By popular demand . . .

Betty, wearing her favorite pink dress, attempts to escape the paparazzi.


Betty: Does this make my hips look big?
Susan: I can't like to you, Betty. . .

Betty and the entire Carrier household wish you all a very happy, healthy, humiliation-free 2009!

(Actually, if we don't have at least one humiliating experience, maybe we're not taking enough risks.)

what does this say?

Someone gave this second hand t-shirt to my 10 year old son a few days ago. It's never been worn and still has the tags on it. It's a really nice shirt but we all agree that he can't wear it until we all know what it is he is proclaiming to "love."

We've established that it is Japanese. It came from here but the web site does not offer up any translations.

So - do any of you read Japanese?

Updated: Perhaps it isn't Japanese, despite coming from a Japanese company. A couple of people have suggested it looks like Arabic. I have no idea. Thoughts?

just like dr. doolittle

Overheard:

Son (to Father) - "Do you ever talk to our animals? Really talk to them? Mama has entire conversations with the dogs."

Father - "Do they talk back?"

In my own defense, I come by my craziness when it comes to love of animals honestly. My sister is every bit as bad as I am with her cat, Iggie, and my mother can talk to and play with just about any animal for hours.

My mom came from a family of thirteen kids. When we were growing up, my sister and I loved hearing the stories of the animals that lived in and passed through her family home. We still beg to be told these stories and have begun to share them with my kids.

There was George, the budgie, who used to perch on my Grandfather's head (and who died when he came in for a landing, missed and ended up on a hot element).

There were many, many cats, including Fiona (the beautiful), Fluffy (who lost the tip of his tail) and Kelly (the favourite). There was Nicky, the dog that loved to ride on the my uncle's motorcycle. And there were the various animals my mother's oldest brother brought home (often rumoured to have been gambling winnings) - the rabbit (it arrived on Easter and my mother collected hundreds of little "raisins" that the rabbit kept "laying." Fortunately, she didn't try and eat any.), the monkey (banished after he started swinging from the curtains) and the chicken (that my Grandmother found tied to the table leg in her kitchen).

Really, compared to the way my mother grew up, my house with its dogs and cat is really very quiet.

And yes, I do talk to my animals. They are very sympathetic listeners.

The CSC hypothesis: recalling some history

More about the CSC hypothesis: Cancer Stem Cells: Fact or Fiction? by Caroline Brandon, Connecting for Kids, December 26, 2008. Excerpts:

In the 1960s there was an unethical experiment where physicians took cancer cells from various types of malignancies and re-injected these cells back into the original cancer patient or another non-cancerous terminally ill patient. The results from this experiment suggested that those with cancer lacked immunity to the disease while “healthy” individuals carried some immunity to the cancer cells. However, another interesting observation was made throughout the experiments: that it requires millions of cancer cells to initiate the growth of a tumor. It is this observation from which two theories emerged in the decades to come regarding tumor initiation and maintenance.

.....

I am hopeful that from studies like this [publication in Nature by Quintana et al] that challenge the current cancer stem cell dogma, new creative approaches will be used to uncover the true culprits behind cancer, be it a rare population of stem cells or a more common population yet to be defined.

For some additional relevant commentary, see this previous post: Tumorigenic cells not rare in human melanoma, December 3, 2008.

Comments: One "unethical experiment" of the kind described in the first excerpt is the Jewish Chronic Disease Hospital case. It has been summarized briefly in the section on injections of cancer cells, in notes entitled Nonconsensual Medical Experiments on Human Beings, by Ronald B Standler (notes created Dec 1996). The initial two sentences:

There were intradermal injections of live human cancer cells into 22 chronically ill, debilitated non-cancer patients in 1963 without their consent in the Jewish Chronic Disease Hospital case, to learn if foreign cancer cells would live longer in debilitated non-cancer patients than in patients debilitated by cancer. Lump at injection site disappeared approximately seven weeks after injection.

For a much more detailed discussion of this case from legal and ethical perspectives, see: Experimentation with Human Beings by Jay Katz, Yale University, Russell Sage Foundation, 1972 [PDF, 58 pages]. Chapter 1 is about The Jewish Chronic Disease Hospital Case. The first sentence of this chapter:

In July 1963, three doctors, with approval from the director of medicine of the Jewish Chronic Disease Hospital in Brooklyn, New York, injected "live cancer cells" subcutaneously into twenty-two chronically ill and debilitated patients.

A publication, apparently based on studies of these patients, is: Rejection of cancer homotransplants by patients with debilitating non-neoplastic diseases by Arthur G Levin, D B Custodio, Emanuel E Mandel, Chester M Southam, Ann N Y Acad Sci 1964(Nov 30); 120: 410-23 [PubMed Citation]. The full text isn't publicly accessible. From the Materials and Methods: "The recipients with non-neoplastic diseases were 19 patients at the Jewish Chronic Disease Hospital ..... The homotransplants consisted of subcutaneous injections of two to five million tissue-cultured cells. Three human cell lines of neoplastic origin were used ...". It seems inconceivable in the light of current ethical standards for human experimentation that these studies could have been carried out and published, but they were. Ethical oversight of such studies was minimal then. The summary from this publication:

Summary

Nineteen patients with advanced, debilitating, non-neoplastic diseases were given two subcutaneous homotransplants of tissue-cultured human cancer cells: one of cell line HEp 2, and one of either HEp 3 or RPMI 41. These recipients rejected the homotransplants promptly, as do normal healthy controls, whereas many patients with advanced cancer have an impaired capacity to reject these cell lines.

These findings indicate that the immunological defect which is evidenced by delayed homograft rejection is not merely a consequence of debility and cachexia.

However, although the defect occurs often in patients with advanced cancer, it is not demonstrable in all cancer patients and it cannot be assumed that it is specifically associated with cancer.

The parallelism of homograft rejection, macrophage mobilization, and delayed hypersensitivity response is discussed.

The full text begins with the statement that: "Previous studies indicate that patients with advanced cancer have an immunologic defect manifested by their inability to reject homotransplants of tissue-cultured cell lines as rapidly as healthy controls ...". The first publication cited in support of this statement is: Homotransplantation of human cell lines, Chester M Southam, Alice E Moore, Cornelius P Rhoads, Science 1957(Jan 25); 125(3239): 158-60 [PDF Extract][PubMed Citation (with the authors listed in a different order)]. Excerpt from the full text:

All recipients were volunteers who were aware of the general purposes of the study and the nature of the implanted materials and who were agreeable to subsequent biopsies ...

It should be emphasized that the standards for informed consent, and the procedures used for obtaining informed consent, were very different in 1957 in comparison with those used now.

An article about these latter experiments was published in Time magazine: Cancer Volunteers (Feb. 25, 1957). The first paragraph on the first page:

On wooden benches in the well-guarded recreation hall of the Ohio Penitentiary at Columbus sat 53 convicts—killers in for life, bank robbers, embezzlers, check forgers. Some wore the white jacket and trousers of hospital attendants (duty for which they had volunteered in the prison); others, fresh from work gangs, wore blue dungarees. As a man's name was called he walked upstairs to a room equipped as an emergency surgery, sat down and proffered a bare forearm. Dr. Chester M. Southam of Manhattan's Sloan-Kettering Institute then proceeded to inject live cancer cells.

