INT190023

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Context Info
Confidence 0.25
First Reported 2006
Last Reported 2011
Negated 0
Speculated 0
Reported most in Body
Documents 15
Total Number 17
Disease Relevance 12.36
Pain Relevance 0.16

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

endosome (Mrc1) signal transduction (Mrc1) plasma membrane (Mrc1)
Anatomy Link Frequency
white blood cells 1
germline 1
spleen 1
epithelium 1
MLH1 1
Mrc1 (Mus musculus)
Pain Link Frequency Relevance Heat
iatrogenic 12 81.72 Quite High
addiction 27 69.64 Quite High
cINOD 24 55.32 Quite High
agonist 12 47.60 Quite Low
Inflammation 66 46.00 Quite Low
cytokine 11 11.96 Low Low
Inflammatory response 9 5.00 Very Low Very Low Very Low
Bioavailability 6 5.00 Very Low Very Low Very Low
Potency 6 5.00 Very Low Very Low Very Low
headache 4 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Cancer 1583 99.96 Very High Very High Very High
Immunodeficiency 24 99.76 Very High Very High Very High
Apoptosis 503 99.62 Very High Very High Very High
Microsatellite Instability 54 99.48 Very High Very High Very High
Death 86 99.36 Very High Very High Very High
Philadelphia Chromosome 24 99.34 Very High Very High Very High
Chromosome Aberrations 14 99.22 Very High Very High Very High
Renal Cancer 48 99.20 Very High Very High Very High
Toxicity 33 98.40 Very High Very High Very High
Colon Cancer 21 98.36 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The observation that human and mouse null mutations for critical MMR genes allow essentially normal development demonstrate clearly that the loss of MMR alone is insufficient to initiation a carcinogenic transforming event, but that additional genetic changes are also required for the transition to frank malignancy.
Negative_regulation (loss) of MMR associated with malignant neoplastic disease
1) Confidence 0.25 Published 2006 Journal Nucleic Acids Research Section Body Doc Link PMC1361617 Disease Relevance 0.67 Pain Relevance 0
The spectrum of cancer susceptibility attributable to MMR deficiency
Negative_regulation (deficiency) of MMR associated with cancer
2) Confidence 0.25 Published 2006 Journal Nucleic Acids Research Section Body Doc Link PMC1361617 Disease Relevance 0.78 Pain Relevance 0
The observation is supported by mouse model studies that show combining MMR deficiency with immunodeficiency (Msh2?
Negative_regulation (deficiency) of MMR associated with immunodeficiency
3) Confidence 0.21 Published 2006 Journal Nucleic Acids Research Section Body Doc Link PMC1361617 Disease Relevance 0.64 Pain Relevance 0.04
The insertion/deletion frameshift mutation phenotype of MMR deficiency is predicted not only to cause gene mutations, but also lead to the creation of novel protein antigens that are generated by the alternate reading frames and expressed in cells.
Negative_regulation (deficiency) of MMR
4) Confidence 0.21 Published 2006 Journal Nucleic Acids Research Section Body Doc Link PMC1361617 Disease Relevance 0.81 Pain Relevance 0
Finally, we propose that not only high proliferation rates, but the rapid acceleration and deceleration of proliferation rates may play a significant role in the specific cell types affected by MMR deficiency, and suggest experiments to test this hypothesis directly.



