Friday, May 24, 2013

The behavior of Penile cancer is peculiar because of the trigger that set off the neoplastic process
but also because of the extent of pertubations/Mutations of  dangerous suppressors genes with impact on major pathways in the the cell. we did discuss about the Human Papilloma Virus (HPV) incriminated in almost half of the penile cancers.  And mentioned in passing Herpes II.  We did elaborate about E6 and E7.
Here we would like to expand on Genes essentially and particularly bring to the attention of the readers the dangerous involvement of critical genes with significant developments and implications.
Aside from the involvement of E-cadherin (CTNNB1), CCND1 and BIRC5, today we chose to comment on DAPK1 which principally interacts with MITF.  MITF will knock down RUNX3 a suppressor gene favoring apoptosis to hyperplasia.  It suppression there for favor Hyperplasia and decreases Apoptosis mainly by suppressing the BIM, a pro-apoptotic gene.   Suppression of the RUNX3 does not stop there, it unfortunately Activate the TLE gene with 2 dangerous development
1. Activation of the Glycoprotein 130 which could eventually block JAK at the receptor, inducing receptor failure for TGF and IL6 receptor,  We have discussed what happen with TGF receptor failure caused while discussing triple negative Breast Cancers (go to article).
2.TLE actions will affect a cross-road GENE called SIX3
SIX3 is a bad gene to bother! (SOME IDENTIFY SIX3 WITH THE SONIC HEDGEHOG PROPER!
At least 4 new genes and pathways are automatically disturbed when SIX3 IS ACTIVATED
1. SOX3
SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic brain development and in determination of cell fate. The encoded protein acts as a transcriptional activator.[3] Mutations in this gene have been associated with X-linked hypopituitarism (XH) and X-linked mental retardation. Patients with XH are male, have short stature, exhibit a mild form of mental retardation and present pan-hypopituitarism. [2] [4]wikipidia

WE HAVE MADE QUITE CLEAR THE IMPORTANCE OF GENE CAUSING "SHORT STATURE" AND WAY THEY OPEN THE DOOR TO USE OF IMMUNOMODULATOR AS A THERAPEUTIC INTERVENTION.  TELLING US THERE IS A ROLE FOR tHALIDOMIDE AND VELCADE IN THIS DISEASE!

2. SIX3 ACTIVATE THE Wnt PATHWAY AND THE SONIC HEDGEHOG
OPENING THE DOOR TO VISMODEGIB

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


Pharmacy News

FDA Approves First Drug Treatment for Metastatic Basal Cell Carcinoma

Cheryl A. Thompson
BETHESDA, MD 30 January 2012—Genentech and FDA today announced the approval of vismodegib, or Erivedge, for the treatment of adults with locally advanced basal cell cancer who are not candidates for surgery or radiotherapy or whose cancer has metastasized.

The drug, FDA said, is the first one that the agency has approved specifically for the treatment of metastatic basal cell carcinoma.

According to vismodegib's labeling (PDF), the dosage is one 150-mg oral capsule daily until the disease progresses or an unacceptable toxicity occurs.
There is no contraindication to therapy with vismodegib.
The drug inhibits the so-called hedgehog pathway, which, FDA and Genentech said, is active in most basal cell tumors but also is important to the development of embryos.
A boxed warning in the drug's labeling calls on health care professionals to advise all patients that vismodegib can severely harm or kill an embryo or fetus. All women of reproductive potential and all men are supposed to undertake measures to prevent pregnancy during vismodegib therapy. Even men who have had a vasectomy are supposed to use a condom with a spermicide during sex with female partners. The drug's medication guide addresses these issues.
During the clinical trials of vismodegib in patients with advanced basal cell carcinoma, the most frequent adverse reactions were muscle spasms, hair loss, a bad taste in the mouth, and weight loss. These reactions occurred at a rate of more than 40%. Diarrhea occurred in 29% of the patients.
FDA said it approved the application to market vismodegib on the basis of the results of a study of 96 patients, 34% of whom had metastatic basal cell carcinoma. All the patients took the drug. The cancerous lesions shrank in 30% of the patients with metastatic disease. Among the patients with locally advance disease, the lesions shrank or disappeared in 43%.
Genentech, a member of Roche Group, said Erivedge will be available within two weeks.
The company said specialty pharmacies will distribute the product.
==================================================================
3. SIX3 ACTIVATES PAX3
INCREASING METASTASIS TO BONE MARROW AND FAILURE RATES 

 "A PAX3/FKHR fusion gene is often associated with the alveolar type of rhabdomyosarcoma,[4] a kind of cancer arisen from striated muscle cells. Translocation between chromosomes 2 & 13 produce fusion protein PAX3/FKHR which serves as a tumor marker in this type of RMS.Also in ARMS expressing PAX3/FKHR increased risk of metastasis to bone marrow and hence increased rate of failure and death were seen."WIKI

" Note: The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving PAX3 is found in rhabdomyosarcoma. Translocation (2;13)(q35;q14) with FOXO1. The resulting protein is a transcriptional activator.
A chromosomal aberration involving PAX3 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with NCOA1 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children."UNIPROTKB

PLEASE NOTE THE INVOLVEMENT OF FOXO1, A POTENTIAL DOOR TO APOPTOSIS WHICH IN THIS CASE IS CLOSE.

4. FINALLY AND NOT THE LEAST
SIX3 INTERACTS WITH NOR1
-----------------------------------------------------------------------------------------------------

 (NOR1) also known as NR4A3 (nuclear receptor subfamily 4, group A, member 3) is a protein that in humans is encoded by the NR4A3 gene.[1] NOR1 is a member of the nuclear receptor family of intracellular transcription factors.
NOR1 plays a central regulatory role in cell proliferation, differentiation, metabolism[2][3] and apoptosis[4]WIKIPIDIA
------------------------------------------------------------------------------------------------------------------

ENSURING PLENTY OF PROLIFERATION OF PENILE CANCER!

AND THIS IS JUST FOR A START, WAIT UNTIL YOU HERE ABOUT THE EZRIN, S100A4, SCCA, KAI-1, MKI67, PCNA,RASSFIA AND OTHERS AND YOU WILL KNOW WHAT WE ARE UP AGAINST!


Post a Comment