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

KRAS

(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
Victoza,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.

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....

Quality Measures for Diabetic patient

In Diabetic patients
1.HbA1c
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?

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?

and

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!

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

WELL NOW WHY AM I INTRIGUED?

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?

 SOST,  also 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!

CA2,  
CSTK,  
TGFB1 and
SLC26A2)
 C/EBPα and
FOXA1
 BMPs
EDMs

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...

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....

For Neuropathy

1.Duloxetine
2.Nortryptilin
3.Neurontin
4.Baclofen, Ketamin gel!
from the literature!

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!

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!

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!

don't finger CRBCM, we are trying!

I was literally stopped to be questioned about statements on my blog!
it is a blog
the statements although based on facts
are inted to shock or tease the readers mind
and query !
they are not scientifically already established
their main objective is to capture the readers' mind
and fashon it a way to tease and prompt an internal reaction
you are not to cure nanism or dwarfism with Dasatinib even in DDR2 positive affected individual
but don't close your mind to the idea
DDR2 checks is not part of standard check covered by insurance, but let's keep on fighting to make it so!
Indeed many known abnormal genes or known Mutations are not currently tested despite their proven importance in clinic.  ROS-1 for example is well known for its importance in lung cancers, but not customarily requested.  The NCCN is slow to come up with these recommendations in order to stay conservative...In a world which cries for more therapeutic answers.  A world in which we know that all cancers are not equal!
There are of course link that we know or suspect to be important but can't prove a thing...not because data are missing but because money is not in research.  We suspect for example that some G-proteins are important in the severity of certain Diabetic vasculitis and Neuropathy, but we wait for funds to test the hypothesis in clinical settings...
Where are our congressman?
Where are funding institutions?
Where are the politicians?

progress at CRBCM!

The CRBCM is continuing to advance...
we are completing our mission in Louisville Kentucky, with expansion into Indiana, from Madison to Seymour IN. (and of course scottsburg).  mission going well.
Our son graduated from Sallisbury, MD
and of course the biggest new is the first payment to CRBCM for its EHR or Electronic record by Medicare...the expansion in on!
we are returning to El Paso to prepare or finalize our CPRIT participation.

what that's means in termes of gene abnormality for humira

The drug increases chances of getting lymphoma
viral infection (hepatitis)
TB
CNS complications
allergies
immune reactions
worsening of these immune diseases
is it a LYN, receptor, or other problem, a quick review is in order
(to be continued)

The case of Urothelial Cancer

Greater east cancer center was referred a case of a 42 year old man with history of previous admission for Peptic Ulcer disease who had reported to the hospital for indigestion, fatigue, 20 lbs weight loss and abdominal epigastric pains.
The patient underwent an EGD which suggested a non raised ulcer. Biopsy at the Stomach revealed an undifferentiated cancer.   A subsequent Colonoscopy revealed the same lesion in the Sigmoid and rectal areas with signet ring characteristics but clearly the same lesion.  Given the suspicion of a Urothelial cancer with plasmacytoid differentiation based on immunochemistry and flow, presence of CD138, it was decided to perform a Cystoscopy which indeed revealed a positive biopsy by the same malignancy.  There was evidence of a significant penetration of the Detrusor.  There was extensive retroperitoneal node invasion with clear evidence of obstructive Uropathy.  Aside for a port placement, bilateral nephrostomies were placed.
It was decided this was a stage IV disease.
Of interest, the patient had history of recurrent folliculitis or abcesses on the skin or infected cysts removed.
(the question is the gene (s) involved may be linked to this abnormality)

The case  brings to genetic studies many questions that remain unanswered in the current state of treatment
1.Should we just proceed with Gemzar-Cisplatin (the Bladder regimen theory in Urothelial cancer treatment)
2 does Carboplatin has a role in the Metastatic setting (the creatinine was 6.0 on admission)
issue of dialysis was raised. But does reduced Cisplatin on a 5 day regimen better in this setting or is-it better to give Oxaliplatin.
3.The literature suggest response to gastric regimen such as EOX (Epirubicin, Oxaliplatin, and Xeloda-propsed by NIH)
frankly the idea of protracted exposure to Xeloda was attractive.
4. The peculiar nature of this disease raise the issue of whether BEP would be a better regimen and not MVAC, and a secondary role of Ifosfamide, Etoposide?
5.Is this cancer related to testicular cancer given the eventual secretion of Beta-HCG (germ cell cancers)
6.The production of CA 19-9, and the response to GI chemotherapy regimens raised many related questions
on whether genetic basis in this disease process mimic the pancreatic cancer process. role of protein 14-3-3,
and related cascade that uses the chaperon HSP-90.  Role of anti-MEK?
and that Cytoplasmic concentration of CDC25 could be a relevant bio-marker,
and activities of the SCHOC-2 and RAF-1 are relevant in this disease,
or Cyclin B1 for that matter (AS DEMONSTRATED IN OUR LUNG CANCER STUDY)!  COULD PREMETREX BE TRIED IN THIS DISEASE?  (REMEMBER THE MVAC -HAS METHOTREXATE!)

