* A trial has shown that Doxepin rinse may reduce pains from oral Radiation induced Mucositis.
*Radiation post lumpectomy does improve survival even in the elderly
*Memantine 20 mg daily did alleviate loss of cognitive functions post whole brain Radiation
* Now that Tamoxifen can be given for 10 Years, people are still suggesting that switching at 5 years to Letrozole in postmenopausal women, is better but may be we need another clinical trial? It is reported that switching to Letrozole lead a a 48% drop of Recurrence and 24% drop in chance of death!
*Should maintenance alpha interferon be given in Esophageal and gastric cancer with Non-mutated Interferon receptors? or cancer with over expressed NF-kB.
does overexpression of FOS predict response to Interleukin or Interferon.
*It is wrong to stop inhibitor to VEGF IN CANCER TREATMENT UNTIL DISEASE PROGRESSION, AND INSTEAD OF STOPPING, REPLACE IT BY AN MTOR INHIBITOR, THIS WILL ADD AN OPTION TO COLON CANCERS!
ESMO DID SHOW THAT UPFRONT COMBINATION OF AVASTIN AND MTOR FAILED TO IMPROVE RESULTS (renal cancers) BUT GIVING MTOR AFTER AVASTIN FAILURE IS STILL BELIEVED TO BE BETTER (PROOF OF CONCEPT. DOES THE ESCAPE MECHANISMS TO AVASTIN OFFER AN OPPORTUNITY TO MTOR INHIBITOR FOR ACTION OR ACTIVITY? WHAT ARE THE PREDICTORS TO MTOR INHIBITORS 'ACTION? IS TISSUE HYPOXIA SECONDARY TO ENDOTHELIAL DISTURBANCES RESULTING FROM AVASTIN A PREDISPOSITION TO MTOR INHIBITOR ACTION?
*SHOULD WE GO AHEAD AND USE NAB-PACLITAXEL AND GEMZAR IN ADJUVANT SETTING NOW?(PANCREATIC CANCER)
*ADDING ERLOTINIB TO AVASTIN AS MAINTENANCE THERAPY AFTER FIRST LINE CHEMOTHERAPY OFFERED BETTER PROGRESSION FREE SURVIVAL (1 MONTH BETTER) IN A PHASE III TRIAL PRESENTED AT ASCO 2012! (COLON CANCER)
Showing posts with label esophageal cancer. Show all posts
Showing posts with label esophageal cancer. Show all posts
Friday, April 19, 2013
Tuesday, April 2, 2013
MSR1, ASCC1, and CTHRC1 (Nomenclature of Genes in Esophageal cancer)
CTHRC1" is a protein that has the ability to inhibit collagen matrix synthesis.
Expression of Cthrc1 is increased in fibroblasts and chondrocytic cells in response to TGF-beta family members including BMP4, BMP2 and TGF-beta. Cthrc1 is also upregulated during tumorigenesis and metastasis;
CTHRC1 has been linked to major signaling pathways such as Wnt and TGF-beta. The ability of CTHRC1 to inhibit TGF-beta signaling via a reduction in Smad 2/Smad 3 (is to be noted!)
Location 8q22.3. (Leclair at al )
Once again this comment suggests that stimulation of growth factor induced secondarily by NF-kB /c-JUn amplification leads to secondary amplification which in this case happens to this gene. This gene comes into play in vascular remodeling suggesting invasiveness of the cancer. This is the stuff used by neurone to find their way down their passage. If it is expressed it marks cellular invasiveness. Please pay marked attention to the pathway with witch it is identified, a pathway we believe is very important but neglected. The Wnt pathway. This is the metastasis pathways, it correlates with metastatic disease and is the stuff you find in triple negative Breast cancer!
Suppression of Smad2 could prevent cancer induced by Irritations? and may be secondary cancers?
2.ASCC1.
This gene encodes a subunit of the activating signal cointegrator 1 (ASC-1) complex. The ASC-1 complex is a transcriptional coactivator that plays an important role in gene transactivation by multiple transcription factors including activating protein 1 (AP-1), nuclear factor kappa-B (NF-kB) and serum response factor (SRF). The encoded protein contains an N-terminal KH-type RNA-binding motif which is required for AP-1 transactivation by the ASC-1 complex. Mutations in this gene are associated with Barrett esophagus and esophageal adenocarcinoma. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]"" (danielsen et al!)
