Many Invitations, so little time!

 SENT TO CRBCM
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Good morning,

The Office of Continuing Medical Education has been in communication with the El Paso County Medical Society to submit abstracts for consideration for publication in their journal.

Dr. Alan Tyroch, MD, the Program Director for the Rio Grande Trauma Conference invites you to participate in the submission process. If you would like for our office to forward the abstract you provided for the 14^th Annual Rio Grande Trauma Conference on December 5^th and 6^th, 2013 for consideration for publication in the El Paso Medical Society’s next issue, please sign the letter attached and send to jesia.boykin@ttuhsc.edu or fax to 915-783-6220 by Friday, February 7, 2014.

If you have any questions, please feel free to contact us at 915-783-6204.
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BUT ONE THING FOR SURE, WE WILL BE IN LAS-VEGAS FOR THE ANNUAL UPDATE IN HEMATOLOGY!

In Lymphoproliferative disorder, particular of dangerous genes

1*Highly conserved Molecule:  This means the molecule has stood the test of time and has been used under that form for years, and may have become critical in basic cellular functions.  In the human cell, some genes that are now "conserved" came from or were adopted from invading Virus.  For such an adoption to occur, the gene must be critical and acquired without antigenicity.  It is believed that ELK-1, ETS, Myb,ERG,ETV EWS, or TEL, could be an evolutive genes that are characterized with high level of co-association and remains most of all within the epigenic zone.    TEL-JAK2 has been suggested in Leukemia(Lacronique et al)
while TMPRSS-ERG has been demonstrated in Prostate cancer (clark et al).
In Breast cancer, "Elk1 also interacts with BRCA1 splice variants, namely BRCA1a and BRCA1b. This interaction enhances BRCA1-mediated growth suppression in breast cancer cells. Elk1 may be a downstream target of BRCA1 in its growth control pathway. Recent literature reveals that c-fos promoter activity is inhibited, while overexpression of BRCA1a/1b reduces MEK-induced activation of the SRE. These results show that one mechanism of growth and tumor suppression by BRCA1a/1b proteins acts through repression of the expression of Elk1 downstream target genes like Fos.<sup>[20]" wikepedia



Watson et al suggested :"</sup>
It has been over 15 years since Ets was originally identified as one of the two genes (Ets and Myb) transduced by the avian leukemia virus, E26 (Watson et al., 1990);" again suggesting these gene that control epigenetic events may be evolutive as suggested above, and keeps attractive co-association capability that may have help them escape cellular immunity !  Their location at the epigenetic location show the points to a cellular zone of weakness. But it also could point to the importance of inhibitor of de-Acetylators in human cancer and point to why we need further efforst to understand epigenetic events.  The fact is that medication targeting Retinoic Acid took over by surprise the world when it comes to treatment of Promyelocytic Leukemias,  re-enforces this notion...
To know more about how gene elements described above interact further with P53, histone de-acetylators, and the Telomeres, read our blog of 1 year ago on 01/31/2013.

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<sup>I cannot pass to the next step without pointing to the fact that distant effect of Traumatic Brain injury (TBI) are not far from these region since they all depend on secondary release of Cytokines which originate from these regions!
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AND SO MUCH STILL TO TALK ABOUT!</sup>

2*young selective development:
3*JAK/STAT involvement
4*The cell wants to achieve selective terminal differentiation and criss cross with gene repair and gene of variable region
5*membranous event with coexistence of Death Receptor
6*factor BSAP expression
7*Activity at TLE4, a negatve regulator of PAX5
8*relation with Ibrutinib
9*Daxx gene
10*The intervention pf the Variable region of IG
11*role of RAG1
12*emu enhancer
13*role of AML1
14*role of TATA and the Retinoblastoma genes
15*Intervention of the Telomere
16*Acetylated P53  (see blog 01/31/2013)

New Challenges to the human cell

In a world where new stimulants and new conditions are created, the human cell, deep in our systems, is confronted and forced to adapt and conform to new environment constantly. And doing so with the human genes that it possesses at the moment.  Yes, while a chemist work hard to create new chemical product to improve our lives (I really hope this), the cell somewhere in the human body does not know it will face this new challenge once it comes to contact with it.  To deal with this new product as a stimulant, the cell has to use its potentials.  It has sometime to rearrange its mechanisms to deal with the new stimulant!  While most of the time quick adaptation to the new product is limited in its impact on the life of the cell, certain stimulants will lead to receptor desensitization, transcription factors amplifications (particularly if gene autophosphorylation is allowed, shutdown of regulators occurs, alteration in splicing, and special miRNA are transcribed,etc.).  The point is even Receptor desensitization itself may lead to shutdown of critical genes.
One of the things that makes the cell vulnerable to the effect of new stimulant, is not only its reliance to old techniques to fight new challenges (ie, activation of the NF-kB) but also proximity and interactivity of the genes particularly those in the proximity of the initial inducing events.  But in a lightening fast action, distant genes are also involved.  The proximity of basic cellular functions is also a player.  Indeed it is common that one event could affect various cellular functions such as proliferation,growth and differentiation.  In fact the ease of recruiting neighbor gene is impressive.  It does not take much for a stimulant to induce de-differentiation to return cellular omnipotence to deal with the new comer, but cellular omnipotence is sitting next to shutting Apoptosis so that the new challenge does not kill the cell, But as seen in many cases, gene repair mechanisms are raised to the ready (in some cases shut down to tolerate mistakes), splicing machines are set  in motion to make new RNA to create adapted novel proteins, multiplication machinery are also ready to clone resistant cells, messaging machinery is put in a "work" mode to notify surrounding cells in case they don't know already.   The most sensitive function of all is the machinery to induce JAK/STAT and the variable domain of immunoglobulins.  Once these are engaged, a potential neoplastic transformation is possible if attachment to the involved gene occurs!

An example of this is what happen in Hodgkin disease, if you read about PAX genes, you will find cellular de-differentiation, PAX1-engage MOX1 but surprise-surprise-BRCA1 is not far.   You will argue that PAX5 is the one in 97% of some Hodgkin Lymphomas, but follow the TLE4,  Daxx, AML1,TATA,and RAG1....you will find that the same story repeats itself!

The CRBCM is following the trail!

Diet is important in cancer control:(case in point, Breast cancers!)

