Thursday, April 11, 2013

NOMENCLATURE OF Genes in Prostate cancers    
==================
The CRBCM does not have a significant laboratory. fOR ANY RESEARCH WORK, we have to contract with our local university (UTEP) and we intend to do so.  The gene discussed here in are easily found in the literature  What we bring to the discussion is our unique perspective that most of the time is still to be proven but appears sound based on available evidence.  We provide this opinion anyway in order to tease researchers around the world to prove us wrong or right.  We do not make up stuff.  We offer an interpretation of facts.   When you look at the genes involved in the pathogenesis of Prostate cancer

1. HPC1.
controversy has marred this one but it is found in several familial Prostate cancer.  Some has advocated this gene as a screening tool for familial Prostate cancer.  Clearly it is not the only one! 

"RNase L is now implicated in protecting the central nervous system against viral-induced demyelination. A role in tumor suppression was inferred by mapping of the RNase L gene to the hereditary prostate cancer 1 (HPC1) gene,
It encodes a ribonuclease that mediates the antiviral and apoptotic activities of interferons." (wikipedia)

2.CAPB

 "Perlecan is a proteoglycan that regulates extracellular and stromal accessibility to growth factors such as SHH, thus allowing for the maintenance of SHH signaling under growth factor limiting conditions. This proteoglycan represents an important central regulator of SHH activity and presents an ideal drug target for blocking SHH effects."
This open the door to use of anti Hedgehog agent such as the one used in Basal cell skin cancer in the treatment of prostate cancer!?

3.BRCA 1,2

" The protein encoded by the BRCA1 gene combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC).[9] The BRCA1 protein associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. Thus, this protein plays a role in transcription, DNA repair of double-stranded breaks[8] ubiquitination, transcriptional regulation as well as other functions.[10]The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression.[19] The ring domain is an important element of ubiquitin E3 ligases which catalyse protein ubiquitination2. Ubiquitin is a small regulatory protein

  BRCA1 interacts with the NELF-B (COBRA1) subunit of the NELF complex.[29]

  the BRCA1 protein interacts with RAD51 during repair of DNA double-strand breaks.[26
Wikipedia and related sources
sources have reported that one form of aggressive prostate cancer was characterized by Mutated BRCA2.
DOES THIS OPEN THE DOOR TO PLATINUM AS THE ANSWER TO THESE TYPE OF CANCERS LIKE IN BREAST CANCER?


4. Androgen Receptor genes

"The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor[6] that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone [7] in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.[8][9]
The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression;[10] however, the androgen receptor has other functions as well.[11] Androgen regulated genes are critical for the development and maintenance of the male sexual phenotype.

testosterone is converted by 5-alpha-reductase to dihydrotestosterone, an even more potent agonist for androgen receptor activation.[12]

  normal male sexual development
 receptors allow the body to respond appropriately to these hormones." WIKIPEDIA AND RELATED SOURCE

ANDROGEN DEPRIVATION IS OF COURSE THE MAIN SOURCE.  REFRACTORINESS IS SEEN IN ADVANCED CANCER WITH ASSOCIATED MUTATIONS TO THE AR  GENE.  BYPASSING THE RECEPTOR AND ACTING ON THE SUBSTRATE OF THESE RECEPTOR IS BEING LOOKED AT.  FOR THE AR TO WORK IT HAS TO BE TRANSFERRED TO THE NUCLEUS,  CYTOPLASMIC MISLOCATION OF THESE AR IS BEING LOOKED AT AS A WAY TO IMPROVE ON ANTI ANDROGEN  (HERE GNB2L1 IS A TARGET)

GOOD CONTROVERSY
 " a DNA segment known as CAG is repeated multiple times. This CAG segment is called a triplet or trinucleotide repeat. In most people, the number of CAG repeats in the AR gene ranges from fewer than 10 to about 36.Researchers have considered a possible relationship between the length of the CAG repeat region in the AR gene and a woman's chance of developing breast cancer. The results of research studies have been mixed. Some studies have suggested that a long CAG repeat region is associated with an increased risk of breast cancer in women,
 Some studies have shown an increased risk of prostate cancer in men with a short CAG repeat region in the AR gene;

Transcriptional activity is enhanced by binding to RANBP9.
The level of tyrosine phosphorylation may serve as a diagnostic tool to predict patient outcome in response to hormone-ablation therapy. Inhibition of tyrosine phosphorylation may be an effective intervention target for hormone-refractory prostate cancer."

