"I have noticed that you failed to come into the lab on several weekends"

A friend of mine sent me this link the other day:
http://boingboing.net/2010/06/25/i-have-noticed-that.html

Basically, it's a letter sent by a CalTech professor to one of his postdocs, chastising the postdoc for not working on weekends and evenings, and telling him how easy it would be to replace him in the lab.

I know I've come across equally endearing academic personalities, and they always make me grateful for my current supervisor's agreeable, flexible, and kindhearted nature.

My friend did a web search on the professor that sent this letter and found the following:

"He is the recipient of the American Chemical Society Award in Pure Chemistry, Nobel Laureate Signature Award, Fresenius Award, a David and Lucile Packard Foundation Fellowship in Science, Alfred P. Sloan Fellowship, Camille and Henry Dreyfus Teacher Scholar Award, Merck Young Investigator Award, Eli Lilly Young Investigator Award, Pfizer Research Award, National Science Foundation CAREER Award, Arnold and Mabel Beckman Young Investigator Award, and a Camille and Henry Dreyfus New Faculty Award. He is also the recipient of the Associated Students of the California Institute of Technology Annual Award in Teaching and a Richard M. Badger Award in Teaching."

At first glance, I thought the letter was material for one of Jorge Cham's PhD comics.  After all, academia is an industry with incredibly flexible hours:  you're allowed to choose which 80 hours of the week you want to work.  While there are a lot of lovely and inspiring people in academia, and I suppose I should find a letter to a postdoc from one of them to make this post two-sided, there are also a handful of folks in academia (or in any competitive industry) who are just arses.  Unfortunate, but unavoidable. 

But giving it a bit more thought, I can come up with several reasons that a professor might have sent a letter like this.

Maybe he has grown accustomed to a 24/7 work ethic, and simply expects his colleagues to join this culture.  If someone subscribes to a certain working style, it's understandable that he or she would want to work alongside people who hold the same attitude.  The harsh wording of the letter could simply be a poor communication effort, and is not intended as harsh, but simply realistic in his view and not intended to be taken personally.

Maybe he wants to hold onto some intimidation factor over his inferiors.  Is this his fault, or is it inevitable in the academic culture?  If you're not completely dedicated to your research, you're not going to make it to the top and get the faculty position or keep the reputation.  To maintain that kind of dedication, I'd imagine a professor would want full commitment from his group members.  Again, communication may not be at its best when delivering the message.

This guy has won all sorts of awards for both research and teaching.  He obviously has a reputation to maintain.  But unfortunately, there's also a side of academia that is prone to bullying and trying to prove one's own toughness, which is the side that comes across in this letter.

And with that, I'm backing up my files and heading to the climbing gym for the evening.  See you on Monday.

Science Careers and Freeze-Thaw Cycles

This blog is about to see some serious neglect over the next couple of weeks, as all my journalism attention will be focused on a story for Science Careers!

Unless of course I decide to post on the observed response of hydrodynamic inclined planes in the Scottish highlands to atmospheric thermodynamical influences and their controls on freeze-thaw cycles.  Hopefully no observations of rapidly developing instabilities and the resultant gravity current leading to turbulent flow in a system of loose particles!

Lunatic Ice Climber with Few or No Funtioning Brain Cells
Cartoon © Tami Knight (Needle Sports Collection)

Mouse guts are good for you

Lung cancer patients who developed a rash after treatment with the drug cetuximab (Erbitux) lived longer and had better progression-free survival rates than patients who did not develop a rash.

The study, led by Dr. Ulrich Gatzemeier from Hospital Grosshansdorf in Germany, looked at patients who received standard chemotherapy combined with cetuximab as well as patients who received standard chemo on its own.  70% of the cetuximab patients developed a rash and did better than the patients--cetuximab or not--that did not develop a rash.

Seems like a controlled study to look at the effects of continuing or stopping cetuximab in patients with the rash would be a good next step.

I'm certainly no expert, but the "-mab" ending of "cetuximab" means that this is a Monocolonal Anti Body, which generally targets specific antigens or epitopes expressed on cancer cells.  It's a "chimeric" antibody, meaning that it's derived from a combination of mouse and human DNA (-xi- before -mab means that there's a combination of human and foreign DNA...-o- would be mouse alone; -uz- would be humanised).