Activating signal cointegrator 1 complex subunit 1 (ASCC1) is a subunit of the activating signal cointegrator 1 (ASC-1) complex. The ASC-1 complex is a transcriptional coactivator that plays an important role in gene transactivation by multiple transcription factors including activating protein 1 (AP-1), nuclear factor kappa-B (NF-kB) and serum response factor (SRF). ASCC1 contains an N-terminal KH-type RNA-binding motif which is required for AP-1 transactivation by the ASC-1 complex. Mutations in the ASCC1 gene are associated with Barrett esophagus and esophageal adenocarcinoma [taken from NCBI Entrez Gene (Gene ID: 51008)].
MSR1
already discussed
Expression of Cthrc1 is increased in fibroblasts and chondrocytic cells in response to TGF-beta family members including BMP4, BMP2 and TGF-beta. Cthrc1 is also upregulated during tumorigenesis and metastasis;
CTHRC1 has been linked to major signaling pathways such as Wnt and TGF-beta. The ability of CTHRC1 to inhibit TGF-beta signaling via a reduction in Smad 2/Smad 3 (is to be noted!)
Location 8q22.3. (Leclair at al )
Once again this comment suggests that stimulation of growth factor induced secondarily by NF-kB /c-JUn amplification leads to secondary amplification which in this case happens to this gene. This gene comes into play in vascular remodeling suggesting invasiveness of the cancer. This is the stuff used by neurone to find their way down their passage. If it is expressed it marks cellular invasiveness. Please pay marked attention to the pathway with witch it is identified, a pathway we believe is very important but neglected. The Wnt pathway. This is the metastasis pathways, it correlates with metastatic disease and is the stuff you find in triple negative Breast cancer!
Suppression of Smad2 could prevent cancer induced by Irritations? and may be secondary cancers?
2.ASCC1.
This gene encodes a subunit of the activating signal cointegrator 1 (ASC-1) complex. The ASC-1 complex is a transcriptional coactivator that plays an important role in gene transactivation by multiple transcription factors including activating protein 1 (AP-1), nuclear factor kappa-B (NF-kB) and serum response factor (SRF). The encoded protein contains an N-terminal KH-type RNA-binding motif which is required for AP-1 transactivation by the ASC-1 complex. Mutations in this gene are associated with Barrett esophagus and esophageal adenocarcinoma. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]"" (danielsen et al!)
Activating signal cointegrator 1 complex subunit 1 (ASCC1) is a subunit of the activating signal cointegrator 1 (ASC-1) complex. The ASC-1 complex is a transcriptional coactivator that plays an important role in gene transactivation by multiple transcription factors including activating protein 1 (AP-1), nuclear factor kappa-B (NF-kB) and serum response factor (SRF). ASCC1 contains an N-terminal KH-type RNA-binding motif which is required for AP-1 transactivation by the ASC-1 complex. Mutations in the ASCC1 gene are associated with Barrett esophagus and esophageal adenocarcinoma [taken from NCBI Entrez Gene (Gene ID: 51008)].
Alternative names for ASCC1 Antibody include activating signal cointegrator 1 complex subunit 1 antibody, ASC-1 complex subunit p50 antibody, Trip4 complex subunit p50 antibody, p50 antibody, CGI-18 antibody, ASC1p50 antibody.
I refuse to comment on this one because it is so obvious, this is at the core of pathogenesis where chronic stimuli act through the NF-kB and C-JUN to induce growth factors which eventually stimulate a secondary amplification that leads to the pathogenesis of cancer, additional mutations such as that occurring in CTHRC1 will complete the dance. This ASCC1 appears to be a CBF like molecular complex driving this transformation and therefore it is a valid target for therapy.MSR1
already discussed
Nomenclature of genes in Esophageal cancer (continued)
FEZ1 , fasciculation and Elongation protein Zeta,
a significant gene intervening in the motility of the Esophagus.
Alteration of this gene also increases cancer susceptibility to viral infection (HIV).
It interacts with NBR1, a gene that confers a certain refractoriness to this cancer
and supports the Idea that Cisplatin may be essential to treatment in this disease.
