Role of autoimmune disease in the young with cancer

The CRBCM has grown to a larger Oncology Clinic
but its interest with Breast Cancer has sharpened.
It is clear that Breast cancer in the young women is clearly associated with not only to obesity as claimed by Pundit but to undefined, undiagnosed autoimmune syndromes.   The link to autoimmune syndrome appears to be stronger despite the fact that it is also the more difficult to ascertain.   There appear to be no consensus among Immunologist as what should constitute a basic work-up for autoimmune syndromes.
There are many autoimmune syndromes and all seem to lead to cancer predisposition.   Autoimmune disease detection remains the biggest challenge and mostly not completed at the time of diagnosis of cancer in a young individual.  Therefore it remains ignored.  In our practice, the basic screening include :
1.ANCA
2.Anti-Saccharomyces Cerevicea for detection of early Colitis and related colon cancer
3.Anti CCP
4.Rheumatoid factor
 5.and ANA
(rarely anti-Smith)

rarely we add the anti-RNP for possible connective tissue disorder.


It is clear that a full Lupus panel would be advised but cost could be prohibitive and, in these days in age, the insurance companies limit our exploration.
Quickly one will note that some tests are "confirmation" test while other are "screening" tests.  In our hands, experience show that many times these so called confirmation test could be positive while the screening test is in the "high normal".  In these instances, suspected diagnosis is  made.  It belongs to the Rheumatologist to actually treat accordingly.

With this approach, countless of Lupus positive young women are found among our Breast cancer patients.  We will publish our findings soon.   The interest is also in the frequency of Bilateral findings of Breast cancer among these patients.  Care should be exercised while following these young patients.
 The patient with Antisaccharomyces  calls for attention to early colonoscopy.  Countless young women approached this way are found with Polyps and at least one patient was found with a non invasive colorectal cancer.   Certainly this antibody will be talk about in the future as we discuss increasingly about early colonoscopy.  (As we speak, I have a 49 year old found with stage IV colorectal cancer who is Rheumatoid Factor Positive and anti-Saccharomyces positive).
In the absence of clear autoimmune syndrome by lab, suspicion is kept in patient with sudden profound fatigue that remains explained, anxiety or Depression, insomnia, and low Vitamin D
arthritic pains and sometime Hypothyroidism.  Those will colitis will report bouts of unexplained diarrhea, or constipation, or hx of Gallbladder disease including history of cholecystestomy  (and ITP).  These are present in autoimmune syndromes.
The reason for the association of autoimmune disease correlation with early cancer remains a mistery and is an area of intensive research.  We are on it.  From "proximity of genes" and something to do with "check points".  We will update you as the thing unfolds.






 

Prayer for the common world

Please do not let me leave the world the way I found it
please give me hope and strength to change the things that I found in a more evolutionary way
so that tomorrow be built not on the things that I found but rather on the things that I was able to build.
Let me not sit here but keep moving things the way it ought to be
because my time should count for some thing in the evolution of the world which is evolving in a ever changing Cosmos.

Rare tumor

In September 2016, a 50 year old Hispanic female was referred to our clinic for an encapsulated mass to the left side of the Vulva.  On CT, the mass seems to contain fat, encapsulated with solid content extending into the labia.   The radiologist felt it could represent a Liposarcoma.   Tissue diagnosis however suggested an Angiomyofibroblastoma.
Surgery was recommended, and on December, 01,2016 she underwent
a resection of the mass which was 22 x8.5x4.0 cm
the tumor was weekly positive for Desmin
strongly positive for Vimentin
ER positive
PR positive
 all other tested immunochemical stains were negative

The case was referred to Massachusset General Pathology for review
there was no  other metastatic lesion
and surgery confirmed the diagnosis

what to do now for this patient
concerns:   The disease is benign- Observation was advised
                   The tumor is too large, and no mention of full removal despite the encapsulation seen on CT.   should she have Radiation to reduce local recurrence.
ER and PR were positive, should we give Tamoxifen now or wait for a recurrence?
The disease had some "Angio" component, will it benefit from anti-EGFR treatment in case it recurs?

