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

The Boxer

Despite the overwhelming odds against her, it's truly amazing to see how much fight is left in this girl.

Rebecca still barrels her way to the bathroom 25 feet away, refusing to use the commode recommend by nurses. She is followed by one of us with arms outstretched in case she teeters during the wobbly sprint. When she gets there, Becca sits on the pot for 20 minutes or so. Can't tell whether she is sleeping or meditating. Just know she's not doing much of what most of us do when we get to the pot.

On Monday night, Abby asked me "Why won't mommy stop fighting this?" That says it all in the form of a question.
On Tuesday, her brother Norman told the social worker who was wondering about Becca's next journey:
"What Becca cared about is the fight and what happens to Abby." That says it all in the form of a statement.

It's Wednesday, and when the bedding and pads are changed, she doesn't just roll over and play dead. That would be too easy. She makes like a stick yogi, arches her back in the bridge position, while others shuffle sheets, pads and bolsters under her. Only then does she lower her distended belly back to the expensive Tempur-Pedic, now branded with her stains. No hospital bed for this one. No rubber sheets. No surrender! OK, surrender the excruciating pain to the liquid methadone stupor. Mouth wide open.

She asks what the date is because she remembers that the first Hospice nurse assessed her mental acuity with that question and other ones, like "what is your name?" It's akin to a referee questioning a just-decked boxer in order to decide whether to stop or continue the fight. Some how, some way she stays on her feet till the bell rings.

Rebecca asks what time it is because she wants to make sure she gets her medication on schedule. And she does this despite sleeping a good 20 hours a day and saying about the same number of words.

They include a sense of humor even though there's nothing to laugh about. She tells Norman: "What are you guys doing today besides carrying me around?" She's even aware enough to comment on her hairy legs. OK, maybe that's not so unusual.

She hasn't lost her sweetness or politeness. Becca wakes to Maryclare crying and tells her it's OK. She nods in agreement when she hears the love being whispered in her ear. She always says thank you if she is present.

No doubt about it, she's here until she gets KOed. She won't take a TKO or a judge's decision to that evil beast in the opposite corner. She will be going soon — too soon — but Rebecca refuses to go down now. Unless it's on her terms.

Resting Comfortably

On a day marked by a frantic stream of friends, food, family and administrative exercises with Hospice care — Hospice officially begins with first nurse today at 2 — Becca rallied late yesterday by displaying her vital signs: a fighting spirit, soft but lucid responses and even a few bed exercises led by the indomitable Maryclare McCauley. Becca had a good night, relatively speaking, or at least compared to Sunday night. As for the rest of us? Put it this way, I remember rubbing what i thought was Abby's back at 4:30 am, only to be corrected by her older sister, Izzy. "Dad, it's me." So if there are any typos...

There's been an outpouring of warm, wonderful e-mails to Becca from other LMS survivors about her inspiration and fighting heart. I wish I could read them all to you. I did read them to Becca. Some day I will post them. But for the rest of us NOT inflicted with this vile disease, I will relay a couple of messages that moved me to tears, hours and buckets into the wee hours of the morning.

A simple and moving message from an old friend who follows the blog: "You are all in our thoughts. I will try to focus on the positive memories, the hikes, the laughs, the long visits over cups of tea... "

And from Abby, the night owl, who likes to crawl in bed around 10 and ruminate till 2:

Abby: "I see photos of mommy and it makes me sad to see her now. I want all those photos of mommy next to the bed."
Me: "Which ones? Can’t picture them. I thought they were mostly of you."
Abby: "The ones where you look so happy together like the two of you when you were so happy in Italy."

Gut wrencher! See why the buckets were out last night. And that was not even the most heart wrenching one. But it is what connects us -- a beautiful picture and memory of happier times. One we will hold onto and cherish. Ones I remind Becca of as she nods in and out of consciousness.

I hope you will join us is sharing those memories. Hold onto those pictures!

Love,

Steve

Space Wanted

Becca's health has taken a turn for the worse in the last five daze. Let's leave it at that. Wanted to say again that Becca needs to conserve her energy, especially so she can save it for Abby. As strange as it sounds, it is quite likely that by not being here you are helping Becca and us more. Time is precious. Becca is a trooper. Your presence is felt whether you are here or not. Take care of yourselves. I promise if anything happens that I will tell you.

Thanks for your understanding.

