INT72138

Context Info Confidence 0.75 First Reported 1997 Last Reported 2010 Negated 0 Speculated 0 Reported most in Abstract Documents 18 Total Number 18 Disease Relevance 17.68 Pain Relevance 1.49

extracellular space (Pthlh) Golgi apparatus (Pthlh) nucleus (Pthlh) intracellular (Pthlh) cytoplasm (Pthlh)

Anatomy Link Frequency parathyroid 4 osteoblasts 2 chondrocyte 1 articular 1 growth plate 1 Pthlh (Mus musculus)

Pain Link Frequency Relevance Heat Snapping jaw 14 95.92 metalloproteinase 1 93.76 melanocortin 1 receptor 1 90.08 Spinal cord 2 85.20 antagonist 3 82.32 imagery 7 69.04 Pain 15 63.48 agonist 1 53.76 Inflammation 6 5.00 Intractable pain 2 5.00

Disease Link Frequency Relevance Heat Cancer 183 100.00 Chondrosarcoma 50 99.92 Breast Cancer 54 99.84 Reprotox - General 1 10 99.84 Prostate Cancer 22 99.56 Diabetes Mellitus 1 99.52 Osteolysis 6 99.44 Obesity 6 99.26 Chondroma 41 99.16 Osteochondroma 82 98.92

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Production of PTH-rP by breast carcinoma cells in bone is enhanced by growth factors produced as a consequence of normal bone remodeling, particularly activated transforming growth factor-beta (TGF-beta).

Gene_expression (Production) of PTH-rP associated with breast cancer

1) Confidence 0.75 Published 1997 Journal Cancer Section Abstract Doc Link 9362421 Disease Relevance 1.02 Pain Relevance 0

Thus, a vicious cycle exists in bone between production by the tumor cells of mediators such as PTH-rP and subsequent production by bone of growth factors such as TGF-beta, which enhance PTH-rP production.

Gene_expression (production) of PTH-rP associated with cancer

2) Confidence 0.75 Published 1997 Journal Cancer Section Abstract Doc Link 9362421 Disease Relevance 1.16 Pain Relevance 0.06

In the case of breast carcinoma, the final step in bone metastasis (namely bone destruction) is mediated by osteoclasts that are stimulated by local production of the tumor peptide parathyroid hormone-related peptide (PTH-rP), whereas prostate carcinomas stimulate osteoblasts to make new bone.

Gene_expression (production) of parathyroid hormone-related peptide in osteoblasts associated with cancer, breast cancer, prostate cancer and metastasis

3) Confidence 0.75 Published 1997 Journal Cancer Section Abstract Doc Link 9362421 Disease Relevance 1.04 Pain Relevance 0

Thus, a vicious cycle exists in bone between production by the tumor cells of mediators such as PTH-rP and subsequent production by bone of growth factors such as TGF-beta, which enhance PTH-rP production.

Gene_expression (production) of PTH-rP associated with cancer

4) Confidence 0.75 Published 1997 Journal Cancer Section Abstract Doc Link 9362421 Disease Relevance 1.12 Pain Relevance 0.05

In the case of breast carcinoma, the final step in bone metastasis (namely bone destruction) is mediated by osteoclasts that are stimulated by local production of the tumor peptide parathyroid hormone-related peptide (PTH-rP), whereas prostate carcinomas stimulate osteoblasts to make new bone.

Gene_expression (production) of PTH-rP in osteoblasts associated with cancer, breast cancer, prostate cancer and metastasis

5) Confidence 0.75 Published 1997 Journal Cancer Section Abstract Doc Link 9362421 Disease Relevance 1.04 Pain Relevance 0

Expression of PTHrP, the PTHR1, and their downstream partner Bcl2 may be correlated with the grade of malignancy in chondrosarcoma [16-19].

Gene_expression (Expression) of PTHrP associated with malignant neoplastic disease and chondrosarcoma

6) Confidence 0.69 Published 2006 Journal Orphanet J Rare Dis Section Body Doc Link PMC1592482 Disease Relevance 1.68 Pain Relevance 0.09

Thus, a vicious cycle exists in bone between production by the tumor cells of mediators such as PTH-rP and subsequent production by bone of growth factors such as TGF-beta, which enhance PTH-rP production.

Gene_expression (production) of PTH-rP associated with cancer

7) Confidence 0.65 Published 1997 Journal Cancer Section Abstract Doc Link 9362421 Disease Relevance 1.12 Pain Relevance 0.05

Thus, a vicious cycle exists in bone between production by the tumor cells of mediators such as PTH-rP and subsequent production by bone of growth factors such as TGF-beta, which enhance PTH-rP production.

