Wednesday, February 26, 2014

CAN YOU PLEASE GET ME TO MELBOURNE, SCIENCE WILL ACTUALLY OCCUR THERE!

"The 2014 meeting of the International Cytokine and Interferon Society is to be held in Melbourne, Australia, during October 26-29, at the state-of-the-art Melbourne Convention Centre. The meeting will provide an outstanding forum for basic science and clinical researchers to present their latest data and exchange ideas relating to the broad role of cytokines and interferons in human disease, and applications to therapies." FROM THEIR SITE!

DO YOU WANT ME TO REPORT TO YOU OR WHAT!?

CYTOKINE IS THE ANSWER, FROM TRAUMATIC BRAIN INJURY TO DIABETES
BUT YOU STILL NEED THE CRBCM ANGLE !? HOW CAN WE GET THERE?...CALL 915-307-3354 IF YOU COME UP WITH SOMETHING!

INSTEAD OF TORTURING PATIENT WITH NODE DISSECTION, HOW ABOUT SIMPLY TESTING FOR VGEF-D

IN BREAST CANCER, AND MELANOMA
OBTAINING SENTINEL NODE HAS BECOME A PREOCUPATION
UNLESS WE REALLY NEED TO (SUCH AS CHECKING FOR MORE ABNORMAL GENE) can we just check VGEF D.
(rattling the cage at CRBCM)

can't make up this stuff:

"
Tumor metastasis to lymph nodes:
Lymph node metastasis is very often associated with several types of human malignancies. Cancer cells’ journey to lymph node takes place largely through lymphatic tunnel located in and around of primary tumor. VEGF-D’s interactions with VEGFR-3 predominantly expressed in lymphatic vessels plays a key role in restructuring lymphatic channel and, hence, able to alter its functions related to fluid and cell transport along the conduits. VEGF-D has been established to be over-expressed in both tumor tissues and patients’ serum samples in several types of human cancer. In addition, VEGF-D expression has been implicated with increased incidence of regional lymph node metastasis. In experimental mice study, genetically modified tumor cell that was forced to produce VEGF-D protein have been established to boost up regional lymph nodes metastases.^{[2]" wikipedia}
^{and instead of the c-FOS, dose the FIGF,}

^{INSTED OF .....DON'T LET ME STARTED NOW, GO WITH WHAT YOU KNOW!}

CSK random phosphorylation/related clinical questions

FYN
LCK
LYN
YES-1
HCK
Src
FRG
BLK
FRK

1.ATRA combined to Geevec as a way to break gleevec resistance?
2.disease with PDGF with STATs amplification could benefit from Gleevec if inhibition of Src is promoted
3.Could ATRA or the Piperazines (Gleevec) disrupt enough deployment of signal pathways to slow down a Cytokine storm (and TBI).
4.Could dampening of CRKL be used as a marker in CML
5.can ADAMs 17 be a biomarker of CML response or Myeloma response
6"PDGFR-beta is a key marker of hepatic stellate cell activation in the process of fibrogenesis.^"wikipedia

^{level of PDGFR in hepatoma?or Glioblastoma/ Nexavar activity linked to effect on PDGFR?}

^{JUST WATCH OUT WITH THESE Random PHOSPHORYLATION, IT IS HOW CASEIN INDUCES TRIPLE NEGATIVE}
^{BREAST CANCERS.}

^{JUST REMEMBER Src INFLUENCES PDGF INDUCED PHOSPHORYLATION OF STATs.}

vain attempt but we keep dancing!

Dear Peggy;

You have been successfully registered for the following training event.

------------------------------
Title: SBA Lending Fair
Location: 9050 Viscount Blvd. , ASC "A" Bldg. (Auditorium), El Paso, TX 79925
Date(s): 2/27/2014
Time(s): 5:30pm to 7:30pm

Description:
Instructions:
------------------------------

Thank you for your participation!

Best regards,

C.G.
El Paso Community College SBDC

Good News at CRBCM

It is official,
DR kankonde became Iterim Director of El Paso 4 Griffols/Talecris Plasma Center starting 03/01/2014.
He is also the full time Center Medical Director of El Paso 2 since 8/15/2013.
we keep progressing slowly but surely!

Pick into the cure!

Cytokines that can induce cellular stress, may also exacerbate P53 induced apoptosis through release of its regulators. Indeed P53 regulators include

Tomasini et al
" that TP53INP1s, in association with HIPK2, regulate p53 transcriptional activity on p21, mdm2, pig3, and bax promoters. Furthermore, TP53INP1s overexpression induces G₁ arrest and increases p53-mediated apoptosis. Although a TP53INP1s and HIPK2 additive effect was observed on apoptosis, G₁ arrest was weaker when HIPK2 was transfected together with TP53INP1. These results indicate that TP53INP1s and HIPK2 could be partners in regulating p53 activity."

the role of TGF on these regulators needs further scrutiny since it it such an important growth factor in breast cancer
could blockage of the Cutlins help?