Cells expressing this antigen are then singled out to be killed.  But people who receive other monoclonal antibodies (monoclonal meaning they target one particular antigen) as part of cancer treatments often have an allergic reaction the first time their immune system has to deal with mouse proteins.  Indeed, their doctors and nurses say that a reaction is a *good* thing (though the poor feverish patient may disagree), as it means that the monoclonal antibody is beginning to do its job and the patient's cells are reacting as they should be.

It was also pointed out to me that some monoclonal antibodies are designed to target other factors which some cancers secrete to stimulate the formation of new blood vessels which the cancer cells need to nourish themselves as they divide and grow. Still other "designer monoclonals" for treatment are designed to neutralize proteins in the blood or tissues called "transcription factors," which  attach themselves to cancer cells and stimulate their growth.

I need to read more to learn why researchers can't just make all monoclonal antibodies entirely from human-derived proteins.  But until they do...mouse guts it is.


http://www.nlm.nih.gov/medlineplus/news/fullstory_106833.html

B-cell Chronic Lymphocytic Leukemia: the “Good” Cancer?

Carl learned this year that he has the “good” kind of cancer. Carl knows a contradiction when he hears one. Although Chronic Lymphocytic Leukemia (CLL) isn’t the automatic death sentence that many of its relatives are, the “good” lies more in the leaps and bounds that research is taking toward effective treatments rather than any good feeling Carl might have had when his doctor told him “if you have to have cancer, this is the good one to have.” The war waged by medical researchers upon the slowly-progressing yet wily disease of Carl's immune system is far from won, but doctors have developed a new arsenal in the past ten years that is rapidly increasing their options for treatment. In this article, we will follow Carl through his diagnosis and treatment options to provide an overview of CLL, how it progresses, a history of treatments and how they work, and new clinical research.

What is CLL?

CLL begins with one mutation in a B-lymphocyte, a white blood cell that fights infection. This cell multiplies, replacing and crowding out normal lymphocytes with CLL cells that can't fight infection (Figure 1). A routine blood test which showed high lymphocyte count, and additional blood tests which showed low immunoglobulin levels and extra lymphocytes with particular antigens or epitopes on their surface brought Carl into the company of 100,760 Americans—most aged 50 and above--living with the most common form of blood cancer.

“CLL progresses very slowly,” his oncologist told him. “While there's no cure, if it does start to act up we can do a lot to treat it. You'd be more likely to die of old age before this one will take you out.”

His physician pointed out that while some people with early stage disease can live with it for twenty years, as the disease advances it decreases quality of life and survival time which prompts the ultimate puzzle: when do you treat CLL? How do you do it?

CLL Staging and Treatment History

Leukemia researcher Dr Kanti Rai developed a staging system (see Table 1) to predict CLL prognosis and determine when to treat patients. It's been accepted in the U.S. and worldwide since 1975. However, the past ten years have brought on board CT scans and flow cytometry techniques—reflecting laser beams off streams of cells and chromosomes suspended in a stream of fluid to provide information about each particle's structure--which tell doctors about patient-specific DNA or the genetic profile of the individual cancer cells so they can better predict the course of the disease (see Table 2).

Carl's high lymphocyte count and a slightly enlarged spleen first prompted diagnosis as low-risk, but his low platelet count is a high-risk prognostic factor.  Actual numbers of CLL cells in the blood and bone marrow are an important prognostic factor, along with the cells' physical appearance under a microscope. So a CLL specialist recommended “watchful waiting” until a rapid change occurred. When lymph nodes started to swell in his neck and white blood cell counts increased, she advised chemotherapy to put the CLL into remission and regain normalcy in blood counts, thus prolonging Carl's life and maintaining its quality. The CLL will eventually come back, but multiple treatments could keep it in check for years.

Twenty years ago, Carl would probably have been given a prescription for the “gold-standard” drug, Chlorambucil, to keep his symptoms in check and then been sent on his way. It achieves 51% partial remission rate for 18 months, but rarely sees complete remission [2]. Combined with other drugs, it could yield higher response, but not longer survival rates. Were Carl a lot younger, physicians might have suggested a bone marrow transplant to stop production of the CLL cells and to let the donor stem cells produce mutation-free lymphocytes. But now, Carl has other, safer options for long-lasting treatments thanks to research that has flourished in the past decade.