I knew this from the Bottom of my heart but pinning the genetic reason was here before me and I just did not see it.  Supply of sugar will ultimately increase Insulin which will increase the demand for Insulin receptor which in cancer is a bad actor.  The increase in Insulin receptor will interact with major genes that affect cancer.  First it affect the JAK /STAT pathways, which leads to Proliferation, second it affects the Gerb gene family which is a "wild" gene, meaning a gene just connected to too many others that will be influenced.  But one of the aspect mostly forgotten by survivors, is the receptor connection to the PTPN11.  A gene that has many links but one particular link is its relation with LAIR1, " is a protein forming a receptor found in the plasma membrane of cells involved in receptor-mediated endocytosis. In humans, the LRP1 protein is encoded by the LRP1 gene.[wikipedia


Involvement of this LAIR1 is bad for you if it leads to consumption of Thrombospondin-1(THBS1 ) which help the cell grow its feet for walking away and metastasizing (Breast cancer has done done quite a bit!  Through the interaction with PGDFR, this pathway will affect even blood clots (destruction of Caveolin) possibly inducing clot to move away and cause strokes and Myocardial infarction (science here is still growing). Drop of Thrombospondin is a major event involving CD38, and certain Integrins (be very careful which! ) and release of Metallo-proteases.  It is amazing that we do not monitor THBS1 today since its drop marks Metastatic disease. (and stroke and MI presumably).  And all this is induced by diet.   Not changing diet in cancer helps residual disease spread.

One of the thing that is important to note, most Estrogen Receptor are covered by a sugar, and Heparan sulfate is in most case the cover.  Guess what, THBS1 interact with Heparan for potentially its removal.  Making thrombospondin potentially a mechanism for cessation of Receptor desensitization.  What would happen in people depending on the preservation of the Receptor function (Tamoxifen)?  can we also infer there is a benefit for sulfur products here?

If you follow this line of thinking, you will also find that cholesterol use by the brain will be affected.  Another effect of LAIR1, opening another Pandora Box!

Eat less sugar is critical to cancer spread.....The CRBCM, work is still ahead.....

Questions for researchers! Melanoma as an example !

When a cancer continues to rise
-it means it is more environmental?
-It means its central mechanism continue to escape us
-It means the isoforms of the genes causing it,  is more frequently found in the population
-It means that many isoforms can lead to it, again here we need to know the basics?  does the frequency of cancer in society firmly linked to the frequency of the gene Isoforms?
-does the frequency means we keep missing the fundamentals?
-Or does it means the tumor has greater facility to penetrate the neoplastic transformation, or reach easily the "wild genes" or genes of importance in differentiation...
or genes capable of autoregulation?
or genes capable of suppressing other genes
or genes susceptible to Vitamin depletion
The prominence of Vitamin and hormones in society seem to suggest this last point!  Or is it vitamin imbalance?
In Melanoma for example it is established that the disease seems to occur more frequently in patients who burn rather than tan. And that sunburn would more likely be the trigger!  What that tells you about their MCIR gene, their FAK and induction of the Wnt (association with LEF1), and Notch,  Now that we are speaking MITF, and GNAQ/GNA11, or is it a deficiency of the SOCS family gene?
-Association with moles?  Dysplastic moles have up to 80% risk of Melanoma development, particularly when familial tendencies are implicated? what that tells us about what gene is involved is it MITF still?or is it PPP3CA (interferes with dephosphorylation of DNM1L, HSPB1 and SSH1)(will Etoposide helps here?with Cisplatin may be?  When you say this, is it POLR2C, the culprit?
or is it PAX3,MEF2, or Calsarcin-3.
well don't forget insufficiency of p16/CDKN2A when insufficiency of inhibitor of this major pathway relieve the block on cell division...
What gets BRAF so involved Or is it the involvement of Rho/ROCK.  What BRAF has to do with MITF
why inability to cope with change in skin color shuts down apoptosis?  Can interfering with splicing affects
What the hell Xeroderma has to do any how?RAD2, ERCC,DDB2,POLH,XPA,XPB.
Or simply BRAF is locked in Autoregulation, being truly a driver mutation, or relieved of its blocker or ubiquitinating substrate?  Is the PTEN present or not (is it more involved in internal Melanoma-lung?)
what about POU3F2 and PIAS, and miRNA-211, should we block TAF15? (sparing TATA and HSP27?)
can blocking the FGF worth while?
what about the expression of c-Kit (lentigo), where are the DNA repair genes? Should we focus on abilty of this cell to deal with hypoxia? (it seems to enjoy this path?)
There is much to be done, but where are we....
AT CRBCM, we are still at work!

Puzzling c-KIT

C-kit presence has been used in the definition of GIST and its presence has been used for the sensitivity to TKI (Gleevec).  But this is proven when C-kit is a driver Mutation (driven by localized or in-situ) autoregulation), in other disease C-kit could be present as a secondary event (mitigated response in response to upstream gene overexpression-this conditioned by normal suppressive downregulation), in those cases, TKI will have a minimal effect....
Can Monteluskast or Zafirlukast improve outcome
or does blocking IL3 receptor change outcome
or should we introduce a JAK-STAT inhibitor to affect outcome since the SOCS genes seems to be involved?  SOCS1 is described as a negative inhibitor of JAK/STAT pathway!  Activators of SOCS1 are being looked at in Hepatoma, How frequently is c-Kit positivity in this disease?  What is the meaning of c-Kit in Adenoid Carcinoma (driver Vs secondary)?  Interesting questions indeed!

In Melanoma, Tribulations of the MITF gene!

The gene is a "wild" gene and can auto-regulate, 2 charateristics that make MITF a dangerous gene!   Moreover, it is implicated in cellular differentiation, it regulates the BCL-2, and shows up when resistance to BRAF inhibitor come to be demonstrated.  It causes a deformation and intervene in cellular ability to resist Hypoxia.  Therefore VEGF amplification is a secondary event meaning it is not a driver Mutation, and Anti-VEGF will have a minimal effect in Melanoma.(This is debatable in Uveal melanoma However - Here it is the GNAQ/GNA11 thing! And PKC and MEK inhibitors may be actors).  Mutations in MITF lead to Tietz syndrome^[5] and Waardenburg syndrome type IIa.^[6]wikipedia
Blocking Wnt 3a, and the Cyclic AMP could be meaningful and alpha MSH could be a bio-marker for BRAF resistance.  Look at PAX3 role and POU3F2!   Interaction with LEF-1 is under scrutiny.   Briefly, we have our eyes on Melanoma and its activity.  The Melanocortin Receptor is also under review...Briefly we know that the cell has predicted that MITF is an agent of differentiation and adaptation (splicing and miRNA 211), it also has planned that if the cell cannot differentiate and adapt, it should quickly die through apoptosis...let melanoma cell choose this natural pass for the cure!
?Does failure to Braf points to susceptibility to Cisplatin or Melphalan?  good question to explore, again is alpha MSH a meaningful Bio-marker under these circumstances?  a good question to further explore!

CRBCM staying in the news!

