Monday, June 30, 2014


Dig this by REN et al! and you will understand that the anti-VEGF is still JUST the begining of the membrane story: "The small Ras-related GTP binding and hydrolyzing protein Ran has been implicated in a variety of processes, including cell cycle progression, DNA synthesis, RNA processing, and nuclear-cytosolic trafficking of both RNA and proteins. Like other small GTPases, Ran appears to function as a switch: Ran-GTP and Ran-GDP levels are regulated both by guanine nucleotide exchange factors and GTPase activating proteins, and Ran-GTP and Ran-GDP interact differentially with one or more effectors."


treatment in Gastric Cancer and G-E Junction

Although Ramucirumab a " fully human monoclonal antibody (IgG1) developed for the treatment of solid tumors. It is directed against the vascular endothelial growth factor receptor 2 (VEGFR2). By binding to VEGFR2 it works as a receptor antagonist blocking the binding of vascular endothelial growth factor (VEGF) to VEGFR2. VEGFR2 is known to mediate the majority of the downstream effects of VEGF in angiogenesis.[4]" wikipedia,   

Has been approved by the FDA, oncologist still have a tough time as to when integrate this drug in their cascade of treatment to offer to their patients with these conditions.  And this despite the clear failure of the many standard therapy offered first.   The average one year survival being given by Gastric cancer current treatment is globally poor since most of the patients affected in our experience are relatively young.  And current result of Cisplatin or Oxaliplatin -5-FU based therapy remain repeated endlessly without progess.   In france, there is more use of Taxane based treatment, particularly in metastatic cancers.  The clear role of this drug, Ramucirumab is currently undefined as it may move from 2nd line (as released by the FDA) and as more clinical trials are moving forward, and also and mainly as oncologists are moving away from standard therapy to target therapy.

In this disease, we are still missing the mark.  And results of current treatments impose this glooming conclusion.
The basic understanding is still predominantly that the disease grows from  a chronic irritation by gastric acid onto an unprepared squamous epithelium of the Esophagus.   This basic idea prompted scientist who eventually won the Noble Process proving that the presence of H.Pylori could induce a neoplastic syndrome.  By Chronic Irritation basic genetic understanding would suggest an onslaught on the NF-kB and an intense activity of the epigenetic area where the c-MYC,
RUNX and c-FOS reside.   Constant infection or Acid induced irritation means also that some receptors will be desensitized to the point of shutting down of downstream genes which will end up methylated or suppressed or even mutated while some transcription factors (and subsequent miRNA ) will be over expressed.  We know this disease to be highly metastatic to the lymph nodes, liver and peritoneum.  We know that seeding through the peritoneum with local invasion to the Ovary (Krukenberg) and local invasion to the rest of the GI track (and the dread occlusion of the GI track).  But none is of these data has been completely explored fully.   And the story of agents acting of the epigenetic zone has not been fully elucidated or tackled!

Even the anti VEGEF, anti EGFR, and anti Her-2 can only act whenever their action reach the epigenetic area....our efforts in this disease can only be significant until the level of c-FOS, the CREB, the cytokines, and effect on Mitochondrial processes are clarified and neatly addressed.   How molecular transfer is affected and how we use this information for therapeutic purposes could make the new difference in this disease.  The mere fact that the there is a transformation to Barret disease, gives tremendous opportunity to stop the disease or at least to bend these events preventively (what is the MEK doing?).

For the time being, the success of the EOX and other combinations continue to make us believe there is a truth in these statements, and our focus should still be from the blast to a targeted therapy in these cancers...
The CRBCM is still at work...from Warsaw Indiana.

Saturday, June 28, 2014

Genes proposed for Molecular testing by Jennel Hodge at al!

