Thursday, October 17, 2013

STATE OF UNSTABLE HOMEOSTASIS: are your cytokines in a balanced state?

You can be thin, you can be average, you BETTER NOT BE OBESE LIKE SOME OF US!  What is important a question is "are your cytokine in balanced state".  Yesterday I met a man who run 7 miles a day, looks fit like a young marine (he is 68 years old) he showed me a certificate he earned from climbing the Kilimajaro a month ago, (If you go to Kilimanjaro get me an extra certificate!) but he was unhappy!  He indeed has noted that he can't built his muscle up, has been losing weight without dieting, and now has tingling sensations in the fingers bilaterally,  A buff of nutrition, he has been consuming a bunch of Vitamin B (B1,B6, B12 and the so called "complex") to no avail.  His neurologist at a loss. Neck radiology clean and Carpal tunnel syndrome Ruled out, I told him its all about the Cytokines!
How do I know about my cytokine state? he asked...
"If you arrived at that question, you understand the crux of the problem" NOBODY MEASURE THE CYTOKINES IN A CLINICAL USEFUL WAY EVEN THOUGH THEY ARE THE EFFECTOR OF ALL PHYSIOLOGIC STATES!
IF YOU LOOK HEALTHY BUT YOUR CYTOKINES IS HIGH, YOU WILL END UP DYING PREMATURELY BECAUSE OF YOUR HOMEOSTASIS IS BASED ON FOUL STATE OF CYTOKINES!  LET BE ANADID ABOUT THIS!  SOON OR LATER, THE UNRAVELING WILL HAPPEN.  WHY, BECAUSE CYTOKINES STIMULATES MANY OTHER UNINTENDED  RECEPTORS, GENES, PATHWAYS AND MORE CYTOKINES!


Activities at CRBCM
One may have noted the slowing down of blog activiTy
we are are planning to sit one more time for Boards
and it is a time occupying deal
CRBCM is meeting contractual obligation in El Paso, same as it did in Houston,
and Austin and Indiana. Now for the forseeable  6-8 weeks we are anchordown in El Paso.
Business getting stronger.
We are excited about the first about, the 1st Biomed research conference, join us!


A Message from Medical Center of the Americas:
Dear Attendees:

We look forward to seeing you at the region’s upcoming BIOMED Symposium on October 26, 2013.
Pre-Symposium Networking Mixer
We would like to invite you to our Pre-Symposium Networking Mixer on October 25, 2013 from 5:30pm-7:30pm at the El Paso Club located at 201 East Main Drive, Suite 1204 in Downtown El Paso. Network with over 200 of the region’s researchers, clinicians and nurses, future leaders and other healthcare professionals.
Symposium Venue & Hotel Accommodations
Venue
The 1st Annual BIOMED Symposium will be held at Camino Real Hotel located at 101 South El Paso Street in Downtown El Paso.
Accommodations
We have reserved a block of rooms at the Camino Real Hotel located at 101 South El Paso Street and DoubleTree Hotel located at 600 North El Paso Street in Downtown El Paso at a discounted rate. Please make hotel reservations as soon as possible, as we anticipate the hotels to fill up fast. When you call to make a reservation, please indicate to the hotel clerk that you are making a reservation for the “BIOMED Symposium” so that you receive the discounted rate.
Symposium Directions & Parking
Directions
To Camino Real Hotel from Del Sol Medical Center (Driving)
  • Head southeast on Gateway Blvd E
  • Slight left toward Gateway Blvd W
  • Slight left onto Gateway Blvd W
  • Slight left onto the I-10 W ramp
  • Merge onto I-10
  • Take exist 22B for US-54 toward Patriot Frwy/Alamogordo/Juarez/Ft Bliss
  • Keep left at the fork, follow sings for Juarez and merge into I-110 S
  • Turn right onto the ramp to US-62 W/E Paisano Dr
  • Keep left at the fork, follow signs for US 62 W and merge onto US-62 W/E Paisano Dr
  • Turn right onto S El Paso St
  • The hotel will be on the left
To Camino Real Hotel from Texas Tech University Health Sciences Center (Driving)
  • Head west on Alberta Ave toward Fulton Pl
  • Take the 1st left onto Boll Pl
  • Turn right onto Alameda Ave
  • Turn left onto S Copia St
  • Take the ramp onto E Paisano Dr
  • Turn right onto S El Paso St
  • The hotel will be on the left
 To Camino Real Hotel from University of El Paso (Driving)
  • Head southeast on Hawthorne St
  • Turn left onto W Yandell Dr
  • Continue onto N Santa Fe St
  • Turn left onto W San Antonio Ave
  • Turn left onto S El Paso St
  • The hotel will be on the left
 To Camino Real Hotel from New Mexico State University (Driving)
  • Head west on N Horseshoe St toward S Espina St
  • Take the 1st right onto NM-138 E/S Espina St
  • Take the 1st right onto E University Ave
  • Merge onto I-25 S via the ramp to El Paso
  • Merge onto I-10 E
  • Take exit 19 toward Downtown/Convention Center/Tourist Information Museums
  • Turn right onto N Santa Fe St
  • Turn left onto W San Antonio Ave
  • Turn left onto S El Paso St
  • The hotel will be on the left
 To Camino Real Hotel from New Mexico Institute of Mining and Technology (Driving)
  • Head north on Leroy Pl toward College Ave
  • Take the 2nd right onto Bullock Blvd
  • Turn left onto California St
  • Merge onto I-25 S via the ramp to Las Cruces
  • Merge onto I-10 E
  • Take exit 19 toward Downtown/Convention Center/Tourist Information Museums
  • Turn right onto N Santa Fe St
  • Turn left onto W San Antonio Ave
  • Turn left onto S El Paso St
  • The hotel will be on the left
To Camino Real Hotel from Instituto Technologico y de Estudios Superiores de Monterrey, Campus Chihuahua (Driving)
  • Head north on Av Heroico C. Militar toward M. Aguilar Saenz
  • Take the 3rd left onto Calle Mercurio
  • Turn right onto Ave. Tecnologico
  • Continue onto Chihuahua-Miguel/Ahumada/Mexico 45
  • Continue onto Av 16 de Septiembre
  • Turn right toward Juarez
  • Turn left at Gral Rivas Guillen
  • Turn right onto Juarez
  • Continue onto S El Paso St
  • The hotel will be on the left
To Camino Real Hotel from DoubleTree Hotel (Walking)
  • Head southwest on E Franklin Ave toward N Santa Fe St
  • Turn left onto N Santa Fe St
  • Turn left onto Sheldon Ct
  • Turn right onto S El Paso St
  • The hotel will be on the right
Parking
Parking is available at the Camino Real Hotel parking lot and is first-come first-served basis. The rate for the day is $4. Additional parking is available at nearby garages for a charge and free parking is available on the street.
Please contact me at nsehgal@bmiamericas.org if you have any additional questions. We look forward to seeing you at the Symposium.