Improving the Odds Against Lung Cancer

Last Updated on Thursday, 23 January 2014 15:39

By Nadia M. Whitehead
UTEP News Service
For many, lung cancer is diagnosed too late.
“About 85 percent of people diagnosed with lung cancer will die of that condition,” said Mutombo Kankonde, M.D., referring to the most fatal cancer in the United States.
Mutombo Kankonde, M.D. (left), a local El Paso oncologist, and Jianying Zhang, Ph.D., a cancer biologist at UTEP, are working together to develop a test for the early detection of lung cancer. Photo courtesy of Dr. Kankonde.
Those striking statistics — more people die of lung cancer each year than of colon, breast and prostate cancer combined — are what compelled Kankonde to study the disease and recently assemble a team of local scientists to develop a test to detect lung cancer much earlier.
“I haven’t done much work on lung cancer myself, but I have been able to identify biomarkers of liver cancer,” said Jianying Zhang, Ph.D., a biologist at The University of Texas at El Paso who forms part of the research team. “Dr. Kankonde knows this and wants to apply the same approach that I used in my lab to detect lung cancer earlier.”
Lung cancer is currently diagnosed after a CT scan, MRI or chest X-ray — when the tumor has already become visible as a mass in the lung and is at an advanced stage.
“If we use that sort of technology for diagnosis, it’s usually too late for the patient,” Zhang said. “That’s why we want to find a way to identify the cancer before there’s a tumor.”
In an effort to develop a breakthrough kit that detects lung cancer with either blood or saliva samples, Zhang, the oncologist, and Brad Bryan, Ph.D., a biomedical scientist at Texas Tech University Health Sciences Center, are studying 50 lung cancer tissue samples and the genes that compose them for phase one of the project.
The specialists are searching for three particular cancer-related genes in the tissue that have been associated with lung cancer at an early stage.
“We want to know, ‘What is the frequency of these gene abnormalities in these known lung cancer samples?’” said Kankonde, who is interested in the genetics of cancer.
If the genes are overexpressed in the tissue samples, as the team suspects they will be, they can be used as biomarkers, or early indicators of the disease.
The next phase of the project would be to develop a test kit that can detect the specific cancer-related genes in a patient’s blood or saliva, and test the diagnostic method on frequent smokers — who are at the highest risk for lung cancer. If a smoker tests positive for the genes, he or she would undergo a PET scan to see if a tumor is present.
“This has the potential to achieve cancer intervention at an early stage,” Zhang said. “In this way, the patient can still survive and have surgery done before it’s too late.”
If the team’s research is successful, they’ll eventually be able to put their test kit on the market for doctors to use on patients who are at risk for lung cancer.
Kankonde added that another team objective is to determine which lung cancers are sensitive to Avastin, a standard drug used to reduce the size of lung tumors.
Not all patients respond to the drug, and Kankonde believes this also may be linked to a patient’s particular genetics.
“We want to identify genetically why some patients are sensitive to Avastin and why some are not,” he said.
If they can determine and validate the gene that causes a reaction, doctors could potentially determine whether Avastin will be a worthwhile treatment for a patient with lung cancer on a case-by-case basis.
Kankonde, who operates his own oncology clinic in El Paso, says he has positive expectations for the outcome of the study.
If he’s right, he may well be applying the tests in his own clinic one day.

One of the reason we have kept silence these few days is our return to Indianapolis to complete the various tasks that keeps CRBCM a float! Many contracts remain to be fulfilled, and CRBCM intends to accomplish one and every single contract to the fullest...so we are sometime on the move.  Indiana was covered with snow so the mission was perilous (looking at your plane de-icing makes one critically uncomfortable, particularly when the de-icing fluid freezes on your plane window), but we are seeing the light as we progress deliberately!  We still keep staying in the news though!  Our research was posted in the UTEP NEWS!

DO NOT UNDERESTIMATE THE POWER OF ONE (RECEPTOR)

"IRAK1b, a Novel Alternative Splice Variant of Interleukin-1 Receptor-associated Kinase (IRAK), Mediates Interleukin-1 Signaling and Has Prolonged Stability*"

Liselotte E. Jensen‡"

Please just go to article, but it is clear that TGF Beta is clearly important particularly in Breast Cancer.  Anything that can autophosphorylate should make any-researcher nervous because it can set its self up and initiate something up (driver mutation).  When it is a molecule that can help cancer cell elude autoimmune destruction, when it help the auto-growth, and avoid apoptosis through death receptor or otherwise, when it interfere with cellular differentiation, when its level is require at strong presence, and when it is a conserved mechanism, it is an important part of the neoplastic transformation.   Through the Tollip, it can be reached by targeting the Tankyrase!  CRBCM is on it!
IRAK-1 is a critical component to cancer production!
Involvement of the NFKB suggests it (through TRAF 6, PKC, and TAB)
Through the RACs and RICs, IRAK reaches Metastasis (Rho/ROCK) and the BARC1 (breast cancers). (by touching Myd...of course).
Its activity through tampering with a gene regulator (IKK) should make you double nervous and doubling with autophosphorylation means it can be a driver on its own and achieve autocrine role for the new Cancer!

Through the CHUK it acts as a multiple site hitting of the NFkB but also reaches the Wnt through CTNNB1. Hitting NCOA means the engagement of all other Hormone receptors including the "wild" gene, Andogene receptors!  Once again The Tankyrases better be your Target to stop all this upstream...
And you know through the Dead Box, P53 will be spared and through mechanisms shared above, your Retinoblastoma gene will soon come into play.  And I guess I should not mention the Ubiquitin C or the NOTCH!...they all are involved!

The lesson here is that it is not the gene to look at when you are trying to find a therapeutic intervention, it is its common Receptor or substrate.  Don't look at IL-1, look at their receptors ...such as IRAK-1!

BAD THINGS LOOK ALIKE, BUT TRY TO WALK WITH ME THROUGH THE MAZE OF GENES! LIGHT IS BORN!

AMBRY-GENETICS"
"Pancreatitis Panel includes concurrent full gene analysis for PRSS1, SPINK1 and CFTR. Pancreatitis Panel can detect 99% of PRSS1 and SPINK of known mutations and 97-98% of of CFTR mutations. Testing does not include CTRC gene analysis."

