INT187422

Context Info Confidence 0.57 First Reported 2005 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 23 Total Number 24 Disease Relevance 11.75 Pain Relevance 0.24

lipid binding (MTTP) transport (MTTP) small molecule metabolic process (MTTP) Golgi apparatus (MTTP) lipid metabolic process (MTTP)

Anatomy Link Frequency plasma 4 proximal 2 intestine 2 liver 1 MTP 1 MTTP (Homo sapiens)

Pain Link Frequency Relevance Heat headache 5 100.00 Spinal cord 5 93.24 nud 1 66.32 Pain 10 55.84 ischemia 25 40.84 Osteoarthritis 133 33.56 cytokine 23 28.16 Inflammation 26 5.00 cva 18 5.00 dexamethasone 18 5.00

Disease Link Frequency Relevance Heat Fatigue 10 100.00 Headache 5 100.00 Fever 4 100.00 Chills 3 100.00 Adverse Drug Reaction 1 100.00 Leukemia 3 99.84 Fibromyalgia 2 99.32 Weight Loss 4 99.04 Myeloid Leukemia 4 98.76 Chronic Myeloid Leukemia 1 98.72

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In 1992, a deficiency of microsomal triglyceride transfer protein (MTP) activity was suggested to be the proximal cause of ABL [4].

Negative_regulation (deficiency) of MTP in proximal

1) Confidence 0.57 Published 2008 Journal Orphanet J Rare Dis Section Body Doc Link PMC2467409 Disease Relevance 0.66 Pain Relevance 0

In 1992, a deficiency of microsomal triglyceride transfer protein (MTP) activity was suggested to be the proximal cause of ABL [4].

Negative_regulation (deficiency) of microsomal triglyceride transfer protein in proximal

2) Confidence 0.57 Published 2008 Journal Orphanet J Rare Dis Section Body Doc Link PMC2467409 Disease Relevance 0.66 Pain Relevance 0

Imatinib was one of the first successful targeted therapies, initially developed as a specific inhibitor of the bcr-abl kinase aberrantly expressed in chronic myelogenous leukemia.

Negative_regulation (inhibitor) of abl associated with chronic myeloid leukemia

3) Confidence 0.57 Published 2007 Journal Breast Cancer Res Section Body Doc Link PMC2242654 Disease Relevance 0.72 Pain Relevance 0.03

Such long-term experience in ABL is relevant particularly since pharmacological MTP inhibition has recently been proposed as a therapeutic option for patients with severe hypercholesterolemia [22].

Negative_regulation (inhibition) of MTP associated with hyperlipidemia

4) Confidence 0.50 Published 2008 Journal Orphanet J Rare Dis Section Body Doc Link PMC2467409 Disease Relevance 0.81 Pain Relevance 0

The clinical presentation is very heterogeneous and previous reports had suggested that MTP deficiency is not the sole cause of ABL [11].

Negative_regulation (deficiency) of MTP

5) Confidence 0.42 Published 2008 Journal Orphanet J Rare Dis Section Body Doc Link PMC2467409 Disease Relevance 1.37 Pain Relevance 0.05

Imatinib mesylate (Glivec®) was originally developed for tailored inhibition of the oncoprotein bcr-abl in chronic myeloid leukaemia (CML) and is today part of CML standard therapies.

Negative_regulation (inhibition) of abl associated with leukemia and myeloid leukemia

6) Confidence 0.42 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2925350 Disease Relevance 0.98 Pain Relevance 0

Patients with unresectable and metastatic gastro-intestinal stromal tumors (GISTs) have an improved PFS and overall survival when they are treated with imatinib.56 Imatinib is an oral tyrosine kinase receptor inhibitor whose mechanism of action is not inhibition of angiogenesis – it acts mainly by inhibiting the activity of the fusion protein bcr-abl.

Negative_regulation (inhibiting) of abl associated with cancer

7) Confidence 0.42 Published 2010 Journal OncoTargets and therapy Section Body Doc Link PMC2895781 Disease Relevance 0.52 Pain Relevance 0

Eight mice lacking apoB100 (Mttp?

Negative_regulation (lacking) of Mttp

8) Confidence 0.42 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2582480 Disease Relevance 0.06 Pain Relevance 0

Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha, beta and c-kit.

Negative_regulation (inhibitor) of abl

9) Confidence 0.42 Published 2010 Journal BMC Cancer Section Abstract Doc Link PMC2925350 Disease Relevance 0.31 Pain Relevance 0

Imatinib mesylate is a potent, selective inhibitor of PDGFR alpha (PDGFRa), PDGFR beta (PDGFRb), BCR-abl, KIT, ARG and c-FMS protein-tyrosine kinases [12,14].