Sincerely,

Neyha Sehgal | Assistant Director of Market Analysis
BioMedical Institute of the Americas
201 East Main Street, Suite 401
(P): (915) 773-5804
(F): (915) 231-1949      
BIOMED - MCA Biomedical Research Symposium
Hosted by Medical Center of the Americas
Saturday, October 26, 2013 from 7:30 AM to 6:00 PM (PDT)
Camino Real Hotel - Downtown El Paso, 101 South El Paso Street, El Paso, TX 79901  |  Directions


This invitation was sent to drkcancerclinic@gmail.com by Medical Center of the Americas the organizer. To stop receiving invitations from this organizer, you can unsubscribe. Eventbrite
Eventbrite | 651 Brannan St. Suite 110 | San Francisco, CA 94107

Tuesday, October 15, 2013

11 GENES AND RELATED COMPOUND TO INVESTIGATE IN SARCOMA

1. TGF BETA 1
2.SOST GENE
3.LIPOFUSCIN
4.RANKL AND RANK
5.CHLORIDE CHANNEL GENE
6 CTSK GENE
7.PORCN GENE
8. LEMD3
9. GNAS GENE
10. FGFR 3
11, INSULIN

THESE ARE MALFORMATION INDUCING GENES.
THE MOST DANGEROUS ARE THE ONE CONNECTED TO ANGIOGENIC GENES, THEY RAISE THE STAKE! LET'S FIND THEM!

PREDICTING OSTEONECROSIS OF THE JAW? THE CYTOKINE WORLD

CAN LEVEL OF PYRIDINOLINE,  (ALKALINE PHOSPHATSE) AND PRIOR EXPOSURE TO MEASLE (OR PARAMYXOVIRUS) PREDICT FOR OSTEONECROSIS OF THE JAW IN PATIENT RECEIVING BIOPHOSPHONATE?

ARE PATIENT WITH PAGET DISEASE PRONE TO OSTEONECROSIS OF THE JAW?

PAGET DISEASE IS THE BEST EXAMPLE OF CYTOKINE DRIVEN DISEASE IN THE ENTIRE WORLD OF DISEASES! (IL-1,IL-6,TNF, RANKL, OSTEOPROTEGERIN, TGF BETA-1 ETC.)

Saturday, October 12, 2013

so you know or don't know!


Important Safety Information Prescribing Information
www.fosrenol.com www.fosrenolontrack.com
FOSRENOL® (lanthanum carbonate) — Noncalcium Binder Therapy
FOSRENOL (lanthanum carbonate) is indicated to reduce serum phosphate in patients with end stage renal disease.

IMPORTANT SAFETY INFORMATION
FOSRENOL is contraindicated in patients with bowel obstruction, ileus, and fecal impaction.

This is a promotional message from DoctorDirectory.com on behalf of Shire. This material is intended specifically and exclusively for US Healthcare Professionals.
Dear Mutombo Kankonde, MD:
Dietary Challenges Associated with the Management of ESRD
Struggling with the Renal Diet
Ronald is a patient undergoing hemodialysis who has been receiving therapy three times weekly for the last 1.5 years. He is obese with a BMI of 33.0 and readily admits to having difficulty following dietary recommendations.