HNF1A    HRAS    IDH1   IDH2    JAK2       JAK3     KDR
KIT      KRAS    MET     MLH1    MPL    NPM1     NRAS
RB1   SMAD4   SMARCB1   SMO   SRC  STK11    TP53   VHL







Could cytoxan-Oxaliplatin +/- antiandrogen    Vs Cytoxan -Oxaliplatin +/-Nexavar
makes a difference for Hepatoma

yes I know the French  had some success  with  GEMOX in Hepatoma
but is Cytoxan a better drug given the infectious origin of the Hepatoma
could stimulation of the CREB cycle prompts better fight against the viral load

Thursday, June 26, 2014

As target therapy continue to advance, increasingly first line treatment will be a combination of these therapy
and cost will be increasingly the limiting factor:
After Paloma, is it right to propose Letrozole alone (Vs a combination with Palbociclib) particularly in Metastatic disease.  One may want to try Letrole alone and add Palbociclib when there is progression but do remember the study compare the combination to Letrozole alone upfront with a doubling of the progression free survival...Then come other aspects of the problem, What is the role of Fulvestrant or should we keep it after the failure of the combination...and then one will ask should you stop CDK4 inhibition while using Fulvestrant?  At least it is a good thing to have these choices for our patients!
It is important to mention that combination do not always work better:

Clemons:" Result suggest that the addition of vandetanib to fulvestrant did not improve biomarker response, PFS or OS in patients with bone metastases. Baseline bone turnover was prognostic for PFS and OS."  I should stress that Vandetanib is an anti-VEGF (different apple all together!)

When Her-2 is positive
Boix-Perales et al:
"The demonstration of clinical benefit for pertuzumab was based on a single, phase III, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel in previously untreated patients with locally advanced or metastatic HER2-positive breast cancer."
Here 18 months VS 12  PFS
and 80 V 69  OS

Now is it right in Metastatic Melanoma to give an Anti-BRAF knowing well it is a short lived (or add Ipilimimumab after 3 to 4 months? or of course a combination Ipilimumab-Nivolumab...what is the cost?  Is it worthwhile an English may ask?  But here comes the choices again...Target therapy, still creeping up in all of us...But clearly the way to go...

Wednesday, June 25, 2014

Keep it alive! 3 steps ahead...

No need to create a new Hospital
no need to create a new cancer center
but transform a wing of a old hospital in a cancer treatment wing
because it is not the shape and blings that makes a cancer center
but what the mission of the wing remains
and how good they accomplish the mission
the need is there, and progress could be achieved
and with each step we make, particularly with Target therapy,
more can be accomplished....
Our eyes have risen,  the challenge is being met,
and with every day new discovery,  the walk to cancer cure is becoming
increasingly possible...the fight is complex, but the devil is in the details,
because it is not enough to predict the behavior of a cell, because believe me it is going to react to
our attempts, but it is to think before it reacts, and plan ahead of it, 3 steps ahead...
It is easy said then done because of gene heterozygosity, and because of our inefficiency to control intersecting interactions with other genes or surrounding molecules....but let keep saying that within the walls of that new wing will be practiced only medicine of tomorrow!

