Tuesday, December 16, 2014

CTCs and Cancer


CTCs, Circulating Tumor Cells, are those cancer cells that have managed to get back into the blood stream. Thus CTCs are just what the name implies; malignant cells sloughed off and sent into the blood stream. Their point of origin may be unknown and they may actually be from a variety of locations if the cancer is metastatic and further the genetic makeup of each cell may be different depending on how the cancer may have progressed. What is certain is that they carry information as regards to the status of the malignancy and potentially its progression.

In a recent paper by Tseng et al the authors present an interesting summary of CTC and their identification[1]. From Table 1 in the paper they characterize various ways to isolate CTS. We depict the results below:


As Tseng et al conclude:

CTC identification and characterization is meaningful for the interpretation of metastatic cancers (breast, prostate, colon, and lung cancer). The promise of CTC research in the early stages of cancer is largely unmet, requiring more sensitive and reproducible technologies. The “real-time biopsy” potential of CTCs is a key area for further intensive research and appropriate animal models provide the foundation for studies of the molecular regulation of CTCs in cancer and CTCs as biomarkers for therapeutic efficacy. The envisioned future is one in which a simple blood test will permit molecular tumor characterization, identification of treatment targets, and aid in the selection of the most appropriate targeted therapy from an armamentarium of agents.

The number of CTCs has a potential be an effective prognostic and predictive biomarker, which could assess therapeutic responses of metastatic disease in several cancers. The detection of CTCs in early stage cancer needs the further improvement of CTC assays. Since the heterogeneity of CTCs, the assays used to detect CTCs need tumor-specific rather than one technology for all cancer types. In conclusions, the better understand of the biology and clinical meaning of CTCs will help to improve CTC assays and further to apply in clinical utility.

In a PNAS article they indicate the complexity of CTC analysis[2]:

Cancer patients have only between 5 and 50 CTCs per teaspoon of blood, so their presence is dwarfed by blood cells. However, in the past decade emerging technologies have, for the first time, allowed the isolation of CTCs from patients’ blood samples. Some methods, among the first established, rely on the cells’ physical properties. When a blood sample settles or is spun in a centrifuge, red blood cells, white blood cells, and other components of blood separate into layers. Based on their buoyancy, CTCs can be found in the white blood cell fraction. Then, because CTCs are generally larger than white blood cells, a size-based filter can divide the cell types.

Yet at the same time they seem to have prognostic value for many cancers. In the paper by Hu et al[3]:

Perhaps more promising than enumeration is the ability to study CTCs in order to molecularly characterize a cancer. The ability to take a “liquid biopsy” at different time points in treatment creates opportunities for therapeutic decisions informed by the specific phenotype of a patient’s cancer, moving closer towards the goal of personalized cancer therapy. Molecular characterization of CTCs, however, represents new challenges. For example, whereas white blood cell contamination may be tolerable when detecting (“yes” or “no”) the presence of disease-related genetic aberrations (e.g., TMPRSS2-ERG fusion product), moving towards more quantitative analyses (e.g., mRNA transcript levels of gene expression) necessitates ultra-pure CTC samples. Technological improvements have helped overcome some of these obstacles, leading to early successes in genomic and transcriptomic profiling of CTCs, sometimes with as little as one cell….The role of CTCs in PCa is rapidly evolving. CTCs provide a window into the hematogenous spread of cancer and can drastically improve oncologic understanding and patient care. In metastatic PCa, CTC enumeration is an accurate method for monitoring disease and has been used in clinical trials as an intermediate endpoint. CTCs can be detected in localized disease and hold the potential to detect early metastasis. Perhaps the most exciting feature of CTCs is that they provide a platform for noninvasive, repeated inquiries into a cancer’s molecular behavior, ultimately enabling individualized, adaptive and more effective management of PCa over time.

Thus CTC have reached the stage of having potential for diagnostic and prognostic value. Their overall acceptance will take some time but they may have substantial merit.


[1] Tseng, J., et al, Dynamic Changes in Numbers and Properties of Circulating Tumor Cells and Their Potential Applications, Cancers, V 6 pp 2369-2386, 2014. http://www.mdpi.com/2072-6694/6/4/2369

[2] Williams, S., Circulating Tumor Cells, PNAS | March 26, 2013 | vol. 110 | no. 13 | 4861

[3] Hu, B., et al, Circulating Tumor Cells in Prostate Cancer, Cancers 2013, 5, 1676-1690.

And We Keep Making More Lawyers!

The current debate on broadband seems to be between lobbyists and lawyers. It is akin to a discussion on how to treat a cancer patient that is held between the mortician and the witch doctor. Not very beneficial to the patient, or customer.

