Women of Teal is a play on the words "Man of Steel" used to describe Superman. I have found my fellow ovarian cancer survivors to be the strongest, most helpful women in the world. They are truly Women of Teal!
I hope women diagnosed with ovarian cancer who live in New Jersey and around the country will find this site useful.
This month, Gynecologic Cancer Awareness Month and Ovarian Cancer Awareness Month, I am taking the
#GynCan Challenge sponsored by the Gynecologic Cancer Awareness Network .In addition to
information on ovarian cancer and my thoughts about being an ovarian cancer
survivor I will also share some information about the other “Below the Belt” women’s
cancers - cervical, uterine(endometrial),vulvar, vaginal, fallopian tube and primary
e-patients prepare for the MedX Conference this year I started to reflect back
on my experience and what impact it has made on my role as an e-patient and
Connections With Other E-patients
I met Janet Freeman-Daily for the first time at MedX. Janet, a metastatic lung cancer patient, and one of the best lung cancer advocates I know. After the conference Janet and I continued to
interact via Twitter and e-mail. In June, at the ASCO Annual Meeting in Chicago
I joined her and a few other lung cancer advocates for dinner. Other ovarian
cancer advocates might want to limit their interacts with only other ovarian cancer advocates
but I have found that interacting with other cancer advocates from MedX like Janet and Marie Ennis-O’Connor
allows me to be an empathetic well-rounded cancer advocate. It helps to
understand the latest treatments for other cancers as the treatments are
becoming more mutation based than organ based.
While at MedX I didn’t just develop friendships with other
e-patients who were cancer survivors . I learned what is was like to live with rheumatoid arthritis from Annette McKinnon, the importance of patient safety from Meredith Hurston (my
roommate), the difficulties patients with prosthesis experience from Joe Riffe and our rights as patients to use and analyze our own data
from diabetes e-patient, Doug Kanter.
Putting It Into Practice
I read two books and a number of articles on design thinking
in preparation to the MedX IDEO challenge. (Thanks Dennis Boyle.) But actually putting that type of
thinking into practice at the conference was invaluable. I loved working in a
team to come up with a solution to my problem: How Might We help cancer survivors understand what to expect after treatment ends?
To this day I find myself putting design thinking into
practice as the co-moderator of the #gyncsm community / chat. I have even used
it when discussing problems and their solutions in the 55 + community I belong
to. When I read health articles online I
wonder if the authors asked the patients/survivors what information would be important
to them. I actually asked a question along those lines at an ASCO Annual
Meeting session on integrating survivorship care plan information into
electronic medical records. By the way , the researchers said they had not
asked the patients what information was important to them. I suggested they may
want to ask them in future studies.
I hope that all the e-patients who attend this
year’s Med X conference will not only share their stories with others but
will be open to the stories of the other conference attendees. Those stories may move you to tears or make you laugh but I assure you they will make an impact on your life. Oh and don't forget to take Zoey for a walk!
Part two of my interview with Dr Eva Schmelz (Virginia Tech) regarding her ovarian cancer research. You may find part one here.
4.Other research you are doing involves synthetic
sphingolipid metabolites. What are they?
are a large, very diverse group of membrane-bound lipids, containing a
sphingoid backbone, a fatty acid and a more or less complex headgroup.This individual components vary among species
(plants and bacteria contain different sphingolipids than mammals) and several
hundreds of different sphingolipids have been identified. They are structural
components of the cell membranes, affect the membrane fluidity, can mediate
cell-cell or cell-matrix interactions and have many more functions depending of
the types of sphingolipids present, their concentrations and where in the cell and
in which cell they are located.Most
interestingly for our research is their function as second lipid messengers,
mediating the response of cells to growth factors, stress, inflammatory
compounds etc., and regulate cell growth and cell death, motility and many
other functions that are also important for cancer cells.Most of our daily foods contain
sphingolipids, the highest amounts are found in soybeans and dairy products.In the intestinal tract, they are digested to
the same bioactive molecules that are generated in the cells to regulate cell
growth and death.By feeding
sphingolipids in the diet, we can expose the cancer cells in mice to these
bioactive molecules and suppress their growth and reduce tumor formation while
not affecting normal cells.Natural
sphingolipid metabolites are very quickly cleared from the circulation and from
cells; we have used synthetic sphingolipids developed in Dr. Merrill’s lab that
avoid clearance and stay active in the cells for longer.They have therefore a higher toxicity towards
cancer cells but also a higher toxicity towards normal cells, causing more side
effects than natural sphingolipids. The correct dosing is therefore very
important in order not to cause severe side effects of the treatment.