Options in Renal cell cancer treatment

First Line Metastatic disease:
-----------------------------------

1.Sutent
2.followed by Nexavar in those who cannot tolerate Sutent
3.Sutent 50   has been equivalent to Lapatinib 800 daily
Other first line Bevacizumab +/- Interferon
Temsorilimus
But if you consider Bevacizumab think of combining to Alezolizumab (there is Synergy)
4.Other 2nd line:
---------------------

4.a.  Everolimus
4.b.Cabozantinib

Cabozantinib has been compared to Everolimus
there was a 33 % reduction of dying with Cabozantinib

4.c. Other alternative in 2nd option is Nivolumab which has risen to standard second line after Sutent
Nivolumab has been found superior to Everolimus

4.d  Levantinib
which has been sometime conbined to Everolimus
this combination has been superior to to each drug used separately.

4.e future trial Nivolumab +  Ipilimumab

4.f.  Axitinib

OPTIONS IN TRIPPLE NEGATIVE BREAST CANCER

1.CARBOPLATIN +  VELIPARIB

2.ABRAXANE    +   CARBOPLATIN

3.ADRIAMYCIN  +   CARBOPLATIN    +  TAXANE

WITH TAXANE WEEKLY X12
WHILE CARBOPLATIN IS GIVEN WEEKLY X 6

4LESSER ALTERNATIVE :   GEMZAR  (1000)+  ABRAXANE(125)


5.XELODA



OF NOTE: THE MORE THE NUMBER OF NODES INVOLVED, THE MORE THE BENEFIT OF ANTHRACYCLINS



FOR  METASTATIC DISEASE
1.ADD ENZALUTAMIDE  IN TRIPLE NEGATIVE WHICH HAS AN ADROGEN RECEPTOR POSITIVE, THERE WIL BE A 9 MONTHS BENEFIT

2.TARGETING GLYCOPROTEIN

3.PI3K
USE MTOR INHIBITOR
PACLITAXEL   +   AKT INHIBITOR

4.SNDX
ALEZOLIZUMAB  (1200 )+  ENTINOSTAT:   19%rr

ALEZOLIZUMAB  +  ABRAXANE

5.PARP INHIBITOR
OLEPARIB 400 MG PO BID
RUCAPARIB  600MG PO BID

GENETIC MARKERS AND RELATED MEDICATIONS FOR TREATMENT

IF A TUMOR EXPRESSES

PICA/PTEN--------------------------------------------EVEROLIMUS
TOP3A--------------------------------------------------DOXORUBICIN
PARP1---------------------------------------------------OLIPARIB CISPLATIN
VEGEF--------------------------------------------------BEVACIZUMAB
TYMP----------------------------------------------------XELODA
ROS1-----------------------------------------------------CRIZOTINUB

PROGRESS IN BREAST CANCER TREATMENT

Progress in Breast Cancer treatment:

1. ER Positive

These tumors of course can be treated with Tamoxifen in premenopausal patient (some have required 2 years from last Menses to consider someone Post Menopausal) and Aomatase Inhibitors (AI) for post Menopausal.

In those with recurrent disease (or progression )
Anastrazole or Fulvestran being strong suggestions.
But the game has been improved as more options have been proposed
1.o.   Palbociclib(125) +   Letrozole(2.5)
check day 14 CBC for frequent episode of Neutropenia and fever
time to progression with this combination 22 Vs 14 months

2.o  for the 50% who will not respond to the first option
consider Everolimus + Entinostat
3.o  Everolimus  (10) +  Exemestane

watch for stomatitis,fatigue,Dyspnea,Hyperglucosuria, LFTs, and pneumonitis

4.o   Palbociclib   +   Fulvestran
5.o   Monarch 1 may have proposed Abemaciclib as an option in these instances
6.o   Abemaciclib can be combine with either Letrozole or Fulvestran
7.o   don't forget that Entinostat can also be proposed in combination with Examestane


These same agents can be used in Neoadjuvant setting, when confronted with Locally advanced disease for 16-18 weeks prior to definitive surgery.