Negative_regulation (inhibitor) of abl associated with fibromyalgia

10) Confidence 0.41 Published 2010 Journal World J Surg Oncol Section Body Doc Link PMC2892497 Disease Relevance 0.31 Pain Relevance 0

Because pharmacologic inhibition of MTP is being developed as a novel approach to reduce plasma cholesterol for prevention of cardiovascular disease, defining the long-term clinical features of patients with a natural deficiency in MTP might provide some insight into the possible effects of such treatments.

Negative_regulation (inhibition) of MTP in plasma associated with cardiovascular disease

11) Confidence 0.37 Published 2008 Journal Orphanet J Rare Dis Section Abstract Doc Link PMC2467409 Disease Relevance 0.70 Pain Relevance 0

In addition, the inhibition of the mitochondrial permeability transition pore (MTP), a mitochondrial channel which mediates cell death at the time of myocardial reperfusion by uncoupling oxidative phosphorylation and inducing mitochondrial swelling (Hausenloy and Yellon 2003), has been identified as a downstream target of the RISK pathway (Davidson et al 2006; Bopassa et al 2006).

Negative_regulation (inhibition) of MTP in MTP associated with pressure and volume under development and death

12) Confidence 0.21 Published 2007 Journal Vascular Health and Risk Management Section Body Doc Link PMC2291307 Disease Relevance 0.39 Pain Relevance 0.06

Abetalipoproteinemia, a genetic disorder characterized by low plasma cholesterol and TG levels, is caused by a functional deficiency of MTP.

Negative_regulation (deficiency) of MTP in plasma associated with hypolipidemia

13) Confidence 0.20 Published 2005 Journal BMC Cardiovasc Disord Section Body Doc Link PMC1262701 Disease Relevance 0.31 Pain Relevance 0

This finding led to the suggestion that MTP inhibition could be used as a possible lipid lowering therapy.

Negative_regulation (inhibition) of MTP

14) Confidence 0.20 Published 2005 Journal BMC Cardiovasc Disord Section Body Doc Link PMC1262701 Disease Relevance 0.33 Pain Relevance 0

By blocking MTP, JTT-130 reduced the secretion of VLDL particles, and therefore, the formation of LDL in the plasma.

Negative_regulation (blocking) of MTP in plasma

15) Confidence 0.20 Published 2005 Journal BMC Cardiovasc Disord Section Body Doc Link PMC1262701 Disease Relevance 0.20 Pain Relevance 0

Because of this, we speculate that due to MTP inhibition, less TG were transferred to the chylomicron particle being packaged in the intestine.

Negative_regulation (inhibition) of MTP in intestine

16) Confidence 0.20 Published 2005 Journal BMC Cardiovasc Disord Section Body Doc Link PMC1262701 Disease Relevance 0.06 Pain Relevance 0

MTP inhibitors may be used to promote weight loss [19], but they may have detrimental side effects, such as fat accumulation in the liver and small intestine.

Negative_regulation (inhibitors) of MTP in liver associated with weight loss

17) Confidence 0.17 Published 2008 Journal BMC Genomics Section Body Doc Link PMC2519092 Disease Relevance 0.10 Pain Relevance 0

This study also demonstrates that MTP inhibitor which is mainly targeted towards the intestine may open a new avenue for treatment of hyperlipidemic patients who are at high risk for cardiovascular diseases.

Negative_regulation (inhibitor) of MTP in intestine associated with cardiovascular disease

18) Confidence 0.17 Published 2005 Journal BMC Cardiovasc Disord Section Body Doc Link PMC1262701 Disease Relevance 0.51 Pain Relevance 0

Certain animal and human studies [6,7] have shown that the inhibition of MTP blocks the hepatic secretion of VLDL and the intestinal secretion of chylomicrons.

Negative_regulation (inhibition) of MTP associated with disorder of lipid metabolism

19) Confidence 0.15 Published 2005 Journal BMC Cardiovasc Disord Section Body Doc Link PMC1262701 Disease Relevance 0.53 Pain Relevance 0

It is believed that blocking MTP will not only reduce plasma total and LDL cholesterol (LDL-C) but also plasma VLDL and TG by affecting the packaging and secretion of VLDL and chylomicrons.

Negative_regulation (blocking) of MTP in plasma associated with disorder of lipid metabolism

20) Confidence 0.15 Published 2005 Journal BMC Cardiovasc Disord Section Body Doc Link PMC1262701 Disease Relevance 0.67 Pain Relevance 0

General Comments

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