Tuesday, June 24, 2014

Further speculation on lipid deposition

Before I start, let me be clear that the following is clear speculations
but it is a speculation based on preliminary facts thats seems to
results from our understanding of gene behaviors and major clinical events.
The fact is we build up cholesterol or lipid Atheromas in the blood vessels
and that simple factleads to major devastating events which at time terminates our
life in terms of stroke or cardiac attacks.
It is worth examining the the build up of Atheromas in a more detail fashon if we intend
to make a difference.
Our current understanding is that at one time in our life, during the normal development,
the build up of Atheroma starts.  We are talking about lipid deposition in our arteries.
for Artery to receive and capture  fat molecules, there must be structures and potentially cells that
must be ready to receive them, and receive them tightly in order to hold them for what appears to be years at
a time.  We suspect that the chemical structure of Laminin, fibronectin, or fibrin or one of these structures(other will add Pectin, Perlectan,Entactin)
that we commonly deem "cellular environment" appears to hold on to lipid matters somewhat tighly relatively.
However, the capillary "cellular environment" over the years, is constantly undergoing a shift under hormones,
cytokine and various stresses. This shift in composition, ultimately impacts the very nature
of the underlying molecules, and therefore lipid to parietal molecule interactions, jeopardizing the tight neat
relation at lipid-laminin or lipid-elastin interaction.  It is clear that cytokines may chance the very nature
of "cellular environment" and changing so very drastically as, at cellular level, mutations or gene line shutdown could
follow changes in cytokine or ambiant hormonal milieu.
The very example of Menopause and the rise of cardiovascular events in women is a perfect example of this phenomenon. The disapearance of Estrogen during
menopause affects drastically this interaction marking a rise in coronary events in women (what stabilize this event should be a lesson for all to learn)
And the disapearance dwindeling of Elastin content in the composition of blood vessel with advancing age
appears to be another evidence of these changes that go completely unnoticed but clearly affect our future life!
The structural composition of laminin has long attracted the observation of scientists, indeed this molecule has
many locations where binding to specific structures is made easy, we speak of chemical bonds. And certain Ateromas may feel
confortable sitting here and tightly!  The point of the matter is that at any given location,
the cellular environment makes it possible for Atheroma seeding.  The perfect example is the disease called Xanthelasma or tuberous Xanthomas, this is a mere
deposition of lipids in a part of our body where for all suspicions must haVE A SPECIAL CELLULAR ENVIRONMENT that provide seeding of lipids.  I bet you those eyelids
have special laminin or fibronectin composition.
And it is clearly foolish to believe that fat deposition does not have consequences.  This is the same foolishnes that
made our leaders debate for long time that obesity was not a disease state.  Fat deposition has profound consequences because it
other directly induce reaction or secondarily provoke secondary effects...and my suspicion if a new burse of cytokines that
will induce the "disease state".   Clearly, the resulting Arthropathy is evidence of such reaction.  All chholesterol disturbances are linked to Arthropathies
as a result.
An interesting question being explored currently is the role of pericytes.  There is no no single pericytes,
and locally, at site of cholesterol deposition, the pericyte composition may be not the same as other locations.  And the pericyte type predominant
in an area of Atheroma may not be the same as an area of absent lipid deposition.  Scientist are digging deeper at gene level, this is where the nature of integrins
and G-proteins may also vary.  This point links us to why diabetic patients particularly present various levels of Vasulitic process, some ending in Amputations
and various leg wounds, and some none...clearly Integrins (alpha, Beta family) and G-proteins have something to do that is worth examining...And then there is PDGFR-beta, NG2 and gets more complex )
CRBCM is clearly with you in this path to knowledge...

Monday, June 23, 2014

Down the road of many cancers, our understanding is still increasing....

It is increasingly puzzling that Gene suppression could be one of the most powerful way to induce cancer and most likely to affect cellular migration in a process well identified as Metastasis.  This fact is true Whether you discuss RB1, or PTEN or in some cases BRCA2 or WT1. (or the Cadherins for that matter) In squamous cancer of the head and neck, suppression of the FAT1 has been clearly documented in the neoplastic transformation. The question is what can possibly  cause this decrease of gene expression affecting tumor suppressor.   Mutation is one mechanism we can't rule out or avoid or sometime even address.  The example of Colon cancer expressing KRAS Mutation comes to mind.  Wild type KRAS reassures the observer that the EGFR system is still intact and medication affecting this system could work.  But what is exactly the intact EGFR system.  There is increase evidences these gene mutations could be induced by Methylation.   This facts warrants further exploration as "demethylation" of specific genes could have a therapeutic effect.   This speculation also re-emphasized the fact that combining Anti-EGFR with de-methylating agent could open certain doors therapeutically in some diseases.  Along this line, one may assume that certain gene loss we observe actually remove certain list of genes from the "relative danger" of methylation.  The fact is the level of Methylation in certain cancer (MDS,Leukemic processes) needs further clarification.
Please do not forget that certain Cytokines may in fact promote methylation of genes that were not meant to that fate!

Package insert:"
Vectibix is an epidermal growth factor
receptor (EGFR) antagonist indicated
for the treatment of wild-type
(exon 2) metastatic colorectal cancer
(mCRC) as determined by an FDA-approved test for this use"

Medication Index

Abilify depression
Invokana,Canagliflozin is an SGLT2 inhibitor, DM
Patanol,watery eyes, allergic conjunctivitis
Topiramate: seizures, Migraine in adult patient
Farxiga 5mg  DM
Chlorhexidine, Gingivitis
Wechol, bile acid sequestrant
Lovaza, omega-3
acarbose, DM

Activities at CRBCM

*About to start Oncology work in warsaw Indiana for the first 2 weeks of July...
*Working with local University on CPRIT project
*Finalizing our lung cancer project funded by MDHonors
*waiting for Graduate student to finally analyze our survey on Cielo-Vista mall
* Waiting to hear about our study submitted at NIH_SBIR
*Continuing work with Talecris
*continuing taking new cases mostly from local referrals
*Finishing up on transition from local assumption of service from retiring physicians
*Covering local calls for Hospital 
*Looking into new research projects
Thank you and congratulation to our new staff!
CRBCM looking forward to more expansion...and opportunity.