Is the black hole evidence of the existence of parallel universe

We all agree that black hole exist, they suck universal objects such as planets and suns and moon
but for where....matters sucked will go where?
it is true that we started off as a big bang
or was it a big bang, did we come from the other side of a black hole?   in a parallel universe
is the big bang the explosion that follows from the furnaces of a black hole...is the black hole the origin of the dark natters that seem to offset the rules of Physics...indeed it has been calculated that in its tourbillon of a galaxy, matters should be moving faster while at the periphery things should going a lot slower ...but it is not thru as peripheral bodies of a Galaxy are like charged up by "dark" matter as they spin at exhilarating speed ...black (?from black holes)  matters seems to foil the predictions....black matter is Energy...may be by mixing with tangible matters at the periphery of Galaxies...but where things go after an absorption by black holes...do they just vanish or may be transformed in true black matters...or come  out the other side in a parallel universe?...if it is true that nothing is created all transform...where things go after passage through the black holes...?

The promises at CRBCM

Dear Dr. Kankonde,


We will forward the kits for HLA typing of his sibs.
I will inform our Cell and Gene therapy unit.


G.

From Baylor University to CRBCM	2:42 PM (18 hours ago)

"Augmented Hyper-CVAD based on dose-Intensified Vincristine, Dexamethasone, and Asparaginase Therapy"  Katarjian et al...

This is what Baylor University has recommended for our patient with refractory ALL. (peristant MRD)  we thank them...

If all will end

According to most astrophysicists, the world will end in an explosion caused by comet that will be large enough to cause cataclysmic shifts how ever you can imagine them...but with all evidence this all could be avoided at least theoritically...because the velocity and masses of the incoming meteorite could be predicted years ahead, science should be ready to "deflate" the speed of the incoming and arrange for a "softer" landing.    Today we see vehicle sent to mars covered in Balloon to avoid a tough impact on Landing, why can't a comet be assured a soft unnatural  landing...on Balloons or after repeated deflagrations and deflations....we need to start thinking about this now and not accept the fate of the dinosaurs...In principle, all this is possible, if we know how to govern the forces already present in the Cosmos.    We know a ray of some sort can pulverize anything of in its path...ie a ray from a Pulsar, can we have such a ray...can we maximize laser to bombard incoming meteorites...don't just shoot down satellites...but sizable meteorites aimed at earth...that may breach our atmospheric layer of protection...should the human race be doomed because we played the victims by accepting the fate of our planets...the forces that led to our existence have designed us to dominate the Universe and Cosmos...they did not tell us how but it is in our souls, our minds to figure it out...Today we look upon the sky to see the distant sky...but we know we can one day "warp" through the interstellar like going to Walmart...The fact is earth itself is traveling around the Sun at thousands of miles just by using gravity toward the Sun...who say we cannot "sling shoot" into Cosmos inside a "Dirigeable"toward new worlds...It is for us to make this happen...our trip started with the comet that brought us to Earth...Let's not stop here!...

life a continuuum of things...B

The news from space is still coming in
it is new for me but certainly old for those who have been following it closely
it is a time striking  and at the same time soothing
striking that life was started by some kind of an explosion that caused creation of gamma rays
soothing that we are probably the extra-terresterial we have been looking for brought in by a comet...and that our composition is same as our sun, we can now relate...which soothes my heart...
the same information tells me about preliminary notion of quantum physics such as quantum enigma...
Delving into the minuscule after looking at the sun makes perfect sense because we all part of the same continuum...from the particules making the neutron to the macroscopic us and the sun to the making of cosmos ...It is in this context that we can understand the intricacies of genetics...and its causing of diseases such as cancers.   The notion that Helium is created constantly in our Sun through bombardement so to speak by activity of electrons, creates in effect matter elements similar to what we are made of at a rather more complex state but yet the same matter...similitude at molecular level explain our susceptibility...If our DNA has Cytosine in its composition for example, any compound which react easily with Cytosine, will have implication at DNA level...directly...(see how easily products in a cigarette smoke can act directly on DNA...)  this where the crux of the matter is as it goes back to...our simple component...similar to the Sun...
then goes this notion that different atoms have a symetrical atoms distant away and no matter what distance there is similarity in their activities (the doppelganger effect)...this goes deep...that any of us has a doppelganger... spooky in a way....but I believe it....what this tell us...