Blocking these regulator could decrease cancer dependance on rescue measure and restore the effectiveness of Hypoxic apoptosis?

GO TO ARTICLE!

TP53INP1s and Homeodomain-interacting Protein Kinase-2 (HIPK2) Are Partners in Regulating p53 Activity*

Richard Tomasini‡§ et al!

Tuesday, February 25, 2014

new NF1 case stumbled upon!

As if things were not enough today a case of metastatic Head and neck cancer with vertebral involvement showed up, the interest in abnormality in G-proteins and may be the SProuty2 may be growing.
what does the NF-1 gene has to do with these propensity to Neoplasm. The patient had severe bipolar syndrome!

Its mutation release cell control through removal of RAS regulation, growth becomes uncontrolled.
Its ATPase shape affects deeply activity of the G-proteins.
Mutation in NF1 seems to be a trigger to EGFR expression (and erbB2) and may contribute to mass formation, in other words, recuperation of some embryonal fucntion is at the basis of tumor formation
?those with NF-1 Mutation becomes sensitive to anti-EGFR inhibition?
NF-1 mutation is also cause for over expression of Insulin Growth Factor Receptor and associated EMA/GLUT-1, and CD34 particularly on Fibroblasts, and S-100. (identifying several bio-markers and detection, may be prognosis in several research pertaining to NF-1)

other genes involved
Snx5
MIB-1
Neur2
Zath1
E2, DPK and DIP
Delta and the Notch

reference

Mind Bomb Is a Ubiquitin Ligase that Is Essential for Efficient Activation of Notch Signaling by Delta

Motoyuki Itoh¹, Ch

====================================
and into the details of negative activity

The mechanism of growth-inhibitory effect of DOC-2/DAB2 in prostate cancer. Characterization of a novel GTPase-activating protein associated with N-terminal domain of DOC-2/DAB2.

Wang Z¹,

all these identify new targets?

And now it comes

In sarcoma particularly GIST
people seems to try Pazopanib added to Gleevec!
and Panobinostat seems the selected HDAC inhibitor of choice!
"
Panobinostat (LBH-589) is an experimental drug developed by Novartis for the treatment of various cancers. It is a hydroxamic acid^[1] and acts as a non-selective histone deacetylase inhibitor (HDAC inhibitor)." wikipedia

In Gist, a sudden interest in the SRC gene! more work for CRBCM, will look into this!

and questions keep ringing the deep senses!

Does random phosphorylation induced by Casein and related decrease of AP-1 critical to Breast cancer (TNBC) development
can we equate or parallel depression of PTEN under HIF influence to Casein phosphorylation induced depression of AP-1 in inducing cancers?
The same phosphorylation affect the RELA causing cross talking of the NOTCH and Catenins
all this putting center epigenetic phenomena to Neoplastic transformation
does this justify the cancer preventive force of certain anti-inflamatory drugs
can the effect of neoplastic prevention be linked to expression of c-fos
how does BCL-2 expression linked to c-fos
As easy at it sound, only certain facts leads to c-Fos expression...suggestion is overexpression of c-fos indicates that certain condition in the cell have been satisfied!
Are we in the belly of the beast when it comes to Breast and Pancreatic cancers, Are we at the bottom of the GTX combination used in Pancreatic cancer ?(the founders was talking of enzyme limiting activities and saturation?

check it out!

Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity

Anning Lin ^★,

Monday, February 24, 2014

Role of the RELA gene in Triple negative Breast cancer

Is it the best biomarker
Is it the gene at play?
Is it the sign of Involvement of the epigenetic Zone
Is it a sign of Etoposide activity
Is it at play in hair discoloration
Is RELA sufficiently connected to be an adaptor gene, a wild gene? could it be a driver gene through autophosphorylation?
Pivotal role of the RELA in Breast Cancer though cross talking with the NOTCH, the steroidsand the Catenins?
Is RELA's role underestimated in Breast Cancer (TNBC)?
These are just some of the questions that the RELA gene raises !

Sunday, February 23, 2014

An interesting clinical case, A CLASSIC CASE OF GENE INTERFERENCE

a 49 year hispanic woman passed out while taking a shower, she was taken to the ER, further work-up revealed a 6.4 mass in the in her stomach which passed the physical wall of the and into the peritoneal wall. The mass turned up to be A GIST (Gastrointestinal stromal Tumor). An interesting finding by itself since it twist positively the prognosis and raise considerable interest for surgical Intervention.

The internet and the American cancer society suggest "

"Based on people treated between 1992 and 2000, the overall relative 5-year survival rate of people diagnosed with a malignant GIST was estimated to be about 45%.

