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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Suppression of androgen levels in blood of stage D2 prostate cancer patients has been the prominent treatment for advanced prostate cancer. However, the duration of hormone sensitivity of prostate tumor is variable. The type of initial response to hormonal treatment, the length of response and patient's survival are in direct association with disease aggressiveness. Recently, an arithmetic formula expressing disease aggressivity was computed using pretreatment values of prostatic acid phosphatase (P.A.P.), alkaline phosphatase (A.P.), degree of tumor differentiation and number of bone metastases. This aggressiveness score was related to disease response and patients outcome receiving hormonal treatments. The use of an arithmetic formula to express disease aggressivity could result in a subdivision of the disease. The identification of the subgroup of stage D2 patients destined not to benefit from hormonal manipulation could change the strategies employed up until today for the treatment of advanced prostate cancer.
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PMID:The assessment of disease aggressivity in stage D2 prostate cancer patients (review). 218 59

Several prognostic parameters of prostatic carcinoma needed to help guide treatment in individual patients are discussed. Tumour volume, nodal and bone metastases, grading, prostate-specific antigen and DNA ploidy have been correlated with prognosis. Recent studies have analysed tumour volume in detail. However, currently there is no single prognostic factor which can predict tumour aggressiveness on an individual patient basis to rationalize decisions. Multivariate analyses are therefore in progress to determine independent prognostic variables.
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PMID:The value of prognostic factors in prostatic cancer. 786 Feb 2

Suppression of androgen levels of stage D2 prostate cancer patients has been the prominent treatment for advanced prostate cancer. An arithmetic formula expressing disease aggressivity computed by the pre-treatment levels of alkaline phosphatase (AP), degree of tumor differentiation and number of bone metastases correlated well with disease response and outcome in stage D2 patients treated by chronic administration of the gonadotropin-releasing hormone agonistic analogues (GnRH-As; buserelin) or orchiectomy. In the present study we analyzed retrospectively disease response and outcome in 262 previously untreated stage D2 prostate cancer patients who received combination hormonal treatment (GnRH-A plus flutamide) using this aggressiveness score. Mean value of this aggressiveness score between patients who were grouped with reference to type of disease response according to the criteria established by the National Prostatic Cancer Project (NPCP) was statistically different (Kruskal-Wallis, p > 0.001). Pairwise comparison documented that this was true between all but the stable and progression groups. Linear regression analysis documented significant correlation of this aggressiveness score with length of response and survival (r = 0.59, and 0.45, respectively: p > 0.0001). Analysis of slopes obtained by linear regressions between aggressiveness score and survival in patients treated with GnRH-A plus flutamide and with GnRH-A monotherapy documented that disease response and outcome was superior among patients who received combination hormonal treatment. These data indicate that this aggressiveness score correlated well type of disease response, length of response, and survival with patients given combination hormonal treatment, and as such it can be used as an objective tool for analyzing clinical data.
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PMID:Stratification of stage D2 prostate cancer patients by a disease aggressiveness score and its use in evaluating disease response and outcome to combination hormonal treatment (GnRH-A plus flutamide). 801 Jul 19

Primary breast cancer imaging can be done by various means. Mammography is the most widely used technique because of its excellent diagnostic performance, patient compliance, and cost-effectiveness ratio. Other radiological techniques (such as ultrasonography) are indicated in particular circumstances, while some (such as digital mammography and magnetic resonance imaging) seem very promising but are still under evaluation. The recent technological progress in nuclear medicine has resulted in the availability of two diagnostic procedures that have been validated by extensive international clinical experience: scintimammography with Sesta-MIBI and positron emission tomography (PET) with fluorodeoxyglucose (FDG). The general advantage of nuclear medicine imaging is that tumor-seeking radiopharmaceuticals accumulate in cancer lesions, which makes scintimammography and PET fundamentally different from the radiological techniques that image the tumor mainly on the basis of morphological alterations. Scintimammography is indicated for the study of breast lesions in patients in whom mammography is non-diagnostic or difficult to interpret; it may be useful also to assess and even predict the response to primary chemotherapy. FDG-PET is increasingly used in oncology and is particularly useful in breast cancer as it gives more accurate information than scintimammography in the evaluation of patients with ambiguous mammographies and in discriminating between viable tumor, fibrotic scar or necrosis following surgery, chemo- or radiotherapy. The FDG uptake in the tumor correlates with the histological grade and potential aggressiveness of breast cancer, which may have prognostic implications. In addition to its usefulness in the study of breast lesions, FDG-PET shows great efficacy in detecting lymph node involvement prior to surgery. Whole-body PET provides information on soft tissue and bone metastases in a single scanning session, and has an important clinical role in detecting recurrent metastatic disease. On the basis of the above-mentioned evidence, nuclear medicine techniques, integrated with radiological techniques, offer an interesting opportunity to improve the diagnostic imaging yield in breast cancer, which will eventually lead to better patient management. This paper reports on the latest developments in this field.
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PMID:Nuclear medicine advances in breast cancer imaging. 1176 74

The aim of this study was to describe a child with a right cerebellar hemisphere metastasis from primary clear cell sarcoma of the kidney without evidence of bone metastases, and to investigate the immunohistochemical features of primary and metastatic tumors. A 12-month old boy was admitted our hospital due to an abdominal mass. Abdominal computed tomography revealed a large right renal tumor. Tumor was removed with nephrectomy. Histopathologic examination of tumor revealed clear cell sarcoma of the kidney. The patient received radiotherapy and chemotherapy in postoperative period. He suffered from gait disturbance and confusion 8 months later. A computed tomography scan revealed a tumor that was enhanced with contrast medium at right cerebellar hemisphere concomitant with ventricular enlargement. After ventriculo-peritoneal shunting procedure, tumor was excised totally and histopathologic diagnosis showed metastasis of clear cell sarcoma of the kidney. Immunohistochemically vimentin, actin, desmin, neuron specific enolase, cytokeratin, P 53, Ki-67 and P-170 were performed using formalin fixed, paraffin embedded sections. Both of the tumors were positive for vimentin and negative for desmin, actin, neuron specific enolase, cytokeratin and P 53. Scattered nuclei were stained by Ki-67 in primary and metastatic cerebellar tumor. Both primary and metastatic tumors were negative for p53 and P-170. The treatment consisted of surgery, radiotherapy and chemotherapy. The patient is alive and well without evidence of recurrence 16 months after second surgery. Clear cell sarcoma of the kidney is most commonly associated with bone metastasis. Cerebellar metastasis of clear cell sarcoma of the kidney is very unusual. To the best of our knowledge, this patient is second case in the English literature. With review of the literature, our immunohistochemical findings support the theory that relapse and metastasis of primary clear cell sarcoma of the kidney are not related with increase of aggressiveness.
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PMID:Cerebellar metastasis from clear cell sarcoma of the kidney. A case report with immunohistochemistry. 1191 76

Mouse bone marrow cells cultured with human breast cancer MCF-7 cell-conditioned media showed osteoclastogenesis with an increment of bone resorption, although conditioned media from an adriamycin-selected MCF-7 clone (MCF-7ADR) had no effect. Consistently, MCF-7 cells induced 5-fold more in vivo experimental osteolytic bone metastases, with no soft tissue lesions, compared to MCF-7ADR cells. Paracrine factors stimulating (interleukin (IL)-6, IL-1beta, tumor necrosis factor-alpha (TNF-alpha)) or inhibiting (IL-12, IL-18, granulocyte macrophage-colony stimulating factor (GM-CSF)) osteoclastogenesis were significantly increased in MCF-7ADR relative to MCF-7 cells, suggesting that the inhibitory cytokines could selectively overwhelm the effects of the stimulatory ones. Treatment of osteoblast primary cultures with MCF-7-conditioned medium induced a selective upregulation of IL-6 expression, suggesting an indirect stimulation of osteoclastogenesis via the osteoblasts. MCF-7 and MCF-7ADR showed no difference in proliferation rate. However, a higher ability to migrate and invade gelatin and matrigel was observed in MCF-7ADR. Enhanced invasiveness might result from increased metalloproteinase (MMP) activity and cytoskeleton rearrangement. MCF-7ADR cells expressed higher levels of c-Src, focal adhesion kinase (FAK), and protein tyrosine kinase 2 (PYK2) involved in cell adhesion and motility. MCF-7 and MCF-7ADR expressed high and faint levels of functional estrogen receptor alpha (ERalpha), respectively. MCF-7ADR also showed significantly higher levels of the protein kinase C (PKC) alpha and beta2 and a selective activation of PKC compared to MCF-7, where the most abundant isoforms were beta1 and delta. Heat shock protein 27 (Hsp27) was more abundant in MCF-7 cells, but failed to translocate to the nucleus in response to heat shock. In conclusion, we have demonstrated that despite the fact that MCF-7ADR cells showed a more invasive phenotype relative to MCF-7, they have low potential to induce osteolytic bone lesions and stimulate osteoclastogenesis and osteoclast activity. Therefore, we believe that reduced aggressiveness of breast carcinomas could correlate with a greater osteolytic activity featuring their bone metastases.
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PMID:In vivo bone metastases, osteoclastogenic ability, and phenotypic characterization of human breast cancer cells. 1505 Sep 1

The use of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the evaluation and management of patients with malignancy continues to increase. However, its role in the identification of bone metastases is far from clear. FDG has the advantage of demonstrating all metastatic sites, and in the skeleton it is assumed that its uptake is directly into tumor cells. It is probable that for breast and lung carcinoma, FDG-PET has similar sensitivity, although poorer specificity, when compared with the isotope bone scan, although there is conflicting evidence, with several articles suggesting that it is less sensitive than conventional imaging in breast cancer. There is convincing evidence that for prostate cancer, FDG-PET is less sensitive than the bone scan and this may be tumor specific. There is very little data relating to lymphoma, but FDG-PET seems to perform better than the bone scan. There is an increasing body of evidence relating to the valuable role of FDG-PET in myeloma, where it is clearly better than the bone scan, presumably because FDG is identifying marrow-based disease at an early stage. There are, however, several other important variables that should be considered. The morphology of the metastasis itself appears to be relevant. At least in breast cancer, different patterns of FDG uptake have been shown in sclerotic, lytic, or lesions with a mixed pattern, Furthermore, the precise localization of a metastasis in the skeleton may be important with regard to the extent of the metabolic response induced. Previous treatment is highly relevant and it has been found that although the majority of untreated bone metastases are positive on PET scans and have a lytic pattern on computed tomography (CT), after treatment, incongruent CT-positive/PET-negative lesions are significantly more prevalent and generally are blastic, which presumably reflects a direct effect of treatment. Finally, the aggressiveness of the tumor itself may be relevant. The most important question, however, is irrespective of whether a lesion is seen on x-ray, CT, or bone scan and irrespective of lytic of blastic morphology: if the FDG-PET study is negative, what is the clinical relevance of that lesion?
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PMID:Positron emission tomography and bone metastases. 1576 76

Prostate cancer frequently metastasizes to bone where it forms osteoblastic lesions through unknown mechanisms. Bone morphogenetic proteins (BMP) are mediators of skeletal formation. Prostate cancer produces a variety of BMPs, including BMP-6. We tested the hypothesis that BMP-6 contributes to prostate cancer-induced osteosclerosis at bone metastatic sites. Prostate cancer cells and clinical tissues produced BMP-6 that increased with aggressiveness of the tumor. Prostate cancer-conditioned medium induced SMAD phosphorylation in the preosteoblast MC3T3 cells, and phosphorylation was diminished by anti-BMP-6 antibody. Prostate cancer-conditioned medium induced mineralization of MC3T3 cells, which was blocked by both the BMP inhibitor noggin and anti-BMP-6. Human fetal bones were implanted in severe combined immunodeficient mice and after 4 weeks, LuCaP 23.1 prostate cancer cells were injected both s.c. and into the bone implants. Anti-BMP-6 or isotype antibody administration was then initiated. Anti-BMP-6 reduced LuCaP 23.1-induced osteoblastic activity, but had no effect on its osteolytic activity. This was associated with increased osteoblast numbers and osteoblast activity based on bone histomorphometric evaluation. As endothelin-1 has been implicated in bone metastases, we measured serum endothelin-1 levels but found they were not different among the treatment groups. In addition to decreased bone production, anti-BMP-6 reduced intraosseous, but not s.c., tumor size. We found that BMP-2, BMP-4, BMP-6, and BMP-7 had no direct effect on prostate cancer cell growth, but BMP-2 and BMP-6 increased the in vitro invasive ability of prostate cancer cell. These data show that prostate cancer promotes osteoblastic activity through BMP-6 and that, in addition to its bone effects, suggest that BMPs promote the ability of the prostate cancer cells to invade the bone microenvironment.
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PMID:Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. 1616 4

Epithelioid sarcoma is a rare soft tissue sarcoma with a propensity for local aggressiveness, regional nodal spread, and pulmonary metastases. We report a case of epithelioid sarcoma in a neonate with bilateral optic nerve hypoplasia who developed liver, kidney, and bone metastases. The unusual presenting features and pattern of disease progression in this patient suggest that a different disease evaluation strategy should be considered for infants with epithelioid sarcoma.
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PMID:Neonatal epithelioid sarcoma: a distinct clinical entity? 1681 48

Osteosarcoma is the most common primary bone malignancy in children and is associated with rapid bone growth. Parathyroid hormone-related peptide (PTHrP) signaling via parathyroid hormone Type 1 receptor (PTHR1) is important for skeletal development and is involved in bone metastases in other tumors. The aim of this study was to investigate the status of PTHrP/PTHR1 and its possible role in osteosarcoma. In a preliminary screening, a higher level of PTHR1 mRNA, but not PTHrP, was found in 4 osteosarcoma xenografts as compared with 4 standard cell lines, or 5 patient derived cell lines (p < 0.05) using quantitative RT-PCR. It was therefore extended to 55 patient specimens, in which a significantly higher level of PTHR1 mRNA was detected in metastatic or relapsed samples than those from primary sites (p < 0.01). Cell behavior caused by PTHR1 overexpression was further studied in vitro using PTHR1 transfected HOS cell line as a model. Over-expression of PHTR1 resulted in increased proliferation, motility and Matrigel invasion without addition of exogenous PTHrP suggesting an autocrine effect. Importantly, the aggressiveness in PTHR1-expressing cells was completely reversed by RNAi mediated gene knockdown. In addition, PTHR1 over-expression led to delayed osteoblastic differentiation and upregulation of genes involved in extracellular matrix production, such as TGF-beta1 and connective tissue growth factor. When cocultured with bone marrow derived monocytes, PTHR1 transfected HOS cells induced a greater number of osteoclasts. This study suggests that PTHR1 over-expression may promote osteosarcoma progression by conferring a more aggressive phenotype, and forming a more favorable microenvironment.
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PMID:Over-expression of parathyroid hormone Type 1 receptor confers an aggressive phenotype in osteosarcoma. 1741 May 35


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