Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dermatofibrosarcoma protuberans (DFSP) is a soft tissue neoplasm of intermediate malignancy that is initially localized to the skin from where it can invade deep structures (fat, fascia, muscle and bone). It is the most frequent fibrohistiocytic tumor, comprising approximately 1.8 % of all soft tissue sarcomas and 0.1 % of all cancers. It has an estimated incidence of 0.8-5 cases per one million persons per year. Treatment of localized disease consists in complete surgical excision of the lesion by conventional surgery with wide margins (>3 cm) or by micrographic Mohs surgery. Although the cases of metastatic DFSP do not reach 5 % of the total, almost all of them appear after previous local relapses. The prognosis for metastatic cases is very poor with a survival of less than 2 years following detection of metastatic disease. Patients with locally advanced DFSP are not candidates for an initial radical surgical therapy therefore neoadyuvant treatment is required prior to surgery in order to reduce tumor burden. In this regard, chemotherapy and radiotherapy have not been highly efficacious so it is necessary to consider new alternatives. The demonstration of the oncogenic power of the translocation COL1A1-PDGFB in DFSP has allowed the successful introduction of drug therapy with antagonists of the PDGFB receptor for metastatic or locally advanced cases.
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PMID:[Dermatofibrosarcoma protuberans]. 1739 92

Primary and metastatic so-called malignant fibrous histiocytoma/undifferentiated high-grade pleomorphic sarcoma (MFH) is rare in the gastrointestinal (GI) tract with approximately 50 primary and five metastatic cases reported so far. We evaluated two primary gastric and three metastatic intestinal high-grade pleomorphic sarcomas with features of storiform-pleomorphic MFH. Gastric tumours occurred in a 79-year-old man and a 68-year-old woman. One patient died post-operatively, and the other was disease-free at 6 months. Three patients presented with GI metastasis 24, 60 and 0 months after diagnosis of MFH of the heart (n = 1) and the thigh (n = 2). Metastases were located in the small (n = 1) and large bowel (n = 2) and were characteristically pedunculated and polypoid with oedematous haemorrhagic stroma. Concurrent metastases (brain, lung, bone) were present in all three cases. Tumours expressed alpha-smooth muscle actin (four of five), platelet-derived growth factor receptor (PDGFR) alpha (three of three) and PDGFRbeta (two of three) but were negative for CD117, CD34 and other lineage-specific markers. Ultrastructural examination revealed myo/fibroblastic features. Both gastric MFH were wild type for KIT and PDGFRalpha. In conclusion, primary and metastatic MFH of the GI tract commonly express PDGFRalpha and show a myo/fibroblastic phenotype. They should be distinguished from a variety of primary and metastatic pleomorphic neoplasms, in particular high-grade sarcomatous GI stromal tumours (GIST), pleomorphic leiomyosarcoma, sarcomatoid carcinoma and other mimics.
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PMID:Primary and metastatic high-grade pleomorphic sarcoma/malignant fibrous histiocytoma of the gastrointestinal tract: an approach to the differential diagnosis in a series of five cases with emphasis on myofibroblastic differentiation. 1787 30

The skeleton is the second most frequent site of metastasis. However, only a restricted number of solid cancers, especially those of the breast and prostate, are responsible for the majority of the bone metastases. Metastatic bone disease is a major cause of morbidity, characterised by severe pain and high incidence of skeletal and haematopoietic complications (fractures, spinal cord compression and bone marrow aplasia) requiring hospitalisation. Despite the frequency of skeletal metastases, the molecular mechanisms for their propensity to colonise bone are poorly understood and treatment options are often unsatisfactory. TGF-beta and the signalling pathway it controls appears to play major roles in the pathogenesis of many carcinomas, both in their early stages, when TGF-beta acts to arrest growth of many cell types, and later in cancer progression when it contributes, paradoxically, to the phenotype of tumour invasiveness. Here we discuss some novel insights of the TGF-beta superfamily-including BMPs and their antagonists-in the formation of bone metastasis. Increasing evidence suggests that the TGF-beta superfamily is involved in bone homing, tumour dormancy, and development of micrometastases into overt bone metastases. The established role of TGF-beta/BMPs and their antagonists in epithelial plasticity during embryonic development closely resembles neoplastic processes at the primary site as well as in (bone) metastasis. For instance, the tumour-stroma interactions occurring in the tissue of cancer origin, including epithelium-to-mesenchyme transition (EMT), bear similarities with the role of bone matrix-derived TGF-beta in skeletal metastasis formation.
Clin Exp Metastasis 2007
PMID:TGF-beta and BMP7 interactions in tumour progression and bone metastasis. 1800 74