5.What role does synthetic sphingolipid
metabolites play in ovarian cancer prevention?
We have used synthetic sphingolipids administered directly
into the peritoneal cavity to eradicate metastatic cells but have not yet found
a formulation that guarantees a slow release that kills cancer cells but only
minimally affects the normal cells lining the organs and the peritoneal cavity.Orally adnminitstered synthetic sphingolipids
have been used in other rodent cancer models but they seem to cause more side
effects than the natural compounds.
6. How will this research be translated to prevent
ovarian cancer or treat it?
have used dietary sphingolipids to suppress metastatic ovarian cancer in mice (manuscript
in preparation) – similar to many other natural compounds, the success of this
way of administration is restricted to the less aggressive cancer or earlier
stages.We have not been able to stop
fast-growing tumors of any kind (breast, ovarian) that develop lethal disease
in 3 weeks. However, less aggressive disease can be reduced in mice,
significantly enhancing the lifespan of these mice. Other groups have also
shown that non-toxic doses of sphingolipids can enhance the effect of
conventional drugs, thus reducing the side effects.We have not yet had an opportunity to test
this in women but this is an exciting possibility.
7. We are hearing more every day about
immunotherapy and targeted therapies to treat cancer. Which avenues of ovarian
cancer research do you find most exciting?
I think immunotherapy for ovarian cancer is very promising
since it utilizes the specific gene changes in the tumor of an individual woman
to train the immune system to detect these cancer cells- even the dormant ones-
rather than trying to kill cancer cells with highly toxic compounds that by
themselves can cause severe DNA damage in normal cells. The same would be true
for targeted therapies if we can get the information of the response of the
individual cancer.Especially ovarian
cancer has such diverse and individual genetic changes and redundant pathways
to bypass targeted signaling pathways that make it more difficult to suppress
cancer growth by specifically inhibiting one target.I believe that taking a step back, looking at
the tumor microenvironment rather than only the tumor cells alone and identify
the factors that are important for ovarian cancer cell implantation at the
omentum and other metastatic sites independent of the specific genotype
of the cancer cell is a novel avenue to deal with this heterogeneity.We then can develop drugs that prevent the
interaction of the supporting factors with the cancer cells and thereby
suppressing the deadly metastatic outgrowth irrespective of the individual
genetic changes. This is a more
preventive approach against metastasis compared to the immune or
Novel treatment approaches that also do not rely on the
individual genetic changes in the cancer cells have also been subject to
investigation here at Virginia Tech.Dr.
Rafael Davalos, also featured in the VT magazine article, uses the
bioelectrical fingerprint of cancer cells to either selectively eradicate
cancer cells or enrich for cell populations of interest- tumor cells, stem-like
cells, tumor associated cells- for diagnostic purposes or treatment decision
making and efficacy control.To this
end, we have published the first reports that indicate we can identify ovarian
cancer cells by their unique bioelectrical fingerprint which are different in
benign and aggressive cells.I believe
that in addition to individualized medicine that specifically utilizes the
individual genetic makeup of a cancer cell for treatment decisions, the methods
that utilize biophysical or bioelectrical properties that are altered in cancer
cells independent of their specific mutations, epigenetic changes or changes in
non-coding DNA are a promisingway to
detect and treat many cancers including ovarian in the future.
Thank you Dr. Schmelz for your responses and your continued research to better understand what causes metastasis and how to treat and prevent ovarian cancer.
Last month I read my son's copy of the Summer 2015 edition of VT Magazine. My son has a BA and MA from Virginia Tech. The cover had a photo of ovarian cancer cells and the inside held articles on the cancer research being done at Virginia Tech including a piece on Professor Eva Schmelz's research.
I was fascinated by the cover and so interested in her line of research that I looked on the Tech website and found her e-mail. I wrote to her as an ovarian cancer survivor, blogger and Hokie Mom. I asked her if she would answer questions about her research for my blog. Professor Schmelz was gracious enough to agree to answer some of my questions. While the answers are lengthy, the details are so important that I did not want to edit them. I will be presenting the questions and answers in multiple posts. In this first post you will hear about Prof Schmelz's background, what got her interested in ovarian cancer research and the research she is doing with Dr. Chris Roberts.
-->1.You are currently an Associate Professor of human
nutrition, foods, and exercise at the College of Agriculture and Life Sciences at
Virginia Tech. Tell us more about your academic background and what sparked
your interest in ovarian cancer research?