The last paragraph on the first page:

The blobs of fluid containing the cancer cells made little bumps on each man's arm. In a matter of hours or days, some of these swelled up and became tender and inflamed; the healthy body's natural defenses were at work and plain to see. In other cases the men felt no appreciable discomfort, and the swelling disappeared without any noticeable inflammatory stage; the body's defenses had worked just as effectively but less conspicuously.

What have we learned during the 5 decades that have gone by since these studies were done? A lot about the ethics of human experimentation. A lot about how to avoid rejection, by the recipients, of transplanted cells obtained from unrelated donors. Quite a lot about tumor immunology and other aspects of tumor-host interactions. But, not enough (yet) about bioassays designed to detect, enumerate and characterize human CSC.

You look healthy

I giggled yesterday after my doctor told me, "You look healthy."

Of course, he couldn't understand why this remark was funny. I explained that I was used to the social hyperbole of "You look great" or "You look fabulous," but lately friends have been commenting, "You look well" or "You look healthy." The funny thing is that I love it when friends tell me I look well, because I know that I didn't look or act that way a few months ago.

I not only look well, I look normal - not like someone who battled cancer. Not like someone who was laid low by eosinophils. Not like a 105 pound weakling who passed out on the way to the bathroom.

At a Hanukkah party on Saturday, our gracious host introduced me to a guest wearing a fashionable turban, but I knew right away that the head covering was more than a fashion statement. The host added, "I think you two have something in common." I don't think anyone else would have noticed, but I saw her face twitch. We both wanted to be happy revelers stuffing our faces with latkes and apple sauce, not patients comparing treatments. I made an excuse and then slipped away to fill my plate with freshly fried potato pancakes.

Normal. Well. Healthy. Not long ago I would have chafed at the thought of anyone using these boring words to describe me, but now they're music to my ears.

"You look fabulous," my doctor teased as I left the exam room. That sounded pretty good too.

New perspectives

A cancer survivor friend was telling me today about the many stresses currently overwhelming her. They are very significant stressors. But then she said how great it was to be freaking about something other than potentially dying of cancer. I laughed. I've felt the same before...grateful for things that overwhelmed me that weren't cancer. Stress after a cancer diagnosis was redefined, even sometimes enjoyed. What had once been stressors to be avoided had become greatly appreciated distractions.

Another newly diagnosed cancer patient told me this week how much she appreciates sleeping. She reminded me that sleep was my escape from cancer too, early on...even though falling asleep was difficult. I remember first waking up in the days after I was diagnosed and feeling great....for about 60 seconds. Then I'd remember that something was wrong, my life had changed. I'd remember that I had cancer. I just wanting my normal mornings back. To wake up without the dark curtain falling.

I also celebrated this year that at my family's annual holiday gathering on Christmas Eve only ONE person took my picture!!! The first family Christmas get together after my diagnosis I noticed everyone pointing cameras and camcorders in my direction, I was very conscious of it. Everyone kept saying they were sure I was going to beat it, but they kept taking pictures and more pictures of me...just in case.

I now have a kind of annoying need to always be productive...it's harder for me to just do mindless things, I always have a todo list. I feel badly if I don't make good use of a day. I need my time to be spent in meaningful ways, I guess? I don't relax as easily. I have a timer now to monitor my on-line use, I don't want to spend too much time on the computer. Too easy to waste time you may not get back.

I'm also just less fearful in general. Old fears turned out to not have much substance in comparison to the cancer monster. I no longer have any fear of flying at all, bumpy flights and storms are fine. I even recently flew in a very old rickety small prop plane. Loud and interesting but not scary. I don't mind being in small boats in large ocean waves. I don't worry about bears when backpacking in bear country. I don't worry about contaminated water. I totally disregard expiration dates on food.

But while I'm less fearful for myself, I am more fearful for my kids, I think. I'm probably more protective, which is tricky now that they are approaching adulthood and I need to respect their independence. I know personally that bad things can happen, that good and loving and deserving people aren't immune, and that in an instant things can change. I know that we are all vulnerable. So I try harder to keep my kids safe and healthy. I put vitamin D supplements in their Christmas stockings this year after what I learned at my most recent cancer conference (more on that later).

Before cancer I also used to say I'd want to know ahead of time before I died...I think I'd wanted to organize my stuff and clean up my messes before I checked out, to not embarrass myself for posterity? Or maybe it was the control freak in me that didn't want to be taken by surprise. Now I'd much more appreciate dying quickly without having to contemplate my demise ahead of time...a heart attack or a plane crash would be preferable, probably why I no longer have a fear of flying!

Life after a cancer diagnosis just changes things. Our perspectives are different, we are changed.

book review: "no such creature"*

I really like Canadian writer Giles Blunt and enjoy his series set in Northern Ontario. All his books feature interesting storylines and are populated by complex characters. The setting of Algonquin Bay (modeled on North Bay) is itself a character in the book - cold, dark and somewhat remote.

And the books really are dark, even compared to other murder mysteries. By The Time You Read This, the last in the series featuring police detective John Cardinal, opens with the suicide of Cardinal's wife. I found it heart-wrenching and I can understand why the author chose a change of pace for his latest novel.

No Such Creature is in some ways very different from Blunt's police procedurals but despite the injection of humour and the relocation to sunnier climes there are a couple of twists that are no less devastating than the author's previous novels.

"Tooling across the American southwest in their giant Winnebago, Max and his nephew, Owen, seem harmless enough, the actorly old fellow spouting Shakespeare like a faucet while his young charge trots him through select tourist destinations along the road. But appearances, as you might imagine, can be deceiving.

Old Max is actually a master thief, and young Owen's summer vacation is his careful apprenticeship in a life of crime. Pulling heists is scary enough, but ominous signs point to the alarming fact that The Subtractors are on their tail, criminal bogeymen who stop at nothing to steal from other thieves. The road trip soon turns into a chase, by turns comic and horrifying. The most disturbing twist: Owen's slow realization that the person he loves most in the world is the one who can do him the most harm."

The book features snappy dialogue, characters that are larger than life, events that test the "willing suspension of disbelief" and little touches or irony that have the ring of authenticity. I was reminded of both Elmore Leonard and Carl Hiaasen but I never felt like I had read this book somewhere before.

In some ways, Blunt tries to do too many things with this novel. I was never sure if I was reading a caper, coming of age book or a story about fathers and sons. But Blunt mostly succeeds in creating a story that's about all of these things. Certainly, I cared about the characters, laughed out loud several times, felt the mountain tension and found myself turning pages compulsively.

No Such Creature is entertaining, amusing, heart-breaking and surprising. You might be disappointed in the ending but you will never be bored.

And you know, those books where you can see the ending coming a mile away? Even with lots of foreshadowing, I was still wondering what would happen ten pages from the end.

You can read an excerpt here.

*This is book was sent to me via Library Thing's Early Reviewer Program.

Criteria for review of pre-applications to CIRM

Pre-Application Review Process for Basic Biology RFA, CIRM, Agenda Item # 4, ICOC Teleconference Meeting, December 23, 2008 [PDF]. Excerpts:

The ICOC, at its most recent meeting, considered a proposal from CIRM staff to introduce a pre-application review process, on a trial basis, for use in the upcoming Basic Biology I & II and Disease Team RFAs.

.....