In fact, several neurological receptors are involved in Esophageal cancer
and may contribute to the disease's poor prognosis and epithelial morphology presentation.
RHBF2
--------
a significant gene intervening in the motility of the Esophagus.
Alteration of this gene also increases cancer susceptibility to viral infection (HIV).
It interacts with NBR1, a gene that confers a certain refractoriness to this cancer
and supports the Idea that Cisplatin may be essential to treatment in this disease.
In fact, several neurological receptors are involved in Esophageal cancer
and may contribute to the disease's poor prognosis and epithelial morphology presentation.
RHBF2
--------
Saturday, March 30, 2013
PTGS2 & MSR1
PTGS2:
The very existence of the amplification of this gene attests to the fact that in Esophageal cancer the stress imposed by chemical and traumatic irritants will involve inflammatory pathways and over-expression of Cyclins and growth Factors. Over-expression of COX-2 that this gene amplification represents leads to the formation of prostaglandins which decrease membrane protection by PGH2 and PGI2, with ulceration at the tumor level resulting. When you see an ulcerated cancer in the stomach or at the base of the Esophagus, you understand what happened!
It points to the potential importance of Interferon treatment as an adjunct therapy.
MSR1 (Macrophage Scavanger Receptor 1):
This gene amplification may stop Macrophages from removing irritated and altered cancer cells,. Irritated neoplastic cells often contain HSP (Heat shock proteins) altered proteins that should trigger action by the scavenger. But Mutation at MRS1 leads to a tolerance of the existence of these neoplastic cells. The HSP are normally generated by HSPA1A, a gene " located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins."(wikipedia)
In a normal cell, HSP will interact with ASK1 (Apoptosis Signal-Regulating Kinase1) and trigger independently Apoptosis, or use the same molecule as MAP3K5 to stimulate c-JUN (the stress pathway). And don't tell me we didn't warn you that, in the pathogenesis of Esophageal cancers, irritants will stimulate C-JUN the stress related family member of the MAP Kinases. ASK1 interacts with TNF alpha Receptor and a bunch of DNA protein Kinases that will lead to the production of inflammatory factors including the Autoimmune Antigen Ku!
There you have it, do not be surprised that HSP has much to do with other altered proteins called Amyloids...and you start getting the right idea that Alzheimer's disease is around the corner! Yes, the tolerance induced by Mutated MSR1 and HSP has something to do with the disposition of Amyloid deposits!
The very existence of the amplification of this gene attests to the fact that in Esophageal cancer the stress imposed by chemical and traumatic irritants will involve inflammatory pathways and over-expression of Cyclins and growth Factors. Over-expression of COX-2 that this gene amplification represents leads to the formation of prostaglandins which decrease membrane protection by PGH2 and PGI2, with ulceration at the tumor level resulting. When you see an ulcerated cancer in the stomach or at the base of the Esophagus, you understand what happened!
It points to the potential importance of Interferon treatment as an adjunct therapy.
MSR1 (Macrophage Scavanger Receptor 1):
This gene amplification may stop Macrophages from removing irritated and altered cancer cells,. Irritated neoplastic cells often contain HSP (Heat shock proteins) altered proteins that should trigger action by the scavenger. But Mutation at MRS1 leads to a tolerance of the existence of these neoplastic cells. The HSP are normally generated by HSPA1A, a gene " located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins."(wikipedia)
In a normal cell, HSP will interact with ASK1 (Apoptosis Signal-Regulating Kinase1) and trigger independently Apoptosis, or use the same molecule as MAP3K5 to stimulate c-JUN (the stress pathway). And don't tell me we didn't warn you that, in the pathogenesis of Esophageal cancers, irritants will stimulate C-JUN the stress related family member of the MAP Kinases. ASK1 interacts with TNF alpha Receptor and a bunch of DNA protein Kinases that will lead to the production of inflammatory factors including the Autoimmune Antigen Ku!
There you have it, do not be surprised that HSP has much to do with other altered proteins called Amyloids...and you start getting the right idea that Alzheimer's disease is around the corner! Yes, the tolerance induced by Mutated MSR1 and HSP has something to do with the disposition of Amyloid deposits!