Gene_expression (production) of PTH-rP associated with cancer

8) Confidence 0.65 Published 1997 Journal Cancer Section Abstract Doc Link 9362421 Disease Relevance 1.16 Pain Relevance 0.06

Production of PTH-rP by breast carcinoma cells in bone is enhanced by growth factors produced as a consequence of normal bone remodeling, particularly activated transforming growth factor-beta (TGF-beta).

Gene_expression (Production) of PTH-rP associated with breast cancer

9) Confidence 0.65 Published 1997 Journal Cancer Section Abstract Doc Link 9362421 Disease Relevance 1.02 Pain Relevance 0

Condylar cartilage growth, polymorphic cell proliferation, and PTHrP expression were all inhibited, and growth plate organization and chondrocyte gene expression patterns were abnormal.

Gene_expression (expression) of PTHrP in chondrocyte

10) Confidence 0.54 Published 2007 Journal Dev. Dyn. Section Abstract Doc Link 17191253 Disease Relevance 0.39 Pain Relevance 0.39

In wild-type mouse embryos, Ihh expression was already strong in condylar cartilage by embryonic day (E) 15.5, and expression of Ihh receptors and effector genes (Gli1, Gli2, Gli3, and PTHrP) indicated that Ihh range of action normally reached apical condylar tissue layers, including polymorphic chondroprogenitor layer and articular disc primordia.

Gene_expression (expression) of PTHrP in articular

11) Confidence 0.54 Published 2007 Journal Dev. Dyn. Section Abstract Doc Link 17191253 Disease Relevance 0.43 Pain Relevance 0.43

In addition to RANKL, parathyroid hormone-related protein and interleukin-6 are produced by prostate cancer cells and can promote osteoclastogenesis.

Gene_expression (produced) of parathyroid hormone-related protein in parathyroid associated with reprotox - general 1

12) Confidence 0.47 Published 2002 Journal Drugs Today Section Abstract Doc Link 12532187 Disease Relevance 2.21 Pain Relevance 0.11

IL = interleukin; OPG = osteoprotegerin; PTHrP = parathyroid hormone-related peptide; RANK = receptor activator of NF-?

Gene_expression (parathyroid) of PTHrP in parathyroid

13) Confidence 0.38 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2374958 Disease Relevance 0.59 Pain Relevance 0.04

IL = interleukin; OPG = osteoprotegerin; PTHrP = parathyroid hormone-related peptide; RANK = receptor activator of NF-?

Gene_expression (parathyroid) of hormone-related peptide in parathyroid

14) Confidence 0.33 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2374958 Disease Relevance 0.59 Pain Relevance 0.04

Both the therapy with SB431542 as well as tumors transduced with the inhibitory protein SMAD-7, showed significantly less osteolyses, longer survival and lower expression levels of osteolytic factors such as parathyroid hormone-related protein and interleukin-11 [96].

Gene_expression (expression) of parathyroid hormone-related protein in parathyroid associated with cancer and osteolysis

15) Confidence 0.21 Published 2010 Journal Journal of Oncology Section Body Doc Link PMC2871186 Disease Relevance 1.16 Pain Relevance 0

At the protein level, re-expression of several of these signalling molecules (FGF2, FGFR1, p21, PTHrP and Bcl-2) was found in secondary peripheral chondrosarcoma and the expression increased with increasing histological grade [94].

Gene_expression (expression) of PTHrP associated with chondrosarcoma

16) Confidence 0.10 Published 2004 Journal Hered Cancer Clin Pract Section Body Doc Link PMC2840003 Disease Relevance 1.19 Pain Relevance 0

Indian Hedgehog (IHh)/PTHrP signalling in the growth plate

Gene_expression (signalling) of PTHrP in growth plate

17) Confidence 0.08 Published 2004 Journal Hered Cancer Clin Pract Section Body Doc Link PMC2840003 Disease Relevance 0.06 Pain Relevance 0

The Avy/-agouti mouse, one of the oldest obese mouse models, is characterized by maturity-onset obesity and diabetes as a result of ectopic expression of the secreted protein hormone, agouti protein.

Gene_expression (expression) of protein hormone associated with diabetes mellitus and obesity

18) Confidence 0.05 Published 1999 Journal Int. J. Obes. Relat. Metab. Disord. Section Abstract Doc Link 10193863 Disease Relevance 0.73 Pain Relevance 0.16

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