Proposal: Criteria for Review of Pre-Applications

Pre-application review will focus on the essential aspects of the scientific proposal, without requiring Principal Investigators (PIs) to finalize or describe detailed research plans, budgets, collaborations or personnel. This review will consider a subset of the standard GWG criteria, tailored to the level of information we will seek in the preapplication:

1. Impact and Significance. Whether and to what extent the proposed research: addresses an important problem; significantly moves the field forward, either scientifically or medically; moves the research closer to therapy; and changes the thinking or experimental or medical practice in the field.

2. Innovation. Whether and to what extent the research approach is original, breaks new ground, and brings novel ideas, technologies or strategies to bear on an important problem.

3. Feasibility. Whether and to what extent the aims of the research can be reasonably achieved in the specified timeframe of the award.

4. Responsiveness to RFA. Whether and to what extent the proposed research project or activity adequately and appropriately addresses the goals and objectives presented in the RFA.

CIRM science staff and outside scientific specialists will apply these standard criteria. As with the criteria for GWG review of full applications, science officers will prepare guidelines that describe how these criteria apply to the concept for a specific RFA. These guidelines will be published as part of the RFA, so that PIs can address them in their preapplications.

Note that these criteria will be applied to the Disease Team RFAs.

See also: Stem cell board fails to muster quorum, skips cash request, John M Simpson, Consumer Watchdog, December 24, 2008. Excerpt:

The stem cell agency's staff had to report on the criteria they'll use in the pre-review process. They did and it's outlined here.

For a relevant previous post, see: CIRM/CSCC Joint Announcement: Disease Teams Awards, Cancer Stem Cell News, October 23, 2008.

Breast Reconstruction With Tissue Much Safer Than Implants When Radiation Planned After Mastectomy

A study published in the November issue of the International Journal of Radiation Oncology*Biology*Physics examined the effect of radiation therapy on different methods of immediate breast reconstruction surgery. For breast cancer patients who receive radiation therapy after a mastectomy and immediate breast reconstruction, autologous tissue reconstruction (ie reconstruction using their own tissue) provides fewer long-term complications and superior cosmetic results than breast reconstruction with a tissue expander and subsequent breast implant.

Many women choose to undergo breast reconstruction surgery at the same time as their mastectomy procedure (under the same anesthetic). This avoids many of the psycho-social issues women face when dealing with a flat chest after mastectomy alone. However, frequently radiation can negatively affect the outcome of reconstruction and increase the risk of long-term complications.

Radiation therapy is increasingly becoming the standard of care for high-risk breast cancer patients after mastectomy in an attempt to decrease local cancer recurrence. However, this can cause a problem for both patients and their radiation oncologists.

Researchers at the Department of Radiation Oncology at Long Island Radiation Therapy in Garden City, N.Y., the Department of Surgery at Long Island Jewish Hospital in New Hyde Park, N.Y., the Department of Surgery at North Shore University Hospital in Manhasset, N.Y., and the Department of Surgery at Winthrop University Hospital in Mineola, N.Y., looked at whether the type of reconstruction performed in women receiving radiation after a mastectomy had an impact on their long-term outcomes.

Two general types of breast reconstruction are available for patients facing mastectomy for breast cancer: autologous tissue reconstruction utilizing the patient's own tissue (eg DIEP flap, GAP flap, TRAM flap, or latissimus flap) transferred to the chest to recreate the breast(s); and tissue expander/implant reconstruction which involves placement of an inflatable tissue expander (temporary saline implant) and exchange for a permanent implant (saline or silicone) at a separate procedure later on.

This study involved the largest reported series of patients who sequentially underwent mastectomy, immediate reconstruction and postmastectomy radiation therapy. Ninety-two patients were observed for a period of 38 months following breast reconstruction and radiation therapy.

Researchers found that autologous breast reconstruction is better tolerated by breast cancer patients because it is associated with fewer long-term complications and better cosmetic results than tissue expander/implant reconstruction.

None of the 23 patients reconstructed with their own tissue required further surgery while 33% of tissue expander/implant patients needed surgery to correct a problem with their reconstruction. Eighty-three percent of autologous reconstruction patients reported acceptable cosmetic results, as opposed to only 54% of implant patients.

"This study is useful for patients who are candidates for either [method of reconstruction] and are making a decision with regards to reconstruction technique," Jigna Jhaveri, M.D., lead author of the study and a radiation oncologist at Advanced Radiation Centers of New York in Hauppauge, N.Y., said. "Our study provides evidence that patients who undergo autologous tissue reconstruction and radiation therapy have fewer long term complications and better cosmetic outcomes than those who undergo tissue expander/implant reconstruction and radiation therapy."

*****

Here's my take....

While some plastic surgeons will disagree with this statement I strongly believe that breast implants and radiation therapy do not get along (at all). I feel the complication rate in implant-reconstructed women receiving radiation therapy is very high, particularly long-term. The handful of women that "do fine" in the short-term will very frequently end up with hard, uncomfortable breasts as the irradiated tissue firms-up over time and squeezes down on the implant. In my opinion the re-operation rate is too high for tissue expander/implant reconstruction to be offered as a routine option when radiation is on the table. This study confirms that breast reconstruction using the patient's own tissue is far safer than tissue expander/implant reconstruction in women facing radiation therapy after mastectomy.

Dr C

******

Dr Chrysopoulo is a board certified plastic surgeon specializing in breast reconstruction surgery after mastectomy, particularly advanced perforator flap techniques such as the DIEP flap procedure. PRMA Plastic Surgery, San Antonio, Texas. Toll Free: (800) 692-5565. Keep up to date with the latest breast reconstruction news by following The Breast Cancer Reconstruction Blog.

******

The case of the missing Grandpa and the headless maid

WCK's other big Christmas present was a Fisher-Price Loving Family Dollhouse. I picked it out because I thought it looked like a cute dollhouse; little did I know that every little girl in the whole entire world received one for Christmas this year. The house came with a mom, a dad, two baby twins, and a table and chairs. All other furniture and dolls are sold separately, and they were incredibly hard to find. After some searching (remember, Santa shops online), Santa found several rooms, and both of WCK's grandmas found a few rooms, and the house was complete.

Well, almost complete. We were able to find a doll set that came with a Grandma and an older brother, but we could not find Grandpa anywhere. After looking through the brochure that came with the dollhouse, we realized that Fisher-Price does not even make a Grandpa. Really? Why? Is Grandma a widow? Did she walk out on Grandpa? Is the "older brother" really Grandma's 25-year-old boyfriend? If you look closely at the mom and dad, you can see judgement in their eyes.

But after all the worry about finding the right people, WCK's favorite "person" in the house is the bathrobe stand that came with the bedroom set. You can see it in this photo:



WCK makes the bathrobe stand have all kinds of adventures. Earlier today, the bathrobe stand took the Loving Family's minivan downstairs and picked up some food at the Fisher-Price grocery store and took it back to the family. For some reason the bathrobe stand spends a lot of time cleaning the toilet (yes, the toilet came with a teeny little toilet brush), which makes me wonder if the stand is the family's maid. I say, if you're going to splurge for a maid, you might as well go all out and have the cleaning service send over one that has no head, so you can avoid any judgemental looks about the messy state of your bathroom.

Two reviews about CSCs

1) An update on the biology of cancer stem cells in breast cancer by José María García Bueno and 8 co-authors, including Carmen Ramírez-Castillejo, Clin Transl Oncol 2008(Dec); 10(12): 786-93 [PubMed Citation].