Here, we examined the status of stromal Cav-1 expression in patients with benign prostatic hypertrophy (BPH), primary prostate cancers (PCa), and prostate-cancer metastases (Mets). Interestingly, an absence of stromal Cav-1 directly correlated with prostate cancer disease progression. For example, virtually all BPH samples showed abundant stromal Cav-1 immunostaining. In contrast, in a subset of patients with primary prostate cancer, the stromal levels of Cav-1 were significantly decreased, and this correlated with a high Gleason score, indicative of a worse prognosis and poor clinical outcome. Remarkably, all metastatic tumors (either from lymph node or bone) were completely negative for stromal Cav-1 staining. Thus, stromal Cav-1 expression may be considered as a new biomarker of prostate cancer disease progression and metastasis. Mechanistically, stromal Cav-1 levels were inversely correlated with the epithelial expression levels of Cav-1 and epithelial phospho-Akt. Thus, loss of stromal Cav-1 is predictive of elevated levels of epithelial Cav-1 and epithelial Akt-activation. This provides important new clinical evidence for paracrine signaling between prostate cancer epithelial cells and the tumor stromal micro-environment, especially related to disease progression and metastasis.
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PMID:An absence of stromal caveolin-1 is associated with advanced prostate cancer, metastatic disease and epithelial Akt activation. 1955 67

Extracranial metastasis of glioblastoma multiforme (GBM) is very rare, in spite of very aggressive tumor behavior and being documented in only a few patients. In this article we present a 25-year-old man with secondary glioblastoma associated with extracranial progression and distant metastasis. He was diagnosed by magnetic resononce (MR) with an intracranial lesion in the right parietofrontal region, which was subsequently resected. Histology revealed a diffuse astrocytoma (grade II). The tumor recurred 1 year later and the patient received a second craniotomy. A diagnosis of GBM was made. After radiotherapy, he presented with right cervical lymph node metastases. The cytomorphological features supported a diagnosis of metastatic glioblastoma multiforme. The neck dissection was made and histology confirmed the fine needle aspiration diagnosis of glioblastoma multiforme. MR with diffusion-weighted imaging revealed right cervical lymph node metastases and multi-bone metastases (mainly pelvic bone) 3 weeks later.
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PMID:Multiple extracranial metastases from secondary glioblastoma multiforme: a case report and review of the literature. 1989 45

We investigated 30 patients with advanced and metastatic breast cancer who underwent capecitabine therapy in our department from July, 2004 to April, 2009. Patients' backgrounds: 35-82 years of age (median, 62 years of age). Performance status (PS): 0 approximately 1 in 21 cases, PS:2 in 7 cases and PS:3 in 2 cases. 63% of patients were positive ER and/or PgR, and 33. 3% were positive HER2. Of these patients, 17 had bone, 15 lymph node, 13 lung, 7 liver, and 4 skin metastasis. The capecitabine response in these patients was evaluated as follows: partial response (PR) in 9, stable disease (SD)in 6, long SD in 4, and progressive disease(PD)in 11, indicating a response rate(RR)of 30% and a clinical benefit rate (CBR) of 43. 3%. In comparison with after third-line treatment, capecitabine proved more effective as first or second-line treatment. Interestingly, the capecitabine response in HER2 negative-expressing patients, especially in HR(+)/HER2(-)subgroup, was significantly better than that in HER2-over-expressing patients. The soft tissue lesions(primary tumor and metastasis of skin and lymph nodes)showed a significantly better response to capecitabine treatment than other metastases such as lung, liver and bone. There was a significant difference in the response rate between soft tissue metastasis (lymph nodes, skin and primary tumor)and other types of metastasis (lung, liver, and bone). Finally, it was suggested that use of capecitabine in upfront line for HER2-negative expressing cases or soft tissue metastatic cases contributed to the prolongation of time to treatment failure(TTF)and overall survival.
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PMID:[More effective positioning of capecitabine for advanced and metastatic breast cancer]. 2041 20

