INT75501

Context Info Confidence 0.76 First Reported 1998 Last Reported 2010 Negated 3 Speculated 3 Reported most in Body Documents 90 Total Number 94 Disease Relevance 60.86 Pain Relevance 5.93

cytosol (CCND1) nucleoplasm (CCND1) nucleus (CCND1) intracellular (CCND1) enzyme binding (CCND1) cell division (CCND1)

Anatomy Link Frequency mammary glands 2 embryos 1 cleavage 1 DLD-1 1 epithelial cells 1 CCND1 (Homo sapiens)

Pain Link Frequency Relevance Heat metalloproteinase 19 99.64 Dismenorea 8 99.04 cINOD 65 98.84 aspirin 9 97.24 qutenza 46 96.12 Inflammatory stimuli 1 95.64 interstitial cystitis 8 95.62 withdrawal 3 95.36 Inflammation 172 87.76 Analgesic 2 86.96

Disease Link Frequency Relevance Heat Cancer 3456 100.00 Breast Cancer 2207 100.00 Retinoblastoma 21 100.00 Sarcoma 15 100.00 Chronic Lymphoid Leukemia 261 99.92 Melanoma 273 99.84 Hyperplasia 43 99.80 Endometriosis 16 99.76 Mantle-cell Lymphoma 115 99.64 Prostate Cancer 148 99.60

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Mutation

Event

Anatomy

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Disease term

We found that the extract effectively blocked cell cycle progression by inhibiting the expression of cyclin D1 and E in A549 cells.

Gene_expression (expression) of cyclin D1 in A549

1) Confidence 0.76 Published 2002 Journal Am. J. Chin. Med. Section Abstract Doc Link 12230019 Disease Relevance 0.60 Pain Relevance 0.13

Since it was reported that lymphomas with a mantle cell lymphoma morphology and CD5 expression, but without cyclin D1 overexpression, exist in about 10% of mantle cell lymphoma cases, we diagnosed his disease as mantle cell lymphoma.

Gene_expression (overexpression) of cyclin D1 associated with mantle-cell lymphoma, lymphatic system cancer and disease

2) Confidence 0.76 Published 2001 Journal Hepatogastroenterology Section Abstract Doc Link 11462900 Disease Relevance 0.80 Pain Relevance 0.08

Salicylate significantly inhibited serum-induced progression from G1 to S phase, cellular proliferation, and the expression of cyclin D1.

Gene_expression (expression) of cyclin D1 associated with hyperplasia

3) Confidence 0.74 Published 2000 Journal J. Gastrointest. Surg. Section Abstract Doc Link 10631359 Disease Relevance 0.57 Pain Relevance 0.17

Cyclin D1 expression was determined by Western blot analysis and prostaglandin E2 expression by enzyme-linked immunosorbent assay.

Gene_expression (expression) of Cyclin D1

4) Confidence 0.74 Published 2000 Journal J. Gastrointest. Surg. Section Abstract Doc Link 10631359 Disease Relevance 0.62 Pain Relevance 0.12

Overexpression of cyclin D1 has been observed in many human tumors and is likely to promote cell proliferation and differentiation by shortening the G1/S transition.129,130,139 Amplification of the cyclin D1 gene has been detected in about 15% of breast cancers, while overexpression of cyclin D1 at mRNA and protein levels is seen in up to 50% of primary breast cancers, mostly ER-positive and well-differentiated tumors.129–131 A representative picture of cyclin D1 overexpression in human breast cancer is shown in Figure 2b.

Gene_expression (overexpression) of cyclin D1 associated with cancer and breast cancer

5) Confidence 0.66 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.54 Pain Relevance 0

High cyclin D1a expression inversely correlated with the Ki67 proliferation marker, but was not associated with clinical outcome.

Gene_expression (expression) of cyclin D1a

6) Confidence 0.66 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.84 Pain Relevance 0

Overexpression of cyclin D1 has been observed in many human tumors and is likely to promote cell proliferation and differentiation by shortening the G1/S transition.129,130,139 Amplification of the cyclin D1 gene has been detected in about 15% of breast cancers, while overexpression of cyclin D1 at mRNA and protein levels is seen in up to 50% of primary breast cancers, mostly ER-positive and well-differentiated tumors.129–131 A representative picture of cyclin D1 overexpression in human breast cancer is shown in Figure 2b.

Gene_expression (Overexpression) of cyclin D1 associated with cancer and breast cancer

7) Confidence 0.66 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.50 Pain Relevance 0

Interpretation is further complicated by suggestions that under some circumstances, cyclin D1 overexpression may worsen clinical outcome by conferring resistance to endocrine treatments.149,150 Consistent with this possibility, one small clinical study suggested that the duration of response to tamoxifen was significantly longer in ER-positive patients with low cyclin D1 than those with high cyclin D1.150 Resolution of these issues must await more detailed analysis of cyclin D1 expression and patient outcomes in the context of prospective randomized clinical trials.