I received a MS degree in Human
Nutrition from the Justus-Liebig University in Giessen, Germany, and a Ph.D. in
Human Biology/Nutrition from the same University in 1992.This provided me a strong background in
biochemistry, physiology and nutrition although at that time, my research
projects were not cancer related. I had the opportunity to join Dr. AH
Merrill’s lab in the department of Biochemistry at Emory University in 1992 for
post-doctoral research, investigating the potential of dietary sphingolipids to
suppress chemically-induced colon cancer in mice.This was a very successful project and we
found a 50-70% reduction of tumor incidence in mice fed doses of complex
sphingolipids that could be achieved in the human diet—not pharmacological
doses. There were also no deleterious side effects of the treatment.This encouraged us to investigate if cancer
of other organs could also be suppressed. When I moved to the Karmanos Cancer
Institute in Detroit, we next focused on breast cancer and found that dietary
sphingolipids could suppress the progression of early stage breast cancer but
had little effect on fast-growing tumors.Taking a step back from considering only at the cancer cells as target
cells for our treatment (toxicity, molecular mechanisms etc.), we wanted to
investigate the impact of our treatments on the tumor microenvironment,
focusing on female cancers.Ovarian
cancer is especially challenging because it is so genetically and
histologically heterogeneous, deadly when detected late and early stages cannot
be investigated because of the lack of a model. However, there was no mouse
cell model available that could be used in mice with an intact immune system- most
researchers use human cells in immune-deficient mice so these can grow aggressive
human tumors. The immune system is important since inflammatory cells are now
directly linked to the generation of a “permissive niche” that allows for the
survival and growth of the tumor cells. I
therefore collaborated with researchers who had developed a model for
progressive ovarian cancer that could be injected into mice and would allow for
investigations of multiple stages of the disease.This model is called the Murine Ovarian
Surface Epithelial or MOSE model, and consists of benign cells that do not form
tumors, cells that are transitioning to the aggressive disease, cells that can
form tumors albeit slowly (slow-developing disease) and those that can develop
lethal disease in a very short period of time with few cells (fast-developing
disease). In collaboration with Dr. Chris Roberts, we have since then
characterized the molecular changes in the ovarian cancer cells that are
associated with their progression, and identified important functional
categories that could be targeted for the suppression of metastatic disease.
Other information: I am also the
co-director of the Cancer Biology Focus of the new Translational Biology,
Medicine and Health graduate program.This is a new doctoral program that integrates genetics, molecular
biology with tumor physiology and novel approaches to treat and detect cancer.
This is intended to broaden the view of the new cancer researchers of how to
2.The cover of VT Magazine was a photo of ovarian
cancer cells credited to you. How was the photo taken? How do those cells
differ from normal cells?
Researchers usually grow cancer
cells on plastic culture dishes for their experiments, taking advantage of the
programming of epithelial to attach to a surface in order to grow.However, ovarian cancer cells metastasize
throughout the peritoneal cavity as single cells that can cluster together
(sometimes named spheroids or tumor spheres).When we grow our cells under conditions that prevent attachment,
tumorigenic cells very rapidly form these spheroids also in cell culture.
Benign cells that cannot form tumors in mice are not able to form spheroids and
they will die off over a short period of time. The images were taken of live
spheroids with an inverted microscope with 40-fold magnification, documenting
the clustering of aggressive MOSE cells.However, if you put about a million cancer cells into the culture dish,
in a few days all of them have aggregated and we are able to see those without
magnification.The images in the article
itself show the aggressive cells forming spheroids and –in green- macrophages
that loosely associate with those cells. When we inject cancer cells into the mouse
and after several days flush the peritoneal cavity and take the cells back out,
many cells have aggregated similarly to what is shown in the picture and we are
currently using this culture technique for our studies to mimic more closely
what is happening in the peritoneal cavity.
3.The VT Magazine article “Cancer Under Attack- Virginia Tech community forms a strong front
against cancer” noted that you are collaborating with virologist
P. Christopher Roberts (Virginia-Maryland College of Veterinary
Medicine) to develop an animal ovarian cancer model. Tell us
more about that research. Which animals are you using? Are the studies
conducted in vitro or in vivo? How will this model help you discover the initial
changes that occur when cancer develops?