Sclerosing epithelioid fibrosarcoma (SEF) has distinctive morphology and occurs mainly in deep soft tissue of adult extremities. Approximately 59 cases of SEF have been reported, with only 12 previously described in head and neck locations. Lesions involving the oral and maxillofacial region (OMFR) and intraosseous examples are rare. We present five cases of OMFRSEF. The OMF Pathology Department Registry was searched for cases coded from 1990 to the present as "SEF," "fibrosarcoma not otherwise specified" or "neoplasm of uncertain histiogenesis." Inclusion required OMFR location, an abundantly sclerotic sarcoma with epithelioid features, and lack of other phenotype by immunohistochemistry. Five cases of SEF included 3 males and 2 females. The age of the patients were: 19, 22, 35, 47 and 47 years. Tumor location included the infra-temporal fossa, buccal mucosa (recurrence extending into bone), anterior mandible (intraosseous primary, focally extending into soft tissue), and left parotid and submandibular gland (with metaplastic bone) regions. Tumor sizes ranged from 1.0 to 5.7 cm, median 3.5 cm. Histologically, the tumors were well delineated and multinodular, separated by fibrous septae. The spindled to primarily epithelioid tumor cells formed moderately cellular sheets and cords of irregularly contoured medium to large, round to oval, occasionally overlapping nuclei, indistinct nucleoli, wispy eosinophilic (retracting) cytoplasm, and distinctive cytoplasmic borders, embedded in osteoid-like stroma. Hemangiopericytoid (HPC-like) vessels were observed. Despite numerous apoptotic cells, mitoses were generally low; necrosis was present in two cases. Three tumors were graded as 2/3 and two 1/3. Immunohistochemically, the tumor cells were positive for vimentin, 1 case focally for CD34, whereas all cases were negative for S100 protein, keratins, EMA, desmin, and SMA. Wide or radical excision was performed with no adjuvant therapy. Follow-up revealed that 4 cases recurred at a range of 12-120 months. One case had no recurrent/residual disease at 3 months. Metastatic disease was present in 2 cases, to chest wall and lumbar/thoracic spine at 12 and 21 months, respectively. One patient died of disease complications at 15 months. OMFRSEF occur in adults in various locations, but with a common propensity to involve bone; there is recurrent potential and morbidity with higher grade lesions. The differential diagnosis for these tumors in this site includes sclerosing carcinoma, Ewing/PNET, osteosarcoma, osteoblastoma, and benign and malignant myoepithelial salivary gland tumors. The collagen, focal spindle cell features, HPC-like vasculature, and weak focal CD34 reactivity in one case might have raised a possible relationship between OMFRSEF and low grade malignant solitary fibrous tumor, but the intraosseous propensity, epithelioid features and relative lack of CD34 make this a distinctive entity.
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PMID:Oral and maxillofacial sclerosing epithelioid fibrosarcoma: report of five cases. 2061 75

Skull metastases are malignant bone tumors which are increasing in incidence. The objectives of this study were to characterize the MR imaging features, locations, and extent of metastatic skull tumors to determine the frequency of the symptomatic disease, and to assess patient outcomes. Between September 2002 and March 2008, 175 patients undergoing routine head MR imaging were found to have metastatic skull tumors. Contrast-enhanced study with fat suppression was used in some cases when required. Classification of metastases was simplified to three yes/no questions: first, with regard to location (either in the calvarium or in the cranial base); second, with regard to distribution within the plane of the cranial bone (either "circumscribed" meaning clearly demarcated and confined to one bone, or "diffuse" and likely to spread across a suture to another bone); and third, with regard to invasion ("intraosseous" in cranial bones only, or "invasive" spreading from the skull, either out into the scalp or inward to the dura and perhaps further in). Primary sites were breast cancer (55%), lung cancer (14%), prostate cancer (6%), malignant lymphoma (5%), and others (20%). The mean time from primary diagnosis to skull metastasis diagnosis was 71 months for cases of breast cancer, 26 months for prostate cancer, 9 months for lung cancer, and 4 months for malignant lymphoma. Calvarial circumscribed intraosseous metastases were found most frequently (27%). The patients were mainly asymptomatic. However, some patients suffered from local pain or cranial nerve palsies that harmed their quality of life. Treatment, mainly for symptomatic cases, was by local or whole-skull irradiation. Metastatic skull tumors are not rare, and most are calvarial circumscribed intraosseous tumors. MR images contribute to understanding their type, location, and multiplicity, and their relationship to the brain, cranial nerves, and dural sinuses. Radiation therapy improved the QOL of patients with neurological symptoms.
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PMID:Metastatic skull tumors: MRI features and a new conventional classification. 2111 Feb 18