Steve

Call First

According to my bouncers, too many people are being turned away at the door. Call first (510) 848-2415 so you don't waste your time. As mentioned in last post, you're free to visit Becca when it's convenient for you because I have no way of knowing when it's the right time for Becca and it will just confuse me if you ask me when a good time to come over is. I know you know this, but if you do come by, handle with care: look for a note on the door, (which might say she is asleep), play it by ear and most of all don't wear her out by having a long gab fest. She needs to conserve.

Thanks,

Steven L. Cohen
House Manager
2742 Derby Street
Berkeley, CA 94705

Not a Pretty Picture

It makes me sick writing this, but she asked me to...

Becca continues to fight gamely, but she is clearly enveloped in pain, nausea and her body is depleted, weak and frail. The tumor in her abdomen swells while the rest of her body shrinks. Her hemoglobin count was 8.1 today, so she’s back in the cancer center for a transfusion on Saturday.

Not a lot of options, but they pretty much boil down to trying another treatment or getting some sort of hospice or palliative care. Quality of life versus quantity (of days). Inside I know she’s struggling with that. So are we. Outside, she fights on doggedly, and her fighting spirit told her to go with the treatment today. She’ll be starting Temador in a couple days, a chemo prescribed more often for brain tumors that is taken orally and which is very well tolerated by most people, meaning it doesn’t generally effect blood counts or cause nausea. Keeping those pills down may be another story. With Temador Becca could get more stability to keep the disease from growing, but she’s unlikely to see shrinkage. So best case, it’s a life extender that is not a huge risk. It will be six weeks before she even gets a scan. In the meantime, Xrays will suffice to see if there’s blockage.

If the tumor continues to expand or spread, the worst-case scenario would be a bowel obstruction. Or the tumor could impinge on something else in the area, like a kidney. While she could not survive a major operation, which would be a last resort, smaller procedures might be possible that involve different ways to drain the area, such as a nasal tube, a colostomy, a tube in through abdomen in other parts of stomach.

How much time does she have? No one knows. No one wants to ask.

Rough Patch

Becca has been getting worse since October 10, when she had another successful benefit for LMS at Julia Morgan Theater. She made it to Santa Monica to get the Yondelis (mentioned in her previous post) but she never got it because some enzyme in her liver wouldn't cooperate, so she had to return home the next day. The enzyme is still too high to go back down so she's tweaking the pain medication to see if that helps. She is also getting hydrated for a couple days at Alta Bates Cancer Center. Appetite is not great, and constipation is a constant problem. I wish I had better news to report.

There was a really good article that chronicles Becca's plight and her caring cancer community in the East Bay Monthly, just out on Tuesday. It includes good photos too. Check it out here:http://www.themonthly.com/feature1011.html

...and think good thoughts. She needs them. We need them.

Love,

Steve

Update

Life is not easy, no one every said it would be. These last weeks I have felt that the tumors were growing, I could feel shifts and changes in my back and pelvis. Given these feelings, I pushed my scan date up two weeks. The scan showed that the tumors have grown, argh. As you can imagine this was VERY depressing news as I was hoping to get some relief on Votrient.

My plan now is to do what they call a compasstionate care clinical trial (a drug called Yondelis) in Santa Monica which I will start in just under 3 weeks, not soon enough in my mind but a "flush out" period is need before I start the new drug.

I am trying to keep my head up and look on the bright side, which isn't easy. The "bright" side is the are no new tumors, nothing in vital organs other than the right kidney, and one only needs one kidney, right?

This is not fun.

Becca

not feeling great

despite the "good" news I am emotionally very tenuous, the other word for this is depressed. I ve been closing in and been spending lots of time alone with the exception of a few folks. I am having a hard time staying in touch. Thank you everyone for continuing to reach out even when I don't respond.

I just got an email from Dr. Sabbatini saying that the response I got on the Votrient is typical, and he thinks it's good news. That makes me a bit happier.

one of the contributing factors to my depression is I am not fully funtional; my back is really tight where the tumor is and my left leg is slighlty numb....arghh. Okay, enough.

Some good news is we're having the second annual LMS Benifit on October 10th at 7. The Performer is Don Reed, he's fantastic! tickets will be available soon.

Becca

Stability

Apologies for being a bad uninvited and unauthorized guest blogger...

The news is good. After two weeks of radiation and about four weeks of Votrient, scan showed the tumor in pelvis area is smaller, the one in chest is stable, and there are tiny (1 mm) increases in nodules in right kidney and one lung lobe since last scan in early July. More encouraging is that the pain has been on the wane for two weeks. The pain meds have been dropping out and the woman looks better, too. The insurance appeal even went through.