PLENTY OF TARGETS!!!

(SIMILARITY FOR AR )  Belongs to the nuclear hormone receptor family. NR3 subfamily.
Contains 1 nuclear receptor DNA-binding domain.
---------------------------------
Related AND UNDER THE THUMBS OF THE AR gene are the TMPRSS-ERG, and ETS,ETV1,  TMPRSS-ERG fusion  (WE DISCUSSED THESE EARLIER)

5.ELAC2
----------------
6. ERG
7.PSA:  strategy here is to use this prominent protein to selectively deliver a powerful chemotherapy drug like in the T-DM1 experience
8.chrXq27.3
9.PCAP
10.MRS1
11.GALACTIN-1
12.SNP
13TGFB1
15NCOA1
16HIPK3
17ZIPK/DAPK3
18GNB2L1
19EFCAB6/DJBP
20NR0B2 AND PELP1

Underclinical investigation you find more the HER-2, Bcl-2, VEGF, Endothelin receptor gene, and the PSA

(several quotes are left intact here to tell you we don't make this stuff up!)
Posted by at No comments:

Today's viewer's origins as of 1pm Mountain Time:

Russia
60
Germany
26
United States
24
United Kingdom
12
Ukraine
3
Argentina
2
South Korea
2
Poland
2
Pakistan
1
Romania
1
Posted by at No comments:

Join me at RNA-Seq 2013



Paul Kayne
11:05 AM (1 hour ago)

to me
  Dear MUTOMBO,







If one was so inclined, RNA-seq could be considered in the context of a symphony. The first movement, as with Beethoven’s Symphony No. 5 in C minor, started with an Allegro con brio, “with vigor”. The advent of next generation sequencing empowered pioneers to look into the life of cells with unprecedented resolution. 

Details of new species of RNA, allele specific expression, and more began to emerge, with a new discovery almost every day. That we were only in the first movement likewise became clear. How to prepare samples, what platform to choose, how to work with the data, were questions without easy answers. Just as conductors fought over the correct interpretation of Beethoven’s score, so scientists brought their individual perspective to RNA-seq.

Second movements in symphonies are typically slower, but Beethoven chose an Andante con moto, “with movement and certain quickness”, describing well the state of RNA-seq today. Our field is moving forward deliberately now, towards answers as to how best to use these new capabilities, with exciting discoveries along the way.

And you have the opportunity to further your part in the symphony. I invite you to join me at RNA-Seq 2013 in Boston, June 18-20, 2013. You will hear from leaders using this technology to drive research and make decisions.

Presentations will address sample prep methods, analysis methods, platform choices, characterizing complicated expression patterns, choosing solution providers, application to drug discovery and more. Add your voice to our panel discussion on customizing analysis to meet your needs. Join us as we move towards the next movement in RNA-seq.

I understand that early registration closes in a month so book soon to get the best prices. You can see the full agenda and speaker line up here: www.rna-seqsummit.com. 

I look forward to seeing you there.

Kind regards,

Paul

Paul Kayne
Senior Principal Scientist,
Head of Genomic Technologies
Bristol Myers-Squibb




If you no longer wish to receive updates about this meeting click here
To unsubscribe from all further email communication from Hanson Wade click here.
This email was sent to you at: drkcancerclinic@gmail.com
Hanson Wade respects your privacy
© 2012, Hansonwade | Charter House | 13-15 Carteret Street | London | SW1H 9DJ
Posted by at No comments:
A milestone crossed, more than 15,000 reviews

Coalition for the Reversal of Breast Cancer Mortality in African American Women  ·  Stats  ›  Overview

Apr 4, 2013 8:00 AM – Apr 11, 2013 7:00 AM
New post
Graph of Blogger page views

Pageviews today            
74
Pageviews yesterday
      118
Pageviews last month       
2,930
Pageviews all time history
   15,030
Don't track your own pageviews