Despite dietary intervention in the past, Ronald’s protein intake is high and his serum phosphorus is trending up.

...Is Ronald Ready for Noncalcium Binder Therapy?
Hypothetical Patient Profile for patient Ronald Age 55, Male, African American, Height: 6 feet 1 in., Weight: 250 lb (BMI, 33.0), ESRD, 1.5 years on thrice-weekly hemodialysis, Hypertension for 10 years, Patient admits to having difficulty following dietary recommendations | Key lab trends: PTH: 225 pg/mL, Controlled; Ca: 10.0 mg/dL, Borderline high; P: 7.5 mg/dL, High; Albumin: 4.6 g/dL, Normal; nPCR: 1.4 g/kg/d, High; Kt/V: 1.4, Adequate for hemodialysis prescription; Abbreviations: Kt/V clearance expressed as a fraction of urea or body water volume; nPCR, normalized protein catabolic rate; PTH, parathyroid hormone.
Start Noncalcium Binder Therapy with FOSRENOL (lanthanum carbonate)
Efficacy in placebo-controlled trial7

aRandomized, double-blind, placebo-controlled, parallel-group trial evaluating the control of serum phosphorus with FOSRENOL (lanthanum carbonate) or placebo. Hemodialysis patients (N=126) with serum phosphorus >5.9 mg/dL after the predosing washout phase entered a 6-week, open-label FOSRENOL dose titration phase (750-mg initial daily dose divided with meals; titration up to 3000 mg in order to achieve phosphorus control [≤5.9 mg/dL]). Patients who entered the randomization phase were randomized to continue FOSRENOL (n=49) or received placebo (n=44) for 4 weeks. Mean serum phosphorus levels at the end of dose titration were 5.49 ± 1.48 mg/dL in patients subsequently randomized to continue FOSRENOL and 5.62 ± 1.61 mg/dL in patients subsequently randomized to placebo.
Safety Information
Most common adverse events during randomized treatment were nausea (6.0% vs 4.5% [ FOSRENOL vs placebo]), vomiting (6.0% vs 2.3%), diarrhea (4.0% vs 6.8%), and dialysis graft occlusion (6.0% vs 2.3%)

Sustained reduction of serum phosphorus in patients who remained on therapy8–10
FOSRENOL® Mean Serum Phosphorus in Patients Who remained on FOSRENOL after the initial 6 month study chart
Abbreviation: ITT, Intent to Treat
aOptional 2-year extension phase of an initial 6-month, randomized, open-label trial comparing FOSRENOL (lanthanum carbonate) to calcium carbonate with a 6-month, open-label extension phase. Data shown are from patients who received FOSRENOL throughout the 3-year study. Dotted line represents the target for controlled serum phosphorus, defined as ≤ 5.6 mg/dL.
Phosphorus reductions maintained for up to 3 years (n=46) 8,9

Safety Information
Adverse events in long-term extension studies 9
In the initial 6-month extension, 23% of patients discontinued because of adverse events; the most common adverse events included nausea (15%) vomiting (14%), diarrhea (12%), and hypotension (11%)
In the optional 2-year extension, 2.4% of adverse events led to withdrawal; the most common adverse events included diarrhea (4%), abdominal pain (3%), and nausea (3%)

the content of this article has been removed.  it was not meant for public consumption!















*

The center role of cyclins/ NEED FOR A CYTOKINE UNIVERSTY

It is increasingly recognized that Cyclins are the ultimate effectors of health.  Yes the fascination with the DNA, its replication in cell division, its activities with RNA transcription which translate in protein formation, its very nature of keeping the the code of cellular destiny, all that is nice and dandy.   But beyond the genes, what will determine the state of your health, what makes live long, healthy or sick, what makes it happen, ARE THE STATE OF YOUR CYCLINS!
1.It is the cyclins that make you grow (growth factors)
2.It is the cyclins that control passage of stage to stage during  cell division  (the name CYCLIN-dependent Kinase-Cdk comes to mind..
3.It is the cyclins that makes obesity a disease
4.It is the that kick the kinase gene into motion
5.It is the cyclin that inhibit and promote...makes feminine or masculine...
6.It is the cyclins that kill post synaptic cell in Traumatic Brain Injury or strokes
7.It is the cyclins that call specific inflammatory cells to the theater of infection
8. It is the cyclins that determine the virulence or resistance (persitence of a cancer) of a cancer
9. It is through cyclin control that the NF-kB operates to insure survival and adaptation
10. It is through cyclins that some mutations occur, some genes are amplified or repressed and therefore entire pathways are affected,  and more importantly it is through the cyclins that some Receptors are desensitized!
It is through cyclins that Stem cells are stem cells!
It is through cyclins that old people look frail, their muscle hypotrophic!
when a cancer is uncontrollable such as melanoma and kidney cancer, give a cytokine ! (Interleukin-2 or Interferon!)
FOR MOST DEMENTIA TO DEVELOP! LOOK INTO THE CYTOKINS!

So with all this, it is surprising that we don't hear more about the Cyclins!
some are inhibitory, some are promoters, although they can belong to the same family
you die old or from infection because of the cytokines!
so it is a surprise that these no CYTOKINE UNIVERSITY!