BUT DO YOU REMEMBER SPINK5
IN THE NETHERTON SYNDROME
WHERE THEY SPEAK OF ICHTHYOSIS AND LEKTI
AND STRATUM BASALE

AND PSORIASIS AND STRATUM BASALE, WHERE BASAL LIKE CELL COME FROM AND SEEN IN TRIPLE NEGATIVE BREAST CANCER,

REALLY LOOK IT UP, IN PSORIASIS THEY SPEAK OF CCHCRA1
WELL DOWNSTREAM THIS WE FIND POLR2C WHICH TALK TO TAF15 THEN SAFB WHICH ACTIVATES ESTROGEN RECEPTOR AND HNRPD WHICH INTERACTS WITH HSP27 AND LATER SPEAKS WITH TGFB AND PTPN12 AND BAMMMMM! IT REACHES BCAR1.   AND BRCA1 BECOMES FOUND IN TRIPLE NEGATIVE BREAST CANCER WHICH IS NOT FAR FROM PANCREATIC PROCESSES.     BUT IN ALL THE MAZE OF GENES OUR FOCUS REMAINS ON SP1, EP300,SIN3A,GATA1.

THE FACT REMAINS THAT TATA SPEAKS ALSO TO POLR2C, THE SAME POLR2C THAT SPEAKS TO TAF15.   HMMMM....AND TATA binding protein SPEAKS TO TAF15.

PTPN12 INTERACTS WITH SHC1 BUT WATCH IT ATTACKING SHC1 (REGULATOR OF APOPTOSIS) BECAUSE IT HAS THE FAMOUS SH2 DOMAIN LIKE A GAZILLION OF OTHER MOLECULE INCLUDING THE STATS AND THE JAKs.  YOU JUST DON'T KNOW WHAT YOU WILL TOUCH.

ON THE OTHER HAND UBIQUITICN C KEEPS ATTRACTING RESEARCHER FOR WHAT IT CAN DELIVER!  ONE NEEDS TO STRATEGIZE THIS APPROACH!

For fun, we also do!

Hello Clement Albert,(or DR Kankonde)

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We think you'll agree that Radio Airplay is a better promotional tool than ever. More than 50,000 artists rely on Airplay to get their music out there, and here's why:

Play to the right listeners (message to me!)

Cancer research questions, so many it is mind troubling!

1.Can disruption of the Nuclear CAP be used as therapeutic intervention in dividing cell?
lewis et al:
"The defects in splicing and U1 snRNP binding caused by CBC depletion can be specifically reversed by recombinant CBC. In summary, efficient recognition of the cap-proximal 5' splice site by U1 snRNP is facilitated by CBC in what may be one of the earliest steps in pre-mRNA recognition. Data in Colot et al. (this issue) indicate that this function of CBC is conserved in humans and yeast."

It is a conserved process for a reason! CAN INTERFERING WITH SPLICING BE USED IN CANCER THERAPY?

2. Could blocking Transportins (1,2) or A1 be a novel therapeutic approach in Breast cancers since levels of Molecule transfer seems of importance in this disease.
Can these molecules (transporters in general) be biomarkers of cellular activities in breast cancers.  What is the role of targeting the poly tail (A) of RNA, should that limit the movement of these RNA

3. Should BH3 domains, presence of BNIP3 activation,  BCL2, NOTCH activation,  be surrogates for anti-apoptosis in cancer biology? what about SHC1


4. Should presence of activity at CD47 be consider a biomarker of BCL-2 activity? Anti-apoptosis?
CD47 (IAP).
wikipedia:"By blocking TSP1 from binding to its cell surface receptor (CD47) normal tissue becomes nearly immune to cancer radiation therapy and assists in tumor death."

5.GIPC 1 could turn out to be an important Target in Ovarian cancers! because of DAB2 and LRP interactions.

So many things to test, it is mind "troubling" or is it "mind buggling",they say!

Importance of cancer Metastasis

One thing for sure Metastasis is just not another characteristic of Cancer. It is one of the characteristics of tumoral cells that make them cancerous.  Cancer will not kill anybody unless it spreads (with the exception of Brain cancer, but even in this disease, it is the tentacular infiltrations of these cells that ultimately kill.  Cancer on the move kills.  So it is important to focus on genes that lead to cancer spread.   Prostate cancer or colon cancers will not kill if invasion and metastasis will not occur.   And survivors will not be at risk if the disease stopped popping up somewhere else (in most cases, since local recurrence could be dealt with vehemently with an aggressive local treatment!).  Spread has become sophisticated, from Putative genes such as MTS1, to motion evidence with non muscle Myosin (II, and sometime V)/Actin, to SNAIL and SLUG (E-Cadherin).  It goes on to hiding behind P53 of which activation can increase phosphorylation of MK5 and you know what effect this will have on RAS.  In Breast cancers in particular, you know about RSK dependent TGF accumulation of MK2.   Increase of RSK4, decrease CXCL family member which in turn activates the Claudins...Other pathways of importance VEGF,LIMK1,P38.  Putative role of RhoA/Rock.   MLCK, BNIP and even LAR genes.   We have so many chances to act but sit on our hands...talking to governors who have nothing to do with these markers...The Ultimate blocker to cancer research is still Human...wearing Tuxedo, unaware or innocent to science!  Work with CRBCM to stop cancer, not find reasons...and you know the rest....CRBCM progressing slowly but surely ... we will continue to fight until we find a cure...and enemies become irrelevant to the fight! (So many markers, so many chances to stop cancer, but nothing substantial done to capture the moment! and politics keep going...they lost their soul! )

?new Breast cancer Biomarker

There must be a marker in Breast cancer displaying a mutation in the fanconi like gene.
We know that disturbance in Fanconi disease affect mobilization of molecule such as Cystine.
And Fanconi gen alteration is cited a lot in Breast cancer, Is there a Beta albumin secretion when SLC gene is abnormal in Breast Cancer.   take serum and Breast cancer specimen, if mutation in SLC gene is found, does the serum gives us a Beta-albumin like molecule in the serum?   easy to find a biomarker...ok let's go to work.
Is SLC gene marker a surrogate of Crizotinib activity? secondary reason for investigation?
PALB2 is associated  with BRCA-2, is there a secretion of protein linked to it?

CAMPTEN ! IN NEURO-ENDOCRINE TUMORS!