EntryPageviews
United States
10953
Germany
766
Russia
350
United Kingdom
245
France
232
Poland
145
Ukraine
104
Sweden
86
Taiwan
78
South Korea
59



TOTAL PAGE VIEWS    15,030 WITHOUT A SPONSOR
JUST PURE BIOLOGICAL SCIENCE!
Posted by at No comments:

WE ESCAPED SMARTLY IN THE MELI-MELO OF AGING JUST TO DIVERT OUR ATTENTION ON GENES INVOLVED IN ALZHEIMER. DON'T ASK ME WHY, BUT WE DID. WE CAME OUT MORE PUZZLED THEN ANYTHING ELSE!

MANY QUESTIONS THOUGH:

Many of the striking things and questions

1.Can calcium inhibitors slow down Alzheimer progression?
2. Is Namenda's role to slow down apoptosis in neurons by giving non specific stimulation to Glutamate receptors ?  Or this really by counterbalancing or increasing the effect of cholinesterase inhibitors? We know that when the disease is advanced and cell death has occurred, Namenda does not do much.
3. Can S100B be a more reliable way of monitoring Alzheimer's progression?
4. Does Alzheimer reflects a deficiency of Macrophage function and therefore Colony stimulating factors a way of treatment?
5. What is the effect of GM-CSF on NG2 glial cell and can this slow down Alzheimer?
6. What can slow down tau-protein phosphorylation, will ubiquitination work in detoxifying cells ?
7. What is the effect of disrupting the exosome, could this cause abnormal cell to be cleaned up earlier...? ....before plaque build up!
8. What is the real relation between Vit. D and DAG (diacyl glycerol), the phosphorylator, APOE and Presenilin?

Many question to struggle with...but the challenge is thrown at you, let's go to work!
Posted by at No comments:

FYN, A CRAZY GENE...

IT DOES NOT KNOW WHEN TO STOP INTERACTING
IT IS INVOLVED IN CRAZINESS (ALZHEIMER'S)
BUT YET IT KEEPS DOING ITS THING.
CAN WE STOP IT ELECTIVELY?
WE ARE WORKING HARD!

FYN

From Wikipedia, the free encyclopedia
Jump to: navigation, search
FYN oncogene related to SRC, FGR, YES

PDB rendering based on 1a0n.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols FYN; SLK; SYN; p59-FYN
External IDs OMIM: 137025 MGI: 95602 HomoloGene: 48068 ChEMBL: 1841 GeneCards: FYN Gene
EC number 2.7.10.2
RNA expression pattern
PBB GE FYN 210105 s at tn.png
PBB GE FYN 212486 s at tn.png
PBB GE FYN 216033 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2534 14360
Ensembl ENSG00000010810 ENSMUSG00000019843
UniProt P06241 P39688
RefSeq (mRNA) NM_001242779 NM_001122892
RefSeq (protein) NP_002028 NP_001116364
Location (UCSC) Chr 6:
111.98 – 112.19 Mb		 Chr 10:
39.37 – 39.57 Mb
PubMed search [1] [2]
This box:
Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.[1]
This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein.

Interactions

FYN has been shown to interact with:

References (WIKIPEDIA)

WITH THIS MANY INTERACTIONS, IT IS A CRITICAL GENE, BUT WATCH OUT NOW, IT NEEDS TO BE HANDLED WITH CARE.  HIT IT ONLY IN A VERY SELECTIVE FASHION NOW! OR YOU LOSE THE HOST!

 

another crazy gene

 

Androgen receptor has been shown to interact with:

 wikipedia! remember what we said about short stature

this one also is that kind, lack of it lead to short stature so it it is a powerful gene, suppression here cures prostate cancers!