In cancers, It is remove the break and release!

Many cancers are allowed to occur when Breaks in genetic pathways are removed
and abnormal proteins are being released (or formed) as a result of failures.
Of course one of the way the gene acting as a break failure is through Mutations  (of course heterozygosity, missing or omission, or blockage will be the other ways of failing)...The failure is not alone...subsequent consequences result in the pathways leading to aberrations that ultimately engage the cancerous process.
These consequences end up amplifying a normal or abnormal gene (c-Myc) resulting in amplification of other genes in the pathways...and cancerous disease develop.   It is important to note that while this is happening, mechanisms to protect this dangerous development also are engaged...Mucus is formed to protect the cancer from detection (ie Colon cancer cells) and most importantly genes such as the PD-1/PDL-1 are also formed to hide the process even more deeply ...
say you want to check for Lynch Syndrome, you will find that the APC gene which is Mutated is not stopping the Wnt-signaling pathway which leads to "mutated proteins" or dysfunctional proteins which could block the Beta-Catenin from transcribing more resulting Oncogenes...This is an early event in the cancer development...making the cell loose the sens of containment and shape, a polyp will result...

Few GI update

*capecitabine with Avastin now a standard first line in elderly with Metastatic colorectal cancer
*S1 better then Gemzar in adjuvant setting in Pancreatic cancer
a drug that was for long time not available in the USA...
* and now what was suspected is now confirmed that Cisplatin-FU could be a second alternative to Mitomycin-5-FU as Radiation sensitizer for Anal Cancer...
*IN GE-junction Cancer, EGFR no
and Her-2 yes but with Trastuzumab (not Lapatinib)

life, a continuum of structures

Life secret is hidden in several dimensions
distance among the suns and various planets, continuum of life structures, limitations of our minds, limitations in our lives etc...
I was talking to someone about how far is Orion, he tells me "I don't have to worry about this, I will never see it"...this attitude let the secret get a second wind...particularly at the time where "New Horizon probe is penetrating the intercelestial world beyond Neptune,  even scientists were lost  (lacking an objective for their probe)  until the new glacial object in this space became an objective for 2019.  In the same time, beyond the atome and electron, even smaller particules are being discovered  while we still don't know if our mountains, full of rocks, are "alive".   We can move while trees can't but they live longer than us...Methane is a proof of life on earth, but there is full of Methane on Titan a moon of Saturn, a planet which is still surrounded by moving "stones" which make this planet's belt and we recall our own history that earth too was surrounded by water and heavy stones that shielded the planet from sun rays and resulting cooling led to the disappearance of the dynosaurs...it seems like Saturn is still in that transition after being hit by a moon or a comet...we can still see the belt today...some speculate people from Saturn saw the comet coming and some may have mooved to Titan, therefore the Methane there...plenty of organisms may have survived there, those who can survive the cold...underwater...on Titan...aquatic life you see!   you have to go under the waters to meet them!...the methane is a proof of life...some speculate their membrane is not like our with bilayer lipid but "Methanic"... to sustain the cold...indeed they are so far away from the sun.  they get the sunlight but not the heat!   Beside there is time when they get eclipsed by Jupiter...the bigger planet...likely this is rare since these things spin around the sun at different speed...what an eclipse that must be...
In this world when we live less than a century...things have been happening for billions of years
so has to keep life secret beyond us...and trees which lives longer can,t tell us...can't write these things down to transfer the knowledge...our savants die off in the "flower" of their ages...living the deep mysteries of life untackled!...the mystery lives on...unimpaired!!!