9.Cyclin B could serve an initial event.  Can Cyclin B level be followed by immuno?
10. Could cyclin B  and the HSP chaperon role play into the global elevation play into GI susceptibility to metastasize or to initiate in multiple level of GI tract
11 what is the role of STUB1 and Parkins?

IS CYCLIN B ------RAF1  THE MAIN CANCER ROUTE?

COULD THE SUSCEPTIBILITY TO TREATMENT THE SAME AS DISUSSED IN PANCREATIC CANCERS?  SEE NOTES FROM LAS VEGAS?   WHAT THE LINK WITH EMBRYONAL CANCERS OR SARCOMA---IS RAF 1/CDC25 STILL THE CULPRIT?

ROLE OF VELCADE IF UBIQUTYLATION IS INTO PLAY AS EXPECTED! It is plasmacytoid isn't it!

THE CRBCM WILL NOT HAVE THE MONEY TO ADVANCE THESE QUESTION GIVEN THE CURRENT NATURE OF LOCAL AFFAIRS!  YOU WHO CAN PLEASE CHALLENGE US! 

Case in point : Urothelial Cancer with plasmacytoid histology

>the tumor is bad news
1.It is Multicentric, Multifocal, and therefore metastatic at time of diagnosis
2.Its signet rings characteristic has deep meaning and may have had something to do with its tolerance by the body and metastatic or invasiveness. (and dyscohesive or non cohesive nature of cells at morphology of cell suggestive of Micro-environment corruption)
3.plasma cell characteristic "CD138"
4.secretion of Validated Biomarkers CA 19-9 and Beta-HCG
5.response to Platinun based regimen (Bladder---Gem-Cisp Vs GI origin---EOX)
6. Affect the young maximizing life loss
7.poor prognosis outlook
8.Wang et al. "The immunohistochemical profiles of the tumour cells were focal positive for E-cd, PCK, EMA, CAM5.2, CK7, CD138, AE1/AE3, and CK20, but negative for LCA, Vim, and S-100."
9.Nabbout et al:" After receiving 6 cycles of neoadjuvant chemotherapy (epirubicin, oxaliplatin, capecitabine), the lesions responded well and the patient underwent a complete gastrectomy with jejunoesophageal anastomosis."

The tumor current evaluation rarely include gene evaluation and therefore is inadequate.

by producing CA19-9 proximity to Pancreatic cancer is unquestionable

Genes with dangerous behaviors

1.Do remember that in the selection of genes to silence, find one that causes a Malformation  when mutated or deficient
i.e the BRAF gene can cause some of the cases of Leopard Syndrome
i.e always remember the story of Thalidomide and the reason it was banned, interacting with related genes paid off!

2.dangerous genes are those that can auto-activate or auto-inhibate, you know if some thing goes wrong, wild neoplasm can ensue!

3.now we learn that some gene like Casein can phosphorylate several other gene
watch out for the lighting of other genes!

4.Gene regulators of main pathways (ie...PTEN)

5.Genes at check points

6.Genes that are at terminal pathways, their lack terminates a function, but now derailing compensating mechanisms or bypass mechanisms can be neoplastic

7.genes that stop or derail differentiation

8.genes that are important in vital mitotic steps

9. the telomerases

10.genes that makes the cell move!

11. genes dominating the microenvironment and genes involved in protein transport within the cell (i.e the molecular chaperones) clathrin, Auxillin, HSP(s)

12. and in a class of its own, the Ubiquitins!   lung cancer seems to occur because of the direct effect on the Ubiquitins!   MDM2!  particularly the Adenocarcinomas!

13 belong to "a family of conserved regulatory molecules" ie 14-3-3....full of "conserved regions".  Once a cell decided to conserve it...it becomes a critical gene!

