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)

Osteofibrous dysplasia (OFD) and adamantinoma are rare and most commonly arise in the tibia of young individuals. Although OFD has typical histopathologic features, areas resembling OFD have often been noted at the periphery of otherwise classic adamantinomas, and some have suggested that OFD may be either a precursor to or a regressive phase of adamantinoma. The so-called OFD-like adamantinoma encompasses some features of both OFD and adamantinoma. We studied the clinical, imaging, histopathologic, immunohistochemical, ultrastructural, and molecular features of 16 OFD and 8 adamantinomas (5 OFD-like and 3 classic) in an attempt to further define their morphology, clinical course, and relationship. Patients with OFD were generally younger than those with adamantinoma. Osteoblastic and osteoclastic activity was more prominent in OFD than in OFD-like adamantinoma. In addition to the inconspicuous small clusters of epithelial cells in OFD-like adamantinoma, isolated keratin-positive cells with a unique ultrastructural hybrid fibroblastic-epithelial phenotype were found in the stroma of all OFD and OFD-like adamantinomas. Fluorescence in situ hybridization analysis revealed trisomies 7, 8, and/or 12 in the spindle cell stroma of OFD, OFD-like, and classic adamantinoma, supporting a neoplastic origin of OFD and a common histogenesis for all 3 lesions. Trisomies were not observed in osteoblasts or osteoclasts suggesting that the osseous component is reactive and non-neoplastic. Of the 11 OFD patients with follow-up (median, 4.5 y), all 3 who underwent incisional biopsy had persistent, nonprogressive disease and 2 of 8 who underwent curettage or wide excision had recurrence; none developed adamantinoma. All 6 adamantinoma patients with follow-up (3 classic and 3 OFD-like) were treated with wide excision. One with classic adamantinoma died of pulmonary metastases 9 years after presentation; the other 5 were free of disease with a median follow-up of 12 years. None of the classic adamantinomas evolved into OFD-like adamantinoma or OFD. Although the histopathology, immunohistochemistry, ultrastructure, and cytogenetics indicate that these lesions are closely related, our data and the literature suggest that only classic adamantinoma has malignant potential. OFD, OFD-like adamantinoma, and classic adamantinoma appear to show a progressive complexity of cytogenetic aberrations, perhaps indicative of a multistep neoplastic transformation.
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PMID:Osteofibrous dysplasia and adamantinoma in children and adolescents: a clinicopathologic reappraisal. 1830 Aug 15

Feline myeloma-related disorders (MRD) are rare neoplasms of plasma cells. The multistep transformation model of myeloma in humans is based on the premise that plasma cells undergo neoplastic transformation primarily within the intramedullary compartment and that over time they become poorly differentiated and metastasize to extramedullary locations. Historically, diagnostic criteria used for human multiple myeloma have been applied to the cat, with the assumption that feline MRD commonly arises in the intramedullary compartment. Our objectives were to describe the features of feline MRD confirmed by cytology, histopathology, histochemistry, and immunohistochemistry and to categorize these tumors. A priori hypotheses were 1) tumor category predicts survival and 2) cats with well-differentiated tumors commonly have extramedullary involvement in contrast to human myeloma patients. This multicenter, retrospective study identified 26 MRD cases. There was good agreement between histopathologic and cytologic tumor categorization. Histochemistry and immunohistochemistry were shown to be valuable adjunct tests in the diagnosis of MRD. Cats with well-differentiated tumors had increased median survival relative to those with poorly differentiated tumors (254 versus 14 days). We have reported that marked extramedullary involvement at initial clinical presentation is significantly more common in the cat than in human MRD patients. In this study, we demonstrate that cats with well-differentiated tumors more commonly have extramedullary involvement than human myeloma patients with well-differentiated tumors (90% versus 20%, P < 0.0002). These results contrast strongly with the human myeloma model of primary intramedullary neoplastic transformation and suggest that primary extramedullary neoplastic transformation may be more common in feline MRD.
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PMID:Histopathologic, immunohistochemical, and cytologic analysis of feline myeloma-related disorders: further evidence for primary extramedullary development in the cat. 1842 28