The Past 10 Years

The three types of drug now used to treat CLL are alkylating agents which damage the DNA in cancer cells; purine analogues which mimic structures in DNA in order to inhibit enzymes in DNA replication; and monoclonal antibodies which bind to particular structures called antigens or epitopes on the CLL cell to identify it for destruction by the immune system.  Combining them is most effective.

Fortunately Carl's health insurance will cover him for the current recommended first-line treatment: a cocktail called “FCR.” Purine analogue Fludarabine (“F”) on its own was hailed as the gold standard as it achieved an overall response rate — complete and partial remission— of 80% over the past decade [3]. But overall response further increased when combined with alkylating agent cyclophosphamide (“C”) and increased again with the addition of monoclonal antibody Rituximab (“R”). Rituximab resulted in a huge step forward, as it targets one of the most common antigens ( ‘CD20’ where the cluster designation number, CD, identifies a specific protein) on CLL cells without killing as many normal cells as Fludarabine would. This is pretty potent stuff, so it's a good thing that Carl worked to maintain his level of fitness; he should, therefore, be able to handle the side effects better than a weaker patient who would have to be given a less potent combination.

Ill patients, or those in whom standard treatment is useless due to a specific CLL gene mutation or other poor prognostic factors (see Table 2), have other options. Cambridge University researcher Herman Waldmann led the development of Campath (alemtuzumab, a monoclonal antibody that targets heavily-expressed CD52 antigen), which, administered on its own, yields results in patients with one high-risk mutation form of CLL that renders FCR useless. The risk? Lots of other good cells express CD52 and can get wiped out in the process. And Campath can be deadly when combined with fludarabine and cyclophosphamide [6].

Unfortunately, even the most potent treatment won't cure CLL—the mutated cells will gradually grow back and might be nonresponsive to a repeat of the original treatment.  If it comes back before 6 – 12 months or the treatment just didn't work, treating with alemtuzumab alone, a combination of alkylator bendamustine with Rituximab that has fewer side effects than FCR, or one of many clinical trials can send CLL into another, albeit likely shorter, remission.  Additionally, cancer cells can mutate and lead to worse prognoses over time or even to other types of cancers.

Current Developments

Carl hoped that he could wait to start CLL treatment, because the rate of developing clinical trials is soaring and a new drug might further increase overall response rate and progression free survival time. But waiting to treat can make it harder to control the disease. The key to longer-lasting treatments may lie in eliminating minimal residual disease, traces of CLL leftover after chemotherapy that can then be singled out and cleaned up with monoclonal antibodies. Minimal residual disease is said to be “none” when blood counts show less than one CLL cell per 100,000 lymphocytes [3].

Bring on the radiation. Tositumomab, branded as Bexxar and conjugated with radioactive iodine, binds to CD20 antigen in relapsed or refractory CLL, then delivers radiation to kill the tumor cells that weren't already killed [9]. Carl hopes for longer-lasting effects from the very specifically tailored dose. But he's not going to wait until his CLL no longer responds to therapy. His physician has suggested he volunteer to participate in a Bexxar clinical trial just a few months after his last FCR treatment.

And, in the unlikely event that Carl doesn't respond well to FCR and Bexxar, he'll probably participate in another clinical trial of a potent drug that's been shown useful in relapsed and refractory CLL (that is, CLL that has returned after the last treatment): flavopiridol inhibits the cell reproduction cycle at a key step; lenalidomide helps raise immune response, and oblimersen blocks the production of a protein that makes cancer cells live longer [7]. Additionally, monoclonal antibody Ofatumumab was granted approval by the US Federal Drug Administration in 2009 for use when Rituximab is ineffective as it has a higher affinity for CD20.

If things get really bad, adding Rituximab to a combination of cytotoxins is a salvage treatment for refractory CLL that doesn't respond to fludarabine [8]. But Mayo Clinic's experimental treatments include replacing fludarabine with pentostatin in the classic FCR cocktail to see if the remission will occur and be maintainable with Campath treatment. The duration of cycles of treatments is also under analysis, as lower doses and fewer cycles may make room for other innovative agents [3].