14. Gene that affect several members of the same genes (CABIN-1 affects  MEF(s))

have you heard from the state

State Health Commissioner

To

Today at 12:39 PM

Nationwide Increase in Measles Cases

 

According to the Centers for Disease Control and Prevention (CDC), the United States is having more reported cases of measles this year than usual. Many healthcare providers in the United States have never seen a patient with measles and may not recognize the signs and symptoms. Healthcare providers need to be more alert than ever to the possibility of measles.

Health care providers should consider measles in patients who

·         present with febrile rash illness and clinically compatible measles symptoms [cough, coryza (or runny nose) or conjunctivitis (pink eye)],

·         recently traveled internationally or were exposed to someone who recently travelled

·         have not been vaccinated against measles

Healthcare providers should also consider measles when evaluating patients for other febrile rash illnesses, including Dengue and Kawasaki’s Disease. 

basic research 2

Secondary malignancy

When a receptor is permanently blocked Or destroyed
When a gene is over stimulated
When bypass activation exist and may involve an important pathways
Addition of immunomodulator to an alkylating agent. Seems of concern

Pomalidomide
Dinaciclib
ARRY 520

For CLL
FCR remains standar of care
And bendamustne rituxan an alternative
And ibrutinib for bulky diseases

 Secondary tumor produced by a known gene alteration
Should be treated by blocking a gene within the same pathway either upstream or down stream.  Instead of using standard of care for that tumor.

In pancreatic cancers most of the intervention
Have not confronted  the NF kB

Review the NOTCH pathway

Spark level associate Ted with good prognosis in pancreatic cancer
Spar level

still a question today 2 years into this?

Basic research idea

Pattern of transcription genes cancer cell Vs normal cell using microarray technology as a way to identify critical specific acquired change by cancer cell

Alteration of pattern of receptors on cancer cell
Are some receptors more specific to cancer cell

Persistence of life in red cell in the absence of nuclear material, what gives?

Why mismatch repair failure fails to trigger P53 activation in cancer cell
Is there deregulation of P53
Is there a transcription factor inhibiting P53

Inducing quiescence in cancer cells
 triggering senility in cancer cell
inducing differentiation which reverse blastic aptitudes in cancer cell?

questions in liver cirrhosis

A 65 year old African American man came for consultation
he is known to have  Hepatitis C since 1982 when he first  noted jaundice
He met with my predecessor and 2 GI DRs who have advised him current therapy with Interferon and ribaverin, his alpha fetoprotein is 4.  But his Viral load 4 million. His Viral genotype undetermined
and whether such determination matters is a question, since H is "old school" and decline therapy be cause he feels fine! And grant it the Viral load has no defined prognosis value per certain authors.He will only be convinced to treatment if there is evidence of early cirrhosis.  That's where Liver imaging CT sonogram or MRI comes  in.
But is there a way of determining that Cirrhosis is on its way
can genes for fibrosis be detected in time to force the hands of such patients?
literature search brings the importance  of Fibronectin,fibrinogen,laminin Tenascin, TGF-Beta1, Metalloproteiases, TIMP1, Plasminogen-PAI-1, and even CTFRs

Interest in the Quiagen article cited below, is this the way of the future!?
Can we compare this gene abnormality-expression to MRIs of the liver for direction.
what are the biomarkers to use?



From Quiagen (for discussion only)
"Pro-Fibrotic: Acta2 (a-SMA), Agt, Ccl11 (Eotaxin), Ccl12, Ccl3 (MIP-1a), Ctgf, Grem1, Il13, Il13ra2, Snai1
(Snail).

Anti-Fibrotic: Bmp7, Hgf, Ifng, Il10, Il13ra2.
Extracellular Matrix & Cell Adhesion:
ECM Components: COL1A2, COL3A1.
Remodeling Enzymes: Lox, Mmp1a (Collagenase 1), Mmp13, Mmp14, Mmp2 (Gelatinase A), Mmp3, Mmp8, Mmp9
(Gelatinase B), Plat (tPA), Plau (uPA), Plg, Serpina1a (a1-antitrypsin), Serpine1 (PAI-1), Serpinh1, Timp1, Timp2,
Timp3, Timp4.
Cellular Adhesion: Itga1, Itga2, Itga3, Itgav, Itgb1, Itgb3, Itgb5, Itgb6, Itgb8

Inflammatory Cytokines & Chemokines:Ccl11 (Eotaxin), Ccl12, Ccl3 (MIP-1a), Ccr2, Cxcr4, Ifng, Il10, Il13,
Il13ra2, Il1a, Il1b, Tnf.
Growth Factors: Agt, Ctgf, Edn1, Egf, Hgf, Pdgfa, Pdgfb, Vegfa.