Galectin-3 plays important roles in cell adhesion, cell proliferation, apoptosis, neoplastic transformation, and metastasis. Galectin-3 expression has been evaluated in various malignant neoplasms to determine its effectiveness in differential diagnosis from benign lesions and its effects on carcinogenesis. There are few and somewhat controversial results regarding its changes through cancer progression in thyroid malignancies. We studied the presence of galectin-3 expression immunohistochemically and its relation with tumor invasiveness and lymph node metastasis in 89 cases of papillary carcinoma of the thyroid. Galectin overexpression was less frequent in cases with lymph node metastases compared with cases without lymph node metastasis (P = 0.001). Metastatic foci in lymph nodes showed a lower degree of galectin-3 overexpression than their primary lesions (P = 0.001). Degree of galectin-3 overexpression was also lower in larger tumors (P = 0.009). Additionally, a decreased level of galectin-3 overexpression was observed at the invasive edges of the tumors (P = 0.001). Galectin-3 overexpression is more profound in early stages of papillary carcinoma, and its expression intensity decreases during tumor progression. This finding is consistent with roles for galectin-3 in cell adhesion to other tumor cells and the matrix.
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PMID:Galectin-3 expression in tumor progression and metastasis of papillary thyroid carcinoma. 1858 Dec 71

SP is an undecapeptide that belongs to the family of related neurokinins termed tachykinins. SP is one of the mediators responsible for the neural-immune/hematopoietic cross-talk. It is released from the nerve fibers of the autonomic and enteric nervous systems in lymphoid organs and is also produced by the resident, stromal or hematopoietic cells. SP stimulates the production of hematopoietic cytokines (e.g. IL-1, IL-3, IL-6, SCF, GM-CSF) by bone marrow stromal cells. It enhances the proliferation of bone marrow progenitors, both directly by binding to progenitor's receptors and indirectly by interacting with marrow stromal cells. SP can also modulate immune and hematopoietic functions like phagocytosis, immunoglobulin production, lymphocyte proliferation and platelet aggregation. SP fragments derived from endopeptidase activity could also exert immune and hematopoietic regulation. The biological effects of SP are mediated through interactions with certain G protein-coupled receptors: the neurokinin (NK) receptors. Different studies have shown that NK receptors are localized on immuno-competent cells, including monocytes/macrophages, neutrophils, mast cells, dendritic cells and T or B lymphocytes, bone marrow stromal cells and hematopoietic progenitors. The disturbance of the neural-hematopoietic-immune axis may be implicated in hematological malignancies. SP seems to be important in the neoplastic transformation of bone marrow, leading to the development of acute leukaemia in children; myelofibrosis and also metastases to bone marrow of solid tumors in early stages of these diseases.
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PMID:[Substance P as a regulatory peptide of hematopoiesis and blood cell functions]. 1925 69

Fhit protein is known to play a role in the process of neoplastic transformation. It has been demonstrated that FHIT gene inactivation is manifested by a lack or very low concentration of Fhit protein in tissues collected from tumours in many organs, including head, neck, breast, lungs, stomach or large intestine. The study included a group of 80 patients with advanced gastric carcinomas. The expression of Fhit protein was assessed by means of the immunohistochemical method (avidin-biotin-streptavidin) in the sections fixed in formalin and embedded in paraffin, using rabbit polyclonal antiFhit antibody (Abcam, UK) at 1: 200. Statistical analysis did not show any correlation of the expression of Fhit protein in the main mass of tumour and in the metastasis to lymph node with gender, depth of wall invasion, histological differentiation, Lauren's classification, Bormann's classification, metastases to local lymph nodes or Helicobacter pylori infection. However, a strong statistical correlation was revealed of Fhit protein expression in the main mass of tumour with patients' age (p=0.04) and tumour location in the stomach (p=0.02). No relationship was found between Fhit expression in the main mass of tumour and survival time (p=0.26).
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PMID:Immunohistochemical assessment of Fhit protein expression in advanced gastric carcinomas in correlation with Helicobacter pylori infection and survival time. 1941 37