If the tumor was confined to the organ where it started, the 5-year relative survival was 64%.
If it had grown into nearby tissue when it was first diagnosed, the 5-year relative survival was around 30%.
If it had spread to distant sites when it was first diagnosed, the 5-year relative survival was 13%. "

from the same sources

"

A few families have gastrointestinal stromal tumors (GISTs) caused by a DNA mutation passed down from parent to child. But most DNA mutations related to GISTs are not inherited. These changes occur for no apparent reason, and are called acquired or sporadic.

The cancer cells of most patients with GIST have a change in an oncogene called c-kit. The c-kit gene is found in all cells of the body. It directs the cell to make a protein called KIT, which causes the cell to grow and divide. Usually the c-kit gene is inactive. It is only active if there is a need for more interstitial cells of Cajal (ICCs). In most GISTs the c-kit gene is mutated and is always active. This may explain why the cancer forms. The cells are always growing and dividing. In some families that have many members with GISTs, doctors have found inherited mutations of the c-kit gene.

In about 5% to 10% of GISTs, the cancer cells have mutation in a different gene called PDGFRA, which causes the cell to make too much of a different protein (also called PDGFRA). This has the same effect on the cell as does KIT.

Most GISTs have changes in either the c-kit or the PDGFRA gene, but not both. A small number of GISTs do not have changes in either of these genes. Researchers are still trying to determine what gene changes lead to these cancers."

Most of these stromal tumors stained positively for CD34 (). The KIT protein is a transmembrane receptor for stem cell factor. The intracytoplasmic portion of this receptor functions as a tyrosine kinase. The availability of the immunohistochemical marker, CD117, to the KIT protein, has revolutionized the diagnosis of GIST, by identifying a treatment target. Approximately 95% of GISTs stain positive for CD117, making it a very useful marker for diagnosis (). This has led to the development of the targeted therapy imatinib mesylate (STI-571; Glivec^®, Novartis, Basel, Switzerland). This drug inhibits several tyrosine kinase receptors with varying affinity, including KIT, the BCR-ABL fusion protein, and the platelet derived growth factor receptor (PDGFR) (, ). DIN et al

The surgeon have discussed the case and referred the case for Neoadjuvant Gleevec.
-------------------------------------------------------------------------------------------------------------------
"As imatinib targets the ATP (adenosine triphosphate) binding site of the KIT receptor (encoded by exon 11), tumors with exon 11 mutations treated with imatinib have a significantly better partial response rate, event free and overall survival compared to exon 9 or no detectable mutation. A partial response rate of up to 83% has been achieved, showing how sensitive these tumors can be (; ; )."DIN

(DO PATIENT NEEDS TO REDUCE ATP PRODUCING MOLECULES IN THIS DISEASE ?)
(HOW DOES CAJAL CELL ACTIVITY LINKED TO TUMOR PROGRESSION/PRODUCTION)
(IS IT CRITICAL TO KNOW WHICH GENE IS AFFECTED IN AN INDIVIDUAL PATIENT)
DON'T GET EXCITED WE KNOW THE ROLE OF EXON 11.

and like any good thing, Gleevec comes with a word of caution per DIN et al:
--------------------------------------------------------------------------------------------------------

" The main circulating metabolite is an N-demethylated piperazine derivative which accounts for 16% of the AUC (area under the curve) for imatinib. This, with imatinib accounts for most of the activity, but there are a number of smaller metabolites. CYP3A4 is the major cytochrome P450 involved in imatinib metabolism. Thus, drugs that are co-administered may alter the pharmacokinetics. Erythromycin, fluconazole, and rifampicin have shown inhibition of imatinib metabolism. Imatinib increases exposure to simvastatin. Alprazolam, caffeine, clindamycin, clonazepam, cortisol, ethinyl oestradiol, and verapamil may cause toxic effects when given with imatinib. St. John’s wort increases imatinib clearance by 43%. Patients should avoid excessive amounts of paracetamol as both are metabolized by CYP3A4 (; ).

What makes this case even more interesting are 2 additional informations (and believe me I would not bring forth this case if there are no more twists), few months back the dermatologist had seen the same patient for Neurofibromatosis. Indeed she has disseminated on her skin "NEVI" like lesions typical of this disease. NOT ONLY SHE HAS THE NF-1 RELATED GENE, BUT SHE ALSO HAVE "CAFE AU LAIT " SPOTS
--------------------------------------------------------------------------------------------------

RAISING THE POSSIBILITY :" Mutations in the NF1 gene have been linked to NF-1, Juvenile myelomonocytic leukemia and Watson syndrome. A condition with a separate gene mutation but similar Café au lait spots is Legius syndrome which has a mutation on the SPRED1 gene.Patients without Neurofibromin 1 or SPRED1 mutations may have SPRED2, SPRED3 or SPRY1, SPRY2, SPRY3 or SPRY4 mutations.^[5]...." WIKIPEDIA

and

Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth factor receptor downregulation

Kaisa Haglund,"

(raising the possibility of anti-EFR in this disease)

AND A NEW CULPRIT IS BORN: ANDERSON ET AL.

