The core of Autoimmune diseases?

TGF alpha WITH ITS CONNECTION TO HLA-DR1 Vs. MIF,
the alpha 4 Beta Integrin WITH THE VASCULITIS!
E3 AND ITS INHIBITORS and the CXCR4 GENES

THAT IS IN THE CORE OF THE BELLY OF THE BEAST!
DO YOU NEED A FULL TEXT, CALL ME,
WANT MORE, HOW ABOUT NCK1? POWERFUL TARGET IN LEUKEMIA!
GO FIGURE!

STILL DON'T BELIEVE
THIS IS THE SUPPORTIVE EVIDENCE

Lupus. 2007;16(8):587-92.

Macrophage activation syndrome in juvenile systemic lupus erythematosus: an under-recognized complication?

Pringe A, Trail L, Ruperto N, Buoncompagni A, Loy A, Breda L, Martini A, Ravelli A.

Source

Istituto di Ricovero e Cura a Carattere Scientifico Giannina Gaslini, Genova, Italy, Hospital Pedro de Elizalde, Buenos Aires, Argentina.

Abstract

Macrophage activation syndrome (MAS) is a life-threatening complication of rheumatic diseases that is thought to be caused by the activation and uncontrolled proliferation of T lymphocytes and macrophages, leading to widespread haemophagocytosis and cytokine overproduction. It is seen most commonly in systemic juvenile idiopathic arthritis, but is increasingly recognized also in juvenile systemic lupus erythematosus (J-SLE). Recognition of MAS in patients with J-SLE is often challenging because it may mimic the clinical features of the underlying disease or be confused with an infectious complication. This review summarizes the characteristics of patients with J-SLE-associated MAS reported in the literature or seen by the authors and analyses the distinctive clinical, diagnostic and therapeutic issues that the occurrence of MAS may raise in patients with J-SLE.

Secondary Hematologic Malignancies

Japanese researchers suggested in a retrospective study of patients treated with Temodar for Glioma, that there is an increased occurrence of secondary Myelodysplasia, leukemias and particularly Acute Lymphoblastic Leukemia.  It is interesting to look further, beyond the simple observation and speculate as to what leads to such a transformation at the gene level.
Leukemias are a disease not only of pathways, but of deep derangement at the Histone-DNA level and include particularly not only protein complexes similar to core binding factors, but also regulator genes which appear to be specifically amplified in leukemias!
It is pertinent to also look closer at Proteins Kinases affecting or interacting with DNA.  Temodar is an Alkylating agent per the researcher's report.
The interval between the treatment and the occurrence is also interesting, and suggests that the secondary Leukemia results from a secondary amplification of proliferative genes after the onslaught on cellular receptors by the chemical stimulus. The NK-kB, c-JUN must be in play.  Blocking these pathways could prevent such malignant occurrence. We will soon find that secondary malignancy could be prevented by simply blocking some tumor growth factors.  We don't need to accept these complications any more.  I learned that my first patient who was diagnosed with Hodgkin disease, a curable disease, died later on with an Acute Leukemia.  She was free of Hodgkin disease. Our current follow-up is inadequate in this regard, as we sit and wait for secondary leukemia to set in.  Lets look into blocking Tumor growth factors to stop secondary leukemias!

S100A4, AN IMPORTANT TARGET FOR SURE! LOCATED AT 1q21

The importance of a molecule in the body is determined  by its chemical properties, the pathogenesis of the disease in which it is  participating or how critical a function it is performing in the cascade of a pathway. The importance of a gene is determined by its product's shape and function which is sometimes defined by atoms hanging at its periphery, ready for business of attracting other electrons or ions.  It is also determined by genes in a linkage relationship at the chromosome level. This last point is important to be clarified by researchers who have the tools to explore the coexistence of genes on an arm of a specific chromosome.  And a lot of research forgets to look at that aspect of the problem gene. (don't forget "q" most of the time portends for worse prognosis than "p" , that is it may induce a malignant phenotype.  In fact, co-expression of homologue "p" will mitigate the phenotype. And the homologue gene is on a p arm and on a different numbered chromosome)

By now you also know that cell life is directed in one direction at a time frequently.  Cells are under function performance, differentiation, proliferation or neoplastic transformation.  Neoplastic cells are in concert with surrounding cells from which it avoids to be in conflict with to escape detection.  Neoplastic Cells will be soon stressed because of their increased needs and through the c-JUN -FOS will increase a Tumor Growth factor liberated from the cellular membrane with concomittent release of Metalloproteases in the extracellular membrane through flippase-floppase activity.  The Metalloprotease goes out, the Growth factor goes in.
IT WOULD BE GOOD TO KNOW WHICH METALLOPROTEASE IS SPECIFICALLY LINKED TO WHICH PROTEIN IN ORDER TO KNOW WHAT IS GOING ON INSIDE THE CELL JUNK BY DETERMINING WHICH OF THE METALLOPROTEASE   FAMILY MEMBER IS IN THE EXTRACELLULAR SPACE OR BLOOD!   NICE LITTLE PROJECT RIGHT THERE.  "WHICH TYPE OF METALLOPROTEASE FOR WHICH CANCER"  I BET, BRAIN TUMOR WILL RELEASE A DIFFERENT METALLOPROTEASE THAN OVARIAN CANCER.  BECAUSE THE GROWTH HORMONE RELEASED IN THE CELL WILL BE DIFFERENT.