What happens next

With forward-thinking doctors and doing his part to maintain good health, Carl has every chance of having a long progression-free survival. He knows it's not good to have CLL, but good questions are being asked: Are there treatments that are better than the current standards? Can treatments be better tailored to individual prognoses? Can novel anti-CD20 antibodies enhance treatments?

“CLL patients can now reap the benefits of the years of exciting research ” he comments, “but the complexity of tailoring a specific treatment to an individual makes one appreciate that medicine is a combination of art and science.”

References

[1] Byrd, J., A new twist for CD38 antigen expression in CLL. Blood 105:3002 (2005).

[2] Eichhorst, B.F. Et al., First line therapy with fludarabine compared to chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood 114.16:3382-3391 (2009)

[3] Hallek, M., State-of-the-art treatment of chronic lymphocytic leukemia. American Society of Hematology 440-449 (2009).

[4] Jurisic, V. et al, Analysis of CD23 antigen expression in B-chronic lymphocytic leukaemia and its correlation with clinical parameters. Med Oncol 25:315-322 (2008).

[5] Klatt et al., Blood (1994).

[6] Lepretre, S. et al., Immunochemotherapy with Fludarabine (F), Cyclophosphamide ©, and Rituximab ® (FCR) Versus Fludarabine (F), Cyclophosphamide (C) and MabCampath (Cam) (FCCam) in Previously Untreated Patients (pts) with Advanced B-Chronic Lymphocytic Leukemia (B-CLL). American Society of Hematology 51^st Annual Meeting Abstracts (2009).

[7] Maddocks, K.j. And Lin, T.S., Update in the management of chronic lymphocytic leukemia. Journal of Hematology & Oncology 2.29 (2009).

[8] Tonino, S.H., R-DHAP is effective in fludarabine-refractory chronic lymphocytic leukemia. Leukemia 24:652-654 (2010).

[9] Vose, J.M., Bexxar: novel Radioimmunotherapy for the Treatment of Low-Grade and Transformed Low-Grade Non-Hodgkin's Lymphona, The Oncologist 9.2:160-172 (2004).

Tables and Figures

Figure 1: Purple-stained leukemia B cells under a microscope (photo: Klatt 1994)

Table 1: Rai CLL Staging

STAGE	CHARACERISTICS	RISK
0	High lymphocyte count (>15,000/mm^3) only	Low
I	High lymphocyte count and enlarged lymph nodes	Intermediate
II	High lymphocyte count and enlarged spleen or liver with our without enlarged lymph nodes	Intermediate
III	High lymphocyte count and low red blood cell count (hemoglobin <11g/dL), with our without enlarged spleen or liver or lymph nodes	High
IV	High lymphocyte count and low platelet count (<100,000/mm^3), with our without enlarged lymph nodes, liver, spleen, or low red blood count	High

Table 2: CLL Prognostic Indicators

TEST	WHAT IT IS	POSSIBLE OUTCOMES	PROGNOSIS
Flourescence in situ hybridization (FISH)	An antibody is attached to a flourescent dye and mixed with population of cells; cells with the anigen that can bind to the antibody will flouresce. This picks up abnormalities in chromosomes.	Deletion in long arm chromosome 13 [del(13q)]	Normal
		Trisomy chromosome 12	Slightly worse than del(13q)
		Deletion in long arm of chromosomes 11 or 6 [del(11q)] or [del(6q)]	Worse than del(13q) and trisomy 12
		Deletion in short arm of chromosome 17 [del(17p)]	Inferior: resistant to standard therapy
		Mutation of 53p	Inferior, resistant to therapy
Imunoglobulin variable-region heavy chain (IgVH) mutation status	Whether or not the gene controlling the shape of immunoglobulin on the B-cell has undergone the mutation that lets it fight a specific antigen	Unmutated	Inferior
		Mutated	Superior
ZAP-70 expression	Expression of zeta-chain associated protein kinase 70 on CLL cells; indicator of IgVH mutation status, more viable test than IgHV sequencing	Positive	Inferior
		Negative	Superior
Immunophenotype	Expression of surface antigens—proteins that recognise certain antibodies and can defend against them--compared to normal B cells	CD20, CD19, CD79b low expression	Normal diagnostic
		CD23 low expression	Poor: decreased in advanced stages [4]
		CD38 expression	Poor: drug-resistant [1]

And just one more...