Let me give an example. There is some lawyer whose book I reviewed a while back who is at it again. Bemoaning broadband. But she may have learned something, not too much, but something.

She states: 

Who needs fiber? Mobile wireless is the future.” This is like saying that because we have airplanes we don’t need airports. A wireless signal is just the last 50 feet of a wire; wireless and wired connections are complementary. A 20 Mbps local wireless connection — between your handset and a cell tower, say — is no good if the wire running from the tower to the core network (the “backhaul”) doesn’t have enough capacity to carry that number of bits or is having latency issues. When that wire is a fiber optic line, it can carry an enormous amount of information. To haul all our mobile wireless data back from us to the Internet, particularly when we’re uploading a ton of data, we’ll need fiber deep into the places we live, work and entertain ourselves. Fiber, the glass tubes themselves, is cheaper to maintain than copper and can be easily upgraded. And without a major change in policy in the U.S. we’re not going to have it — even as other countries take it for granted and start building the new uses and new societies that are based on ubiquitous, vanishingly cheap communications.

In reality as we have demonstrated, wireless has superb capacity. Using 4G we get 10 bps/Hz and with 20 MHz that is 200 Mbps. Not bad. 5G raises that another factor of 10. She kinda now accepts that. In her book it was missing so perhaps someone got to her. In my opinion she seemed a bit clueless. Yet we all are entitled to our opinions. But as to the backhaul, what does she think is there, copper wires. Almost all of the backhaul is fiber, it is cheaper and easier to maintain not to mention the greater bandwidth. That she recognized and so did the telcos, two decades ago. 

Now she does have a point about cable. Imagine, if you will, the cable interface. Designed almost two decades ago, still the same. A big clumsy box, when Google and Amazon have USB chips! The wireless companies have iPhones and Androids, changed out at least every year! Does anyone ever remember a cable box being upgraded? And you pay $10 per month per box!

That should be her argument, not bemoaning wireless.

Oh and by the way, that 20 Mbps is only the beginning, and the telcos want your revenue so they will make certain they can carry it, at zero marginal costs to them! That should be the concern, not digging up my lawn for a fiber connection!

Monday, December 15, 2014

The French, the English, and Dumb Men

The world is in turmoil, Russia in Ukraine, Middle East afire, terrorists in Sydney, and overall monetary instability, and what do we see in Le Monde: 

Les hommes sont plus idiots que les femmes : c’est la science qui le dit 

 Cette année, le BMJ a décidé de frapper fort. Il consacre son titre principal de l’édition de Noël à une étude britannique qui se propose de démontrer la « différence des sexes dans les conduites stupides ». Pour ce faire, il a choisi comme échantillon l’ensemble des lauréats des Darwin Awards. Depuis vingt ans, ces prix décernés en Californie récompensent ceux qui « ont choisi d’améliorer le patrimoine génétique de l’espèce… en s’en extrayant définitivement ». Dit autrement, ils honorent les morts les plus bêtes.

Yes, men are beasts! From BMJ we have: 

Sex differences in risk seeking behaviour, emergency hospital admissions, and mortality are well documented. However, little is known about sex differences in idiotic risk taking behaviour. This paper reviews the data on winners of the Darwin Award over a 20 year period (1995-2014). Winners of the Darwin Award must eliminate themselves from the gene pool in such an idiotic manner that their action ensures one less idiot will survive. This paper reports a marked sex difference in Darwin Award winners: males are significantly more likely to receive the award than females 

 Yes, most dumb things resulting in hospital are done by men. Is that good or bad. Then there was Madame Curie, and her radium and other radioactive substances used indiscriminately around Paris. People just died in that case and she got a Nobel Prize.

Then there is the MIT Technology Review article. This used to be the alumni magazine, like other Universities, but it was taken over by some Silicon Valley hipster I gather and has become a mouth piece from trendy stuff, and has little if anything to do with MIT. But the piece mentioned above is an interview which has the individual stating: 

...the upper levels of tech, you are generally dealing with white men who have been coddled their entire lives, and they have rarely encountered even mild criticism. They take it as a really crushing, violent blow to their egos. It’s a big challenge for people from marginalized and underrepresented groups: we have to walk around the workplace all day on eggshells, treating them like soft kittens.

That is part of the nicer part of the interview. So men are stupid, they are privileged, get what they do not earn, etc....

I guess given the performance of some MIT faculty recently that one could walk away with such an opinion....just stay away from the faculty who glow...it may be radium. Oh, and yes, what about that fund raising request again?

Friday, December 12, 2014

Microsoft Does it Again!

How stupid are these folks! Another update that disables Windows 7. The patch should work, we hope.