2) Cancer stem cells: How can we target them? by Ivan Ischenko and 4 co-authors, including Karl-Walter Jauch and Christiane J Bruns, Curr Med Chem 2008(Dec); 15(30): 3171-84 [PubMed Citation].

[The full text isn't publicly accessible for either of these reviews].

CSCs in a mouse glioma model

Cancer stem cells are enriched in the side population cells in a mouse model of glioma by Molly A Harris and 8 co-authors, including Kyuson Yun, Cancer Res 2008(Dec 15); 68(24): 10051-9. PubMed Abstract:

The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100beta-verbB;Trp53. In this glioma model, CSCs are enriched in the side population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared with non-SP cells from the same tumors. Furthermore, gene expression analysis comparing fluorescence-activated cell sorting-sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human glioblastoma multiforme cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the CSC hypothesis.

[The full text of this article isn't publicly accessible].

Mutts Like Me

Photo of Betty (half Aussie, half Welsh) by Skye

President-elect Barack Obama has made it cool to be a racial mix, or, as he calls it, a "mutt."

What's not cool is the difficulty that bi- and multi-racial patients have in finding a bone marrow match. Just ask Ann, a hapa (half Asian, half Caucasian) who just completed her second life-saving bone marrow transplant. Or talk to Krissy, another hapa, who's still searching for her match.

Read more about mutts and marrow in this opinion piece that appears in Sunday's Pasadena Star News (as well as sister papers, Whittier Daily News and San Gabriel Valley Tribune.)

If you're a minority (black, Latino, Asian, Native American) or racially mixed, contact A3M (Asians for Miracle Marrow Matches) in Southern California or AADP in Northern California to find a drive near you. Or, go to the website for the National Bone Marrow Registry and sign up online or find a drive near you.

You could end up being the life-saving match for someone - maybe even a mutt like Obama or me. How cool would that be?

Subway: Eat fresh

Santa came through: WCK got her set of plastic Subway food on Christmas morning. Whew. If you'll recall, WCK has been asking about this set almost on a daily basis since about August or September. She reminded Santa in person twice, and once via letter. She keeps asking me how Santa managed to find it, since we couldn't find it ourselves at Toys R Us. Santa is magic, I say. Also, he shops online.

Here's a photo of it from Christmas morning:



Now we spend nearly every moment playing "Subway". First, WCK tells us that Subway is closed, and we have to leave the room while she carefully sets all of the pieces on the coffee table. Then she tells us that Subway has opened, and we have to step up to the coffee table and order our sandwiches, salads, cookies, and bottled water. She prepares everything carefully and puts it on our tray, and then rings it up on her toy cash register. I usually pay via a fake credit card with WCK's photo on it that we got from a machine at Chuck E. Cheese. My mom even wrote "Subway" on some pieces of tissue paper, so we could wrap up the sandwiches and have them to go.

Is there anything better than plastic cheese?

NEW ARRIVALS

We received a few new things this week, mostly replenishment:

Cantillon Kreik
Cantillon Classic Gueze
Cantillon Rose'De Gambrinus
Cantillon Iris
Cantillon Grand Cru
Fantome Hiver
21st Amendment Watermelon Wheat
Hair of the Dog Doggie Claws (get it while you can)
Lost Coast Winter Braun

Also just received a large shipment of Irish/English Christmas candies, bangers, rashers, susage rolls. So come Irish up your holiday at healthy spirits and while your at it have a few drinks.

Nate

One degree of se-purr-ation

Bob, Puss's former owner, danced with Eartha Kitt when she was a member of the Katherine Dunham dance troop. Both Bob and Eartha died from cancer at age 81.

Puss has nine lives to go.

Update

I found the receipt for the Little House set and discovered it cost about half of what I thought it did. Thank goodness. Now I can watch the episode where Laura and Mary have to save up a penny to buy a new pencil for school without getting stressed out.

WCK can't go to college now because ...

... Jay got me the entire series of Little House on the Prairie on DVD. It's huge. It has 60 discs and comes in a case shaped like a covered wagon. I'm a little shocked.

Yes, I knew he was getting me something related to LHOTP, but I honestly assumed it would be, I don't know, one season on DVD or a book or something. If you'll recall, I mentioned how I coveted the giant set a few months ago, but no normal person would spend that much money on DVDs. Then again, are any hard-core Little House fans normal people? I once stood in line for hours in the blazing sun to meet the actor who played Almanzo, and I didn't see any normal people around me.

I alternate between feeling guilty and queasy over how much was spent on my gift and feeling a little giddy that I can watch the episode where Harriett takes over the town newspaper any time I want. Jay says I deserve it because I have to put up with him every day. Hmm. Putting up with Jay is not very difficult, but OK.

Anyway. Today I watched the one where Charles falls out of a tree and breaks his ribs and can't stack the sacks of grain for the evil feed-store owner. It was so good.

a traditional holiday

My family is cross-cultural and, at least, when it comes to my spouse and our kids, very secular. We do, however, celebrate both Chanukah and Christmas and, the last few days, I have felt the stress of preparations for familial celebrations acutely.

Most of this was of my own doing. I was feeling inadequate and judging myself for having such a messy house. There are no decorations (except the tree, which we put up on Monday) and I have certainly not done any holiday baking.

Every level surface was covered in layers of clutter. I also found that stuff that doesn't usually bother me so much (the fact that most of the knobs are missing from our kitchen cupboards, our counter tops desperately need replacing, our bathmats and towels are all frayed and, in a number of places, the wallpaper has been torn off the walls) was making me absolutely nuts.

I did manage to put a dent in the mess but not until I had driven everyone in the house crazy, too. By the time afternoon rolled around my spouse was trying to get me to take deep breaths and my oldest son was referring to himself as "S-erella".

Then, when everyone (my parents and sister and brother in law) arrived, I just decided to let it all go (OK, the wine helped). As the evening unfolded and I relaxed, I was reminded that we were all there to enjoy each other, that I am a grow-up now (even if I don't always act like it) and that all expectations around our own particular traditions were being met.



These are the things you can count on during the holidays at my house:

1. We will light the Chanukah candles (we have a felt menorah and the real thing) and, in lieu of a prayer we will sing loudly and off-key. We call Chanukah "the festival of fried things" and we always make sure that we eat lots of them (latkes are a particular favourite and my spouse and his brothers each believe that theirs are the best).

2. On Christmas Eve, everyone will come over in the late afternoon. My spouse will have to run one last errand after the guests arrive and I will excuse myself to go wrap all my presents (careful wrapping is not a priority in my family).

3. My mom will bring chicken pot pie and tourtiere (a French Canadian traditional pork pie). My sister will bring a celiac-friendly, kosher chicken pot pie (my sister and I are both married to Jewish men).

4. We will begin to unwrap all our presents to each other shortly after dinner. Despite the fact that we will all have declared that we planned on restraint, we will open presents for hours.

5. The first present we each get will be socks.

6. My spouse will put out crackers, cheese and pickles that almost no one will eat because we are still full of tourtiere and pot pie.

7. My sister and I and the kids will all get pajamas.

8. My brother-in-law will give my mom a bottle of wine.

9. We will put out a snack for Santa (we tracked his travels on Google Earth). This year, we left him a banana, blueberry, chocolate chip muffin and apple juice).

10. The next morning, D. will wake up first. We will keep him in our bed for a while so that the others can get a bit of sleep (this morning, D. woke me up to say, "Mama! You fell back asleep!" but he also read to himself for more than an hour).