"
Sprouty (Spry) proteins modulate the actions of receptor tyrosine kinases during development and tumorigenesis. Decreases in cellular levels of Spry, especially Sprouty2 (Spry2), have been implicated in the growth and progression of tumors of the breast, prostate, lung, and liver. During development and tumor growth, cells experience hypoxia. Therefore, we investigated how hypoxia modulates the levels of Spry proteins. Hypoxia elevated the levels of all four expressed Spry isoforms in HeLa cells."

PLEASE INTERFERE WITH SPROUTY ABSOLUTELY......
AND THIS INCREASES THE ROLE OF THE RAS AMPLIFICATION IN THIS DISEASE, AND MAKES ANTI-MEK EVEN MORE IMPRORTANT....AS A POTENTIAL AMPLIFIER DOWNSTREAM!
CAN SPROUTY EXPRESSION BE A BIOMARKER IN THIS DISEASE?

====================================================
Just as you start to get comfortable with the case
let me bring up yet another twist to this genetic rich case,
as I examine the patient, I find out quickly she has been unable to raise her hands for years and has been told to be ANA antibody positive....Now if you have been a careful reader, you may have noted that Juvenile Myelomonocytic Leukemia is part of this syndrome, pointing to a potential disruption of Monocyte which are incriminated in autoimmune diseases. Polymyositis came to mind as I examine the woman
" Another important event in the pathogenesis of Polymyositis is the increased expression of MHC proteins by m/s cells. Auto-Ag is presented in association with MHC-I molecules on the surface of Myocytes and is recognized by CD8 cytotoxic T cells that subsequently initiate m/s destruction."wikipedia

Pachman et al!
" It is our premise that JDMS is a distinct disease entity and that the increase in HLA-B8 and -DR3 in JDMS places this disease in the company of other immunopathic disorders. There are conflicting data concerning immunological abnormalities in JDMS , but there appears to be impairment of natural killing and evidence of complement activation. The frequent positive ANA in JDMS raises the speculation of its relationship to the antinuclear antibody, Jo-1, found in some adults with PM, which has specificity for tRNAHis. Most newly diagnosed JDMS patients have antibodies to Coxsackie B which may be related to the pathogenesis of this disease. Specific pathological findings of endothelial cells containing reticulotubular inclusions are associated with vessel occlusion, subsequent obliteration and increased Factor VIII levels in clinically active disease."

SHOULD I TEST FOR COXSACKIE, WHO IS GOING TO PAY!

THE LADY WAS FOUND WITH A PULMONARY EMBOLUS
AND COULD NOT BE ANTICOAGULATED AND A FILTER WAS PLACED
SHE HAS AN HARDENED RIGHT THIGH

AND TO CONCLUDE, HER FATHER DIED OF PANCREATIC CANCER

AND SHE HAS AN INQUISITIVE DAUGHTER WHOM I MAY BE FORCED TO TEST ALSO AS TO HER PREDISPOSITION TO THIS CALAMITY SYNDROME!

Friday, February 21, 2014

Side effects at the cellular level

The development of unintended consequences is one of the most significant events full of duplicity. It leads to unplanned events that could unravel the whole experiment. The cell knows it is not perfect and has prepared itself to a world of various stimulants that scientists around the world and nature keep creating. The cell keeps its options open, ready to adapt. Its flexibility to conversion expands its potential to undergo unplanned events or side effects. Some of the side effects are favorable, other neutral, but still some have deleterious effects.

1. One such example are Reuptake inhibitors:
----------------------------------------------
Whether it is a serotonin or Dopamine, inhibitor or reuptake, it results in increased extracellular concentrations of the targeted compound. Now it is always of use to remind ourselves that not all compounds are target specific and that certain compounds can stimulate several receptors, therefore raising the possibility of creating unintended consequences that we can call "side effects".

2.Co-stimulation of several Receptors Versus Co-binding of several Receptors.
----------------------------------------------------------------------------------
Multikinases have the advantage of blocking several of their targets, and may shutdown or activate several pathways. Generally, this is a positive thing. Side effects come along when some receptors blocked in the process lead to obligatory vital pathways or processes that are also shutdown or impacted, leading to miserable consequences. One of the things most researchers fear is the distant presence of an unplanned receptor in the Brain! You give a medication planned to act on a Muscle or a white cell, and you get a significant seizure side effect (real case).
Some Multikinases are so effective that they shut down the effect of other therapeutic interventions (don't try anti-VEGF and M-TOR inhibitor concurrently until you are sure of your purpose).

