Tuesday, March 5, 2013

Bladder cancer in 2012:
Prevalence 73.5 Thousand patients in the USA
Deaths 14.9 thousands died with this disease.
Only 15% of patients have localized disease
50% of patients who have muscle invasion will eventually progress, Median survival in Metastatic disease is 14 months.
Smoking is an established risk factor for Bladder cancer

When the Bladder Muscle is invaded, Giving 3 cycles of chemotherapy (MVAC) before surgery is standard of care and lead to a 77 months median survival Versus 46 months with surgery alone (SWOG 8710.) . But only 20% of people receive Neoadjuvant Chemotherapy.   Mostly because the disease affect the elderly who's perfomance is judged poor for the chemotherapy, because of renal failure which preclude use of Cisplatin, and related comorbidilties which would make chemotherapy hazardous.

Genes reported in Bladder cancer:

MRE11
RAD50
NBS1
ATM
_______________________________________________-----These 4 genes all involves a close pathway.   Under chemical effect there is breakage of double chains DNA in bladder cells  The DNA Break trigger stimulate ATM by phosphorylation or similar activation, MRE1-RAD50-NBS1 is a complex molecule which must allow repair of the breakage by exposing it through "histone remodeling".  Mutations here will hamper this sequence of Activity.  "Breakage of DNA" and HOP, P53 activation is not far.  This is why intact P53 or wild type marks an early cancer. and Mutation of P53 is more a sign of an advanced Bladder cancer.
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H2AX-during Histone remodeling H2Ax replace H2A and participate in the triggering of check point arrest and therefore a key point to the Histone complex activity which is to control DNA transcription.
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CSS (Calpain family) contain DeK1 and CysPc and other anchors/molecules (Now you are going closer to treating AML)
Resistance to Cisplatin: ERCC1
Bcl-2
Overexpression of HRAS (in early disease)
70% have Mutation in FGFR3
P53 and Rb more advanced disease
P21, and P16 are also bad prognosis predictors.

NMP22 may be identified in the Urine for early detection of superficial bladder cancer



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