11. The kids will go and wake up my mom in the attic guest room and we will go downstairs.

12. Santa will have come. Euphoria will ensue. This year's haul included DS games, a hot wheels set (for D.) and a big red bean bag chair (for S. but D. has been eyeing it).

13. We will all find chocolate in our stockings (fair trade, except for D. who has a nut allergy. Santa hasn't been able to find a distributor of fair trade chocolate that's safe for him. D. gets a Mars bar).

14. My brother-in-law will bring a bottle of Baileys (one of the many reasons I love my brother-in-law) and most of the grown ups will pour liberal amounts into our breakfast coffee.

15. I'll go for a post-breakfast dog walk with S. and my sister. They will wear their pajamas.

16. We will have a Christmas dinner, consisting of a turkey with all the fixings. T. will roast the turkey and veggies, mom will make the cranberry sauce and my sister makes the stuffing and desserts. We will all eat until we can't move.

Something we did last year, which we are making into a tradition is watch a movie on Christmas day. Last year it was Elf. This year's choice is Get Smart. Going to go do that now.

May you all be enjoying your good traditions, surviving the meshugas and spending time with people you love.

Happy holidays!

I'm dreaming of a wet Christmas

Raindrops are falling, logs are burning and the monkey bread is up to its business in the oven.

Wishing you all a very merry!

Cookies and sprinkles and icings, oh my!

Cynthia created this beautiful "pretty in pink" angel cookie. Leave it to my fashionista to make a Christmas cookie stylish and sexy. Note the highlighted hair, the heels and the plunging neckline.

Two days before Christmas, and I'm finally getting into the spirit. Find out how we made these beautiful cookies at Open Mouth, Insert Fork.

Alter Egos

The mutant radiation-chemo combo has given me the power of the Alter Ego. Observe:





Hey guys, I feel great. I am single-handedly making cancer my bitch and I've also got this great Linsdsey Lohan hairdo. I will be back before you know it!







oh, hey, an eskeemo only a mother could love. Right after chemo; I've just puked. I'm really scared of dying right now. My eyebrows are falling off. I'm hopefully half way done but I cry at the thought of enduring this for another 3 1/2 months. I cry A LOT. I feel I've lost all of my friends and I miss them dearly.



Unfortunately the latter has become the norm.



Lately I have succumbed to numbness- perhaps I've just become used to my situation. When the pain becomes too much to bear, my mind just pops right off from my body like a balloon. I feel separated from everything, just floating and unfeeling. I span time like this. Nothing else matters. Great coping mechanism, huh?

Have Yourself a Merry Little Christmas

Brings a little tear to my eye:

Going to Moscow

Hello everyone,
I will be leaving tomorrow evening for Moscow, so if you have any beer questions or need anything, you can either call the store at 415-255-0610, or leave them on the blog. Thank you to everyone for making 2008 such a great year for Healthy Spirits.
Have a happy holiday, and while you're at it, have a couple of drinks.

cheers,

dave

now this is snow

More photos of my snowy backyard on Flickr.

Prognostic potential of CSC analysis in glioblastoma

Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme by Roberto Pallini and 10 co-authors, including Ruggero De Maria, Clin Cancer Res 2008(Dec 15); 14(24): 8205-12. PubMed Abstract:

PURPOSE: Cancer stem cells (CSC) are thought to represent the population of tumorigenic cells responsible for tumor development. The stem cell antigen CD133 identifies such a tumorigenic population in a subset of glioblastoma patients. We conducted a prospective study to explore the prognostic potential of CSC analysis in glioblastoma patients. EXPERIMENTAL DESIGN: We investigated the relationship between the in vitro growth potential of glioblastoma CSCs and patient death or disease progression in tumors of 44 consecutive glioblastoma patients treated with complete or partial tumorectomy followed by radiotherapy combined with temozolomide treatment. Moreover, we evaluated by immunohistochemistry and immunofluorescence the prognostic value of the relative presence of CD133(+) and CD133(+)/Ki67(+) cells in patient tumors. RESULTS: In vitro CSC generation and the presence of >/=2% CD133(+) cells in tumor lesions negatively correlated with overall (P = 0.0001 and 0.02, respectively) and progression-free (P = 0.0002 and 0.01, respectively) survival of patients. A very poor overall (P = 0.007) and progression-free (P = 0.001) survival was observed among patients whose tumors contained CD133(+) cells expressing Ki67. Taking into account symptom duration, surgery type, age, O(6)-methylguanine-DNA methyltransferase promoter methylation, and p53 status, generation of CSCs and CD133/Ki67 coexpression emerged as highly significant independent prognostic factors, with an adjusted hazard ratio of 2.92 (95% confidence interval, 1.37-6.2; P = 0.005) and 4.48 (95% confidence interval, 1.68-11.9; P = 0.003), respectively. CONCLUSIONS: The analysis of CSCs may predict the survival of glioblastoma patients. In vitro CSC generation and presence of CD133(+)/Ki67(+) cells are two considerable prognostic factors of disease progression and poor clinical outcome.

See also: Prognostic relevance of SOCS3 hypermethylation in patients with glioblastoma multiforme by Maurizio Martini and 5 co-authors, including Luigi Maria Larocca, Int J Cancer 2008(Dec 15); 123(12): 2955-60 [Epub 2008(Sep 3)][PubMed Citation].

[The full text of these articles isn't publicly accessible].

Goth girl

The following story is something that would only happen when my camera's not working:

Some of the party favors at WCK's third birthday party were little dinosaur stampers with the ink inside. We have a bunch of them left over, and WCK loves those things. She'll stamp anything that will stand still long enough to be stamped. I try to never let her play with them unsupervised, or the results would be ... ah ... colorful.

Today, however, a blue pterodactyl stamp managed to end up in her room during "naptime". (Actually, I call it "rest time" now, although she neither naps nor rests. It would be more accurate to call it "Trash your room time".)

When she emerged after trashing her room, she had painted both of her lips, her eyelids, her fingers, and her toes dark blue. She looked very Goth-like. The stuff mostly washed right off, although it was hard to get it all out of the little folds of her eyelids. I took my three-year-old to church looking like she was wearing a hint of blue eyeshadow.

By the way, I'm not sure where she got the idea to put on lipstick and eyeshadow, since she has never witnessed her mother doing either one. Unless you count chap stick.

The lazy food blogger makes butternut squash and sweet potato gratin

I swear I must be the laziest food blogger in the world wide web. After Pinch My Salt posted her recipe for butternut squash and sweet potato gratin, she received loads of comments from fellow bloggers and cooks who tried and loved the recipe. Not one of them whined about the sweat-inducing labor of working with butternut squash or the tedium of stripping the tiny leaves from a sprig of thyme. The first time I made this dish I swore, "Never again."

But then I tasted it and two weeks later I was back to whittling butternut squash and stripping those pesky leaves from the thyme branch.

Yes, it's that good. Find out how to make this at Open Mouth, Insert Fork.

Articles about CSC in Stem Cells journal (Dec 2008)

Articles on CSC in the December 2008 (Vol 26, No 12) issue of the journal Stem Cells:

The Stem Cell-Associated Antigen CD133 (Prominin-1) Is a Molecular Therapeutic Target for Metastatic Melanoma by Germana Rappa, Oystein Fodstad, Aurelio Lorico, Stem Cells 2008; 26(12): 3008-17 [Epub 2008(Sep 18)][PubMed Citation].