...just one more self-indulgent opinionated post on music.  Just one more.

J.S. Bach stands out from other composers of his era because, in my humble opinion, there is no other way that any of his music could have been written.  Handel, Vivaldi, Corelli...somebody else with a good understanding of music theory could have composed equally satisfying variations on their work.  But not Bach's.  He thought of everything.

Bach wrote The Musical Offering in response to a challenge from King Frederick II to improvise a six-voice fugue on a complex musical theme, a challenge perhaps intended to humiliate the composer.  Two ricercars, ten canons, and one four-movement trio sonata later, Bach published his work on "the theme of the king."  With riddle canons inscribed in Latin above variations on the theme, Bach comments that "as the modulation rises, so may the king's glory," or "may the fortunes of the king increase like the length of the notes."  Cheeky.

It never fails to amaze how Bach so puposefully works the theme into every possible nook and cranny of the Musical Offering triosonata.  The few bars in the second movement where I the violinist state the theme openly and pragmatically above everyone else is one of my favourite moments in classical music.  The theme has been twisted and turned and hidden and hinted at for page after page up until this moment, then everything else quiets down so I can say "look guys, here's what we're talking about."  And then the flute takes it and then the bass and then we're back into an intricate game of hide-and-go-seek until the end.  Every time we get to that bit, I ask if we can go back and play it again.

The other moment in which Bach brings his audience to their knees is the Chaconne of Partita No. 2 for solo violin.   The 56th bar of the movement reaches the highest note of the piece--indeed, of all four preceding movements--and flirts with a key change to reach the high note, then drops back into the tonic and takes off on a trajectory of modulations and new ideas which are explored to the furthest limit and touch every possible human emotion.  Relaxing to a pastoral calm at bar 113 with a transition to the relative major, a new range of sensations are played out and the listener/player is yet again held in awe until the music yields to the original d minor at 209 and begins to summarise and recapitulate and tie everything together until the end.

I'm not the only one who holds this piece in such high esteem, as Johannes Brahms wrote of the Chaconne to his sweetie Clara Schumann:

"On one stave, for a small instrument, the man writes a whole world of the deepest thoughts and most powerful feelings. If I imagined that I could have created, even conceived the piece, I am quite certain that the excess of excitement and earth-shattering experience would have driven me out of my mind."

Anybody can study music theory and compose decent music, but how does somebody put ideas down on paper that are so timeless?  Art often seems to have a fuzzy boundary with religion, and the subject of many paintings has been to capture a divine moment or god-inspired idea.  Perhaps Bach's inspiration was no different.

Hallelujah!

My roommate as an undergraduate often compared the satisfaction she took in doing physics to the satisfaction she found in music.  Now, she was good at both physics and music, so I think this had a lot to do with the connections and "bigger picture" stuff that people who love physics seem to go on about.  I see that in music, easily, and there have been a few rare moments when I've seen that in physics.  Very rare.  So I can admit a vague understanding of the notion that the beauty of good physics--whether solving a problem or just reading about a theory--is similar to the beauty of good music, whether playing or listening.

There.  Is that enough justification to spend one post writing about music?

Handel's Messiah is a marathon of a piece.  My orchestra performed it on Saturday evening at West Road Concert Hall in Cambridge, England.  Simply put, it's an oratorio with libretto taken mostly from the Old Testament to illustrate the coming of Christ; the birth and miracles and ascension of Jesus; and Christ's final victory over death and sin.  But while we're actually playing the Hallelujah chorus (Hallalujah, for the Lord God Omnipotent reigneth, Hallelujah!), and the audience stands for the duration of the number as is tradition; on the occassion that I can take my eyes away from Leon's conducting, I see rows of people with broad smiles whom I think would attest that in those few moments of music, Handel managed to write down pure JOY and HAPPINESS.