As PC World notes:

Windows 7 users may have automatically updated themselves into a pickle with a recent patch from Microsoft. Microsoft has confirmed that the KB3004394 update it issued on December 10 can cause various problems. What's worse is that it may also prevent users from installing newer updates. The problems are reportedly limited to Windows 7 machines, and don't affect users running Windows 8 or newer. Although Microsoft didn't specify all the problems users have been experiencing, ...the update can prevent the system from installing new graphics drivers—which is particularly troublesome as AMD's feature-stuffed new Catalyst Omega drivers launched the same day the borked Windows update rolled out. According to Infoworld, users on Microsoft's support forums have pointed out a litany of other issues, including failure to launch Windows Defender, problems with running VirtualBox and strange errors from User Account Control.

 Besides their arrogance, the clumsy products, they now add deadly updates. How long does this group have in the market?

Wednesday, December 10, 2014

What's Up With Professors in Cambridge?

In just the past week we have seen rather strange behavior in Professors at those institutions in Cambridge.

1. The Economist: We by now all know who this is, the MIT Economist who assisted with the ACA. This is the rather arrogant, in my opinion, fellow who says we are all stupid and that he has some extreme level of wisdom we should all align with.

2. The Business School Guy: The Telegraph reports on some HBS who is threatening a poor little Chinese restaurant over a $4 error in a bill. Frankly I most likely would never see the problem but he clearly wants to make this a Federal, or Commonwealth, matter. At what point do we understand proportionality? Are not these Professors to be examples?

3. The Physicist: Then there is the MIT Professor Emeritus who allegedly was harassing some female in his on line MOOC course. Now he is close to 80 and been retired for a while yet as a result of this claim he has lost all ties to MIT.

Character counts, and character means being seen by both your peers and by society in general as representative of your institution. The Physicist was defrocked totally. The Economist seems to be extolled for his work, and the Business Professor is a work in progress.

There once was a time that your behavior reflected on your institution and if it did so poorly then you suffered consequences, in an equitable manner. It is a shame that such is no longer the case. Some of these are still to be played out so it is worth watching.

UPDATE: That Business School Guy has placed the following on his web site:
 
Many people have seen my emails with .... restaurant in ....Having reflected on my interaction with ..., including what I said and how I said it, it's clear that I was very much out of line. I aspire to act with great respect and humility in dealing with others, no matter what the situation. Clearly I failed to do so. I am sorry, and I intend to do better in the future. I have reached out to ... and will apologize to him personally as well.

I guess someone got to the teacher. Either that or perhaps those possible consulting contracts with possibly China were all cancelled, at least that is what it seems to me in my opinion.

Peer Review: A Generational Difference

Peer Review serves a purpose if and only if it results in an improved presentation of factual research. A good peer review should be accomplished as follows:

1. Managed by a know and credible Editor
2. Performed by those expert in the field in an unbiased manner
3. Provide any objections in a credible fashion and if the work was done previously the reviewer should present references substantiating such claims.
4. An ability to seek an arbitration if there is a material difference of opinion.
5. Some openness on the part of who the reviewers are.

In fact I have often argued for full openness in knowing who the reviewers are. That way the reviewer puts their reputation on the line in the review. One could keep the process confidential within the individuals but not knowing who the reviewer is often leads to negative reviews with no basis. However in all cases the process is confidential.

Now along comes PubPeer. In a Wired article they are taking the approach of the current generation, namely allowing anyone in a totally anonymous manner to review an article. It is akin to so many other social media mores, namely throwing an unsubstantiated opinions on a wall and seeing what sticks. It is however generational, it is the point of view that anyone's opinion is as good as anyone else. In fact a knowledgeable reviewer is a benefit, some reviewer with a bone to pick is not.

They state:

PubPeer works because we allow anonymous comments. Without that anonymity, most scientists would fear professional retribution if they criticized their peers’—or perhaps their future employers’—work. But with that anonymity, our users have generated a steady stream of comments highlighting problems in basic scientific research on any number of topics: cancer, stem cells, diabetes, and more. 

I would strongly disagree. In fact public anonymity just creates noise. There is no professionalism and no way to determine whether the reviewer has any true expertise in this area. 

At another extreme is the posting of one's research as it is in progress and allowing people to send the writer their comments. It creates a dialog, it allows for the correcting of errors, before publication.  Yes that approach is different and it flies in the face of first to publish but it is a research community approach. 

In my opinion the above mentioned approach of anonymous reviewers is highly counter productive. Yet it is an expression of that generational view that every child get on the Honor Roll, and perhaps we can send out bumper stickers, "My Child is an Anonymous Reviewer".