By now you also know that in certain proliferative processes, there is an increased aspect of only 1 or 2 functions.  In Leukemias, for example, it is amplification of a certain Core binding complex which attaches certain molecules with specific functions.  And the cell follows the cascade of functions to go in a certain cell life trend.  Some of these proteins are gene regulators.  In fact, Leukemia would be better controlled if we just determined the proteins on CBF and the regulators that are promoted in the cell.  ANOTHER EASY PROJECT : THE PATTERNS OF GENE REGULATORS IN A SPECIFIC LEUKEMIA (BY WETERN OR SOUTHERN BLOT).

One of those regulators is the S100A4, a potent regulator which not only is at the differentiation, meaning when mutated or amplified it will create phenotypic havoc for sure.  It is handling Calcium, therefore will affect some Microtubules (good or bad for Taxanes?):  Time to find out more! Read these articles!

1. High expression of S100A4 in cytoplasm at the advancing front of stage C colonic tumours indicates a poor prognosis.
2. The S100A4 protein, mostly studied in cancer, is overexpressed in the damaged human and rodent brain and released from stressed astrocytes.
3. we show for the first time the intratumoral knock down of S100A4 via systemic application of S100A4shRNA plasmid DNA, restricts metastasis formation in a xenografted mouse model of colorectal cancer.
4. SRX forms a complex with S100A4 (and has stronger affinity for S-glutathionylated S100A4), regulates its activity, and mediates redox regulation of the interaction of S100A4 with nonmuscle myosin heavy chain II-A.
5. S100A4 and its downstream factors play important roles in pancreatic cancer invasion, and silencing A100A4 can significantly contain the invasiveness of pancreatic cancer.
6. HBXIP up-regulates S100A4 through activating S100A4 promoter involving STAT4 and inducing PTEN/PI3K/AKT signaling to promote growth and migration of breast cancer cells.
7. S100A4 and VEGF mRNA levels were up-regulated in clear cell renal cell carcinoma (CCRCC), tissue compared with control; upregulated tumour S100A4 and VEGF mRNA levels were independent risk factors for the presence of invasion and/or metastasis
8. High S100A4 is associated with ovarian cancer invasiveness.
9. FSP1 localized to podocytes in focal segmental glomerulosclerosis & minimal change disease. The number of FSP1(+) podocytes per glomerular profile was higher in patients with FSGS than in MCD. There was a corresponding difference in FSP1 mRNA levels.
10. Asymmetric mode of Ca-S100A4 interaction with nonmuscle myosin IIA generates nanomolar affinity required for filament remodeling in epithelial carcinoma cells.

NOTE HBXIP S100A4:  AN IMPORTANT TARGET FOR CERTAIN!

Is A Cure For Cancer Near?

December 10, 2012 | Filed under Health Care | Posted by Doug Johnson

Emily Whitehead photo via

The New York Times is reporting that a disabled form of H.I.V. is being used to reprogram patient’s immune systems to genetically to kill cancer cells.

PHILIPSBURG, Pa. — Emma Whitehead has been bounding around the house lately, practicing somersaults and rugby-style tumbles that make her parents wince.
It is hard to believe, but last spring Emma, then 6, was near death from leukemia. She had relapsed twice after chemotherapy, and doctors had run out of options.
Desperate to save her, her parents sought an experimental treatment at the Children’s Hospital of Philadelphia, one that had never before been tried in a child, or in anyone with the type of leukemia Emma had. The experiment, in April, used a disabled form of the virus that causes AIDS to reprogram Emma’s immune system genetically to kill cancer cells.
The treatment very nearly killed her. But she emerged from it cancer-free, and about seven months later is still in complete remission. She is the first child and one of the first humans ever in whom new techniques have achieved a long-sought goal — giving a patient’s own immune system the lasting ability to fight cancer.
…Three adults with chronic leukemia treated at the University of Pennsylvania have also had complete remissions, with no signs of disease; two of them have been well for more than two years, said Dr. David Porter. Four adults improved but did not have full remissions, and one was treated too recently to evaluate. A child improved and then relapsed. In two adults, the treatment did not work at all. The Pennsylvania researchers were presenting their results on Sunday and Monday in Atlanta at a meeting of the American Society of Hematology.
Despite the mixed results, cancer experts not involved with the research say it has tremendous promise, because even in this early phase of testing it has worked in seemingly hopeless cases. “I think this is a major breakthrough,” said Dr. Ivan Borrello, a cancer expert and associate professor of medicine at the Johns Hopkins University School of Medicine.

Targeted fighting of cancer at the cellular level makes a lot of sense. The problem has always been how to destroy those cancer cells without destroying everything else. This is a very promising development.

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1.  CRBCM will find out what happened at the ASH regarding this reserach.
2.  Despite the reported success which is impressive, could restoring one thing cure everyone (Driver Mutation)?  Cancer cells are different from the normal cells in so many ways that it is hard to believe that this technique is the cure-all. Indeed, 4 patients did not achieve complete remission. These failures send the researchers back to the drawing boards.
3.Computer models are the way to go. The proper answer is to make an inventory of critical changes compared to normal, and address these changes sequentially or concurrently to improve our success.
4. The last point leads to the importance of mapping technology improvement.
5. Nice to see DR IVAN BORRELLO mentioned; I referred a few patients to him while working at Midatlantic Kaiser Permanente.  I worked there for 14 years!