HEAD IN THE SAND AGAIN, OR LOSS OF WHAT IS ESSENTIAL!

Thursday, October 10, 2013

IT IS ALL ABOUT THE CYTOKINES!

The discovery of DNA and nuclear material has led to the emphasis on the alteration of Nuclear functions to fight cancer, indeed most of the original chemotherapy drugs had mechanisms of action centered on breaking or somehow impairing DNA.  This focus to a certain extent affected our judgement in the evaluation of certain drugs.  We are now finding out that the strength of certain drug  (and weakness /susceptibility to resistance) is not really due to their main effect on DNA (ie. epigenetic disturbances induced by  Etoposide).  The discovery that BCL-2 has a mechanism of resistance to certain drugs is point in case that nuclear material induced disturbances have significant limitations that occur away from the nucleus (at the Mitochondria).  Anti-proliferative chemotherapies have now shown their limits and scientists have kept this in our panoply of options against cancer.

Scientists have long been fascinated by the laws of nature, these driving forces that drive in certain ways or directions the chains of chemical reactions within the cells.  From Glycogenolysis to the Krebs' cycle, to the cellular pathways, role of enzymes these catalysts of chemical reaction and gene regulators, our focus has been progressively shifting.   The maximal effect of standard chemotherapy having been realized, the shift now has gone to driver Mutations, blocking pathways and modulating reactions etc.   But beyond the mutation, gene alterations and so forth, one thing that make a cancer spread like a wild fire is its stimulation by a growth factor, or its self dependence in achieving survival most of the time at very different levels of energy expenditure!  This role squarely falls into the area of epigenetics which is the critical area of Cytokine production determination.  Now, once produced, Cytokines, to be effective, must connect to their receptors!  This is where the wheels rub the asphalt to speed up the chemical reactions!

One of the mechanisms of increased cytokine production, aside from their gene amplification, is failure at the receptor.  Indeed, when a receptor fails, the normal reaction (law of nature) is to concur the resistance by sending more of the same cytokine.  While this increase could be partially succesful in restoring homeostasis depending on the level of abnormality at the receptor, the relative increase has other side effects due to the non specificity of receptors.  Co-receptors or other receptors susceptible to the same cytokine find themselves super excited and are driving downstream reactions at higher rates.  A SIGNIFICANT PHENOMENON NEEDS TO OCCUR AT THIS POINT, THAT IS THE DESENSITIZATION OF SECONDARY RECEPTORS, A TRAUMATIC PHENOMENON WITH POTENTIALLY NEOPLASTIC CONSEQUENCES   (TO BE CONTINUED)

Monday, October 7, 2013

WE BELIEVE IN THE CURE FOR BREAST CANCER

In this month of re-commitment to fighting Breast cancer, it is imperative to stop a while in a moment of reflection for those who have lost the fight, remind ourselves of who they were, what lives they touched as they made us who we are today in many ways.   I remember  my mother who was afflicted by this disease, a kind loving soul, who despite our number (family of 15) had managed to make all of us feel special.  I grew up truly believing that of all her kids, I was the one.  But talking to my other siblings, each one of us felt that special feeling! In 1974, 3 years before she was diagnosed and treated in Belgium, she added to my name a secret portion, "Muendela yenda" (the one who will walk alone) and here I am today, far from the country of origin, in  El Paso, Texas, the sole American Citizen of my family!  Preaching to a silent choir on this blog.  Breast cancer victims are our mothers, sisters, daughters and friends who have affected our lives in many ways. Survivors continue their paths and work touching our lives everyday, reminding us that our fight is needed and is just because there is a price to fight for.  Reminding us that until the cure happens, there is no stone that should remain unturned, no places we should not go, no politician we should not talk to, no genes,proteins, and other molecules that could make a difference we should not explore, poke and tease.  We could wander to other matters of our lives, but this month of October, we should renew our commitment to the fight for the cure of breast cancer.

Efforts made so far have made a meaningful difference, our eyes have opened to new dimensions of cancer research, and the belief in the cure has hardened because through advances in targeting therapy and genetic works, THE CURE IS MORE POSSIBLE, REACHABLE AND REAL!
All we need is cast off the doubt, stop infighting, keep the eyes open, and bring the cure to the shores of our daily reality! We have the means, we have the science, we are full of justified hope, let's keep on marching until the victory rings, making the CURE REAL, PALPABLE  AND ALIVE!

Sunday, October 6, 2013

Another misunderstanding? the TGF story

One of the misunderstanding of common practitioner is related to the lack of appreciation of the extent of the impact of TGF or the extent of its actions!  The Tumor Growth factor effects are not limited to growth of cancer cells.  Their mission is not what their name means, remember the cells' aim is not to "grow" it is to survive.  Globally survival means expansion of life but it also means shutting down by inhibition any or most doors to Apoptosis.   In cancer Medicine, Growth factors are probably one of the biggest challenge to therapy because they are the impetus or one of the many driver for cancer resistance!  TGFs block for the cancer as many roads to programmed cell death as possible,  They also function as desensitizers by not only altering Receptors working against their mission, but epigenetically suppress all mechanisms working against them.  And they do this do this effectively by using the c-JUN and the NF-kB. and through their interactions with the Wnt, the Notch and the FAK.
The power and versatility of TGFs action lay in the fact in there no one TGF, but a family of TGFs with numbers attached to them (TGF1,2,3 etc).  And each member having a different effect,  some being completely opposed to each other but circumstances (including location) in the life of the cell will determine which family member will be at work at a given time.

ie. 