Somethings make you scratch your head,
and now you wonder what made them think of it...
In life revisiting stuff is not bad after all...
WHO HAD THOUGHT OF THAT
AND THEN IT MAKES YOU RUN BACK TO THE DRAWING BOARD
COMBINATION OF XELODA AND TEMODAR IN NEURO-ENDOCRINE TUMOR?
THE RESULT IS UNEXPECTEDLY GOOD!
WHAT IS THE GENETIC BASIS OF THIS, CRBCM WONDERS!  LET'S GO BACK HERE....THE SEARCH SHOULD NOT BE LONG, I GUESS......to be this effective the mode of action go to be additive which in gene may mean a more total blockade of a specific gene or pathway, or blockade of 2 competing gene/pathways or may be blockade of 1 pathway and its rescue process.  We have got to go deeper.  And why Neuroendocrine ? Is that mean where Etoposide may work such as in the epigenetic area where Histone Deacetylase are king, or is it in the mitochondria where the CREB genes , BCL-2 are in effect.   Xeloda aims a Thymidilate synthase impairing S-phase but what that have to do with silencing th MGMT gene that unleashes Temodar alkylating effect...does blocking synthase and the need in S phase give a better out look...well we need dig in further...and why neuro endocrine, why the hormone? here focus on epigenetic phenomena is warranted...

c-MYC, a trouble maker in Breast Cancer

The expression of c-MYC suggests downregulation of BCL-2 and may open the road to use of anti-Topoisomerases.
The danger of c-MYC is through its relation with ZBTB17(Zinc Finger) which affects the Host Cell Factor 1 which in turn hits SP1 and the POU2F1.  The latest activates:
"POU2F1 has been shown to interact with SNAPC4,^[3][4] Ku80,^[5][6] Glucocorticoid receptor,^[7][8][9] Sp1 transcription factor,^[10][11] NPAT,^[12] POU2AF1,^[4][13][14] Host cell factor C1,^[15][16] TATA binding protein,^[17] RELA,^[18] Nuclear receptor co-repressor 2,^[19] EPRS,^[20] Glyceraldehyde 3-phosphate dehydrogenase,^[12] MNAT1^[21] and Retinoid X receptor alpha.<sup>[7][22]"wikipedia

Touching the RELA in an uncontrolled fashon is generally a mistake.  It is a "wilder" gene affecting all functions and marks the Wnt/NFkB involvement, and Brings in the Casein Kinases.
The involvement of PPP1R13L further brings in the SP-1, amplifying downstream events.
Amplification of the c-MYC could always be associated with repression of Myb which impacts the mi-RNA 155, and may be associated with explosive expression of the c-FOS that needs Tamper!  Of course presence of c-FOS will lead to more AP-1, should c-JUN be present!  Increase of c-FOS could raise the importance of Histone de-acetylators in this disease!
So the presence of c-FOS and c-MYC could potentially raise the importance of Etoposide and Histone deacetylators!  An interesting trial to suggest....</sup>

Today CRBCM at work

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In triple negative breast cancer, so many things can go wrong!

One of the thing that goes wrong in triple negative breast cancer is that up to 40% of these cancer are BRCA mutation positive.  Decrease in BRCA activity because of Mutation is followed by amplification of ELK1 which in turn engages the Serum Response Element (SRE), a devilish gene that engage among other gene the TEAD1 which affects MAX and the C-MYC, and the MSH2 and all breaks loose.  Just by amplifying activity or the SER, the RELA gets excited and breast cancer of the aggressive kind develops  quickly.   It is not just Apoptosis that is reduced but the level of dedifferentiation in cellular development open doors to therapeutic options of new kinds that have been insufficiently explored, making the job at CRBCM even more undertaking, we have yet to sleep!  looking at P38,JNK,ERK,ELK1, Sap1, HSP27, CRE and SRF as potential targets!
And what with Mutations at the ATF1 and CREBBP...and the cogitations go on!

Increase in ELK1 activates MEK and ....target ? well let's keep going...

And who would have guest that C-fos would be an important Biomarker?  got me totally fooled!

To the survivors, Peace could come through the CENP-F, importin, EGF repeats! But we don't know what we know!

Yes it is true that when survivors of a cancer meet their Doctors, they look to him to tell them if the disease is back or if they should rest some more at peace.  The truth is that science has not work enough to provide good indicators of cancer recurrence particularly when it comes to those cancers missing standard markers.  For example if you follow a colon or ovarian cancer, the CEA and CA-125 will be respectively good markers to follow .  Most clinicians will do these tests serially,  and patient find comfort in following these related number of markers as their disease progresses.  The Marker's number help with decision to move forward with various therapeutic options before both the physician and the patient.  ie. if the PSA is increasing following a series of treatments, Prostate cancer will be supposed to progress or resist the said treatments, and often decision to change treatment will ensue.   On the other hand, Response to a treatment for metastatic prostate cancer will be judged based on how much it drops or decrease the PSA, a valid response criteria in Prostate Cancer.  So clearly, Bio-markers are here for us to be used in clinical practice.

However both the patient and their doctors remain silence when it comes to very dangerous cancers.  Sarcoma, Melanoma or even Brain cancers have no standardized Markers to follow.  It is sad to wait for the mass to grow in a convincing way to tell the patient that the tumor is on the move.  Often as we have our eyes on this tumor, somewhere else something happens to tell us the tumor is indeed on the move.  But one thing for sure, a tumor to grow need to multiply, use more proteins, its nucleus will tell us "I am at work more here" and we have ways to tell.  Mitosis and cell division is always in play when cancer Multiply and CENP-F will tell us,  Notch is in play and EGF repeats will tell the message (amplification of c-MYC will tell us), level of CSL genes will tell us NOTCH is hot or not!  level of Importin or BRAP- all these genes are at our disposal to tell something is up! And even level of Myosin and use of NLSs (Nuclear localization signals) can tell a story, but despite our big talk, we have not done enough to tell our patients the truth because those with means have not let us investigate these potentials to their fullest.  Researchers, the coalition want answers, in breast cancer, Wnt (CTNNB gene) and Notch (EGF repeats) are at work, when we sleep at the wheel.!  wake-up! The Nuclear localisation signals are winking at us, we don't wink back!

Use of genetic in the future (full of controversial speculations to see if you are following!) careful with genes!

1.Today we can assume that alzheimer reflects  disturbance in CREB and related genes
tomorrow, alcoholic will be judge by their level of CREB.  It will be nice to tell someone that because of your isoform of CREB, don't even try Alcohol at all! you will become an alcoholic!
And just tell a man that your memory capacity is doubtful given your CREB activity, your strength is else where (comprehension or other capacity).  Patient with post traumatic syndrome could be evaluated by the status of their CREB! have they become too forgetful....disturbance of CREB could point to old age?
Other genes for this purpose, ELK1 of course which is close by in the viscinity!But also CREBBP!

CANCER RESEARCH FUNDING, A RIGGED GAME

Time and again, MAN comes up with the reason why progress is not achieved to the fullest.  And the allocation of scarce funding does not escape the malignancy of human politics.  The reflex to profit only those we know is entrenched in the core of humans, it bubbles inside of us, somewhat repressed by conscience and known rules of the game, but ultimately suppressed when it comes to reel deeds.  Whether mischievious or unintended, these deeds corrupt the ultimate outcome, unintended or not.
In Texas the early years of CPRIT have been just that.  Although the CPRIT concept was sane and well intended,  putting in development was given to fund raisers of Universities.   And what they put in place was a corrupt system which funneled funding to a few Universities and not the community of researchers as a whole.  It took a few years to blow up in their face.  You don't send to the moon or anywhere men in a political ship. Only a ship that is guided by solid unbiased science will make it through the peripetia of a natural world governed by true physics, mathematical and natural laws.
Although it is said that the review process is independent, you got to be an innocent kind to believe that reviewers are not hand picked, and trained to recognize the source of the submission.  Indeed the CRBCM critics continue to write: "the project is ambitious, however the PI (principal investigator) is unknown".   The merit went to prior knowledge of the man, but not the idea he submitted.   The CRBCM will continue to submit ideas to these organizations because may be, just may there be a chance that one unique good soul is left in that institution, because even crooked minds can have a moment of lucidity and clairvoyance.  So we will keep challenging them...and maybe our efforts help framing our argument as we use their free criticism, biased or not.