3.Adaptor genes:
---------------------
The cell is a master of giving directions to cellular reactions. To achieve this it put stogether "Core Binding Factors" (term used here loosely to make a point) or a congregate of various molecules that may come together to master, interact and shape sometimes one molecule (give this molecule a specific post-translational modification) into a new molecule that will achieve a specific purpose...like a factory would! ie. check the prognosis of CBF presence in Leukemias!
Certain genes, however, orient squarely a molecule to some clear purpose, if a molecule A attaches to the LYN gene Vs Gerb2, consequences are drastically different....Whether a solid tumor or a hematologic disease results could be a matter of which Adaptor gene was used!

4. Co-binding of Receptor
5. Lack of Inhibitors
6. Non specificity, sing the common pathways and possibility of saturation
7. Secondary liberation and release of "second messenger"
8. Unique localization of certain common receptors
9. Susceptibilty of certain Heterogeneic genes
10. The G proteins
etc.; all these could be expanded to justify why side effects develop, like it or not, in cellular life...No wonder we have to give "consents" for clinical trials....
AND GUESS HOW LONG THIS ARTICLE COULD BECOME IF MEATS AND BONES WERE ADDED! A BOOK WOULD NOT CUT IT!

Thursday, February 20, 2014

Still today: Minorities experience longer delays between cancer diagnosis and treatment !

1. Prostate Cancer:
Among men with prostate cancer, African Americans experience longer treatment delays after being diagnosed than Caucasians. That is the finding of an analysis published early online in Cancer, a peer-reviewed journal of the American Cancer Society. The study suggests that efforts are needed to reduce racial disparities in prostate cancer care in order to provide earlier treatment for African Americans.

African-Americans experience longer delays between diagnosis and treatment of prostate cancer

Date: May 28, 2013, Source: Wiley

2. Breast Cancer:
Breast cancer in women between the ages of 15 and 39 years (adolescents and young adults [AYAs]) constitutes 5% to 6% of all breast cancer cases in the United States. Breast cancer in AYA women has a worse prognosis than in older women. Five-year survival rates are lowest for AYA women, and only a few studies have examined the impact of delay in treatment, race/ethnicity, and other socioeconomic factors on survival in AYA women.

CONCLUSIONS AND RELEVANCE: Young women with breast cancer with a longer TDT have significantly decreased survival time compared with those with a shorter TDT. This adverse impact on survival was more pronounced in African American women, those with public or no insurance, and those with low SES.

2013 Jun;148(6):516-23. doi: 10.1001/jamasurg.2013.1680.

Delay in surgical treatment and survival after breast cancer diagnosis in young women by race/ethnicity.

Smith EC¹, Ziogas A, Anton-Culver H.

3. Effects of Health Insurance and Race on Early Detection of Cancer

Our final study population consisted of the 28 237 Florida residents diagnosed with colorectal cancer, breast cancer, melanoma, or prostate cancer in 1994, for whom information was available on both stage and insurance payer (Table 1⇔). Most patients were older than 65 years of age, and Medicare was the most common type of insurance. Table 2⇔ presents the proportion of patients who were diagnosed at a late stage of cancer for each category of insurance payer and race. The insurance payer was statistically significantly associated with stage at diagnosis for each of the four cancers examined. Patients insured by Medicaid and patients who were uninsured were at greater risk for late stage disease. Non-Hispanic African-Americans were at a greater risk of a late stage diagnosis for breast and prostate cancers.

Effects of Health Insurance and Race on Early Detection of Cancer

Richard G. Roetzheim,
Naazneen Pal, Colleen Tennant,
Lydia Voti,
John Z. Ayanian,
Annette Schwabe and
Jeffrey P. Krischer
+ Author Affiliations

Affiliations of authors: R. G. Roetzheim, University of South Florida Department of Family Medicine, and Division of Cancer Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa; N. Pal, C. Tennant, University of South Florida Department of Family Medicine; L. Voti, Florida Cancer Data System, Sylvester Comprehensive Cancer Center, University of Miami, FL; J. Z. Ayanian, Division of General Medicine, Department of Medicine, Brigham and Women's Hospital, and Department of Health Care Policy, Harvard Medical School, Boston, MA; A. Schwabe, Department of Chronic Disease Epidemiology, Florida Department of Health, Tallahassee; J. P. Krischer, H. Lee Moffitt Cancer Center and Research Institute.

Correspondence to: Richard G. Roetzheim, M.D., M.S.P.H., University of South Florida Department of Family Medicine, 12901 Bruce B. Downs Blvd., MDC 13, Tampa, FL 33612 (e-mail: rroetzhe@com1.med.usf.edu).

Wednesday, February 19, 2014

A fast-paced life-style induces 'doc-shopping' with unforeseeable consequences...

In the search of perfect health and instant relief from any noticeable sign from the body, some individuals shop and hop from one doctor's office to the other, often without any measurable relief from the perceptions that the body keeps sending - signs of aliveness, wakefulness, tiredness, excitement, fullness after a great meal, shivers from a fright....
A president-like appointment schedule involving 10 or more specialists charts the course of the week, the daily medical trips are punctuated by the ingestion of up to 36 different medications at meticulously recorded times and separated from or taken during meal times as advised...