Identification of Novel TGF-β/Smad Gene Targets in Dermal Fibroblasts using a Combined cDNA Microarray/Promoter Transactivation Approach*

Franck Verrecchia‡et al!"Members of the TGF-β1superfamily (activin, bone morphogenic proteins, TGF-βs, and decapentaplegic) are multifunctional cytokines that control various aspects of cell growth and differentiation and play an essential role in embryonic development, tissue repair, or immune homeostasis (1, 2). In addition, TGF-β is the prototypic fibrogenic cytokine, enhancing extracellular matrix (ECM) gene expression and down-regulating that of matrix-degrading enzymes. Increased expression of TGF-β is often associated with fibrotic states and abnormal accumulation of ECM proteins in affected tissues (3-6). The TGF-βs signal via serine/threonine kinase transmembrane receptors, which phosphorylate cytoplasmic mediators of the Smad family (7-9). The ligand-specific Smad1, Smad2, Smad3, and Smad5 interact directly with, and are phosphorylated by, activated TGF-β receptors type I. Smad1 and Smad5 are specific for bone morphogenic proteins, whereas Smad2 and Smad3 can be activated by both TGF-β and activin receptors. Receptor-activated Smads are kept in the cytoplasm in the basal state bound to the protein SARA (Smad anchor forreceptor activation) (10). Upon phosphorylation at their SSXS carboxyl-terminal motif, they are released from SARA and form heteromeric complexes with Smad4, a common mediator for all Smad pathways. The resulting Smad heterocomplexes are then translocated into the nucleus where they activate target genes, binding DNA either directly or in association with other transcription factors. Members of the third group of Smads, the inhibitory Smads, Smad6 and Smad7, prevent phosphorylation and/or nuclear translocation of receptor-associated Smads (7-9)."
=============================================
IE.WATCH "ACTIVIN" BECAUSE

"
The ACVRL1 gene provides instructions for making a protein called activin receptor-like kinase 1. This protein is found on the surface of cells, especially in the lining of developing arteries.
The ACVRL1 protein is a receptor. It acts as a "lock" waiting for a specific protein, called its ligand, to serve as the "key." In the case of the ACVRL1 protein, the ligand is called transforming growth factor beta. The interaction between these proteins plays a role in the development of blood vessels. In particular, this protein interaction is involved in the specialization of new blood vessels into arteries or veins."

 ACVR2A has been shown to interact with INHBA,[4][5] SYNJ2BP[6][7] and ACVR1B.[8][9]

=================================================THROUGH IN SYNJ2BP, 


SYNJ2BP has been shown to interact with LRP2,[3] ACVR2B,[1] ACVR2A[1][4] and LRP1.[3]


=========================================================THROUGH  LRP1

 LRP1 has been shown to interact with Apolipoprotein E,[11][12] Lipoprotein lipase,[13][14][15] Urokinase receptor,[16] MAPK8IP2,[17] Tissue plasminogen activator,[18][19] Thrombospondin 1,[20][21][22] SYNJ2BP,[17] DLG4,[17] NOS1AP,[17] calreticulin,[23] APBB1,[24] ITGB1BP1,[17] MAPK8IP1,[17] GIPC1[17] and SHC1.[25][26]


 SHC-transforming protein 1 is a protein that in humans is encoded by the SHC1 gene.[1] SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells.
==============================================================

THAT'S HOW YOU FIND OUT HOW TGF WORKS TO BLOCK APOPTOSIS!
ACTIVIN IS A MALFORMATION INDUCING GENE
IT IS BOUND TO INHIBIN A BAD PROGNOSIS BIOMARKER IN GERM CELL CANCER
IT HAS A LINK TO ANGIOGENESIS (DOES AVASTIN WORKS HERE?)
WANT TO GO AFTER SHC1, BE MY GUEST!
IF WE ARE TREATING CANCER PATIENTS LIKE WE DO TODAY WITHOUT LOOKING AT THE CANCER CYTOKINES, WE ARE MISSING THE BIG PICTURE!

WE THANK THE NIH, MDHONORS, AND WIKIPEDIA FOR THEIR CONTRIBUTION TO SCIENCE AND PROGRESS  TOWARD THE CURE  (WE HOLD OFF ON OTHER FUNDING SOURCES )

Saturday, October 5, 2013

DUPLICITE ROLE OF BMPs (BONE MORPHOGENIC PROTEINS)

While one will see their role in bone formation (BMP3) as evidently suggested by their name, in cancer medicine, the BMPs are more important in their potential to direct metastatic disease to the  bones, to affect response to Androgen in metastatic Prostate cancers (BMP2)
---------------------------------------------------------------------------

Alteration of gene expression in response to bone morphogenetic protein-2 in androgen-dependent human prostate cancer LNCaP cells.