Saturday, June 21, 2014

Rare case of Femoro-Acetabular Impingement

A 41 year old Hispanic woman was referred to us for evaluation 10 days after an MVA.  She was hit on the driver side  (WHICH THE LEFT IN THE USA) but has developed Right femur pains. Apparently, under the shock to the left, her thigh hit to the RIGHT the structure separating the 2 front passengers. She also complained of Headaches without GI complaints.   her Brain MRI did not reveal a new lesion or a subdural Hematoma.   A plain Xray of the femur to make sure there was no fracture However revealed a surprising read:

" The right femoral head-neck junction appears somewhat flattened with a pistol-grip contour which may predispose the patient to a  cam-type femoroacetabular impingement. "

Given the Medico legal issue involved, a bilateral Hip MRI has been requested and an input from Ortho has been entered.

Question, if the Xray was obtained earlier, could Decadron help, will await Ortho imput, pt has been on NSAID....

Thursday, June 19, 2014

Quality Measures for Diabetic patient

In Diabetic patients
2.Neurologic eval
3.Foot care
4.Weight Control (BMI)
5.Retinopathy Monitor
6.Renal preservation/Use of ACE inhibitor and related drugs/albuminuria Vs Proteinuria/Renal consultation
7.BP control if any
8.Leg edema / Venous stasis/leg ulcers
9.Coexistance of Arthropathy
10.Coexistance of CAD
11.Coexistance of Auto-immune disease
12.Coexistance of Thyroid dysfunction/other endocrine disorder (endocrinologist consult)
13.known genetic pattern of abnormality

Opinion on Melanoma treatment

*Having listen to the treatment on Melanoma
it appears to me the V600 or BRAF positive patient
have a short lived progression free because of a rapid development of secondary amplifications of gene that will force a resistance ...
and it may be that there is a secondary activation of lymphocyte during this treatment.   This secondary amplification of activation, prep the disease to use of anti-CTL4 or anti-PD1 or PDL1 (or a combination there of since this combination has greater efficacy)

Meaning in BRAF positive, the anti-BRAF could be used as an induction to have higher response rate but instead of waiting for a more likely recurrence rate, give within 2-3 months a combination of Ipilimumab and Nivolumab to obtain for sure long term progression free survival.  The only objection to this strategy right now is money....what insurance will cover this expensive strategy...But clearly it makes the logical sense!

what worry a local oncologist is of course the episode of Hypotension that may result for the combination of Ipilimumab to Nivolumab or anti-PD-1

My fear is because of expense, what makes sense will not be completed for a decade!
trial should start now please!

fort those with KIT, Sutent could serve as induction therapy prior to combination Ipilimumab-Nivolumab.

Now I wonder if this combination would be appropriate for my patient with NF1 + GIST which failed Gleevec....wonder if she can sign a consent for this!

will check this out
BRAF resistance 
due to reactivation of MAPK pathways through MEK amplification (is there a secondary overexpression of mesodermal expression?) should we measuring COT overexpression, or amplification of c-MET, IGF1R, or PDGFR, can use of ASPIRIN help, can Nexavar prolong the effect of Dabrafenib...? oh hell all thins thinking just drive you crazy....but that one should do in research!

few dosages to check!

Dabrafenib 150 mg PO BID
Nivolumab 1 mg/kg
Ipilimumab 3 mg/Kg
Trametinib 2mg PO QD
Vemurafenib 960mg in 4 tab Q12 h

===============================why the Kerato-Acantoma in anti-BRAF inhibitor, is the receptor in the same membrane fold?

Wednesday, June 18, 2014

post of the day

PALOMA-1 Trial Finds Palbociclib/Letrozole Doubles Progression-Free Survival in Metastatic Breast CancerMay 1, 2014, Volume 5, Issue 7

go to article! 


in another question: what in hell is going on with achondroplasia with breast breast cancer?  2 cases in a year?  I need more gene testing...please.