Over a few innocent weeks and month, unobtrusively, life is turned into a full-time state of disease that demands constant attention, worry, discussion, opposition and scrutiny that ends up creating anxiety not only in the patient, but also in each and every one of his or her family members as they shiver in dark anticipation with every sigh, hiccups, burp and yawn.

The outcry: "Oh well, I don't know what is wrong with me, really!" leads to ever more head scratching... maybe soon these doctors will loose their hair over the puzzling case !
by PK

Help us fund the Testing of Biomarkers to define, monitor and better address OBESITY, A CONDITION OF PROFOUND ENDOCRINE AND CYTOKINE DISTURBANCES, a true state of DISEASE!

Testing Biomarkers to define, monitor and better address OBESITY, A CONDITION OF PROFOUND ENDOCRINE AND CYTOKINE DISTURBANCES, a true disease state

We want to establish new guidelines for monitoring obesity by finding specific biomarkers. Following BMI, lipid profile and pushing diet and physical activity is clearly insufficient. Blocking the central nervous system to force mental rejection of food is not the answer, either.

Obesity becomes a disease because of its high inflammatory state, determined by a relatively high level of Growth factor and Cytokines inducing major deleterious consequences on the muscle skeletal system through the activated NF-KB.

In morbid obesity, RIP140 levels are down-regulated in visceral adipose tissue. The RIP 140 (also known as NRIP1) interacts with DAX1 which involves the COPS2, SREBF1 (the bone modulator) and SF1 ("feminization" of obese individuals). (see literature) In breast cancer, RIP140 is involved in regulation of E2F1, an oncogene which discriminates between luminal and basal tumor types. RIP140 influences cancer phenotype and prognosis.^{. "}In addition, RIP140 has a role in inflammation, since it acts as a coactivator for NFkappaB/RelA-dependent cytokine gene expression. Lack of RIP140 leads to an inhibition of proinflammatory pathways in macrophages and RIP-140 modulation is part of cachexia induced by Tumors.

Also, in a state of obesity, even outside the cell, there is a relatively large number of insulin molecules."
Without receptors to stimulate, they will go downstream and stimulate MAPK AND STRESS LIKE c-JUN/fos, LEADING TO INCREASED CYTOKINES with Interferons and interleukins leading to diseases caused by obesity.

HONESTLY

AS WE PROGRESS IN CANCER SCIENCE, THE TIME FOR DIAGNOSIS OF CANCER WITHOUT GENETIC RECIPE AT THE BASIS OF THE DISEASE IS QUITE PASSED! GIVING OLD CHEMOTHERAPY SHOULD ONLY BE ALLOWED IN REFRACTORY DISEASES...BUT HERE WE ARE, WITH LEADERS DISTRACTED DRIVING US BACKWARDS.... RESARCHERS ARE LEFT FIGHTING OVER WHETHER TO TEST THE DNA, THE RNA OR SIMPLY THE RELATED PROTEIN, AN EXTRA $2000 WOULD HAVE ALLOWED TO PURCHASE THE 50 ELISA KITS, BUT ALL IS FALLING SHORT BECAUSE OF THAT AMOUNT! IF THIS IS HAPPENING HERE...WHAT ABOUT...? SHOULD WE REALLY BE DISCUSSING THIS NOW?

Tuesday, February 18, 2014

The Combination of Etoposide and Histone Deacetylases applied to Cancers with high levels of c-MYC and c-FOS gene expression

The Combination of Etoposide and Histone Deacetylases applied to Cancers with high levels of c-MYC and c-FOS gene expression:

This research project investigates the possibility of combining Etoposide with Histone Deacetylases in the treatment of cancers that display a significant expression of te c-Myc and c-Fos gene. The drugs proposed for this trial are Etoposide and Histone Deacetylases.

Etoposide was first synthesized in 1966 and is a drug widely used in chemotherapy since 1983 when it obtained FDA approval. Etoposide forms a ternary complex with DNA and the topoisomerase II enzyme which participates in the unwinding of DNA, hence prevents the rwligation of the DNA strands, and by doing so causes DNA strands to break. This action then leads to DNA synthesis errors and subsequently to cell death. Etoposide has, however, some reported side effects such as low blood pressure, hair loss, pain or burning at the injection site .

Histone deacetylation has been an effective treatment for various types of cancers. By the removal of acetyl groups from histones, histone deacetylases create a non-permissive chromatin conformation that prevents the transcription of genes that regulate the expression of proteins involved in tumor development such as c-FOS. In addition to histones, histone deacetylases deacetylate a variety of other proteins including transcription factors and other abundant cellular proteins involved in the regulation of cell growth, differentiation and cell death. Histone Deacetylases are among the most promising therapeutic targets for cancer treatment, and they have inspired researchers to study and develop HDAC inhibitors worldwide.

