Showing posts with label mucinous cancer. Show all posts
Showing posts with label mucinous cancer. Show all posts

Sunday, April 21, 2013

ONE IMPORTANT MECHANISM OF NEOPLASTIC TRANSFORMATION COMING OUT OF OUR OBSERVATION:

ONE IMPORTANT MECHANISM OF NEOPLASTIC TRANSFORMATION COMING OUT
OF OUR OBSERVATION: THE FAILURE OF RECEPTORS

LET US TAKE THIS EXAMPLE!
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Tumor necrosis factor-alpha induces mucin hypersecretion and MUC-2 gene expression by human airway epithelial cells.

Source

Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1662.

Abstract

Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional, pro-inflammatory cytokine that is capable of activating a diverse number of target genes within multiple cell types. Little information is known regarding the role of TNF-alpha in the regulation of human airway mucin hypersecretion and MUC-2 gene expression.

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LET'S ASSUME
THAT A GROWTH FACTOR HAS 2 PRINCIPAL RECEPTORS AND 2 SECONDARY RECEPTORS
(IN THIS EXAMPLE TNF- alpha IS SAID TO HAVE  A "NUMBER OF TARGET GENES")
IF FOR SOME REASONS THE GROWTH FACTOR FAILED TO ACTIVATE ITS PRINCIPAL RECEPTORS,  2 THINGS HAPPEN:

1. THE PRINCIPAL RECEPTOR
initiates a stress like response which will involve the HP90, exacerbating the NF- kB
resulting in further activation of promoter genes and formation of MORE TNF- alpha

2. MORE TNF-alpha will exacerbate the effect on SECONDARY receptors still sensitive, leading to the activation/amplification of unwanted genes,

- Amplification of MUC-1 leads to an Adenoma and eventually Adenocarcinoma.
- Amplification of MUC-2 leads to a pseudomyxoma.
- May be MUC-7 will be lung and bladder Cancer?

Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species.

Source

Division of Pediatric Pulmonary Diseases, Duke University Medical Center, Durham, North Carolina 27710, USA.

Abstract

Neutrophil-predominant airway inflammation and mucus obstruction of the airways are major pathologic features of chronic airway diseases, including cystic fibrosis and chronic bronchitis. Neutrophils release elastase, a serine protease that impairs mucociliary clearance and stimulates goblet cell metaplasia and mucin production. We previously reported that neutrophil elastase increases expression of a major respiratory mucin gene, MUC5AC, by enhancing mRNA stability. However, the molecular mechanisms of elastase-regulated MUC5AC expression are not known. We hypothesized that reactive oxygen species, generated by elastase treatment, mediate MUC5AC gene expression.

MUC4 gene polymorphisms associate with endometriosis development and endometriosis-related infertility.

Source

Human Genetic Center, China Medical University Hospital, Taichung, Taiwan.

Abstract

BACKGROUND:

Mucin 4 (MUC4) plays an important role in protecting and lubricating the epithelial surface of reproductive tracts, but its role in the pathogenesis of endometriosis is largely unknown.

MUC3 human intestinal mucin. Analysis of gene structure, the carboxyl terminus, and a novel upstream repetitive region.

Source

Gastrointestinal Research Laboratory (151M2), Department of Veterans Affairs Medical Center, University of California, San Francisco, California 94121, USA.

Abstract

MUC3 is a large mucin glycoprotein expressed by the human intestine and gall bladder.

MUC6 - Wikipedia, the free encyclopedia

en.wikipedia.org/wiki/MUC6
Reid CJ, Harris A (1999). "Expression of the MUC 6 mucin gene in development of the human kidney and male genital ducts.".

PICK A NUMBER AND YOU WILL FIND WHERE THE CANCER WILL BE. THIS IS THE POWER OF RECEPTORS AND THE POWER OF GENE POLYMORPHISM! 

Let's play:
Full Name mucin 10, submandibular gland salivary mucin

MUC12 »  Mucin-12  (MUC-12)
Protein also known as:  Mucin-11 (MUC-11).
Gene name:  MUC12
This protein has been shown to exist at protein level

Expression

Ubiquitous, with higher expression in colon. Down-regulated in colorectal cancer as well as in the colon of patients with ulcerative colitis (UC) and Crohn's disease (CD).  
  • CuratedUniProtKB
Ubiquitous cytoplasmic expression in all tissues at variable levels. Highest expression in gastrointestinal tract. silver HPA027769; HPA023835

THIS EXERCISE CAN BE DONE WITH ALL ADENOCARCINOMAS!

DO YOU SEE PORTRAYED HERE A TARGET FOR THERAPY OR DIAGNOSIS?  
LET'S GO TO WORK!


