INT231987

Context Info Confidence 0.67 First Reported 2008 Last Reported 2010 Negated 3 Speculated 6 Reported most in Body Documents 66 Total Number 75 Disease Relevance 62.58 Pain Relevance 1.78

Anatomy Link Frequency bladder 14 lymph node 2 uterus 2 Brain 1 annulus 1 Tsp1 (Mus musculus)

Pain Link Frequency Relevance Heat Inflammation 465 98.88 agonist 220 97.16 cytokine 53 94.56 metalloproteinase 26 82.72 tolerance 27 81.48 imagery 295 81.12 addiction 57 75.00 Inflammatory response 12 57.28 isoflurane 114 36.12 chemokine 27 6.28

Disease Link Frequency Relevance Heat Cancer 3767 100.00 Targeted Disruption 845 100.00 Apoptosis 261 100.00 Colon Cancer 90 100.00 Malignant Neoplastic Disease 140 99.92 Bladder Cancer 5005 99.84 Reprotox - General 1 440 99.52 Metastasis 117 99.36 Breast Cancer 234 99.32 Recurrence 110 99.26

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Grossfeld et al. [29] found that patients with low TSP1 expression in BC had an increased risk of recurrence and decreased survival and that the expression of TSP1 was dependent on p53 expression: 96% of tumors with wildtype p53 expressed moderate to high levels of TSP1 protein, and only 58% of tumors with altered p53 protein overexpressed TSP1.

Gene_expression (expression) of TSP1 associated with cancer, bladder cancer and recurrence

1) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 1.36 Pain Relevance 0

Grossfeld et al. [29] found that patients with low TSP1 expression in BC had an increased risk of recurrence and decreased survival and that the expression of TSP1 was dependent on p53 expression: 96% of tumors with wildtype p53 expressed moderate to high levels of TSP1 protein, and only 58% of tumors with altered p53 protein overexpressed TSP1.

Gene_expression (expression) of TSP1 associated with cancer, bladder cancer and recurrence

2) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 1.43 Pain Relevance 0

Eight of the ten paired samples had greater TSP1 protein expression in the normal tissue compared to the BC.

Gene_expression (expression) of TSP1 associated with bladder cancer

3) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 1.32 Pain Relevance 0

Paired normal and BC frozen biopsies from ten male patients were also examined for expression of TSP1 protein by western blot analysis.

Spec (examined) Gene_expression (expression) of TSP1 associated with bladder cancer

4) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.56 Pain Relevance 0

One paired sample did not express TSP1 in either the normal or tumor tissue, and one paired sample showed higher TSP1 expression in the BC rather than the normal tissue.

Gene_expression (expression) of TSP1 associated with cancer and bladder cancer

5) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 1.42 Pain Relevance 0

We examined TSP1 expression in high grade and high stage human BC.

Spec (examined) Gene_expression (expression) of TSP1 associated with bladder cancer

6) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.95 Pain Relevance 0

In addition, the same study also found that castration of rats increases TSP1 expression and decreases microvessel density counts in the prostate [32].

Gene_expression (expression) of TSP1

7) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.66 Pain Relevance 0.05

Androgens increase tumor cell growth in vitro and in vivo and decrease TSP1 expression, possibly explaining the therapeutic effect of castration.

Gene_expression (expression) of TSP1 associated with cancer

8) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.72 Pain Relevance 0.03

One paired sample did not express TSP1 in either the normal or tumor tissue, and one paired sample showed higher TSP1 expression in the BC rather than the normal tissue.

Neg (not) Gene_expression (express) of TSP1 associated with cancer and bladder cancer

9) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 1.35 Pain Relevance 0

Metastatic prostate cancer patients treated with androgen deprivation therapy expressed a significantly higher TSP1 immunoreactivity in prostatic adenocarcinoma when compared to other metastatic prostate cancer patients who did not receive hormonal therapy [48].

Gene_expression (expressed) of TSP1 associated with adenocarcinoma and reprotox - general 1

10) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.74 Pain Relevance 0.04

Grossfeld et al. [29] found that patients with low TSP1 expression in BC had an increased risk of recurrence and decreased survival and that the expression of TSP1 was dependent on p53 expression: 96% of tumors with wildtype p53 expressed moderate to high levels of TSP1 protein, and only 58% of tumors with altered p53 protein overexpressed TSP1.

Gene_expression (overexpressed) of TSP1 associated with cancer, bladder cancer and recurrence

11) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 1.25 Pain Relevance 0

The molecular weight of TSP1 expressed in mouse and human bladders was slightly less than 50 kDa.

Gene_expression (expressed) of TSP1 in bladders

12) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.31 Pain Relevance 0

In addition, prostate biopsies indicated that patients with metastatic prostate cancer had significantly less TSP1 expression than patients with localized prostate cancer, who also had significantly lower TSP1 expression than patients with benign prostatic hyperplasia [48].

Gene_expression (expression) of TSP1 associated with benign prostatic hypertrophy and reprotox - general 1

13) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 1.20 Pain Relevance 0

Others have reported changes in TSP1 expression in response to androgens in prostate and breast cancer.

Gene_expression (expression) of TSP1 associated with breast cancer

14) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.76 Pain Relevance 0.08

Wild-type mouse expressed significantly more TSP1 than transgenic UPII-SV40T in the bladder (p = 0.0326, Fig. 7A; paired, two-tailed, student's t-test).

Gene_expression (expressed) of TSP1 in bladder associated with targeted disruption

15) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.36 Pain Relevance 0

Others have reported changes in TSP1 expression in response to androgens in prostate and breast cancer.

Gene_expression (expression) of TSP1 associated with breast cancer

16) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.73 Pain Relevance 0.05

Secreted TSP1 was found to be expressed in the bladder stroma of all animals, but TSP1 expression in the urothelium was greater in castrated animals when compared to intact animals (Figure 6).

Gene_expression (expressed) of TSP1 in bladder

17) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.54 Pain Relevance 0

TSP1 expression was greater in 8 (specimens 2, 3, 4, 5, 6, 7, 9, 10; Fig. 8A) of the normal bladder specimens compared to the paired BC specimen.

Gene_expression (expression) of TSP1 in bladder associated with bladder cancer

18) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.57 Pain Relevance 0

Castration of UPII-SV40T male animals resulted in a modest (but not statistically significant) increase in TSP1 expression in bladder protein at days 2–7 post-castration compared to their intact counterparts (Fig. 7B).

Gene_expression (expression) of TSP1 in bladder

19) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.40 Pain Relevance 0

We examined the protein expression of TSP1 in human BC paired with normal bladder tissue from the same patients and found that the ~ 50 kDa TSP1 anti-angiogenic fragment is decreased in human urothelial cancer tissue.

Spec (examined) Gene_expression (expression) of TSP1 in bladder associated with cancer and bladder cancer

20) Confidence 0.67 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 1.32 Pain Relevance 0

General Comments

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