Source

Department of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.

Abstract

Bone morphogenetic protein (BMP)-2, a multifunctional member of the transforming growth factor (TGF)-beta superfamily with powerful osteoinductive effects, has various biological activities in a variety of cells. We observed that BMP-2 inhibits cell proliferation in the androgen-dependent human prostate cancer cell line, LNCaP. To investigate the mechanism of inhibition of androgen-dependent growth by BMP-2, we compared the gene expression in LNCaP cells treated with dihydrotestosterone (DHT) to that of LNCaP cells treated with DHT and BMP-2, using DNA microarray analysis......"
===================================================

BUT ALSO TO AFFECT THE METABOLISM OF IRON

ie.." BMP6 Plays a role in joint integrity in adults. Controls iron homeostasis via regulation of hepcidin."WIKIPEDIA.

THIS IS AN EXAMPLE OF CYTOKINES THAT ARE MADE IN FAMILY WITH EACH OF THE MEMBERS AFFECTING VARIOUS TARGET CELLS, TO ACHIEVE A PANOPLY OF EFFECTS.
Hepcidin is one of the major modulator (regulatory hormone)of Iron  metabolism.  It decreases significantly in Hemochromatosis while increase in Iron deficiency as if increasing liver ability to store Iron!

The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation

Gaël Nicolas,1et al.

----------------------------------------------------------------------------

removal of cellular Iron is "toxic" to certain bacterial and lack of Iron leads to Increase of transferrins (Iron carriers) increasing their chance to interact with class I MHC decreasing innate immunologic defense A BIG WAY FOR CANCER CELLS TO ESCAPE IMMUNOLOGIC SURVEILLANCE.   SURPRISE SURPRISE IRON DEFICIENCY IS NOT GOOD FOR YOU IF YOU HAVE CANCER!

speculations in errors of metabolism!

*How a single nucleotide polymorphism affect
-gene regulator
-messenger RNA
-proteins
-metabolomic effects

Post-transcriptional modification affect the destiny of the resulting proteins
variations in splicing  to protein isoform
prediction of protein plasticity variation based on electronic raprochement and disposition throughout the molecule

patient with nanism
and their susceptibility or not to vascular disease
or metabolic disease,
variation of metabolic flow in nanism

genetic variations that may induce early cancers (through genomic microarrays)

while looking at Butein, select observational SNPs, and P-450,CYP, electrolytes (Mg,Zn,Fe) to see in whom positive effect is observed

what variation in flow is a consequence of the mutation
is there a different metabolite produced (Galactitol-cataract,   G-1-phosphatase-liver and Ovarian failure)
what enzyme is exacerbated as a result of the mutation
does this mutation affect an autophosphorylating gene

Are some forms of dementia linked to galactose-1-phosphate levels? can we slow down the disease through inhibition of G1P.

Is GLI-1 a flippase
and GLI-2 a floppase? located at 2 different pole of the cell


Friday, October 4, 2013

NOT ONE BUT 4 CRBCM ABSTRACTS SELECTED, WE ARE INDEED IN THE KNOW! WORK AHEAD AWAIT!

BIOMED Symposium - Abstracts Accepted
Inbox
x

Neyha Sehgal <NSehgal@bmiamericas.org>
4:48 PM (7 minutes ago)

to me
Dear Dr. Kankonde:

Congratulations! On Behalf of the Selection Committee, I am pleased to inform you that your three abstracts have been selected for presentation at the 1st Annual BIOMED Symposium on October 26, 2013 at the Camino Real in Downtown El Paso. Your posters will be displayed in the Mezzanine (Level 2) and published in the 1st BIOMED Poster Sessions Abstract Book. Poster awards will be announced during the Collaboration Grant Reception and Networking session from 3:30 p.m. to 4:30 p.m.

Registration Information
Pre-registration is required for all poster presenters. Please register online for the event at www.mcabiomed.com. Registration is $25 before October 18, and includes breakfast and lunch. After October 18, registration is $45 online and $65 at the door. Funding opportunities will be available only to presenters who are registered.

Guidelines for Poster Presentations
To assist you in preparing for your presentation, additional information is attached. Should you have any questions or need additional assistance, please contact me at (915) 773-5804 or by email at nsehgal@bmiamericas.org.

Again, let me congratulate you on being selected to present at the Symposium. We look forward to seeing you.

Enclosure:
1.      Guidelines for Poster Presentations

Sincerely,

Neyha Sehgal | Assistant Director of Market Analysis
BioMedical Institute of the Americas
201 East Main Street, Suite 401
El Paso, Texas 79901

Medical Center of the Americas Foundation
The Medical Center of the Americas (MCA) Foundation is a 501(c)3 organization that advances the development of the MCA campus and the region’s biomedical innovation pipeline. The vision is to position the Paso del Norte region as the leader of health services delivery, medical education and research concentrating on issues unique to Hispanic, border and military populations. Go to MCAmericas.org.

