INT86909

Context Info Confidence 0.41 First Reported 1999 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 9 Total Number 9 Disease Relevance 12.65 Pain Relevance 1.70

nuclear chromosome (MSH2) ATPase activity (MSH2) nucleus (MSH2) enzyme binding (MSH2) DNA binding (MSH2)

Anatomy Link Frequency MLH1 2 GALT 1 MSH2 (Homo sapiens)

Pain Link Frequency Relevance Heat Dismenorea 6 100.00 metalloproteinase 7 99.88 cINOD 7 97.36 endometriosis 8 91.08 aspirin 4 87.52 Opioid 1 87.36 Inflammation 13 85.12 chemokine 1 83.08 Piles 3 75.00 Pain 3 67.16

Disease Link Frequency Relevance Heat Dysmenorrhea 6 100.00 Microsatellite Instability 158 99.76 Cancer 386 99.74 Endometrial Cancer 232 99.52 Colon Cancer 118 99.40 Apoptosis 63 96.04 Endometroid Carcinoma 33 95.12 Fistula 3 91.32 Endometriosis (extended) 12 91.08 Chromosomal Instability 2 90.36

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Inactivation of hMSH2, one of the most commonly hMMR genes, is a described alternative pathway in cancer development and progression.

Negative_regulation (Inactivation) of hMSH2 associated with cancer

1) Confidence 0.41 Published 2004 Journal International Journal of Medical Sciences Section Body Doc Link PMC1074709 Disease Relevance 1.55 Pain Relevance 0.11

MSH2 DNA mismatch repair protein MSH2

Negative_regulation (repair) of MSH2

2) Confidence 0.36 Published 2005 Journal BMC Cancer Section Body Doc Link PMC1198222 Disease Relevance 0.68 Pain Relevance 0.40

The tumor specimens showed no MLH1 expression but did show normal MSH2 expression. p53 was not expressed.

Negative_regulation (p53) of MSH2 in MLH1 associated with cancer

3) Confidence 0.35 Published 2007 Journal J Nippon Med Sch Section Abstract Doc Link 17878704 Disease Relevance 2.67 Pain Relevance 0.10

Unlike HNPCC associated colorectal carcinoma, which appears to frequently have MLH1 and MSH2 mutations, endometrial carcinomas have a higher probability of MSH2 and MSH6 mutations [13, 25].

Negative_regulation (have) of MSH2 in MLH1 associated with colon cancer and endometrial cancer

4) Confidence 0.32 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 1.67 Pain Relevance 0

The mechanism for the inactivation of MSH2 is still not clear, as promoter methylation and mutations are rare.

Negative_regulation (inactivation) of MSH2

5) Confidence 0.25 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2852605 Disease Relevance 2.11 Pain Relevance 0

MSI frequency in cells deficient of MMR genes (hMSH2, hMLH1, hMSH6) was markedly reduced after long-term (> 10 weeks) NSAID treatment.

Negative_regulation (deficient) of hMSH2 associated with cinod and microsatellite instability

6) Confidence 0.10 Published 1999 Journal Verh Dtsch Ges Pathol Section Abstract Doc Link 10714217 Disease Relevance 1.32 Pain Relevance 0.53

Loss of heterozygosity in adenomyosis on hMSH2, hMLH1, p16Ink4 and GALT loci.

Negative_regulation (Loss) of hMSH2 in GALT associated with dismenorea

7) Confidence 0.04 Published 2000 Journal Int. J. Mol. Med. Section Title Doc Link 11078826 Disease Relevance 0.74 Pain Relevance 0.56

Because we noted fluctuation in hMSH2 levels throughout the treatment of several patients, it is possible that hMSH2 downregulation occurs at the post-transcriptional level and could be related to the use of chemotherapy based on alkylating agents.

Negative_regulation (downregulation) of hMSH2

8) Confidence 0.01 Published 2005 Journal Breast Cancer Res Section Body Doc Link PMC1064099 Disease Relevance 1.09 Pain Relevance 0

While all 9 tumors with hMLH1, hMSH2, or hPMS2 losses were MSI-H, only 2/5 of the CRCs with isolated losses of hMSH6 were MSI-H; in both cases, just 3/5 markers were mutated and in the other three, none were mutated.

Negative_regulation (losses) of hMSH2 associated with cancer and microsatellite instability

9) Confidence 0.01 Published 2007 Journal Hered Cancer Clin Pract Section Body Doc Link PMC2736982 Disease Relevance 0.83 Pain Relevance 0

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