location

Deep thanks for the condolences, tributes, flowers and glowing memories.

The memorial date will be:
Sunday 1/16/11 2-4 pm
St. John's Church
2727 College Ave. (at Garber)
Berkeley, CA 94705

Contributions may be made to:
LMSdr
In Memory of Rebecca Cohen
http://www.lmsdr.org/donatenow.php

Love,

Steve

Resting in Peace

Rebecca Roberts Cohen
5/11/58-11/18/10

I have the most unenviable task of reporting that Rebecca passed on tonight at 7:15. I am relieved to say that it was the most peaceful passing any one could imagine. It's been quite a journey. Now we're on to the next one together.

Love,

Steve