BioMedical Institute of the Americas
The BioMedical Institute of the Americas (BMIA) is a 501(c)3 created by the MCA Foundation to accelerate growth of biomedical innovations taking place in the Paso del Norte. The BMIA does this through translational research programs, incubation and economic cluster development. Go to MCAmericas.org/bmia.
---------------------------------------------
THE 4TH IS THE LUNG CANCER PROJECT ACCEPTED BY MDHONORS AND BEING IN FULL SWING OF PROGRESS WITH UTEP!  TISSUES WERE PROVIDED BY THE UNIVERSITY OF VIRGINIA TISSUE BANK!

WHAT GOT MY ATTENTION

*THE COMBINATION OF ERIBULIN WITH XEALODA IN TRIPLE NEGATIVE BREAST CANCER.
*WHAT REMAINS A QUESTION IS THE ROLE OF INTERFERON AS AN ADJUVANT  (OR MAINTENANCE )THERAPY IN TRIPLE NEGATIVE BREAST CANCER
*I COULD SEE HOW THE ANDROGEN RECEPTOR WOULD BE OF IMPORTANCE IN LUMINAL A BREAST CANCER GIVEN ITS RICH HORMONE RECEPTOR PRESENCE (WHEN LOW Ki-67 IS PRESENT)

REPORTS FROM VARIOUS SOURCES

*Breast cancer remains the most frequent cancer in women
the 5 year survival has improved however from 75% to the 90%  over the last 30 Years
mostly for early disease because of early detection and better adjuvant therapies!

Metastatic breast cancers remains however incurable (Jennifer Klem et al)

4 types:
Luminal A mostly ER and PR positive (Hormone rich) with low Ki-67
Luminal B (Her-2 negative by ER/PR positive with high Ki-67
Luminal B (Her-2 positive and ER/PR positive with random Ki-67
Basal like which is triple negative
HER-2 positive

Hormone positive treated with Endocrine therapy
Hormone negative treated with Chemotherapy

Combination therapy in patient losing performance status, and Visceral involvement and heavy tumor burden.
For Her-2 positive - Taxol-Herceptin would be an option (Her positive means 3+ on IHC or Fish >2.2 amplification(ASCO),  T-DM1 and perjeta could add to the Herceptin option   while,
for ER/PR positive-addition of everolimus could add to hormone therapy"

"Everolimus Gains FDA Approval for Metastatic Breast Cancer"

Afinitor may be given with exemestane for hormone receptor-positive, HER2 negative disease
August 1, 2012
Written By Nicole Katze, MA, Writer and Editorial Coordinator
Reviewed By Robert A. Somer, MD"

Research Underway at CRBCM! thanks to MDHONORS'FUNDING

INTERNAL COMMUNICATION
Mutombo Kankonde <drkcancerclinic@gmail.com>
Oct 1 (3 days ago)

to Jianying, choi
Good Afternoon,
the five first tissues have been shipped and will arrive at your laboratory tomorrow morning.
Please find below the tracking number and shipment details.
With best regards,
Peggy Kankonde
Office Manager & Research Coordinator
--
We have moved to a new location on Sept.6th, 2013:

Dr. Mutombo KANKONDE M.D., M.Ph.
Greater East Cancer Center & CRBCM
Coalition for the Reversal of Breast Cancer Mortality in African American Women

Thursday, October 3, 2013

Interesting aspects of Herpetic Infections

No infection is as intriguing as the Herpetic infection.  Its interest lays in several facts
1. The mere fact that a Third of the US population may be involved makes this disease one of the most prevalent ones,  but it is also feared.  Whether the fear is justified or not remains a question.
2. Certainly it has something to do with horrific stories of potential recurrence of horrific burning neuropathic pains that we have heard about. Science does not know for sure whether only specific viral serotypes lead to this or whether certain hosts genes isoforms or inflammatory reactions  may be contributing to this presentation.
3. The outbreak is accompanied with guilt and sense of guiltiness that is mostly unjustified...many questions arise after the realization that those painful skin or otherwise lesions could be herpetic...that a partner you have gave this to you and that you may give this to a new partner?  Those questions are valid but with the prominence of the prevalence of this disease in the US, who and when one got exposed to Herpes is one of the great mysteries in herpetic disease.  Herpes 1 has been linked to Over crowding, and Herpes 2 is the one with a sexual connotation.  But one should remember that the Herpetic Virus will invade teguments (particularly abrasions) when contact happens, sexual or not!  And very often this happens in our tender ages of infancy.  Remember the infection can be symptomatic, but most of the time completely without any clinical manifestations. And enters quietly a dormancy.
4. The dormancy itself is quite a puzzling event!  All we know is that the capsule to this double stranded DNA viral particule is from the host!  This may help it to be "tolerated " by the host.  We can speculate that class I MHC will not be bothered. Only the class II may note the invader most likely and provide the Antibody that we can measure!
5. The exacerbation of the herpetic infection is also puzzling in many ways
-It happens when we are under stress (menstruation and exposure to UV light), pregnancy state and post chemotherapy, the so called state of "when the immune system" is down!
-To the writer this is a state of activity of the c-JUN and Fos, the NF-kB and full epigenetic phenomena as if cyclines and TNF, TGFs are in full swing!  Epigenetic events seem to free or unleash genes (regulators or not) that will reactivate the Virus.
-How and where these events occur (Golgi, Nucleus, or cytosolic) remains to be clarified.