And I knew a Cytokine bank is what we need in El Paso

Intralesional Cytokine Therapy in Cutaneous Melanoma: A Call for Clinical Trials

By E. George Elias, MD, PhD
November 1, 2013, Volume 4, Issue 17

In an exploratory study in patients with dermal and subdermal metastatic melanoma, we explored the use of intra lesional therapy with low-dose GM-CSF (500 µg once weekly). In case of failure to obtain a complete response in 4 to 6 weeks, IL-2 was substituted (18 million IU/wk).4 The results revealed that such intralesional therapy was well tolerated without major side effects.
Complete responses were obtained in patients with small lesions ranging in size from a few mm up to 1 cm regardless of whether these were primary, satellite, or in-transit metastases. However, none of the large sclerotic lesions responded to intralesional therapy with either cytokine. The complete responses were noted clinically and confirmed pathologically by rebiopsy of some of the injected sites at 6 to 8 weeks after cessation of the therapy, and showed absence of tumor cells and no mononuclear cell infiltrates."

How can we possibly go wrong????

From TBI
to Diabetes mellitus
to simply getting old
the key role  of Cytokine cannot be stressed enough
every time you experience muscle pains
or wake up with age related flaccid muscles, it is the the Cytokines...
every time with autoimmune disease you cannot put up weight, it is the Cytokine...
obesity would not be a disease without the Cytokines?
so when are we going to wake-up?  and truly fight cancer with the Cytokines?


Obesity Increases Breast Cancer Mortality in Premenopausal Women With Estrogen Receptor–Positive DiseaseJune 10, 2014, Volume 5, Issue 9


what else do you need to really join us and build this up!

Tuesday, June 17, 2014

One Case to struggle with...

A 60 year old smoker presents with Dysphagia, mid epigastric pain and weight loss
cutting through the chase, a work-up suggested an obstructing Adenocarcinoma of the G-E junction.
there was no local nodes or mets in the liver....The patient has a PEG for nutrition


There is a palpable 2 cm Left retro-mandibular hard node, an additional node is in the vicinity with SUV 3
and the lung show small nodules (largest 0.5cm) in the Right lung

A PET scan showed the retromandibular adenopathy with an SUV of 15
but none of the lung lesion had an uptake to make my life difficult
there is suggestion of an uptake in the parotid although the SUV here is very low also
an asymetry of the base of the tongue did not pick-up PET dye

A biopsy of the retro-mandibular nodule is pending
A radiation input is also pending!

Now you tell me what chemotherapy to use
EOX, ECF  or Taxotere-Carbo

and please speak loudly back!

some genes to watch through careful trials!

(CLCN7(defectictive resorption of immature bones), interacts with MITF which in turn interacts with LEF1, the same LEF1 that needs to stay in balance with the Catenins, and therefore the WNT.

TCIRGI,  with the evolving role of Immune intervention against cancer, this gene belong to the family of genes to watch,
could have molecular component containing a V-ATPase important in  T cell activation, how this is involved with initiation of NFAT pathways should be further investigated.  Cellular acidification and initiation of Vacuolization is involved. Then it has family member containing TIRC7, an immunomodulator by excellence how this is involved with TBI (traumatic brain injury) through IL 10 could be investigated...

to the rescue comes wikipidea : "
"TIRC7 is a membrane protein induced after immune activation[2] on the cell surface of certain peripheral human T and B cells as well as monocytes and IL-10 expressing regulatory T cells. During immune activation, TIRC7 is co-localized with the T cell receptor and CTLA4 within the immune synapse of human T cells[5][6] At the protein and mRNA level, its expression is induced in lymphocytes in synovial tissues obtained from patients with rheumatoid arthritis[7][8] or during rejection of solid organ transplants[9][10][11] and bone marrow transplantation[12] as well as in brain tissues obtained from patients with multiple sclerosis."

If you don't see an important biomarker-look again...This one has both sensitivity and therapeutic intervention opportunity.  Wonder if this is the stuff involoved with HUMIRA, (Adalimumab) a TNF inhibiting anti-inflammatory drug...Also Osteopetrose is involved here!  Humm......Enbrel and Remicade may not be far...How about chloroquine?

 SOSTalso linked to Osteopetrose
but what this has to do if anything with sclerosis in general, Bleomycin induced sclerosis of the lung, or defect of the Skull seen in Myeloma, the WNT is not very far once again!