A friend of mine was working at NIH and told me, we usually receive a call to submit or write up a proposal on this or that at the last minute, and often we get the grant!  and when I told him, I am writing a grant proposal, the answer was: "you are crazy wasting your time!"...It is who you know in the end!

Our fight is right, we believe strongly, because it is funded on facts, women continue to die of Breast cancer, and somehow we are managing to grow as if something, somewhere keeps us alive...January 1st, we acquired a new medical office (a retiring physician allowed us to take over his business).  This has increased our foot print tremendously.  These things happen for a reason, our  true, just and innocent purpose of our coalition.  Self funding is our true objective and desired position.  Because anything less corrupts.  CRBCM, still advancing purposefully!

Proposed Genetic Biomarker of fibrosis: SOCS3

1.The fact that administration of GCSF may increase frequency lung induced toxicity in patients on Bleomycin,

2.The fact that IL-6 is now the target for therapy in multiple sclerosis
"

Interleukin-6: a new therapeutic target in systemic sclerosis?
Open

Steven O'Reilly"

3. and some believe IL-10 recruits fibroblasts

"New concepts of IL-10-induced lung fibrosis: fibrocyte recruitment and M2 activation in a CCL2/CCR2 axis.

Sun L, Louie MC"
==========================================
All these facts point to one and only one gene to watch,  SOCS3 and therefore the involvement of the JAK-STAT pathways.   Indeed all Myelofibrosis end up in fibrosis and therefore a focus on SOCS3 is more than warranted.  SOCS3 is first know as an inhibitor of the JAK/STAT pathways.

wikipedia: "The expression of this gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma. The protein encoded by this gene can bind to JAK2 kinase, and inhibit the activity of JAK2 kinase."

SOCS3 is not only an enhancer of KRAS pathways in colon cancer by removing the pathway break (RasGAP), (it should be SOCS3 we should be watching!), but SOCKS3 through its activity with PTPN11, brings you the CEACAM-1 connection (which we follow as CEA in colon cancer)  and beyond the CEACAM, SOCS3 brings Annexin-1 the road to fibrosis.   Remember how Mucinous Gastric cancers end up producing so much fibrosis in the peritoneum that patient die of intestinal obstruction, it is we as Doctors do not monitor IL-6, IL-10, Interferon levels, SOCS3 activity, CEA, and Annexin-1 for that matter.  We think PEG tube instead of blocking Annexin activities!

If you happen not to believe, you should read Wikipidia:

" Patients with a subset of Noonan syndrome PTPN11 mutations also have a higher prevalence of juvenile myelomonocytic leukemias (JMML). Activating Shp2 mutations have also been detected in neuroblastoma, melanoma, acute myeloid leukemia, breast cancer, lung cancer, colorectal cancer.^[7] These data suggests that Shp2 may be a proto-oncogene. However, it has been reported that PTPN11/Shp2 can act as either tumor promoter or suppressor.^[8] In aged mouse model, hepatocyte-specific deletion of PTPN11/Shp2 promotes inflammatory signaling through the STAT3 pathway and hepatic inflammation/necrosis, resulting in regenerative hyperplasia and spontaneous development of tumors. Decreased PTPN11/Shp2 expression was detected in a subfraction of human hepatocellular carcinoma (HCC) specimens.^[8] The bacterium Helicobacter pylori has been associated with gastric cancer, and this is thought to be mediated in part by the interaction of its virulence factor CagA with SHP2.<sup>[9] wikipedia

=================================================================
why do you believe CEA is elevated in Gastric,colon or even Breast cancers!  This pathway is indeed in effect!

Even GUO et al spoke about this in their observation focused on Caveolin in Fibrosis, but stumbled on SOCS3 (Their Caveolin was not far from SOCS3):</sup>
 " Real-time PCR revealed that the expression of the mandarin fish Mx, IRF-1, SOCS1, and SOCS3 genes involved in the poly(I:C)-induced Jak-Stat signaling pathway was impaired by the mCav-1 scaffolding domain peptide (mSDP)."
^{" 
SOCS3 is a powerful gene
and at CRBCM we still believe that a gene that can induce Malformation, is powerful.
SOCS3/PTPN11 is a powerful association:}

Missense mutations in the PTPN11 locus are associated with both Noonan syndrome and Leopard syndrome.
It has also been associated with Metachondromatosis.^{[4]wikipidia
" 
To muscle up both Leonard and Noonan syndromes ("il faut le faire" the french will tell you!)  et le faire fort!(DO IT STRONGLY)
AND THEY MANAGE TO DO THIS THROUGH MITF!}

more speculative notes on triple negative breast cancers

Through the TIAF gene, inhibition of JAK3 could have a role in triple negative Breast cancer.
The RELA,UBE2I and MITF genes could have a prominent role in the development of triple negative breast cancer,
Blocking FGF could shield FGFR in the pathogenesis of triple negative Breast Cancers
POLR2A is our link to Psoriasis and the Basal like morphology! And you really are talking to BRCA genes
If you reach the RELA, you are in the Sp-1 and SF-1 territory and with POU2F1, you are deep in the belly of the beast!
and with SF-1, you are really exploring the MYC gene  through the PUF-FUS (MyC gene/Xeroderma pigmentosus)

Basal cell like triple negative breast cancer has deep connections with autoimmune disease and therefore race (and probably gender)distribution through these mazes of genes.  At CRBCM, we are tracking it down!

Medtronic's renal denervation system in patients with treatment-resistant hypertension failed

KNOW WHAT WORKS! THIS IS IN THE NEWS, CHECK-IT OUT!

WELCOME COTE D'IVOIRE! (OR IVORY COAST!)