Hedgehog Signaling Regulates Brain Tumor-Initiating Cell Proliferation and Portends Shorter Survival for Patients with PTEN-Coexpressing Glioblastomas by Qijin Xu and 4 co-authors, including John S Yu, Stem Cells 2008; 26(12): 3018-26 [Epub 2008(Sep 11)][PubMed Citation].

Brain Cancer Stem Cells Display Preferential Sensitivity to Akt Inhibition by Christine E Eyler and 5 co-authors, including Jeremy N Rich, Stem Cells 2008; 26(12): 3027-36 [Epub 2008(Sep 18)][PubMed Citation].

Quantitative Mass Spectrometry Identifies Drug Targets in Cancer Stem Cell-Containing Side Population by Sebastian CJ Steiniger and 4 co-authors, including Kim D Janda, Stem Cells 2008; 26(12): 3037-46 [Epub 2008(Sep 18)][PubMed Citation].

Human T-Cell Lymphotropic Virus Type 1 Infection of CD34+ Hematopoietic Progenitor Cells Induces Cell Cycle Arrest by Modulation of p21cip1/waf1 and Survivin by Prabal Banerjee and 3 co-authors, including Gerold Feuer, Stem Cells 2008; 26(12): 3047-58 [Epub 2008(Sep 25)][PubMed Citation].

Identification of a Small Subpopulation of Candidate Leukemia-Initiating Cells in the Side Population of Patients with Acute Myeloid Leukemia by Bijan Moshaver and 9 co-authors, including , Gerrit Jan Schuurhuis, Stem Cells 2008; 26(12): 3059-67 [Epub 2008(Oct 2)][PubMed Citation].

OCT4 Spliced Variants Are Differentially Expressed in Human Pluripotent and Nonpluripotent Cells by Yaser Atlasi and 4 co-authors, including Peter W Andrews, Stem Cells 2008; 26(12): 3068-74 [Epub 2008(Sep 11)][PubMed Citation].

[These articles are not publicly accessible, unlike two interviews, with Alan Trounson and Rudolf Jaenisch, in the same issue of Stem Cells].

NEW CUSTOM TASTING SESSION!!!

Now at Healthy Spirits:
A new, custom tasting session for 2 to 3 people.

"THE SIX WIVES OF HENRY THE EIGHTH"

A special session based on the six former queens of England. Comes packaged with complete tasting notes.

Makes a unique and interesting gift.

cheers,

dave

The horror's. The horror's.

I realized this morning that my sworn enemy -- the misplaced apostrophe -- made an appearance on my blog two posts ago. I have a serious problem with misplaced apostrophes. I know I need to relax a little bit about it, but I just can't. I'm thinking this qualifies as a mental illness.

Dear friends -- friends I have known and loved for years -- will use apostrophes incorrectly on their Christmas cards, and I will actually think -- for a split second -- that I'm not sure if I can be friends with them anymore. I recently visited the web site for WCK's school and saw the word "student's" when it should have been "students'", and I briefly considered sending her somewhere else.

In my defense, the Evil Apostrophe occurred in one of the questions on the Christmas quiz that I copied and pasted from my e-mail, so I didn't actually type it myself. Still, my apostrophe-hating brain should have picked it up right away. To make matters worse, the word didn't even need to be pluralized with an "s" at all. It was the word "reindeer".

That's right. The sentence, "Can you name all of Santa's reindeer's?" appeared on my blog.

The shame. The shame. I need to go lie down.

RIP

A friend has died.

Even though I 've only known him a short while, he has provided me more comfort during this ordeal than people I've known for years. He was never afraid to tell me to smile; he had been there before.

It's surprising how much I am mourning- I was praying, errr, sending good energy out into the ether in hopes that he'd make it to christmas.

fucking bone cancer. eat my ass.

still recovering from the concussion (and it wasn't even my head).

On Tuesday afternoon, I was at a craft sale doing some holiday shopping with a friend (who had booked the afternoon off to hang out with me). We had only been there about forty-five minutes when my mobile rang.

I was expecting it to be my spouse, wanting to consult about a present but it was one of the administrative staff from my older son's school. She told me that he had fallen and hit his head at recess. Some time later, he had told his teacher that he was "feeling weird" and she had sent him to the office. The woman who called me said she was worried about him but wasn't able to get much out of him, as he was "being very non-verbal."

Anyone who has ever met my son would never ever describe him as "non-verbal." I knew that something was wrong. When I got there a few minutes later, he was sitting there quietly. He didn't react much when he saw me and seemed to be having trouble speaking clearly (he did say that he didn't want to leave school because they were going to be building K'nex bridges. This was another warning sign for me - my son being distraught at the idea of leaving school). He was also disoriented and unsteady on his feet.

Once we were home, I consulted with Mr. Internet and came to the conclusion that I had to call the doctor. She got us to come in right away, and, after examining him, asked that we go immediately to the children's hospital. She offered to call an ambulance because she didn't want my son to be unmonitored during a potentially long drive (there is a transit strike in Ottawa right now and it has caused traffic to be very backed up during rush hour). Within a few minutes, four paramedics arrived.

We were bundled into the ambulance and taken to hospital. Poor S. had to keep getting his blood pressure taken and answer the same questions over and over again. The paramedics were really wonderful and I could tell that they were as relieved as I was when he went from not knowing what month it was to listing the items on his Christmas list (there are forty-five of them, including a flat screen TV and a Blackberry).

One of the paramedics told me that it is often this way with concussions that they can get better in the first couple of hours or much worse. We were all very relieved to see such a dramatic improvement.

He was so dramatically improved, in fact that when arrived at the children's hospital, we were no longer on the fast-track for treatment. By the time we saw a doctor (a resident, actually) hours later, my son was talking, cracking jokes and the headache and nausea had disappeared.

Diagnosis: mild to moderate concussion. Elapsed time between head bonk and being back at home: eight hours.

By the next day, S. had completely recovered and was giddy with the joy at the prospect of a day in his pajamas.

I on the other hand, am still exhausted. A concussion can really take a lot out of a mother.

onco arts & crafts

I received this amazing thing in the mail today from Carissa:



It is fitting, as I found out this morning that my tumor is almost completely gone. The Radiologist can barely see it. There's still cancer in the bone, but we're working on that...

To pass the days, I've been obsessively coloring in Gray's Anatomy with my Prismacolors. It took me awhile to realize the significance of this- adding bright colors to otherwise mundane medical imagery as a way to cope. It also brings back a certain childhood nostalgia. I think when I'm done with the whole book I'll cut everything out and make some sort of collage.





Thank you to everyone who has sent me mail. It is SO encouraging getting those little treasures during treatment- I could be having a crap day and it will completely turn around due to a letter. I'm slowly getting around to mailing things back...

Cycle 20

OK, I had planned a photo that was going to be a dang hoot. It involved my Revlimid bottle and a gingerbread house made by WCK. Then my digital camera refused to turn on. After a minor panic that I had lost the photos of WCK's preschool Christmas party, a visit to the HP tech support web page and some fancy maneuvering, it seems to be on the mend, but it needs to rest and recharge. You'll just have to imagine the Revlimid and gingerbread.

This cycle, I am starting on 10 mg. I actually got REALLY excited to see what the 10 mg pills would look like. Yes, I am that lame. I was sure they'd be an exciting new color. Pink, maybe purple. Nope. They're blue and white, just like the 15 mg pills. Geez. If the drug company is going to charge $8,000 for 21 pills, the pills should at least look exciting.