Esophageal Cancer (continued)
We have discussed that chemical, traumatic and sometimes burns from caustic solutions that people ingest unfortunately, that will stimulate the cellular membrane receptors which in turn will stimulate RAS, which in turn will amplify PI3K, MAP Kinase and RAL/CDC42. But remember these are stressful stimulations, so instead of the standard MAPK, the stimulation is imposing on RAS to awake the NFkB pathway, the c_JUN and at nuclear level the FOS which results in inflammatory proteins stimulation including cyclin production or liberation from membranes with extracellular release of Metalloproteases. Cyclins combining to CDCs will exacerbate cell divisions and proliferation, growth factors will promote cell growth, there is an associated ligase proliferation that will impact P53 (through MDM2) and c-MYC, NOTCH, and even c_JUN itself through FBW7/hCDC4. This is how the proteasomes come into play!
By now you now
1. that amplification of c-MYC exacerbate proliferation by allowing progression of cells int S-phase and bolster DNA replication, imparting bad prognosis to cancer cells.
(nature is kind and gies you a chance to affect here by freeing RB1 and increasing FBW7. Oh! also find MYCN and the p isoform to q for answers!)
2 Rb1 does sequester E2F. you can look at it both ways. that E2F stabilize Rb1 instead, whichever way one stop the other for acting! Remember E2F activates CPP32 which increase APOPTOSIS! (DRUM UP THOSE TARGET THERAPY!)
3.REMEMBER RAS NEEDS A FATTY ACID MOIETY TO STAY AT THE MEMBRANE FOR ITS ACTIVITY (THIS IS ITS SO CALLED POST-TRANSLATIONAL MODIFICATION) BY THIS PHRENYLATION IS IMPAIRED BY THE FARNESYL TRANSFERASE INHIBITOR
(ie. TIPIFARNIB) THAT WE DO NOT USE ENOUGH I FEEL! ALTHOUGH I AGREE THAT SIDE EFFECTS MAY BE PROHIBITIVE GIVEN THE EXTENT OF WHICH NORMAL CELLS WILL ALSO BE COMPROMISED. BUT IT GOES TO THE FACT THAT WE NEED TO FURTHER TWEAK THIS MODALITY TO MAKE IT USABLE IN CANCERS!
ANTI-MEK HAVE DEMONSTRATED USE IN KRAS MUTATION CANCERS! MAY BE ESOPHAGEAL CANCERS WILL BENEFIT HERE!
4Role of combining Velcade and Carfilzomib in Esophageal cancer to see if c-Myc can be affected? Will it increase the right Ligand (FBW7)?
By now you now
1. that amplification of c-MYC exacerbate proliferation by allowing progression of cells int S-phase and bolster DNA replication, imparting bad prognosis to cancer cells.
(nature is kind and gies you a chance to affect here by freeing RB1 and increasing FBW7. Oh! also find MYCN and the p isoform to q for answers!)
2 Rb1 does sequester E2F. you can look at it both ways. that E2F stabilize Rb1 instead, whichever way one stop the other for acting! Remember E2F activates CPP32 which increase APOPTOSIS! (DRUM UP THOSE TARGET THERAPY!)
3.REMEMBER RAS NEEDS A FATTY ACID MOIETY TO STAY AT THE MEMBRANE FOR ITS ACTIVITY (THIS IS ITS SO CALLED POST-TRANSLATIONAL MODIFICATION) BY THIS PHRENYLATION IS IMPAIRED BY THE FARNESYL TRANSFERASE INHIBITOR
(ie. TIPIFARNIB) THAT WE DO NOT USE ENOUGH I FEEL! ALTHOUGH I AGREE THAT SIDE EFFECTS MAY BE PROHIBITIVE GIVEN THE EXTENT OF WHICH NORMAL CELLS WILL ALSO BE COMPROMISED. BUT IT GOES TO THE FACT THAT WE NEED TO FURTHER TWEAK THIS MODALITY TO MAKE IT USABLE IN CANCERS!
ANTI-MEK HAVE DEMONSTRATED USE IN KRAS MUTATION CANCERS! MAY BE ESOPHAGEAL CANCERS WILL BENEFIT HERE!
4Role of combining Velcade and Carfilzomib in Esophageal cancer to see if c-Myc can be affected? Will it increase the right Ligand (FBW7)?
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