THE CRBCM WOULD LIKE TO ACKNOWLEDGE OUR READERS FROM COTE D'IVOIRE,
REMEMBER SCIENCE DOES NOT BELONGS TO ANYONE, THE CELL IS THERE TO BE DISCOVERED BY ANY OBSERVER PUTTING HIS MIND TO IT!
PROFESSOR FAGNEREY TAUGHT ME THIS BACK IN KINSHASA IN MY BIOLOGY CLASS IN 1974-76 ( YEARS OF BIOLOGY CLASSES IN HIGH SCHOOL).  GRADUATED 1976 AT COLLEGE BOBOTO (EX-ALBERT).  AND NOW HERE WE ARE!
CRBCM, A GOOD FIGHT IS WORTH PUTTING UP!

Avastin, the Hero to beat in Colon Cancer! (aflibercept lurking)

It has made its place and win the argument, in Metastatic Colon cancer, the fight against cancer through the various VEGF receptors cannot be demonstrated better but by what Avastin has achieved.  Avastin has won our heart and the argument, and is now part of standard of care for metastatic Colon cancer.  It is most of the time Given with Folfox.  All Oncologists have had to use this combination of treatment with confidence because it works.  Well, for a while, like most any thing you try to do to a cell, suppression of a pathway is survived by amplification or activation of dormant pathways.  In a normal cell of adult individuals, anything placental has to be "dormant" or clearly "subliminal".   Well think again, if you block the main angiogenic (VEGF1) pathway, you wake up the secondary ones.   Among the one you awake, one is striking, The Placental one called PLGF or Placental Growth factor.  Not only it is awaken, but it is also stealing the show.  If you go to a conference on Colon Cancer these days and no one mention this gene, be assured you went to the wrong conference!   Everyone is talking about this PLGF but be careful, inhibition of this one leave the cell without ability to handle " inflammation".  If you completely inhibit this one, get ready to fight an (give or take) "eclampsia" looking like syndrome  (PLGF is decreased in Pre-eclampsia) .  Handle this one with care!  But scientist have their eyes on this one.  It stole the show from the MTOR inhibitors (MTOR is the other way of developing resistance to VEGF inhibition).(see our previous blogs).  Lack of biomarkers is driving researchers from exhausting all options to their fullest benefit!  We keep hop-here and hop-there! and see what works!

Suffice is to say that Panitumumab (Vectibix) is looking very good right now with Folfiri as a second line, suggestion is that it is  beating Cetuximab (Erbitux) in second line...weigh my word..."suggestion"...
wild type KRAS related of course.

But now the NRAS, we need to dig deep on this one!

In The Kinases, one winner (FDA approved )Regorafenib, we are learning, and patients are waiting!

Activity at CRBCM!

Hello,

This is a courtesy email to let you know that we have processed the yellow fever application and are mailing the stamp this afternoon to the address shown on the application.  Please contact me immediately if there is any problem with this, or if you have any questions. 

Thank you,

Genetic work is fun, Go to town with it! Important questions

*Can disruption at LAT1,2 be achieved through MITF (SLC7A8)
*Is ZFYVE16 a substantial target in Gastric cancers
*should we be monitoring IL-1 in patients with GERD
as a biomarker risk of Gastric cancer
*Inhibition of RFXAP in T cell leukemia,what could be the effect!
*Blocking TOM1 could help in disease where MITF is a driving force (Melanoma).  Are activities at MITF the reason for short duration of BRAF inhibitors?
*What happens when you block CD28 in Ovarian cancer
*Is CD79 a floppase?
*Inhibition of BIRC7 will unleash Apoptosis and could be the way to win over Mutation in MITF
*Should patient with melanoma of the eye avoid Beta Blockers because of effect on the GPC1
*Beta blocker protective or inducer of cancer, what is the state of GPC1 and DAB2 in patient taking this drug
*Role of Beta blocker in Ovarian cancer (connection through DAB2)
*Are the LRP (s) the connection of Fatty food to carcinogenesis?
*Block TOM1 when giving BRAF inhibitor?

Human made lack of progress in cancer research

10 years after the Cancer Genome Atlas project published its findings, some its key findings remain in the closet.  That is very little has reached the bedside of our patients.  Most of the use has benefited research companies that used the information to design drugs most of which remains in clinical trials.   Information that could have benefited the day to day practice of oncology, remains away from the reach of practicing physicians because not fully endorsed by leaders in the field.  For something to be used, approval by the FDA or strong recommendations by leading bodies such as NCCN and the like must occur for Insurance companies to follow, and for practioners to be able to orders pertinent test to use the knowledge.
ie. "Mutation of FOXA1 could be a marker of endocrine sensitivity...Depletion of FOXA1 abolishes Estrogen Receptor binding capacity..." (Cynthia X et al)  That FOXA1 level could predict response to endocrine therapy....This is a major finding.  The lack of endorsement makes this finding insufficiently unused in our community of Oncologist.  In reality this finding should be reported next to the ER positivity to further affirm that success of therapy is more likely, a fact that will further reassure our patients.  In endorsing this fact, technology to make this test will be developed for an easy and more readily use in oncology practice.  To spice things up? well Cyclic AMP should also be reported and monitor over time to predict MTOR activity and resistance build up.  MTOR inhibitor have shown disease free progression advantage when added to AI.  May be we should see resistance coming don't you think?  If not C-AMP, may be CRE...now don't start the polemic...!   HUMAN....  blocking progress....

Mutivitamins' controversy

Vitamin has been defined as an organic molecule that our body needs but cannot synthetasize.  It has got to be provided to our body through food. Today in age most vitamins have been synthetasized and can be sold to us as a pill at various concentrations.  What is peculiar about vitamins, is that generally the body requires these Vitamins at very low amounts. The body has to seek these vitamins hungrily.  Cells have to put out many ways of capturing these vitamin through gene receptors formation.  This is the natural and balanced way of cellular life.  The persistence lack of vitamins or their insufficiency have deleterious effects.  In lung cancer, diets that are deficient in Vitamin C, A, and Beta Carotene have been reported to increase the risk this disease development, However heavy supply of Beta carotene to patient who have had lung cancer did worsen the prognosis because it induced higher risk of lung cancer.  One should stop and wonder what the meaning of this fact is.   Why is it that supply of a needed compound will be linked to deleterious consequences.   The truth is that to any action there is a reaction!
The cell has no clear way of telling our body about its finite needs such as lack of vit D.  It can only do things within the realm of its powers such as increasing its receptors in order to increase its chances to capture Vit D.  This upregulation of receptors will have an impact on downstream pathways when of course the receptor ligand has been supplied particularly if it is provided abundantly!  It is presumed that an exagerated supply of Vitamins may lead to Receptor desensitization at the long run.  (to be continued)

ONE CASE OF EMBRYONAL RHABDOMYOSARCOMA BEING TREATED AT CRBCM!