All told, a pretty nice ride on the roller coaster.

Steve

Good News, Bad News, but on balance, Better News

Becca received a report from an MRI on her pelvis this week. The good news is that her larger tumors, which had not responded to her most recent chemotherapy (AIM), have substantially shrunk by 2, 3 and 6 centimeters, respectively, since her last scan on July 6. They have gone from big and hard to smaller and softer. Speculation centers on the possibility of the Votrient pills she has been taking for about 10 days working super well, but your guess is as good as the next doctor’s.

Secondly, her lungs are clear so that one appears to be status quo.

In the bad news department, there are two newly identified small tumors. There are two areas of concern:

Most concern is the soft tissue area growing out of her sacrum into tissues parallel to it and trapping the nerve root area. This is what has been causing her really, really bad pain. Becca continues to take methadone, which is sort of the “backbone for pain”; Neurontin for nerve pain; and Dilaudid for extra pain as needed.

The second area of concern is a small tumor nearing the spinal canal, and, of course, you don’t want it to let anything into that canal (spinal cord = bad).

Doctor Tracy described the new tumors as “not an emergency” but better to radiate sooner than later. So presto, Becca begins radiation at 8 am sharp on Monday morning, which is as soon as possible. This will be standard external beam radiation, which is not considered dangerous, as it works around the nerve.

Abby and I will be off to Berkeley family camp tomorrow morning, so I wanted to get this off before I go offline.

Best,

Steve

Big Pain, No Gain

This is an unauthorized blog post, but an overdue one nevertheless. It's been a painful couple of weeks for Becca. She started taking the Votrient pills (mentioned in her last post) this week, but it will be a good six to eight weeks to see whether they are doing the trick. Meanwhile the meter is running as the #$%&!@% insurance company denled coverage. We're appealing. Another painful process.

The physical pain is sciatica, an intense deferred pain centered in her right upper thigh area, not near the abdominal tumors. Two theories are a blood clot or bone metasasis. Tomorrow Becca gets an X-ray and a sonogram to see if anything shows up. Then there's the pain medication, which has been ramped up from Vicodin to Dialudid to, as of today, Dialudid and Methadone. Serious stuff, and she is not even trying to kick heroin. That's on top of the Adavan for anxiety, nausea and muscles, and God knows what else.

My mom used to take Adavan during her sunset daze. She also described painful people as "pills" during her glory days. I used to think that was a funny, jaded expression. Now I'm not so sure.

Steve

unexpected news

Last Thursday I got disappointing news that the chemo therapy protocol that I am on is not working. The tumors are growing in both my pelvis and back. This is contrary to the encouraging news from few weeks ago that the tumor on my back was shrinking. After a few days of shock and despair, I contacted Dr. Sabbatini, the sarcoma specialist in MSKCC in NYC and he heavily suggested a drug call Votrient. Votrient is a newly approved FDA drug that is used for renal cancer and is in phase III studies for sarcoma. It's not a chemotherapy but a tyosine kinase inhibitor which blocks proteins, I don't understand it fully but I know the drug works very differently than chemotherapy. I may have some hoops to jump through to get Votrient but I am pretty certain I can get it and I am doing everything I can to expedite the process.

I am still working on keeping my weight up which has become harder because my appetite isn't as hardy as it was. I frequently have abdominal pain which is a real downer for eating and to make things more complicated, I am super finicky about what I want to eat; one minute its roast beef the next cinnamon bread.

I hope next time I post I will have better news.

Becca

it's all about the food

I am eating eating and still look emaciated. I feel better than I look, thanks goodness. I am a roaring 105 pound, and pretty much eat continuously throughout the day, and why do I look so skinny? Don't know, but I am working hard on gaining weight any way I can. Starting with my morning breakfast shake of hemp milk, ground, flax seed, omega 3 oil, ice cream (or Coconut Bliss), banana, dates, berry concentrate, greens mix, protein powder, whey powder and vitamin C goo, whew! I haven't calculated but I think that's a lot of calories.

I have a few more days of home hydration through my port and than I am free!!! I feel suspiciously good, and waiting for the other shoe to drop, maybe it won't, fingers crossed. So far I have had no nausea, no fatigue, no pain, and my digestion is working well. Yes! I can feel the tumor on my back that Dr. Tracy measured two weeks ago and it's definately getting smaller and softer.

All things considered, things are good

Becca