As mentioned above, Dr. Roberts was
instrumental in the generation of the progressive MOSE model.This model can be used in 2D and 3D tissue
culture but also can be injected into mice with a functioning immune system
(syngeneic model= the cells were derived from C57BL6 mice that are also used
for all our in vivo cancer studies).
This is a unique model in that we can compare benign, transitional and
aggressive cancer cells both in vivo
and in vitro (this is limited to
tumorigenic cells as the benign cells do not form tumors).Dr. Roberts has also isolated the stem-like
cells of these lines and we are beginning to investigate those since these are
critical for tumor recurrence. In
collaboration, we have shown the genetic changes that are important in ovarian
cancer progression, focusing on the differing cellular organization and the metabolism
of these cells since most genes that are differentially expressed in the
aggressive cells and can be modulated by the sphingolipids are in these
functional categories. These studies are critical in order to identify targets for
the sphingolipids or other drug treatments to prevent metastasis, and, most
importantly, to control the efficacy in
future human trials.
We are at this point not trying to
prevent primary ovarian cancer but are focusing on the characterization of cellular and
molecular factors that are critical for progression and metastasis since most
women die of recurrent disease. Dr. Roberts’ expertise in virology and vaccine
development has led to the generation of ovarian cancer cells that express
various anti-cancer cytokines on their surface.In a just accepted paper in the Journal of Interferon and Cytokine
Research we report that the local expression of IL-12 on the cancer cells
reduced their tumorigenic potential and impacts the immune cell profile in the
main site of ovarian cancer metastasis, the omentum. This is important because
while IL-12 has been used before to suppress tumor growth, the systemic
administration leads to severe side effects – the local expression in the
omentum, however, does not.
Epidemiological studies have
demonstrated that obesity - specifically in the increase in abdominal
(visceral) fat- is associated with an increase risk of metastatic ovarian
cancer and a lower survival rate.We are
interested in the changes in the peritoneal cavity that convey or contribute to
the increased risk, using the MOSE model to characterize specific changes that
could support tumor cell adhesion and outgrowth. Again, any identified
molecular mechanism could be used as a drug target to prevent secondary tumor
outgrowth after the removal of the primary tumor.Dr. Roberts was also instrumental in the
design and analyses of these studies, investigating changes in inflammatory
markers associated with obesity and obesity-mediated disease.We have since characterized the immune
profile of the omentum in virgin and parity mice and showed differences that
could contribute to a lower risk in the parity group; epidemiological studies
have also shown that child-bearing lowers the risk of ovarian cancer. Currently,
we are investigating if and how obesity alters the conditions in the peritoneal
cavity to support metastatic growth.
I love the sentiment on the front. Then I opened it and saw that it was a thank-you for the seven years I have been a support volunteer. Wow! I remarked to my husband that it sure hasn't seemed like seven years.
Back in 2005 I was upset. I knew the statistics about women diagnosed with late stage ovarian cancer. Jeez I knew that Gilda Radner died from that disease. I just wanted to talk to someone who had the disease and lived. Heck I didn't even meet any women in my cancer center with the disease. So when I saw a brochure for Cancer Hope Network in the waiting room I picked it up and brought it home. I hesitated at first to call. I'm not too keen on cold calling someone. But one afternoon as I sat in bed I went ahead and called. I told the person who answered that I just needed to talk to someone who had been in my situation and lived. She took all my information and said she would call back when she had a match. The very next day she called and said she could connect me right then and there with a volunteer. I spent the next half hour talking to a women diagnosed with 3b, lived in my state, had the same chemotherapy and surgery and was a 5 year survivor. It was wonderful. I was not alone. I could survive too!
When I was out of treatment one year I called Cancer Hope Network and said I wanted to be one of their support volunteers. I did training and within a week or two I was talking to other women with ovarian cancer. I have been volunteering ever since. Although I did take a break when I recurred and was back in treatment but once treatment was done I was back on the phone.
I have spoken to women from NYC, Florida, California, Indiana and Kentucky just to name a few. I have spoken to women treated in the top cancer centers in the country and those going to community cancer centers and oncologists. I have talked to women who are a short ride from their doctor and center and those that drive eight hours or take a plane and stay at hotels when then go for treatment.But each and every time I remark "I felt that way too" the reply is the same " thank goodness I thought it was just me."
Thank you Cancer Hope Network and all their volunteers for supporting those diagnosed with cancer. If you are newly diagnosed with any cancer or a caregiver for someone
diagnosed with cancer you may call( 1-800-552-4366 ) or visit the Cancer Hope Network website online to be matched with a survivor.