In Summary,
Epithelial covers of Mucosa secrete a Mucine to protect it against infection and immune system exactions
and depending on localization the MUCINE is made a different family member of MUC -x  gene
this is helpful when you have a carcinoma of unknown primary, look at the MUC gene amplified

YOU reach the door of MESENCHYMALIZATION when you reach MUC-20, this is where epidermal and endothelial switch, where squamous switch to adenocarcinoma, where the MEK gene is located!

Tuesday, March 26, 2013

A few Genes on Bladder Cancer

MUC1:  Mucinous cancers are known to be dangerous because by the time they are diagnosed, the extent is a little more then first thought.  Mucin is used by cancer cells to hide from immune detection it is believed.  MUC1 interacts with GrB 2 which affects a multitudes of other genes and transcription factors.Through YES1, it interacts with JAK2.  Action through JAK2 may have been why Epogen was prohibited for use in the Curable cancer setting.  JAK2 sensitizes cancer to Epogen, and to other growth factors!
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AZPG1

"Original Article

Oncogene 29, 5146-5158 (16 September 2010) | doi:10.1038/onc.2010.258

AZGP1 is a tumor suppressor in pancreatic cancer inducing mesenchymal-to-epithelial transdifferentiation by inhibiting TGF-β-mediated ERK signaling

B Kong, C W Michalski, X Hong, N Valkovskaya, S Rieder, I Abiatari, S Streit, M Erkan, I Esposito, H Friess and J Kleeff
Epithelial-to-mesenchymal transdifferentiation (EMT) mediated by transforming growth factor-β (TGF-β) signaling leads to aggressive cancer progression. In this study, we identified zinc-α2-glycoprotein (AZGP1, ZAG) as a tumor suppressor in pancreatic ductal adenocarcinoma whose expression is lost due to histone deacetylation."
It is associated with FAT/cahchexic losses in these patients
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TMPRSS2-ERG fusion
NKX3
c-MYC
PTEN
Favorable Gene hCAP-D3
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In Gastric Cancer
LOX
RASSF6
MR1
miRNA 107 (DICER1)
PDCD4
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In Colon Cancer

Annexin
S100A4
SERCA
GF15
BAX

Sunday, November 11, 2012

Hypothesis for Cancer Research: Mucinous Cancer

One of the bad types of gastroenterologic cancers such as Gastric and Colon cancers is the one known as Mucinous Cancer.  Basically, this cancer produces a Mucin assumed to be a viscous liquid surrounding the cell.  This tumor spreads early and deeply. At the time it is found, most of the time, the cancer is in advanced stage.  Researchers have explained this phenomenon by stating that this Mucin contains many ingredients suppressive to immunity (including Cytokines), and soluble Molecules (such as Prostaglandin E2) that may down regulate local immunity against the cancer.  It may also have those metalloproteases that we discussed in our earlier post for research suggestions on Oct, 14, 2012
Prostaglandins in general respond to anti inflammatory agents.
CAN WE MEASURE THE LEVEL OF TISSUE PROSTAGLANDINS IN MUCINOUS CANCERS AS A PREDICTOR OF ANTI-INFLAMMATORY (ASPIRIN) MAINTENANCE THERAPY POST PRIMARY TREATMENT TO DECREASE RATE OF METASTASIS IN COLON AND GASTRIC CANCERS?

CAN ANTI-MUCIN (AFTER WE KNOW THE REAL CONTENT FOR SPECIFIC CANCER TISSUE) PROVIDE AN INCREASE OF ANTIBODY BINDING TO CANCER CELLS?

TREG CELLS are cells involved in tolerance of our own cells.  They work to stop us from killing our own cells.  ARE THEY INCREASED IN CANCERS TO DECREASE CELLULAR IMMUNITY AGAINST CANCERS?

CANCER CELLS SEEMS TO HAVE A SELF GROWTH HORMONE WHICH IS SECRETED IN ITS IMMEDIATE SURROUNDING.  THIS HORMONE ACTS THROUGH RECEPTORS ON THE EXTERNAL MEMBRANE OF THE CELL.  THE PROFILE OF RECEPTORS ON CANCER MEMBRANES IS DEFINITELY DIFFERENT FROM THE NORMAL CELL.  WHY CAN'T WE PRACTICE "PROFILING" BY INVENTORYING ALL THE RECEPTORS (OR CRITICAL RECEPTORS)?
RECEPTORS ARE MADE BY GENES MOSTLY, WE CAN CONTROL THESE THROUGH OUR KNOWLEDGE OF GENETICS.  IF WE KNOW RECEPTORS EXCLUSIVE TO CANCER CELLS,
CAN WE DEVELOP ANTIBODY TO THESE RECEPTORS?