TGFB1 and
 C/EBPα and

Sunday, June 15, 2014

Openings on cancer cure I

The challenge of cancer cure remains closely linked to the mechanism underlying the cause of the neoplastic process that caused any particular cancer.  And the practice of Oncology  of today is clearly with limited vision not adapted to the challenge posed by most cancers.  This challenge is compounded by the inadequacy of insurance reimbursement which does not cover most gene testing, and the lack of knowledge of genes and their pathways.  This lack of knowledge of genes is actually in part due to political pressures that lead to mal-distribution of research funds to mostly ineffective institutions, institutions that compete for funds but with no clear vision...leading to disparate research!

Cancer cure has shown us that unless you know what mechanism is underlying one particular cancer, the treatment will be short lived or clearly ineffective.  Indeed the treatment may be harmful since it may induce new gene alterations that may worsen the clinical setting of the patient.  We also know that even when a cause is known, and the target defined, attacking cancer cell always induce a survival reflex, the cancer cell quickly develop or amplify new pathways to remain alive.  That secondary survival born new mechanism have yet to be significantly approached by modern Oncology.  Indeed, we are still focused on first
treatments.   Is it true that MTOR inhibitors should follow anti-VEGF?  These principle have been mentioned in the literature but not written in stone....In colon cancer, Emphasis have been made on secondary anti-VGEF since these have been known to amplify after use of primary anti-VGEF...

Saturday, June 14, 2014

Some Cellular activity in neoplasms

"The researchers also found that the human genome is peppered with more than 1,200 large regions that are consistently devoid of DNA methylation throughout development. It turns out that many of the genes considered master regulators of development are located in these regions, which the researchers call DNA methylation valleys (DMVs). Further, the team found that the DMVs are abnormally methylated in colon cancer cells. While it has long been known that aberrant DNA methylation plays an important role in various cancers, these results suggest that changes to the cell's DNA methylation machinery itself may be a major step in the evolution of tumors."
From "Ludwig Institute for Cancer Research"

Although this statement states the importance of Methylation of genes in Colon Cancer, none of the histone deacetylators or epigenetic acting medication such as medications such as etoposide are not actively used in Colon cancer. It is also fair to assume that current medications used must have an impact of the cells in this disease despite the fact that we don't deliberately follow relevant biomarker to quantify these effects.  Indeed doing so could lead us to sharpen our use of medicines...
Despite their complexity, epigenetic phenomena are critical in immune defense, cell orientation determination, and here in neoplastic transformation.   Differentiation is somewhat relatively shut down and contribute to cellular return to multiplication involved in cancer.  Some suspect this is due to methylation of differention and gene stopping division (CDKs and ROS modulators to say the least).  New cell orientation is further re-enforced by cellular committment to new mission by 14-3-3 and the consensus NOTCH gene.  Other epigenic facts will precipitate this through Cytokine like factor, the rise in importance of Cyclin B1 should be noted here for lung cancer.

Another way of orienting cellular processes
is the creation or production of transcription factors...indeed the production of certain TF may lead to a shutdown of other line of protein affecting the cell  as well as production of some cell effectors re-orienting the cell....

Change in micro-environment may create new set of circumstances that  favor one cellular orientation or production vs another and could be used as a means of pushing the cell toward a direction Vs another....(Clathrin or no Clathrin) " it performs critical roles in shaping rounded vesicles in the cytoplasm for intracellular trafficking. Clathrin-coated vesicles (CCV) selectively sort cargo at the cell membrane, trans-Golgi network, and endosomal compartments for multiple membrane traffic pathways." wikipedia

formation of these essential structure would be impossible without Clathrin....

Thursday, June 12, 2014

For Neuropathy

4.Baclofen, Ketamin gel!
from the literature!

Wednesday, June 11, 2014

Gene interference!

There is now strong evidence that YWHAG gene abnormality are strong initiator of cancer (biomarker)
that PAK-1 disruption could dissociate Rho from G proteins and slow down Metastasis!

That patient with mood disorder could be candidate to Breast cancer through interaction DISC1-DYNLL1-BRAC1...
That involvement of RUNX2 represent an escalation since this gene can induce Malformation
and again 14-3-3 could mark a dangerous escalation given the auto-exacerbation potential at this gene
and that this amplification should be a biomarker for use of BRAF inhibitor also (to be tested)

The list may go on but these are worth mentioning!