Negative_regulation (deficiency) of MMR
5) Confidence 0.19 Published 2006 Journal Nucleic Acids Research Section Body Doc Link PMC1361617 Disease Relevance 0.12 Pain Relevance 0.03
There are three reasons for thinking that initiation of apoptosis may contribute to MMR defective tumor specificity.
Negative_regulation (defective) of MMR associated with cancer and apoptosis
6) Confidence 0.19 Published 2006 Journal Nucleic Acids Research Section Body Doc Link PMC1361617 Disease Relevance 1.49 Pain Relevance 0
Since cadmium is associated with both inactivation of MMR (135) and sporadic renal carcinoma (RR 2.0) (136,137), testing the hypothesis that this agent induces MMR-deficient renal cancers could be carried out by exposing MMR defective animal models, or measurements of this element in renal tissues from affected patients as cadmium should not be affected by formalin fixation.
Negative_regulation (inactivation) of MMR associated with renal cancer
7) Confidence 0.19 Published 2006 Journal Nucleic Acids Research Section Body Doc Link PMC1361617 Disease Relevance 0.72 Pain Relevance 0.06
Target genes in tumors from germline recessive versus sporadically acquired MMR deficiency
Negative_regulation (deficiency) of MMR in germline associated with cancer
8) Confidence 0.19 Published 2006 Journal Nucleic Acids Research Section Body Doc Link PMC1361617 Disease Relevance 1.10 Pain Relevance 0
Third, apoptosis is particularly critical for all the cell types that are susceptible to cell autonomous MMR deficiency, including gastrointestinal, ovarian and endometrial epithelium and white blood cells.
Negative_regulation (deficiency) of MMR in epithelium associated with apoptosis
9) Confidence 0.19 Published 2006 Journal Nucleic Acids Research Section Body Doc Link PMC1361617 Disease Relevance 0.79 Pain Relevance 0
These results suggest that MMR deficiency can accelerate myeloid leukemogenesis in Nf1+/?
Negative_regulation (deficiency) of MMR
10) Confidence 0.19 Published 2006 Journal Nucleic Acids Research Section Body Doc Link PMC1361617 Disease Relevance 0.81 Pain Relevance 0.03
We evaluate recent data giving insights into the specific tumor types that are attributable to defective MMR in humans and mice under different modes of inheritance, and propose models that may explain the spectrum of cancer types observed.



Negative_regulation (defective) of MMR associated with cancer
11) Confidence 0.19 Published 2006 Journal Nucleic Acids Research Section Abstract Doc Link PMC1361617 Disease Relevance 0.95 Pain Relevance 0
Suboptimal response was defined as incomplete hematologic response at 3 months, less than partial CR at 6 months, less than complete cytogenetic response at 12 months, and less than MMR at 18 months, or acquisition of cytogenetic abnormalities in Ph+ cells, mutations of BCR-ABL or loss of MMR at any time (Baccarani et al 2006).
Negative_regulation (loss) of MMR associated with chromosome aberrations and philadelphia chromosome
12) Confidence 0.10 Published 2008 Journal OncoTargets and therapy Section Body Doc Link PMC2994207 Disease Relevance 0.26 Pain Relevance 0
Hematological resistance is a lack of normalization of peripheral blood counts and spleen size; cytogenetic resistance is a failure to achieve a major cytogenetic response; and molecular resistance represents the failure to achieve or loss of complete or MMR (Hochhaus and La Rosee 2004).
Negative_regulation (loss) of MMR in spleen
13) Confidence 0.10 Published 2008 Journal OncoTargets and therapy Section Body Doc Link PMC2994207 Disease Relevance 0.09 Pain Relevance 0
Third, apoptosis is particularly critical for all the cell types that are susceptible to cell autonomous MMR deficiency, including gastrointestinal, ovarian and endometrial epithelium and white blood cells.
Negative_regulation (deficiency) of MMR in white blood cells associated with apoptosis
14) Confidence 0.06 Published 2006 Journal Nucleic Acids Research Section Body Doc Link PMC1361617 Disease Relevance 0.79 Pain Relevance 0
Zhitkovich and colleagues argue that exposure to Cr(VI) might selectively inhibit the growth or promote the death of normal cells but that cells deficient in MMR “due to spontaneous mutagenesis and epigenetic changes” would continue to proliferate and acquire more mutations because of their insensitivity to Cr(VI) (Peterson-Roth et al., 2005).
Negative_regulation (deficient) of MMR associated with death
15) Confidence 0.05 Published 2011 Journal Toxicological Sciences Section Body Doc Link PMC3003834 Disease Relevance 0.55 Pain Relevance 0
These authors reported that several cell lines deficient in MMR genes were resistant to Cr(VI)-induced toxicity (Peterson-Roth et al., 2005).
Negative_regulation (deficient) of MMR associated with toxicity
16) Confidence 0.05 Published 2011 Journal Toxicological Sciences Section Body Doc Link PMC3003834 Disease Relevance 0.73 Pain Relevance 0
MSI is often a result of the loss or hindrance of DNA MMR, and nearly a third of individuals with colorectal cancers characterized by MSI have hereditary mutations in genes involved with MMR such as MLH1; moreover, 15–20% of the sporadic cases with MSI exhibit hypermethylation of MLH1 (Geigl et al., 2008; Grady and Carethers, 2008).
Negative_regulation (loss) of MMR in MLH1 associated with colon cancer and microsatellite instability
17) Confidence 0.05 Published 2011 Journal Toxicological Sciences Section Body Doc Link PMC3003834 Disease Relevance 1.05 Pain Relevance 0

General Comments

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