Although it's traditional to stand up during this movement (that's what King George II allegedly did during a performance in 1743), I'd like to think that people WANT to stand in some expression of respect or reverence or hope for something beautiful and harmonious that we the orchestra are doing our best to convey.  If there's actually meant to be a Messiah turning up on earth one of these days to bring world peace, a cure for cancer, and a railway service that runs on time, Handel's oratorio would make a pretty good theme song.

Geysering

I said this blog was going to be aimed at research non-related to my PhD, and already I digress.

Carbon dioxide (CO2)-charged cold geysering isn't exactly what my PhD is about (if only I knew *exactly* what my PhD is about...), but it's related in the sense of fluid dynamical processes that occur beneath the ground and lead to eruptions.  I'm more interested in eruptions of the volcanic sense, but the actual process might be similar.  Or it might not be.  Regardless, it's interesting, and it's important for looking at what might happen during carbon capture and storage (CCS) efforts.

So what is a cold geyser?  It's an erupting aquifer system driven by CO2 bubbles rather than steam.  Crystal Geyser near Green River, Utah, is a good example that has been studied extensively by geologists at the Universtiy of Cambridge.  CO2-laden water pools in a confined aquifer.  A borehole drilled through a confining layer, often in an oil field, into the CO2-laden aquifer provides a path for the pressurised water and CO2 to reach the surface.  The water column generally provides enough pressure to keep the CO2 in solution, but a decrease in pressure causes the CO2 bubbles to expand or "boil," displacing the water and starting the eruption.

In a world that's trying to figure out how to deal with excessive amounts of anthropogenic CO2, one of the sexiest plans is to inject it deep into geological formations where it will hopefully stay put for a very long time.  But what will actually happen if there's a route to the surface?

Crystal Geyser may provide some answers.  Field studies document the periodic eruptions of this unintentionally-created geyser that was born when a prospective oil well was drilled into a fault zone above a natural CO2 reservoir.  While it's simple enough to measure eruption duration, it's a bit more complicated to measure gas emission mass.  And even more complicated to measure liquid emission mass.  However, studies by researchers in Cambridge, the US Department of Energy and Lawrence Livermore National Laboratory provide data which could describe a relationship between eruption duration and time until the next eruption as well as the total mass of CO2 emitted over a given period.

One study looks at 76 days worth of eruptions from the summer of 2005.  Sensors at the base of the geyser measure temperature and fluid movement, and the start time and duration of 140 eruptions yield a bimodal distribution:  two thirds of the eruptions were short (7-32min) and one third were long (98-113min), with a strong correlation between eruption duration and time until next eruption.  Indeed, long and short eruptions seemed to alternate over the course of the study.

The detailed physics of the cyclic eruption mechanism are not fully understood, but here's an explanation of the process as summarised in Lu et al 2005:  The water level rises in the well as it recharges from the groundwater.  When overflow starts, the few bubbles rising with the liquid begin to decrease the hydrostatic pressure at the top of the well and any slight density change progresses down the well.  The vapour flash point--the level at which bubbles start to form--drops deeper into the well and more gas is released.  Bubbles coalesce to form slug flow which leads to larger eruptions, and almost all of the fluid in the well contributes to releasing CO2 gas.  At this stage, the fresh supply of fluid that is recharging the well cannot provide the gas required to maintain the slug flow because the fluid pressure is too high for gas to exsolve.  So the water level in the well falls quickly, but the hydrostatic pressure is rebuilt as the incoming fluid rises.  The flash point curve (describing where boiling will occur) moves upward as well.  The eruption repeats when the water level reaches the wellhead and bubbles begin to decrease hydrostatic pressure again.

But we still don't know exactly how much fluid comes out during each eruption.  Nor the details of the physics behind the recharging process.  We've got records of cycles in pressure and temperature deep within the geyser, and geochemical data that show the amount of gas released.  Could we combine all of this to provide a detailed physical mechanism of what's going on beneath the ground?

The ideal way to gain some better understanding would be to build a simple laboratory model in which to recreate some simple gas exsolution processes.  Showing exactly what mechanism results in what eruption timescale, based on experiments using a bubbly fluid that is decompressed to allow bubbles to grow and drive liquid out of the chamber, could yield interesting results and would allow measurements of volume erupted.  The key component would be to recharge themodel chamber with gaseous fluid...and to explain how this recharge occurs in a natural system.