Bone lesions as a consequence of bone metastases in breast cancer patients can increase risk for skeletal-related events (SREs) (i.e., radiation to the bone, a pathological or osteoporotic fracture event, hypercalcemia, spinal cord compression, or surgery to the bone). The mortality risk for breast cancer patients with SREs subsequent to bone metastases is unclear. We assessed this relationship in a large, population-based cohort of breast cancer patients in Denmark. We identified 35,912 newly diagnosed breast cancer patients from January 1, 1999 to December 31, 2007 in the Danish National Patient Registry (DNPR) and followed them through April 1, 2008. Information on stage and treatment was obtained from the Danish Cancer Registry. We used the Kaplan-Meier method to estimate survival, and Cox's regression analysis to estimate the mortality rate ratio (MRR) by the presence of bone metastases with and without SREs, adjusting for age and comorbidity. The 5-year survival was 75.8% for breast cancer patients without bone metastases, 8.3% for patients with bone metastases, and 2.5% for those with both bone metastases and SREs. The adjusted MRR was 10.5 [95% confidence interval (CI) 9.5-11.6] for breast cancer patients with bone metastases, and 14.4 (95% CI 13.1-15.8) for those with bone metastases and SREs, compared with breast cancer patients with no bone metastases but possibly other sites of metastases. A similar pattern persisted when analyses were stratified by stage or treatment. Breast cancer patients with bone metastases and SREs have a poor prognosis compared to those with and without bone metastases regardless of cancer treatment or stage of disease at diagnosis.
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PMID:Survival in breast cancer patients with bone metastases and skeletal-related events: a population-based cohort study in Denmark (1999-2007). 2146 30

Death from prostate cancer is most frequently a result of metastatic disease. A key step in the process of metastasis is the attachment of circulatory tumor cells to target organ endothelium. This process is thought to be mediated by lectins, a class of cell surface proteins that bind two or more carbohydrate groups. Using fluorescent microscopy and fluorescein isothiocyanate (FITC) conjugated lectins, the presence of various carbohydrates was examined in the following tumorigenic and non-tumorigenic cell lines: rat prostate epithelial (EPYP-2, EPYP-1), rat prostate endothelial (YPEN-2, YPEN-1, YPEN-2PV), Dunning rat prostate cancer cell lines (MLL, ML, AT6.3, AT.1, AT2.1, GP9F3), and three tumorigenic human prostate cell lines (LNCaP, PC3, PC3 bone). The lectin Triticum vulgaris (WGA) was found to readily bind the carbohydrates N-acetylglucosamine and sialic acid on the plasma membrane of tumorigenic cell lines. Interestingly, WGA bound carbohydrates located to the nucleus and cytoplasm in non-tumorigenic cell lines, indicating that N-acetylglucosamine and sialic acid residues are preferentially expressed on the cell membrane of prostate cancer cells. Lectin staining patterns in cell lines of varying metastatic potential revealed no significant difference between highly metastatic vs. low metastatic cell lines. Observations revealed an absence of N-acetylgalactosamine and L-fucose in all rat Dunning, epithelial and endothelial cell lines as well as all human prostate cancer cell lines except for the androgen insensitive human prostate cancer cell line PC3, in which L-fucose residues were detected in the nucleus and on the plasma membrane. PC3 bone cells, which metastasized selectively to bone, demonstrated the presence of galactose residues whereas PC3 cells did not, suggesting that preference for target organ endothelium may be influenced by the expression of carbohydrate residues. These data indicate that differential carbohydrate expression may play an important role in prostate cancer biology.
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PMID:Differential carbohydrate expression in tumorigenic vs nontumorigenic prostate cell-lines. 2155 71


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