Research has restarted
This time with completion of our random selection of sera
Indeed 64 patients,friends and neighbors have volunteered their blood samples for for random gene mutation testing.  7 mutations were selected based on availability at UTEP  of Antisera.
c-Myc, Survivin, Cyclin B1, HCC-1, NPM1, P53, and p62 were randomly selected

We are Published!

In the Journal of Oncoimmunology
the article was submitted in Sept 2015
and peer reviewed in December 2015 when it was also Accepted
will be published under "original study"

"Serum MDM2 and Anti-c-MYC autoantibodies as Bio-markers in the early detection of Lung Cancer"
with DR Kankonde, and DR Zhang from UTEP
this will launch CRBCM as Center of genetic research!
The study was completed in established cancer patients
we need to run a similar study in smokers!
the challenge is on!


We cannot thank enough those who have made this research possible
1.MD Honors/World ONE London/UK,which provided initial fund
2.Tissue Bank, University of Virginia,Lung Cancer  Biospecimen Network!
3.Review Board at University of Texas at  El Paso
and DR Zhang team and in China DR Bao-Fa YU


Thank you a all lot!

Dark matter

one controversial matter in astro-physics is the existence of dark matter
but when you think about it, it seems to me that the existence of dark matter is evident
as there is a "no" for a "yes".   Evidences accumulate that increasingly well known phenomena may be explained by the existence of dark matter.   For those in the extreme, the moon circling around the earth is linked to the existence of "waves" of dark matter.   Any circling body around the sun may be driven by dark matter to not fall out. That force of attraction toward the earth center (pesanteur) is govern by dark matter.   one other not well publish fact is the center oriented fact when a light goes out in a dark room, luminosity goes out from periphery to the center (and never the other way) as dark matter moves in....The moon influence the oceans through activity of dark matter...For some the strength of dark matter is concentrated and represented by "Black holes" in Cosmos (while the force of "white matters" is represented by motion driven organisms...At the center of this line of two extremes are motion mess living such as trees...some wonder if rocks are also "living" in a philosophical way.

I come to think of it, if the rock was "living", it may make sense that there are so much rocks into the planets...

Chromosome Translocation, an old scientific curiosity

From Myelodysplasia to most cancers including T cell lymphoproliferative disorder, scientific readings continue to report how chromosomal translocations have such a prognosis meaning for our patients.   They go on to tell us how "breakable" these locations on the chromosome are...
"Loss of Heterozygosity (LOH) is identified in 30 to 60% commonly at 9p,10q, 1p, and 17p"...in cutaneous T cell Lymphomas  (Kuzel et al)
what most literatures does not report is just as important, but may be more important, is the specific gene really involved by the translocations.
for 5q deletion syndrome, a Myelodysplasia, the gene appears to have been discovered so that we can develop new Medicine aside from Revlimid, and may be understand a little more what induce the disease and what can be done more specifically...defining what a chromosomal deletion involves in terms of gene missing or criss-crossing appears more urgent now.

"Recently,RPS14 has been identified as a likely candidate gene involved in the 5q-syndrome" (ASCO)

Striking Facts

*Mutation of BRAF has been seen in all cases of Hairy cell Leukemia
Is that mean that Cladribine  and Pendostatin need to be used in BRAF positive Melanoma
or is this a different BRAF

The opposite is it true? should we use dabrafenib in Hairy cell Leukemia

Are they localized Mutations that differentiate the 2 types of BRAF Mutations...

*As it stands,  CLL treatment include
-FCR
-Chlorambucil +/- Rituxan (or Ofatumumab/Obinutuzumab), R-CHOP
-Alentuzumab
-Rituxan Bendamustine
-Idelalisib, the anti PI3K
- CARTs targeting CD19

Today's GIST

1. Standard treatment
is Imatinib for 3 years for patient with high risk of recurrence
those with Exon 11 in the KIT gene will respond the best

2.The 2nd line is Sunitinib
3.Those who resist these meds, well Regorafenib may work
check your FDA recommended list