The present research project consists in computerized and laboratory testing of the efficacy of combining these two treatments in cases of observed overexpression of both the c-MYC and c-FOS gene. Although the two drugs already exist and are used in cancer therapy, the interaction of the two drugs when used in combination needs to be examined. This can be achieved by using a mouse model bearing specified tumors to be done at the University of Texas at El Paso (UTEP). Preliminary testing should be conducted by implanting cancer cells in the skin of mice. The combined treatment should then be applied indiscriminately to mice presenting high expression of c-Myc and c-FOS, and to those with low expression of these genes. The response to the treatment will be monitored to evaluate the efficacy of the treatment in mice with high c-Myc and c-FOS expression as compared to the control group with low c-Myc and low c-FOS expression. In a later phase, testing would be conducted in cancer patients presenting high expression of c-Myc and c-FOS, especially for patients treated for triple negative breast cancer, but also for ovarian cancer and other types of cancer with an overexpression of c-MYC.

The combination of Etoposide with Histone Deacetylases represents de facto a novelty in cancer treatment, especially in the case of triple negative breast cancer that is until today associated with a worse prognosis than other breast cancer types. It has a characteristic recurrence pattern with the peak risk of recurrence and the majority of deaths occurring in the first 3 and 5 years after the initial treatment, respectively.

Monday, February 17, 2014

What can we quickly improve through Gene interference! Questions?

*Do various viruses who require intracellular multiplication
also require use of EIF4G?
*Can blocking Cap dependent transcription through the PKC delta an effective antitumor activity during maintenance therapy.
*can we afford anhilation/blocking RAFT1?
*should blocking dimerization of EIF4G an effective therapeutic intervention in Cancer
*Does limitation of activity at the RHEB limit activity of an m-TOR and B-raf inhibitor combination, or RHEB Amplification a sign of resistance or otherwise sensitivity to B-RAF inhibitor, can the RHEB be used as a Bio-marker?
*Activity of RYR1, TRDN genes in Alzheimer dementia
*Does suppression of AGAP2 a sign of hormone failure in ER positive Breast cancer?
*Could blocking SHC exacerbate or Increase Apoptosis and c-MYC amplification

Whims of hope are driving the fight for the cure!

We know we will never win all human competitions which are marred with intrigues,
but because our cause is just,
because the cause is what we believe in,
as a coalition we will continue to fight until the reversal of breast cancer mortality becomes a reality.
and this after the effects of hormone therapy, screening mammogram and improvement in chemotherapy.
We believe in target therapy as an answer to cancer. And we believe humanity is at a dawn of several break through in cancer treatment. We believe not to lead from behind but it is not wrong to revisit some known premises that were overlooked! We believe in the use of new technologies to revisit old premises! We believe not all aspects were fully visited as the multitude of genes and their interactions did not allow a more comprehensive study that is today's called for. We believe some will continue to deter the march to the cure because it what they do! And the escape of the cure needs these agents! CRBCM will not shrink from its mission, and will continue its progression no matter what, The cause is too important and too Valuable to let them distract us...we still will summon the rest of our forces to rise to the mission...we will fight until enemies become irrelevant to the train of history, or until the torch to true research is passed on to valiant believers!
It is true the women die of breast cancer every day, and it is true that cure is achievable, and from these premises lie the true nature of our fight, fight that will call many to answer and many will join. The CRBCM find its vigor and reason for existence in these premises
and will continue to work with all its might. Research is an uncharted world, any stone should be turned because where the truth lie is only known to nature and its creator (for those who believe), and many are called to lend a hand in this struggle for the scientific truth that will free those within the scourge of cancer, The CRBCM stand with them. They are not alone! Let this spirit guide our work, until we are convince to have made strides in this war against cancers!

The CRBCM, man enough to show-up!

his is a confirmation e-mail for the following:

Grant-maker: National Cancer Institute - NExT Program
Program: NExT Partnership with NCI (Non-Grants)

Status: Submitted
Status Date: 2/14/2014 10:09:05 PM
Application ID#: 321008
Applicant: Mutombo Kankonde
Institution: Mutombo Kankonde
Title: Etoposide and Histone Deacetylases in Cancers with high c-MYC and c-FOS

To see the updated application status, we recommend that you first logout of proposalCENTRAL and close all proposalCENTRAL browser windows. Then log back in to proposalCENTRAL and access your application from the Manage Proposals tab.

If you need assistance, contact proposalCENTRAL Customer Support at 800 875 2562 (Toll-free U.S. and Canada), +1 703 964 5840 (Direct Dial International) or by e-mail at pcsupport@altum.com.
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Saturday, February 15, 2014

New Consults!

Today 3 new consults at CRBCM referred by UMC network!,
1.Pancreatic
2.Renal cell cancer
3.Hepatoma
opening a panoply of genetic abnormality considerations at CRBCM, Good work!
(After a Myeloma, an Embryonal Sarcoma and 2 Metastatic Colon cancers!)