 (Let raise the eyelid of this dormant disease and look at it through its eyes/pupils without awakening it!)

6. The bad exacerbation could be virally induced or it could be in fact a reaction of the Host  (Neutrophilic Grazymes) or Cyclin effects.  ie. In post Brain trauma injury (TBI) we know that post synaptic nerve death is due to  Cytokins that kill post synaptic nerve, is it the same in this herpetic disease?And if it is, what would be the therapeutic implications?!

Wednesday, October 2, 2013

Reports from various sources

*In Metastatic Renal cell cancer :  Sutent Response rate was 38%
with median response duration 53 weeks
most of the responses were observed in 12 weeks (European Journal)

*In Metastatic HER-2 positive Breast cancers, Adding chemotherapy to Herceptin increases the response Rate from 15-26% to 60-70%, weekly Taxol +/- Carboplatin is one of the option aside from Vinorelbie and Taxotere with improvement of both the one year and overall survival!

*Lapatinib, a dual EGFR-1 and Her-2 Tyrosine Kinase inhibitor, when combined to Capecitabine only increase  (more likely double) for sure progression free survival.  The overall survival could not be proven because of cross-over! (ASCO)

Tuesday, October 1, 2013

And the questions dance continua

1.Can infusion of purified IL-17 boost the anti-cancer property of IL-2?
2.Can infusion of IL4 (IL-10, TGF-beta) helps in treatment of autoimmune diseases
3.can elimination of Treg cells boost the effect of IL-2
4.Can TCR editing or "molecular mimicry" be used in cancer therapeutics.
5 What the associated biomarkers that could be in conjunction with HLA typing to predict response to therapy or cancer responsiveness to  autoimmune therapeutic intervention?
6.Can inhibitors of the  NOTCH pathways or the Wnt treat Pemphigus
7. what is the role of human opsonins in cancer therapy (surfactant A and D, Fibronectin, Vitronectin in lung cancer)

Sunday, September 29, 2013

potential questions in biomedical science

questions in basic medical sciences

1.  Can new heat shock Proteins made to be recognized by the the endosomal immune system?
2.  Can cancer cells express DNA motifs recognizable by the TLR9
3.  Can cytokines (IL11, IL 17, GCSF,Interferon-beta, be used as reliable predictor markers of pulmonary fibrosis in patient treated with Bleomycin)
4.  Can we electively silence MHC class I on cancer cell enough to trigger the "missing self Hypothesis".

(CD159,CD 158, CD 85)

5.Review the full role of Immunoglobulin-like transcription receptors
6.Harvesting Metastatic potential of cancer cell in their tagging with IgG susceptible to trigger FcyR NK cell-antibody dependent cell mediated cytotoxicity.  (survey of cancer cell receptors).
7Quantifying heat shock proteins in normal Vs cancer cells as a way to detect cancer cells, targeting them for increased scusceptibilty to be detected by dendritic cells?
8. Silencing MHC class I gene in cancer cells could be a significant way to trigger NK cells
9. Can perturbation at the FAK, decrease of E-Cadherin be associated with antigenic triggering  changes of memebrane phospholipids?
10. developement of small peptide susceptible to change MHC class I in cancer cells
11.  pertubations of endonuclease in cancer cell as a way to induce changes in TCR
12.  Is TAP (transporter in Antigen Processing) a valid target in cancer therapy?

Saturday, September 28, 2013

OVEREXPRESSION OF TRIB3 AMD SUPPRESSION OF TIAF1,NEW TARGETS IN THERAPY!

Based on our current understanding most receptor failure will go on to induce the stress related pathways which ultimately will go on to produce epigenetic events which will include not only transcription factors production but also significant cytokines production.  Some of these Cytokines includes growth factors which not only have the role of inducing growth of the cell, but also blocking Apoptosis.
The activation of NF-kB, one of our stress coping pathway, happens to induce TRIB3 but this elevation has a negative regulator effect on the NF-kB therefore decreasing the intensity of one of the most significant trigger (in chronic exposure to irritant stimuli) or amplifier  of specific cancers, and driver of cytokine production.   Activating  this TRIB3 could have significant effect in autoimmune diseases and have a significant effect in supportive cancer treatment and maintenance settings.

TIAF1, however, needs to be suppressed because it is the mechanism by the TGF to block death of cells.
In diseases where growth factors are the drivers , block the hell out of this TIAF1 please.     At CRBCM we are trying to see if these 2 interventions may help IL-2 effect in melanoma and Renal cancers.  FUNDS are missing so please help if you can!
What we keep as a secret is the work on anti-granulin (because here Cyclin T is involved, and with it TRIB3)!(HIV is not far a target!)


"The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. The encoded protein is a negative regulator of NF-kappaB, and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein can negatively regulate the cell survival serine-threonine kinase AKT1.[3]

Interactions

TRIB3 has been shown to interact with: