Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastasis to bone occurs frequently in advanced breast cancer and is accompanied by debilitating skeletal complications. Current treatments are palliative and new therapies that specifically prevent the spread of breast cancer to bone are urgently required. While our understanding of interactions between breast cancer cells and bone cells has greatly improved, we still know little about the molecular determinants that regulate specific homing of breast cancer cells to the bone. In this review, we focus on genes that have been implicated in migration and adhesion of breast cancer cells to bone, as well as genes that promote tumor cell proliferation in the bone microenvironment. In addition, the review discusses new technologies, including better animal models, that will further assist with the identification of the molecular determinants of bone metastasis and will guide the development of new therapies.
Cell Mol Life Sci 2002 Sep
PMID:Genes involved in breast cancer metastasis to bone. 1244 Jul 71

Parathyroid hormone-related protein (PTHrP), which has been localized in prostate cancer tissue and cell lines, plays a role in the development of bone metastases, a frequent complication in prostate cancer patients. Tumor cell adhesion to extracellular matrix (ECM) components is mediated via integrin subunits, and plays a major role in the invasion and metastasis of tumor cells. The present experiments examined the ability of PTHrP to influence adhesion of the human prostate cancer cell line PC-3 to several ECM proteins found in normal tissues. Clonal PC-3 cells induced to overexpress PTHrP by stable transfection with PTHrP complementary DNA showed significantly higher adhesion to collagen type 1, fibronectin, and laminin than control (empty vector-transfected) cells. PTHrP-overexpressing cells also exhibited higher expression of the alpha1, alpha5, alpha6, and beta4 integrin subunits. These results suggest that PTHrP may play a role in prostate tumor invasion and metastasis by influencing cell adhesion to the ECM via upregulation of specific integrin subunits.
Mol Cell Endocrinol 2003 Jan 31
PMID:PTH-related protein modulates PC-3 prostate cancer cell adhesion and integrin subunit profile. 1258 88

Over the years several analytical methods have been proposed for the measurement of glucose metabolism using fluorine-18 fluorodeoxyglucose ([(18)F]FDG) and positron emission tomography (PET). The purpose of this study was to evaluate which of these (often simplified) methods could potentially be used for clinical response monitoring studies in breast cancer. Prior to chemotherapy, dynamic [(18)F]FDG scans were performed in 20 women with locally advanced ( n=10) or metastasised ( n=10) breast cancer. Additional PET scans were acquired after 8 days ( n=8), and after one, three and six courses of chemotherapy ( n=18, 10 and 6, respectively). Non-linear regression (NLR) with the standard two tissue compartment model was used as the gold standard for measurement of [(18)F]FDG uptake and was compared with the following methods: Patlak graphical analysis, simplified kinetic method (SKM), SUV-based net influx constant ("Sadato" method), standard uptake value [normalised for weight, lean body mass (LBM) and body surface area (BSA), with and without corrections for glucose (g)], tumour to non-tumour ratio (TNT), 6P model and total lesion evaluation (TLE). Correlation coefficients between each analytical method and NLR were calculated using multilevel analysis. In addition, for the most promising methods (Patlak, SKM, SUV(LBMg) and SUV(BSAg)) it was explored whether correlation with NLR changed with different time points after the start of therapy. Three methods showed excellent correlation ( r>0.95) with NLR for the baseline scan: Patlak10-60 and Patlak10-45 ( r=0.98 and 0.97, respectively), SKM40-60 ( r=0.96) and SUV(LBMg) ( r=0.96). Good correlation was found between NLR and SUV-based net influx constant, TLE and SUV(BSAg) (0.90< r<0.95). The 6P model and TNT had the lowest correlation ( r<or=0.84). SUV was least accurate in predicting changes in [(18)F]FDG uptake over time during therapy. For all methods, correlation with NLR was significantly lower for bone metastases than for other (primary or metastatic) tumour lesions ( P<0.05). In conclusion, three methods with different degrees of complexity appear to be promising alternatives to NLR for measuring glucose metabolism in breast cancer: Patlak, SKM and SUV (normalised for LBM and with a correction for plasma glucose).
Eur J Nucl Med Mol Imaging 2003 May
PMID:Measuring [(18)F]FDG uptake in breast cancer during chemotherapy: comparison of analytical methods. 1264 May 56

The nucleoside analogue 3'-deoxy-3'-[18F]fluorothymidine (FLT) has been introduced for imaging of tumour cell proliferation by positron emission tomography (PET). This study evaluated the use of FLT in patients with thoracic tumours prior to treatment. Whole-body FLT PET was performed in 16 patients with 18 tumours [17 thoracic tumours (nine non-small cell lung cancers, five oesophageal carcinomas, two sarcomas, one Hodgkin's lymphoma) and one renal carcinoma] before treatment. Fluorine-18 fluorodeoxyglucose (FDG) PET was performed for comparison except in those patients with oesophageal carcinoma. For semi-quantitative analysis, the average and maximum standardised uptake values (avgSUV and maxSUV, respectively) (FLT, 114+/-20 min p.i.; FDG, 87+/-8 min p.i.; 50% isocontour region of interest) was calculated. All 17 thoracic tumours and 19/20 metastases revealed significant FLT accumulation, resulting in easy delineation from surrounding tissue. The additional small grade 1 renal carcinoma was not detected with either FLT or FDG. In most lung tumours (avgSUV 1.5-8.2) and metastases, FLT showed intense uptake. However, one of two spinal bone metastases was missed owing to the high physiological FLT uptake in the surrounding bone marrow. Oesophageal carcinoma primaries (avgSUV 2.7-10.0) and occasional metastases showed particularly favourable tumour/non-tumour contrast. Compared with FDG, tumour uptake of FLT was lower (avgSUV, P=0.0006; maxSUV, P=0.0001), with a significant linear correlation (avgSUV, r2=0.45; maxSUV, r2=0.49) between FLT and FDG. It is concluded that FLT PET accurately visualises thoracic tumour lesions. In the liver and the bone marrow, high physiological FLT uptake hampers detection of metastases. On the other hand, FLT may be favourable for imaging of brain metastases owing to the low physiological uptake.
Eur J Nucl Med Mol Imaging 2003 Oct
PMID:[18F]FLT PET for diagnosis and staging of thoracic tumours. 1289 1

The androgen-regulated enzyme fatty acid synthase (FAS), required for de novo lipogenesis, is overexpressed in several cancers including prostate carcinoma and has been associated with aggressive disease. FAS expression was assessed in 81 prostate carcinomas, both by immunohistochemistry in tissue microarrays and by Affymetrix Hu95Av2 oligonucleotide arrays. Both FAS mRNA and protein were significantly overexpressed in prostate carcinomas compared with the corresponding normal tissue. FAS mRNA and protein expression increased substantially from normal to prostatic intraepithelial neoplasia, to low grade, to high grade, and to androgen-independent bone metastases. A significant correlation between FAS mRNA and protein expression was found in two thirds of the cases. In 17% of the cases, FAS protein levels were high despite low mRNA levels, and these tumors exhibited a distinct molecular signature when compared with tumors that did not express FAS protein. Whereas the latter group of tumors expressed some proapoptotic genes, tumors with high FAS levels overexpressed, among other genes, its transcriptional regulator, steroid regulator binding protein, and apolipoprotein E. These data demonstrate (1) the consistent overexpression of FAS in prostate carcinoma compared with the adjacent normal tissue, (2) a strong association between FAS and prostate tumor initiation and progression, (3) the highest FAS expression occurring in androgen-independent bone metastases, (4) the transcriptional and posttranscriptional regulation of FAS in the majority and in a subset of prostate cancers, respectively, and (5) most importantly, the identification by FAS expression of prostate tumors with unique molecular signatures and potentially diverse biologic behavior.
Mol Cancer Res 2003 Aug
PMID:Fatty acid synthase expression defines distinct molecular signatures in prostate cancer. 1293 96

In spite of recent advances in bone cellular and molecular biology, there is still a poor correlation between these parameters and data obtained from bone scintigraphy. Diphosphonate derivatives radiolabelled with technetium-99m (Tc-BPs) have long been recognised as bone-seeking agents with an affinity for areas of active mineralisation. However, during clinical trials with a pH-sensitive tumour agent, the pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS] showed a noticeable osteotropic character only in bone pathologies (bone metastases, Paget's diseases) and lacked accumulation in normal mature bone. To decipher the osteotropic character of Tc(V)-DMS, a study at the cellular level was considered necessary. Moreover, to learn more about the role of Tc bone agents, acid-base regulation by bone tissue or cells was studied. First, biological parameters in body fluid were measured under systemic acidosis, induced by glucose administration, in normal and Ehrlich ascites tumour (EAT)-bearing mice. Then, in vivo biodistribution studies using Tc(V)-DMS or a conventional Tc-BP agent were carried out. The effect of glucose-mediated acidification on the skeletal distribution of the Tc agents in the mice provided valuable hints regarding the differential mediation of bone cells in skeletal tissue affinity for the agents. Thereafter, in vitro studies on osteoblast and osteoclast cells were performed and the comparative affinity of Tc(V)-DMS and Tc-BP was screened under diverse acidification conditions. Moreover, studies were also carried out on acid-base parameters related to the cellular uptake mechanism. Very specific pH-sensitive Tc(V)-DMS accumulation only in the osteoclastic system was detected, and use of Tc(V)-DMS in the differential detection of osteoblastic and osteoclastic metastases is discussed.
Eur J Nucl Med Mol Imaging 2004 Mar
PMID:Skeletal affinity of Tc(V)-DMS is bone cell mediated and pH dependent. 1545 72

Recurrent thyroid cancer can present many complex management problems. Unfortunately, recurrent thyroid cancer is often refractory to radioiodine therapy. The proper use of external beam irradiation and surgical interventions can provide regional control of localized recurrences. Because of the complex nature of these patients, a multidisciplinary team approach to management which includes specialists in thyroid medicine and surgery, head and neck radiotherapy, and nuclear medicine often is required to provide individualized, optimal multimodality treatment recommendations. In this article we review a multidisciplinary team approach to a patient with widespread, radioiodine-refractory bone metastases from follicular thyroid cancer and to a patient with unresectable central neck recurrence of papillary thyroid cancer.
Eur J Nucl Med Mol Imaging 2004 Apr
PMID:Challenging cases in thyroid cancer: a multidisciplinary approach. 1466 83

The leading European and American professional societies recommend that bone scans (BS) should be performed in the staging of lung cancer only in those patients with bone pain. This prospective study investigated the sensitivity of conventional skeletal scintigraphy in detecting osseous metastases in patients with lung cancer and addressed the potential consequences of failure to use this method in the work-up of asymptomatic patients. Subsequent to initial diagnosis of non-small cell lung cancer, 100 patients were examined and questioned regarding skeletal complaints. Two specialists in internal medicine decided whether they would recommend a bone scan on the basis of the clinical evaluation. Skeletal scintigraphy was then performed blinded to the findings of history and physical examination. The combined results of magnetic resonance imaging (MRI) of the vertebral column, positron emission tomography (PET) of skeletal bone and the subsequent clinical course served as the gold standard for the identification of osseous metastases. Bone scintigraphy showed an 87% sensitivity in the detection of bone metastases. Failure to perform skeletal scintigraphy in asymptomatic patients reduced the sensitivity of the method, depending on the interpretation of the symptoms, to 19-39%. Without the findings of skeletal scintigraphy and the gold standard methods, 14-22% of patients would have undergone unnecessary surgery or neoadjuvant therapy. On this basis it is concluded that bone scans should not be omitted in asymptomatic patients.
Eur J Nucl Med Mol Imaging 2004 Jul
PMID:Omission of bone scanning according to staging guidelines leads to futile therapy in non-small cell lung cancer. 1499 Dec 41

18F-Fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) has been evaluated in breast cancer for the characterisation of primary tumours, lymph node staging and the follow-up of patients after surgery, chemotherapy and/or external radiotherapy. In contrast to both the low sensitivity and moderate specificity of FDG PET in the initial detection and characterisation of breast cancer and the low lesion-based sensitivity for lymph node staging, the results from use of FDG PET in re-staging breast cancer patients are very promising. A major advantage of FDG PET imaging compared with conventional imaging is that it screens the entire patient for local recurrence, lymph node metastases and distant metastases during a single whole-body examination using a single injection of activity, with a reported average sensitivity and specificity of 96% and 77%, respectively. In most studies the sensitivity of FDG PET is higher than that of a combination of conventional imaging methods. Limitations of FDG PET in the follow-up of breast cancer patients include the relatively low detection rate of bone metastases, especially in case of the sclerotic subtype, and the relatively high rate of false positive results. The rather low specificity of FDG PET can be improved/increased by utilising combined anatomical-molecular imaging techniques, such as a PET/CT tomograph. First results using PET/CT imaging in the follow-up of breast cancer patients demonstrate increased specificity compared with FDG PET alone. Both imaging modalities, however, offer to detect recurrent and metastatic breast cancer disease at an early stage and thus continue to demonstrate the efficacy of molecular imaging in patient management, despite the limited therapeutic options in recurrent and metastatic breast cancer.
Eur J Nucl Med Mol Imaging 2004 Jun
PMID:Advantages and limitations of FDG PET in the follow-up of breast cancer. 1508 95

A number of studies have demonstrated that bone scintigraphy has high sensitivity and efficacy in the early detection of bone metastases from several tumours, including breast cancer. Bone scintigraphy is the most definitive tool for diagnosing and monitoring metastatic spread of breast cancer. However, in the past decade there has been a wide debate on its impact on survival time, morbidity and quality of life. Worldwide economic restrictions and these studies have led to the adoption of an almost minimalist policy for breast cancer follow-up using evidence-based guidelines. The recommended breast cancer surveillance testing includes only a few procedures (history, physical and breast self-examination, patient education on symptoms, pelvic examination). The routine use of additional tests, such as blood cell count, tumour markers, liver ultrasonography, bone scan and chest X-rays, is not recommended. Accordingly, scintigraphy should be reserved for a limited number of patients. On the other hand, early diagnosis of bone involvement may reduce the risk of skeletal related events, thus leading to a significant improvement in quality of life. Furthermore, new drugs (e.g. bisphosphonates) can now delay the onset of bone metastasis and reduce the number of patients who experience skeletal complications. In conclusion, the evidence of the clinical usefulness of bone scintigraphy (to allow early planning of new treatments in advanced disease) has to be re-evaluated, possibly by large randomised prospective trials.
Eur J Nucl Med Mol Imaging 2004 Jun
PMID:Current role of bone scan with phosphonates in the follow-up of breast cancer. 1508 28


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