Signal Transduction:
TGFß Superfamily: Bmp7, Cav1, Dcn, Eng (EVI-1), Grem1, Inhbe, Ltbp1, Smad2, Smad3, Smad4, Smad6, Smad7,
Tgfb1, Tgfb2, Tgfb3, Tgfbr1 (ALK5), Tgfbr2, Tgif1, Thbs1, Thbs2.
Transcription Factors: Cebpb, Jun, Myc, Nfkb1, Sp1, Stat1, Stat6.

Epithelial-to-Mesenchymal Transition: Akt1, Bmp7, Col1a2, Col3a1, Itgav, Itgb1, Mmp2 (Gelatinase A),
Mmp3, Mmp9, Serpine1 (PAI-1), Smad2, Snai1 (Snail), Tgfb1, Tgfb2, Tgfb3, Timp1.

Others: Bcl2, Fasl (TNFSF6)."

*New study attracting CRBCM attention:
Glembatumumab Vedotin in Metastatic Triple Negative Breast Cancer
(but comparison with Xeloda raises question, is this best in this disease?)

*Ramucirumab, and anti VEGF receptor 2, a noel antiangiogenic with role in Gastric cancer!
8mg/kg IV Q2weeks,  with or without taxanes....

CPRIT meeting again

The Cancer Prevention and Research Institute of Texas  (CPRIT) oversight committee is meeting again
 May 21 2014?
Observers are asking....


1.what will be new
2.who is going to get grant beside universities
3.what the public will hear new
4.is there new strategy that may come out other than giving grants to various university applicants
5.can we read an orientation or trend in these grants....is the new oversight steering research toward a specific goal
6.is it reaching other cities of Texas
7.is El Paso involved
8. 4-5 years into this, are we better off!
9. is the organization listening to us, consumers and research community (other than the huge university who created this!)
10.how should it demonstrate that influence peddling has subsided

Cancer cure is at stake, too much is at stake to keep away!

Mighty puzzling lung cancer!

In the United states along, over 225,000 people will be diagnosed with lung cancers
and 160,000 people diagnosed with this disease, will die from it.  And it is known that 84 percent of people diagnosed of this disease, will die from it.  Indeed, patients diagnosed with stage IA, the earliest stage, have a 5 year survival of only 50% despite our current advances in therapy. Making lung cancer one of the deadliest cancer of all cancers.

Comparative data on survival Breast Vs lung cancer
----------------------------------------------------

 BREAST CANCER 5 YEAR SURVIVAL BY STAGE                            LUNG CANCER 5 YEAR SURVIVAL PUBLISHED

FROM NCI SEER'S DATA BASE                                                             IN 3RD EDITION OF ASCO-SEP PG 157

STAGE 0              100%                                                                                         STAGE IA      50%

STAGE I         100%                                                                STAGE IB  47%
STGAE II         93%                                                                STAGE IIA  36%
STAGE III        72%                                                                 STAGE IIB  26%
STAGE IV        22%                                                                 STAGE IIIA  19%
                                                                                                  STAGE IIIB  7%
                                                                                                   STAGE IV   2%

==========================================================

These figures point to not only which cancer is deadliest, but also how critical it is to detect the disease early in an effort to improve survival.  As most patients with lung cancers present with advanced disease and chances of survival  is relative to stage of disease, It has been a constant effort of researchers to diagnosed lung cancer early.
To date, lung cancer prevention has been attempted by chest X-ray, sputum cytology, and finally the Lung Cancer Action project (ELCAP) and the National Lung Screening Trial (NLST) have tested successfully low dose Cat Scan (CT) in patients 55 to 74, with 30 year pack or more history, to not only detect lung cancer earlier but also to show survival benefit.

Today, attempts to screen and detect lung cancer has expanded to cellular detection of minimal presence of lung cancer cells in the blood.   These efforts are preliminary, and it is unclear at what stage this phenomena could be detected.

The CRBCM with support from the University of Texas in El Paso (UTEP) Biologic  cancer research Department has launched an investigation of to detect early variation in genes that could signal lung cancer development in high risk patients as defined above.

These efforts have been supported by MDHONORS, an London institution, which provided limited funding (the CRBCM has committed its own funding so far) but also by the University of Virginia Tissue Bank  (LCBRN) which provided initial tissue (tissue and sera) specimen.   

The CRBCM insists on thanking these non biased, non political organizations who truly help the progress of science without greed or political gain.  Thank you!