Sunday, June 8, 2014

pondering on this case

A 57 year old male presented in December 2013 to a general clinic complaining of abdominal and diarrhea that was intermittently bloody, the patient maintains he did not have insurance and did not undergo an abdominal cat scan.   By march 2014, he has lost weight and went to Juarez Mexico to be evaluated, There, an abdominal cat scan was also not completed.   Finally 2 weeks ago, he was admitted with leg swelling and shortness of breath, the rectal bleed continued....This time not only he was found with bilateral Deep vein thrombosis (DVT),  a Pulmonary Embolus, A CT revealed a a 7 cm liver Metastatic lesion, the mass in the distal transvers Colon had a "controlled" perforation and an abces like formation was observed through the wall of the Colon at the Ulcerated bleeding mass.  The bleeding was important, in 2 weeks of the evaluation, he received 8 units of PRBC, and anticoagulation could not be performed.  An IVC filter was placed.
A surgical consult was reportedly obtained and somehow decision not to proceed with palliative resection was not immediately made, and the patient was referred to CRBCM for an oncologic opinion and need assessment for Neo-adjuvant chemotherapy.

While an eager Oncologist would certainly Obtain an MRI of the brain, preparing for use of Avastin, place a port catheter for a Folfox infusion, One needs to set back and look at certain aspects of this case.
Treating with chemotherapy
1.May open wide the perforation in light of a shrinking tumor, leading to a frank peritonitis
2.The mass is bleeding, an indication for palliative surgery
3.The "Abces" could also spark a significant abdominal infection/peritonitis when marrow suppression is induced by chemotherapy.
4.The anticoagulation that is contre-indicated by the bleeding mass, could be further exacerbated by chemotherapy which on its own has been linked to DVT.  The thing is removal of this colon lesion would allow easy anticoagulation and diminishing post-phlebitic consequences!
5.We will not dwell on consequential Microangiopathy which will come into play when liver lesion resection will be due!
6.To make this matter interesting genetically, the CEA was below 4 and drastically  so!  0.7 as a matter of fact.
7. And the KRAS not requested by early observers!

This case has touched so many aspect of problems encountered in the management of Colon Cancer that capture our attention....

By the way, we have recommended the palliative removal  of the culprit Colon lesion, the patient does not have insurance and the surgeons are not very eager to proceed...such is life in the real world and there is nothing you and I can do other than advocating for our patients!   Quite frankly, chemotherapy drug makers have been responding to us so far in helping patients but obtaining a service from specialty physicians has been the hardest to achieve!  No one wants to help for free especially institutions which receives millions in public funds!

Our (CRBCM and Greater East Cancer center) work continues though...will see it through...because our fight is just!

Monday, June 2, 2014

Alpha Anti-trypsin, interesting questions

A tour de force of nature going awry, or a simple application of cellular principles that raises questions?
Is it a liver disease or a lung disease or both...What are the biomarkers of disease progression, are the disease anti-secretion proteins or molecules of relevancy to  say breast cancer ?what is the role of Cytokines (IL-1&6)? are they evaluation more reliable than PFTs., importance of the CYP1, CYP2

Careful what you read or should you have a second look into cytokines? YKL-40

There are certain genes that cause concern and are deemed prognosis. That is their presence clearly induces a bad prognosis because they cause either cancer irreversibility (ie. excessive presence of Cyclin B1), cancer resistance (MDR gene) or resistance to therapy (YKL-40 induce resistance to gamma irradiation).However
Certain Cytokines have duplicite or ambiguous roles that is, depending on the scenario or the writer, have a defined role to suit the circumstances in which they are studied.
The YKL-40, like the Metalloproteases and certain prominent cytokines and , have been used to conveniently by many authors to be reported as biomarkers, or prognostic factors.  A recent article suggest they are prognosis in Bladder Cancer.   But it seems that they can be elevated  not only in certain cancers but in inflammatory diseases.  In fact a certain cellular state of Hydroxylation may increase this Biomarker, but also stimulation of a common pathway with no prognosis impact (AKT).  In this case, reversing the gene may not have a meaningful therapeutic role.  
Given its role in Vascular remodeling, this gene  (YKL-40) seems important in the Vasculitis and coronary events!? (bladder inflammation)  or is-it?

Is is a modulator of chemical reactions?  let's pause and reflect!