The Internist's Tumor

No tumor remains of interest as Renal cell cancer, and the interest keeps swelling not only with the incidence of the disease, but with various discoveries in genes and pathways going awry in this disease, scientists working with Target therapy are increasingly embolden to try new staff in kidney disease. The SWOG trial of Tarceva in papillary Renal cancer is just one demonstration of our confidence in Target therapy. And believe me it works as predicted! Overall response of 11% was achieved, and a number of stable diseases yielding an overall control of papillary renal cell cancers in 64 % of patients. Basically nothing to sneeze at! But this reenforce the notion that papillary cancers (primary c-Met) have a strong VEGF dependency, and that it is here that Tensorilimus may be may work better while Sunitinib will serve better in those diseases where VEGF is a secondary expression such as an secondary amplification as a result of Von Hipple Landau primary activity!

Nonetheless, what really made the name of Internist Tumor to Renal cancers is its associated Cytokine release and no further dedicated and detailed investigation has been fully deployed. And the main reasons, wright or wrong, have been around the fact that no clear Cytokine adjuvant treatment has made a difference for our patients (to be continued).

Friday, February 14, 2014

Testing the general population for cancer risk!

It is now set!
Our research in cancer predisposition in the general population is shaping up, the consent has been drawn, where to keep the blood well organized, samples will be collected at CRBCM. they will be stored at the Biomedical science department at UTEP where they will ultimately be analyzed for various Mutations and overexpressions. up to 300 samples are planned and already candidates are piling up in line. People are interested in pure research! We at CRBCM are glad of UTEP's DR Zhang leadership, consent has been devised. Demographic questionaire is being developed, and cancer survivors are available.
we know cancer follow certain paths, we are going to test these paths on innocent bystanders.
Those genes that will be most expressed may enter a kit.
The testing is on!

NOTES TO EXPAND ON!

Resveratrol, in aging and cardio-protection controversy!
Enzastaurin; inhibitor of Protein Kinase C Beta
Panobinostat
ABT-199---BCL-2 INHIBITOR
DASATINIB SRC-ABL INHIBITOR
FOSTAMATINIB SYK INHIBITOR
IDELASIB P13K INHIBITOR
LENALIDOMID IMMUNO-MODULATOR
OBINITUZUMAB ANTI-CD20

BUT WHAT IS
-AVIDIN
-STREPTAVIDIN: " It is currently thought that this high level of binding to adherent cell types, such as activated platelets and melanomas, is a result of integrin binding mediated through the RYD sequence in streptavidin.[1" WIKIPEDIA. THIS IS USED IN NANOTECHNOLOGY TODAY.

GENE THAT COUNT DNA DUPPLICATION AND LIMIT IT TO 1, DOES IT PLAY IN VIRAL REPLICATION?

Wednesday, February 12, 2014

Meeting at UTEP with DR Zhang and DR CHOI

2/11/14
Monthly meeting to mark completion of the first phase of the lung cancer project. This is preliminary completion of gene detection Mutations that will appear in a Kit for early detection of lung cancer. Dr Zhang has obtained 77 additional samples that will undergo the same PCR evaluations.
The Inclusion of MUC1 and MUC7 was also discussed. We are going to test for Avastin resistance through genetic evaluation.
Vista college students were included in the discussion
The insensitivity to stage of disease, and whether or not the patient received treatment was welcome news as the persistence of these genes show strength through time during the neoplastic process and speak to curability particularly if future studies suggest that their persistence point to low disease free progression.

Today we learned from the tissue bank that surrounding tissue that is normal tissue is available as back ground mutations is needed for comparison/ baseline!

We did not look at genes that may be suppressed in lung cancer such as PTEN. With PCR, that information is obtainable but tricky whereas amplified or overexpressed gene seem readily obtainable.

Things are still exciting as we progress toward concrete finding. The MDM2 was the most overexpressed!

Tuesday, February 11, 2014

is c-fos over expression protective for Colon, Gastric and Bladder cancer? question of the day!

Is c-fos expansion or overexpression protective for Colon, gastric, bladder cancer (we are open to an opposite result) THIS IS INVESTIGATION AFTER ALL!
Is it why diabetic have less cancer while on Insulin

"Regulation of c-fos expression in adipose and muscle tissue of diabetic rats.

Olson AL, Pessin JE.

Author information

Abstract

Insulin treatment of control rats demonstrated a marked 8-fold transient increase (15 min) in c-fos mRNA in white adipose tissue, which returns to basal levels by 5 h. Similarly, insulin treatment resulted in a rapid 9-fold increase in cardiac muscle c-fos mRNA, "
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we will look into this and by the way go to article if you need more data!

we believe what is going on with G-proteins and at epigenetic is so preoccupying for the cell that it block key pathway to cancer development....we will further investigate!