We are currently treating a 19 year old who presented with a testicular mass
Guess what was the Histopathology: "Embryonal Rhabdomyosarcoma"
at CRBCM, we are looking at the possibility of a MUSK gene mutation
WHAT DO YOU THINK?
DON'T BE SHY NOW, CALL 915-307-3354!
AND THANK YOU

*PDPK1, THIS STUFF GIVING POWER OF RESISTANCE TO CANCER, WONDER IF IT IS ACTIVATED IN TRIPLE NEGATIVE BREAST CANCER?  IT MAKES MELANOMA TOUGH TO TREAT!

Bromocrptine and Colchine could potentially enter the fight against triple negative breast Cancer (maintenance therapy)

Following our first article about Triple Negative Breast cancer as it could be related to the ROLE OF PROLACTIN, It is evident that Medications that depress the secretion of Prolactin will come into play soon in the maintenance therapy of triple negative Breast cancer if proof of concept is maintained.  One of the comment made was that Prolactin and its receptor could not possibly be the culprit despite the fact that the gene for the prolactin receptor is a "wild gene".  We still believe we are on the right path.  Indeed one of the major role of Prolactin is to promote genes related to Casein.  Many Hormones including Glucocorticoids and potentially (or more likely Insulin) do promote Casein related genes.  One of these genes is Casein Kinase, a major source of substrate phosphorylation for critical Compounds

"Casein kinase 2, alpha 1 has been shown to interact with CHEK1,^[4][5] FGF1,^[6] CDC25B,^[7] CREB-binding protein,^[8] Activating transcription factor 2,^[8] C-Fos,^[8] MAPK14,^[9] RELA,^[10] PIN1,^[11] PLEKHO1,^[12] CSNK2B,^{[12][13][14][15][16]} PTEN,^[17] ATF1,^[8] TAF1,^[18] UBTF,^[19] DNA damage-inducible transcript 3,^[20] Basic fibroblast growth factor,^[6] APC,^[21] HNRPA2B1^[22] and C-jun".^[8]wikipedia

if you did not see the wnt listed, read again my blog of yesterday, because between the frizzled and dishevelled, one of them vividly interacts with CK2 gene.  To find inhibitors to this CK2, leave quickly the US and fly to Padua, Italy:

"Selectivity of 4,5,6,7-tetrabromobenzotriazole, an ATP site-directed inhibitor of protein kinase CK2 (‘casein kinase-2’)

Edited by Giulio Superti-Furga

• Stefania Sarno^{a, 1},
• Helen Reddy^{b, 1},
• Flavio Meggio^a,
• Maria Ruzzene^a,
• Stephen P. Davies^b,
• Arianna Donella-Deana^a,
• David Shugar^c,
• Lorenzo A. Pinna^{a, ,}

• ^a Department of Biological Chemistry, University of Padua, and CNR Biomembrane Research Center, viale G. Colombo 3, 35121 Padua, Italy"
• ======================================
•  
•  
• SO, FORGET ESTROGEN, PROGESTERONE, WELCOME   CASEIN RECEPTORS IN TRIPLE NEGATIVE BREAST CANCERS!
• AND IF YOU DID NOT SEE P300 AMONG THE PHOSPHORYLATED by CK2...GO BACK TO THE DRAWING BOARD! and if you did not notice UBTF, please read wikipedia again!
•  
• CRBCM PUSHING RESEARCH IN BREAST CANCER!  WELL KIND OF, THE FINANCIAL INSTITUTIONS THAT CAN HELP US ARE STILL SITTING ON THEIR HANDS FOR POLITICAL REASONS!

Good work recognized

Dear Dr. Kankonde--

How lucky my Mother and sister Lynn were to find your clinic open Christmas Day. Your thorough, thoughtful and appropriate care of my tough but very ill 94-year-old Mother has been more helpful that I can tell you. And the followup of the RX for albuterol without dragging Mother back out and to your office has been a lifesaver for all three of us! I will be returning to my home in Austin today, but even without ever having met you or your wife, you will be in my thoughts and on my "Thank-you" list forever!  That Mother is doing as well as she is is remarkable but would not have been so without your being available and effective!  Thank you!

Frizzled hair post chemotherapy, a tell-tell sign! ("CURLY HAIR", I AM INSTRUCTED TO ADD)

One of the reality faced by cancer survivors is that they come to need hair treatments because the hair comes back but not the same.  Cancer survivors most of the time report wrinkled hair.  Treatment aimed at straightening the hair is often required.   The Wnt is often involved in cancer, and most chemotherapy will affect it to be effective.  Down the wnt pathway is the Frizzled gene which through the dishevelled gene will affect the the Axin maze of genes which could result on derangement of the AXIN (ACTIN).

If you can describe your hair as "disrupted", think first of the Frizzled and the Dishevelled gene"
wikipidia :"The frizzled (fz) locus of Drosophila coordinates the cytoskeletons of epidermal cells, producing a parallel array of cuticular hairs and bristles"  There is some truth to that!

How this is linked to deeper disturbances is under intense research
remember this pathway involve the Wnt, a versatile gene that can follow canonical and non canonical pathways.  Meaning it can reach the GSK-3B and therefore the Lef-TcF transcription gene or go non canonical on you and reach the MEKK/JNK  with different peculiar downstream transformations.

Currently in Oncology practice, we do not pay attention enough to the resulting hair transformation.  But it is there for us to see.  Dismissing it as a potential message the body of the survivor is telling us...is totally missing the point!

FUTURE IMMUNOTHERAPY IN SOLID TUMORS

From the San Antonio meeting this year, we are having echos that are of interest to the CRBCM
There is a great interest in immunotherapy, that is, how to recruit the innate immunity to the fight against cancer.  The finding that there are lymphocytes that infiltrate the tumor has been observed and further, the presence of Lymphocytes in the tumor seems to confer, most of the time, a better prognosis.
Speculation is that if an effective autoimmune reaction is mounted, metastatic cells could be destroyed at distance from the primary tumor and seeding of metastasis could be delayed or precluded, therefore delaying disease progression.   The question is how to make such autoimmunity directed againt the tumor more effective.  Data collected in Prostate Cancer (Sipuleucel/Provenge) and Melanoma have been encouraging in terms of encouraging this line of research.

Furthermore, the inefficiency of infiltrated lymphocyte in cleaning the site of the tumor, has been attributed to a tumorkine secreted by the cancer to annihilate   the lymphocyte attack.  Tumorkine Receptors on the lymphocyte (and tissue itself for that matter) are now target therapy site potential.

It is of interest that various treatments given to the patient may alter his genes and some of the structure of the cancer cell could become immunogenic.  Studies looking at these changes after neoadjuvant therapies are now being conducted.  The point is that if they were not sufficiently immunogenic, rendering them immunogenic by conjugation with known compounds of immunogenic potential could be an interesting objective that will lead to the use of innate defense against cancer cell...this is a rapidly growing field!