The Christmas quiz

My friend Diane sent me one of those e-mail quizzes, only this one is all about Christmas. I decided to put it up on the blog instead of sending it by e-mail. Everyone else, join in!

1. Wrapping paper or gift bags? Wrapping paper

2. Real or fake tree? Real! We always go chop it down.

3. When do you put up a tree? Usually the weekend after Thanksgiving weekend

4. When do you take it down? A few days after New Year's

5. Do you like eggnog? I'm seriously addicted to it. I want to swim in a vat of eggnog. I want to be hooked up to an eggnog IV. I want an eggnog fountain in my yard. It's a good thing you can only get eggnog for one month a year, or I'd weigh 500 pounds.

6a) Favorite gift received as a child? Hmm. The first thing that comes to mind is a Strawberry Shortcake baby doll that blew strawberry-scented kisses. I also remember my grandma giving me Where The Sidewalk Ends, and I spent all of Christmas day reading it to myself and laughing.

b) Favorite gift received as an adult? Last year I got a pedometer watch that I am still obsessed with each and every day. 15,683 steps today!

7. Hardest person to buy for? Jay

8. Easiest person to buy for? WCK

9. Do you have a nativity scene? Yes. We got a basic set as a wedding present -- Mary, Joseph, and Jesus. Every year, Jay's family gets us a new piece to add to it. We now have all of the wise men, some shepherds, an angel, and various animals.

10. Mail or email Christmas cards? Mail

11. Worst Christmas gift you ever received? In junior high or high school, I got a pink sweater with pictures of cats knitted into the design ... and the cats had rhinestone eyes. And my mom made me wear it.

12. Favorite Christmas Movie? It's a Wonderful Life

13. When do you start shopping for Christmas? Not until after Thanksgiving

14. Have you ever recycled a Christmas present? Well, this year I wrapped up a couple of things I found in the basement, but they had sentimental value. I hope the recipients see it that way, anyway.

15. Favorite thing to eat at Christmas? Seven-layer bars

16. Lights on the tree? Yes, but they can't all blink on and off at the same time.

17. Favorite Christmas song? The ORIGINAL version of "Have Yourself a Merry Little Christmas" with the ORIGINAL lyrics, as sung by Judy Garland in Meet Me In St. Louis.

18. Travel at Christmas or stay home? How would Santa find us if we traveled?

19. Can you name all of Santa's reindeer? Yes, and for the last time, it is "Donder", not "Donner"

20. Angel on the tree top or a star? I got a cheap star from Wal-Mart -- because WCK claimed Christmas would be ruined without it -- and it fell off. But apparently just trying to put it on the tree kept Christmas from being ruined. Whew.

21. Open presents on Christmas Eve or morning? Growing up, we opened grandparent presents Christmas Eve and Santa presents Christmas morning. Now it's pretty much all Christmas morning.

22. Most annoying thing about this time of the year? The way the Christmas season starts on Nov. 1.

23. Favorite Ornament theme or color? Wizard of Oz. I have every Hallmark Oz ornament produced since they started in 1993, and a bunch of other miscellaneous Oz ornaments.

24. Favorite for Christmas dinner? I still don't know what I am going to make. WCK requested bread with butter, cheese cubes, and cookies. Sounds good.

25. What do you want for Christmas this year? Just a fun day.

Two articles linking normal intestinal SC to CSC

1) Crypt stem cells as the cells-of-origin of intestinal cancer by Nick Barker and 9 co-authors, including Owen J Sansom and Hans Clevers, Nature 2008(Dec17) [Epub ahead of print]. Abstract:

Intestinal cancer is initiated by Wnt-pathway-activating mutations in genes such as adenomatous polyposis coli (APC). As in most cancers, the cell of origin has remained elusive. In a previously established Lgr5 (leucine-rich-repeat containing G-protein-coupled receptor 5) knockin mouse model, a tamoxifen-inducible Cre recombinase is expressed in long-lived intestinal stem cells[reference 1]. Here we show that deletion of Apc in these stem cells leads to their transformation within days. Transformed stem cells remain located at crypt bottoms, while fuelling a growing microadenoma. These microadenomas show unimpeded growth and develop into macroscopic adenomas within 3-5weeks. The distribution of Lgr5+ cells within stem-cell-derived adenomas indicates that a stem cell/progenitor cell hierarchy is maintained in early neoplastic lesions. When Apc is deleted in short-lived transit-amplifying cells using a different cre mouse, the growth of the induced microadenomas rapidly stalls. Even after 30weeks, large adenomas are very rare in these mice. We conclude that stem-cell-specific loss of Apc results in progressively growing neoplasia.

See also: Tracking down bowel cancer stem cells by Kat Arney, Science Update Blog, Cancer Research UK, December 17, 2008. Excerpt:

More experiments need to be done before we know for sure whether stem cells play a vital role in human bowel cancer. For now, these results are a promising step in the right direction – and a confirmation that the stem cell theory may well hold true for at least one type of cancer.

If we can understand more about the molecular pathways that control cancer, we can start to design new, more effective ways to prevent and treat the disease.

2) Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation by Liqin Zhu and 9 co-authors, including Richard J Gilbertson, Nature 2008(Dec17) [Epub ahead of print]. Abstract:

Cancer stem cells are remarkably similar to normal stem cells: both self-renew, are multipotent and express common surface markers, for example, prominin 1 (PROM1, also called CD133)[reference 1]. What remains unclear is whether cancer stem cells are the direct progeny of mutated stem cells or more mature cells that reacquire stem cell properties during tumour formation. Answering this question will require knowledge of whether normal stem cells are susceptible to cancer-causing mutations; however, this has proved difficult to test because the identity of most adult tissue stem cells is not known. Here, using an inducible Cre, nuclear LacZ reporter allele knocked into the Prom1 locus (Prom1^C-L), we show that Prom1 is expressed in a variety of developing and adult tissues. Lineage-tracing studies of adult Prom1^+/C-L mice containing the Rosa26-YFP reporter allele showed that Prom1⁺ cells are located at the base of crypts in the small intestine, co-express Lgr5 [reference 2], generate the entire intestinal epithelium, and are therefore the small intestinal stem cell. Prom1 was reported recently to mark cancer stem cells of human intestinal tumours that arise frequently as a consequence of aberrant wingless (Wnt) signalling[references 3, 4, 5]. Activation of endogenous Wnt signalling in Prom1^+/C-L mice containing a Cre-dependent mutant allele of beta-catenin (Ctnnb1^lox(ex3)) resulted in a gross disruption of crypt architecture and a disproportionate expansion of Prom1 cells at the crypt base. Lineage tracing demonstrated that the progeny of these cells replaced the mucosa of the entire small intestine with neoplastic tissue that was characterized by focal high-grade intraepithelial neoplasia and crypt adenoma formation. Although all neoplastic cells arose from Prom1⁺ cells in these mice, only 7% of tumour cells retained Prom1 expression. Our data indicate that Prom1 marks stem cells in the adult small intestine that are susceptible to transformation into tumours retaining a fraction of mutant Prom1⁺ tumour cells.