Although, this may not be what the carbon capture and storage advocates want to hear...

Gouveia, F. and Friedmann, S.J., Timing and prediction of CO2 eruptions from Crystal Geyser, UT., Lawrence Livermore National Laboratory Report (2006).

Lu, X. et al., Measurements in a low temperature CO2-driven geysering well, viewed in relation to natural geysers.  Geothermics 34:389-410 (2005).

Circulating Tumor Cells

Who's going to do well in chemotherapy?

It seems like that's the million dollar question in cancer research these days, as diseases are becoming better understood and treatments are getting more effective.  Certain genetic variations and disease staging can be indicative of how well someone will respond to chemotherapy, but peripheral tumor cells in the blood indicate an all around poor prognosis.

A study presented at the San Antonio Breast Cancer Symposium in Texas last week is the largest of it's type to look at prognoses based on circulating tumor cells (CTCs), according to a National Institute of Health update this week.  The presence of CTCs, which have broken off from the main tumor, suggest that the patient may not do well in the long run.  The French study involved 267 people whose cancer had metastasised and were receiving chemotherapy for the first time.  After following them for 16 months, researchers determined that the more CTCs someone had, the worse they did.  Even a single CTC indicates a poor prognosis.

A German study observed 3,754 patients with high-risk but early stage breast cancer who had surgery followed by chemotherapy, then additional "acid therapy" treatments.  Those who tested positive for CTCs after surgery had an 88.1% three-year survival rate, compared to 93.7% for those who tested negative.  Of the 2,026 patients with completed CTC analyses and monitored for a median of 35 months, 114 have suffered recurrent disease and 66 have died.

Dr Andrew J Armstrong at Duke University and the Duke Cancer Institute in Durham, N.C. commented that while CTCs might not indicate which treatment is best, they might indicate the need for more aggressive treatment.  He also notes their importance due to being the actual cancer cell rather than some spin-off mutation, thus they could be useful for monitoring an individual's response to treatment and tailoring further therapy.

The presence of CTCs may allow earlier detecion of metastasis-capable cancer.  These reports give the basic findings of a large study, but don't provide much information about the mechanisms by which CTCs are detrimental to the patient.  It seems that a high CTC count would suggest that the cancer has reached a later stage and thus be more resilient to chemotherapy, but the German study sites CTC cells present in early-stage patients.

If just a single CTC yields a poor response to treatment, and small increases in CTC count go with rapid declines in prognosis, does this open a new area of research into when and how CTCs are released from the main tumor?  Are CTCs a necessary prerequisite for metastastic cancer or are they just an indicator?  Does metastasised cancer exist without any CTC, and are treatment effects different?

Definitely something about which to read more...

http://www.nlm.nih.gov/medlineplus/news/fullstory_106528.html
http://www.medpagetoday.com/MeetingCoverage/SABCS/23918

First Post

"If you want to be a writer, then you should write.  That's what writers do."

Or so I've been told.  And it makes sense.  Therefore, it's time for me to overcome my phobia of most things technical and start an online blog.

As a PhD student and aspiring science journalist (and on the personal side, a mountaineer and a musician), I'm trying to juggle my research with active steps toward building up experience in writing about science and research.  As far as I can tell so far, this seems to involve some combination of reading, networking, schmoozing with editors, begging to do unpaid work, agonising over the wording of a pitch, and writing.  But not enough of the last one.  There should be more writing!

A good friend of mine from the Cambridge University Mountaineering Club (a source of many good friends and inspiring people) blogs about his own zoological research and related findings.  A journalism mentor from Science Careers pointed out that by spending just a half hour each day writing about science, I could learn a lot about writing about science.  In a discussion over Thanksgiving dinner about why people write academic articles, my Scottish mountaineering friend argued that it's done to share information about a topic that is worth sharing.

With a tendency to get pigeon-holed into my own area of research, I need to pay more attention to interesting science that's going on in other areas not only related to my own field of geophysics, but to broader areas of research.  This blog's purpose is to provide an outlet to write about interesting science, ask some questions, and hopefully attract the attention of other folks who will comment and bleed over what I've said.