Posted by at No comments:

Medscape Medical News from the:

NCCN Issues New Treatment Guidelines for Penile Cancer

Roxanne Nelson
Mar 22, 2013
Hollywood, Florida — The National Comprehensive Cancer Network (NCCN) has issued new treatment guidelines for penile cancer.
"The first thing people ask me is why develop guidelines for such a rare cancer," said Philippe  E. Spiess, MD, genitourinary oncologist at the H. Lee Moffitt Cancer Center in Tampa, Florida.
In 2010, an estimated 1250 new cases of penile cancer were diagnosed in the United States and there were about 310 related deaths. Penile cancer accounts for 0.4% to 0.6% of all malignant neoplasms in the United States and Europe.
Dr. Philippe Spiess
Dr. Spiess presented highlights of the guidelines here at the NCCN 18th Annual Conference.
There is a high degree of heterogeneity in the way penile cancer is treated in North America and globally, he explained. "The standard of care remains complete tumor excision and eradication of negative margins."
However, there has been increasing consideration of less or noninvasive management of primary penile tumors, based on stage and grade, he added.
Less and Noninvasive Therapy
For carcinoma in situ and superficial verrucous carcinoma, a British study showed that 5-fluorouracil or imiquimod produced response rates of 60% to 70% at 5 years (World J Urol. 2009;27:179-187). In this setting, CO2 and Nd:YAG laser ablation can also be used, although retreatment rates are quite high (about 20% to 30%), explained Dr. Spiess.
Total gland resurfacing and wide local excision with circumcision are also options.
There is some evidence for the use of topical therapies. In a recent retrospective review of all primary and recurrent cases of penile carcinoma in situ treated with topical 5-fluorouracil and imiquimod over a 10-year period (Eur Urol. 2012;62:923-928), "the response rates were excellent," said Dr. Spiess. "A complete response was seen in 57% of the patients, with a partial response in 14%."
No response was seen in the remaining 29.5% of patients, but none of the patients recurred or progressed. Toxicity was also low; 10% of patients reported local toxicity and 12% reported an adverse event.
Another study, looking at penile-preserving surgery for patients with penile Tis and PT1 tumors, found that there was a recurrence rate of 21.4% in both subgroups (J Urol. 2011;186:1303-1307). At 5 years, 13.8% of patients had a late recurrence, but none of the patients with pTis tumors had progressed to invasive or metastatic disease.
"These patients can recur fairly late, so it is important to follow them for at least 10 years," Dr. Spiess pointed out.
"As far as penile-preserving therapy, the take-home message is that clinical stage is everything," Dr. Spiess explained. However, he went on to emphasize that "it has to be a patient with a small superficial lesion, where you can obtain negative margins. If you can't, then you need to look at more radical options in surgery."
Another treatment option is brachytherapy. A recent French study found a 10-year penile recurrence rate of 20% and a 10-year inguinal recurrence rate of 11% (Int J Radiat Oncol Biol Phys. 2009;74:1150-1156). However, "centers of excellence that have experience with penile brachytherapy are few and far between," he cautioned. "That's why the guidelines...are somewhat cautious in making recommendations until we see a wider experience using penile brachytherapy."
He emphasized the importance of stringent surveillance after radiotherapy to the penis; up to 40% of patients who receive radical radiotherapy will eventually need surgery for disease recurrence. Surgery in this population can be challenging because irradiated tissues are brittle and poorly vascularized, making them less than ideal for grafting.
Sentinel Node Biopsy
Dr. Spiess discussed the concept of sentinel lymph node biopsy in penile cancer, which was proposed more than 30 years ago. One study reported a false-negative rate of 18% using a combined preoperative injection of technetium-99m labeled sulfur colloid and isosulfan blue dye (J Urol. 2002;168:76-80).
A more recent prospective study found a sensitivity of only 71%, with 2 false-negative results reported (J Urol. 2007;177:2157-2161). But a review found that false-positive results can be minimized with preoperative ultrasound and fine-needle aspiration cytology on suspicious nodes (World J Urol. 2009;27:197-203).
However, this technique has not yet been embraced in this setting. "We are somewhat cautious about promoting this technique, although clearly it is something very interesting and something that can be used at a center that has high expertise in sentinel lymph node biopsy," said Dr. Spiess. "At this point, it is not being widely used in North American centers."
National Comprehensive Cancer Network (NCCN) 18th Annual Conference.
 
Posted by at No comments:
Subscribe to: Posts (Atom)