See also: Molecular marker identifies normal stem cells as intestinal tumor source, News Release, St. Jude Children's Research Hospital, December 17, 2008. Excerpt:

Scientists at St. Jude Children’s Research Hospital have answered a central question in cancer biology: whether normal stem cells can give rise to tumors. Stem cells are immature cells that can renew themselves and give rise to mature differentiated cells that compose the range of body tissues. In recent years, researchers have developed evidence that cancers may arise from mutant forms of stem cells.

NEW ARRIVALS

Got some new beer today.

1. Bruery Orchard White Ale
2. Bruery Black Orchard
3. Bruery Saison Rue
4. Bruery Partridge in a Pear Tree
5. Hair of the Dog Doggie Claws
6. Ridgeway Very Bad Elf
7. Ridgeway Seriously Bad Elf
8. Fox Barrel Mulled Cider
9. Baird Kurofune Porter
10.Jolly Pumpkin Weizenbam

Come and get it!

cheers,

dave

Tweet tweet? Tweet!

Sometimes WCK pretends to be an animal, and I am always impressed by her commitment to her role. A few days ago, she was a tyrannosaurus rex, and she would only communicate by roaring. Tonight, she was a bird, and she'd only communicate by saying, "Tweet, tweet!" in different tones of voice. She also would not get into the bath until I called it a "bird bath", and she would not brush her teeth until I told her we were brushing her "beak." She spoke non-bird language long enough to tell me we could only read bedtime stories about birds, so we read, "Are You My Mother?"

She would not break character for anything else, even a potty break. She is a fine actress. I hope she mentions me in her Oscar speech.

Making up for lost time!

I want to share what I read on another woman's cancer blog today....I loved this! This is an excerpt from Jill Cohen's Dancing With Cancer. Jill has been dealing with metastatic breast cancer for 10 years.

Cancer is the only disease I can think of where people say that those of us who've got it must have a positive attitude. Well, there's very little about cancer to be positive about! Having cancer is terrible. No one would choose to have cancer. And those of us who have cancer need to be able to express ourselves. If we feel good, that's fine. But if we feel ill, or the treatments are rough on us, or we're depressed, or we're angry, or you name it -- we need to be able to express those feelings.

When I was diagnosed, so many people thought I needed to "think positive" or "have a positive attitude" to survive. I was certainly in fight mode, but I was not always positive. Many times I felt, though, that I had to put on the expected positive face when I talked to friends and family. They were so sure that my positive attitude was going to save me.

Kind of interesting- some are sure a positive attitude will save us, others feel our tumors are a result of repressed emotions and feeling. Yikes..it's a no win situation!!!

I don't believe either is true.

In the end I think honesty is best. There is no science that indicates a positive attitude is associated with better outcomes. This long term study of cancer patients was published in the journal Cancer in October of 2007:

Emotional well-being doesn't affect cancer outcome

Many of us with cancer sometimes feel depressed, sad, angry and desperate...and under the circumstances those are normal and justified feelings. The person who was the greatest help to me was my best friend...I could call her sobbing about how my life was in a bad place and tell her I was afraid and sad...she understood. She even agreed with me, she'd feel the same if it were her. She never once thought or said I needed to have a positive attitude to beat my cancer.

This was also helpful to me, an excerpt from the chapter "The Tyranny of Positive Thinking" from Jimmie Holland's book "The Human Side of Cancer":

It's dangerous to generalize about attitudes and their impact on cancer without more information. The present-day tyranny of positive thinking sometimes victimizes people. If thinking positively works for you, well and good. If it doesn't, use the coping style that's natural to you and has worked in the past. (I discuss different modes of coping in Chapter 6.) Trying to get you to "put on a happy face," to pretend you are feeling confident when in fact you are feeling tremendously fearful and upset, can have a downside. By feigning confidence and ease about your illness and its treatment, you may cut off help and support from others. You may also be hiding anxious and depressed feelings that could be alleviated if you told your doctor how you really feel. Also, this tyranny of positive thinking can inhibit you from getting the help you may need out of fear of disappointing your loved ones or admitting to a personality some people think is fatal. If you are surrounded by "the positive attitude police'" ask your doctor, clergy, or therapist to call them off, letting them know that this is an important time for you to be honest about your feelings so that you can get all the help you need. (Or give your or friends this chapter to read.)....

It is ironic that many negative, pessimistic people survive cancer, while others who believe positive attitudes will cure it do not. While members of the former group are stunned by their survival, those in the latter group are made to feel guilty or ashamed that they were not "up to" beating an aggressive disease. This is unfair. I do not believe for an instant that people whose cancer progresses have a weaker spirit or character than anyone else.

I think the people I cherish and respect most in my own life are the people who are honest about their lives and their feelings, who are genuine, who seek help when they need to, who don't feel they always have to paint a rosy picture of their lives. We all have down times in our lives and need help and support. We need to be able and unafraid in expressing how we feel and to be able to seek help and comfort.

Nobody Likes Blago--Not Even Komen

Maybe Blago will keep sliding away until he's gone from the the frame.

The Dallas Morning News blog tells us that Susan G. Komen for the Cure foundation gave nearly $45,000 to our disgraced governor. The story? Tony Rezko spent the money on Blago, then the guv paid it back by giving the tainted funds to charity--mostly to Komen. Komen didn't want it and gave it back. Opines the DMN: And it's folks like Blagojevich that no doubt makes them Run from the Cur.

Cancer Bitch reported on this earlier, quoting Capitol Fax.

For a pic of our guv and Trickie Dickie, click here.

Quantifying normal human mammary epithelial SC

Human mammary glands in mice by Simone Alves, Nature Reports Stem Cells 2008(Dec 11). Excerpt:

A new technique identifies regenerative cells

Even when an organ is believed to harbour stem cells, the cells themselves can be elusive. The standard method used to hunt for mammary stem cells involves injecting cells into the mammary fat pad of mice and seeing if the cells regenerate mammary tissue. Unfortunately, this approach is time consuming, highly variable and allows no way to count the cells. In this month's Nature Medicine, Connie Eaves and her team at the British Columbia Cancer Agency, Canada, report a new technique which has allowed them, for the first time, to characterize and quantify mammary gland stem cells in humans¹.

.....

This [work] could have important implications in our understanding of breast cancer.

.....

Reference

1. Eirew, P. et al. A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability. Nature Med. advance online publication, doi:10.1038/nm.1791 (23 November 2008). | Article |

Another link to the same article: Peter Eirew and 6 co-authors, including Joanne T Emerman and Connie J Eaves, Nat Med 2008(Dec); 14(12): 1384-9 [Epub 2008 Nov 23]. PubMed Abstract:

Previous studies have demonstrated that normal mouse mammary tissue contains a rare subset of mammary stem cells. We now describe a method for detecting an analogous subpopulation in normal human mammary tissue. Dissociated cells are suspended with fibroblasts in collagen gels, which are then implanted under the kidney capsule of hormone-treated immunodeficient mice. After 2-8 weeks, the gels contain bilayered mammary epithelial structures, including luminal and myoepithelial cells, their in vitro clonogenic progenitors and cells that produce similar structures in secondary transplants. The regenerated clonogenic progenitors provide an objective indicator of input mammary stem cell activity and allow the frequency and phenotype of these human mammary stem cells to be determined by limiting-dilution analysis. This new assay procedure sets the stage for investigations of mechanisms regulating normal human mammary stem cells (and possibly stem cells in other tissues) and their relationship to human cancer stem cell populations.

[The commentary in Nature Reports Stem Cells is publicly accessible, but the article in Nature Medicine is not].