Gene_expression (expression) of cyclin D1

8) Confidence 0.66 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.31 Pain Relevance 0

Interpretation is further complicated by suggestions that under some circumstances, cyclin D1 overexpression may worsen clinical outcome by conferring resistance to endocrine treatments.149,150 Consistent with this possibility, one small clinical study suggested that the duration of response to tamoxifen was significantly longer in ER-positive patients with low cyclin D1 than those with high cyclin D1.150 Resolution of these issues must await more detailed analysis of cyclin D1 expression and patient outcomes in the context of prospective randomized clinical trials.

Gene_expression (overexpression) of cyclin D1

9) Confidence 0.66 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.27 Pain Relevance 0

Overexpression of cyclin D1 has been observed in many human tumors and is likely to promote cell proliferation and differentiation by shortening the G1/S transition.129,130,139 Amplification of the cyclin D1 gene has been detected in about 15% of breast cancers, while overexpression of cyclin D1 at mRNA and protein levels is seen in up to 50% of primary breast cancers, mostly ER-positive and well-differentiated tumors.129–131 A representative picture of cyclin D1 overexpression in human breast cancer is shown in Figure 2b.

Gene_expression (overexpression) of cyclin D1 associated with cancer and breast cancer

10) Confidence 0.66 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.56 Pain Relevance 0

Indeed, MMTV-cyclin D2 mice show increased proliferation of mammary glands in pregnant females, but alveolar differentiation is partially or completely inhibited.157 In one report, cyclin D3 was overexpressed in breast cancers, but there are limited data on its relationship to the phenotype of breast cancer and prognosis of patients.158 Keyomarsi et al showed that the absence of cyclin D1 or cyclin D3 protein expression was associated with improved disease-specific and overall survival, but the correlations were less striking than those for cyclin E.159 Cyclin E

Gene_expression (expression) of cyclin D1 in mammary glands associated with breast cancer and disease

11) Confidence 0.66 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.68 Pain Relevance 0

Cyclin D2 is more ubiquitously expressed in tissues than cyclin D1.

Gene_expression (expressed) of cyclin D1

12) Confidence 0.66 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.98 Pain Relevance 0

did not influence cyclinD1 nor p53 levels, as shown by immunoblotting (Fig. 3C).

Gene_expression (levels) of cyclinD1

13) Confidence 0.65 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885411 Disease Relevance 0.08 Pain Relevance 0

This case suggests that the overexpression of CD117, p53 protein, cyclin D1, and HER2/neu might be involved in the progression from lower-grade ACC to solid-type ACC and HGA.

Gene_expression (overexpression) of cyclin D1 associated with adenocarcinoma and adenoid cystic carcinoma

14) Confidence 0.59 Published 2006 Journal Virchows Arch. Section Abstract Doc Link 16133359 Disease Relevance 2.32 Pain Relevance 0.07

However, parameters involved with key features such as cyclin-D and PSA expression were relatively well constrained (CV50%).

Gene_expression (expression) of cyclin-D

15) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2812491 Disease Relevance 0 Pain Relevance 0

The relationship between overexpression of cyclin D1 and breast cancer outcome has been controversial, with studies reporting both positive and negative findings.141–143 Subgroup analyses within relatively few patients have also hampered definitive conclusions.

Gene_expression (overexpression) of cyclin D1 associated with breast cancer

16) Confidence 0.57 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.74 Pain Relevance 0

The utility of cyclin D1 as a predictor of breast cancer prognosis is controversial, but cyclin D1b overexpression is associated with poor prognosis.

Gene_expression (overexpression) of cyclin D1 associated with breast cancer

17) Confidence 0.57 Published 2010 Journal Clinical Medicine Insights. Oncology Section Abstract Doc Link PMC2883240 Disease Relevance 0.59 Pain Relevance 0

Overexpression of cyclin D1 has been observed in many human tumors and is likely to promote cell proliferation and differentiation by shortening the G1/S transition.129,130,139 Amplification of the cyclin D1 gene has been detected in about 15% of breast cancers, while overexpression of cyclin D1 at mRNA and protein levels is seen in up to 50% of primary breast cancers, mostly ER-positive and well-differentiated tumors.129–131 A representative picture of cyclin D1 overexpression in human breast cancer is shown in Figure 2b.

Gene_expression (overexpression) of cyclin D1 associated with cancer and breast cancer

18) Confidence 0.57 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.57 Pain Relevance 0

In spite of these limitations, there appears to be a relationship between cyclin D1 gene amplification and poor disease outcome in ER-positive patients.144–146 In contrast, cyclin D1 protein expression is associated with a good prognosis in some studies,141,147 potentially as a consequence of its positive relationship with ER expression and negative relationship with RB mutations.

Gene_expression (expression) of cyclin D1 associated with disease

19) Confidence 0.57 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.39 Pain Relevance 0

However, the cyclin D1b protein was upregulated in breast cancer, independent of cyclin D1a levels, and exhibited heterogeneous levels in breast cancer specimens.

Gene_expression (levels) of cyclin D1a associated with breast cancer

20) Confidence 0.57 Published 2010 Journal Clinical Medicine Insights. Oncology Section Body Doc Link PMC2883240 Disease Relevance 0.83 Pain Relevance 0

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