Phosphatase and tensin homolog (PTEN) belongs to the group of gatekeeper tumor suppressor genes and is involved in multiple mechanisms leading to cellular defense against neoplastic transformation and progression. Twenty-four dogs and 17 cats were submitted to a 2-year follow-up study, and clinicopathologic features were recorded and compared with immunohistochemical PTEN staining. PTEN-negative status occurred in 33% of canine and 76% of feline mammary carcinomas. In canine mammary carcinomas, there was a significant (P < .05) correlation between loss of PTEN protein expression and simple carcinoma histotype, lymphatic vessel invasion, lymph node metastases, distant organ metastases, tumor dedifferentiation, tumor recurrence, and shorter overall survival. In feline mammary tumors, a significant correlation between loss of PTEN protein expression and lymphatic vessel invasion was found. Loss of PTEN expression could be a useful prognostic marker in canine mammary carcinomas.
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PMID:Reduced PTEN protein expression and its prognostic implications in canine and feline mammary tumors. 1942 83

Colorectal cancer immunotherapy is limited by the paucity of available target antigens fulfilling the necessary criteria of tumor-specificity, sufficient immunogenicity and universal association with disease. A novel class of immune targets, cancer mucosa antigens (CMAs), whose expression normally is confined to mucosae but maintained during neoplastic transformation, promises to overcome these imitations, enjoying the advantage of immune compartmentalization, preventing autoimmune disease, while permitting therapeutic anti-tumor responses. Indeed, therapeutic immunization against the model CMA guanylyl cyclase c (GCC) extends survival in mouse models of established parenchymal colorectal cancer metastases with antitumor efficacy superior to currently available antigens. Here adjuvanation of therapeutic antitumor immunity to GCC was explored employing the cytokines IL-2 and GM-CSF in a mouse model of metastatic colorectal cancer. Combining plasmids expressing murine IL-2 or GM-CSF with recombinant viral vector immunization to GCC enhanced antitumor efficacy beyond viral vector immunization alone. These studies support the incorporation of IL-2 and GM-CSF in CMA-targeted immunization regimens for established colorectal cancer metastases.
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PMID:Cytokine adjuvanation of therapeutic anti-tumor immunity targeted to cancer mucosa antigens. 1995 76

Human cancer can arise due to inherited and sporadic genetic and epigenetic changes. These changes consequently inhibit the function of tumor suppressors and pro-apoptotic genes, while activate oncogenes. Most human cancers arise as benign tumors; after acquiring additional genetic and epigenetic changes, they become malignant and eventually metastasize to distal organs. Recent studies have implicated multiple tumor suppressing mechanisms that prevent neoplastic transformation and thus have anti-cancer activities. Among these, cellular senescence has emerged as an important tumorigenesis regulatory mechanism, which not only modulates tumor initiation but also affects tumor progression and maintenance. Cellular senescence is also observed in response to genotoxic chemotherapeutic agents and has been linked to cancer recurrence and drug resistance. Thus improved understanding of regulators of chemotherapy-induced cellular senescence will allow us to explore rational and targeted therapies against various human cancers. In this review, we aim to describe the mechanisms and regulation of three major forms of cellular senescence: replicative senescence (RS), oncogene-induced senescence (OIS) and accelerated cellular senescence (ACS). We also discuss the role of cellular senescence in human cancer and high-throughput genomics-based methods to identify the regulators of cellular senescence. Finally, we highlight aspects of cellular senescence that could be targeted for alternative, yet viable cancer therapies against a variety of human cancers.
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PMID:Exploiting cellular senescence to treat cancer and circumvent drug resistance. 2011 55

Colorectal cancer (CRC) arises as a consequence of the accumulation of genetic and epigenetic alterations in colonic epithelial cells during neoplastic transformation. Epigenetic modifications, particularly DNA methylation in selected gene promoters, are recognized as common molecular alterations in human tumors. Substantial efforts have been made to determine the cause and role of aberrant DNA methylation ("epigenomic instability") in colon carcinogenesis. In the colon, aberrant DNA methylation arises in tumor-adjacent, normal-appearing mucosa. Aberrant methylation also contributes to later stages of colon carcinogenesis through simultaneous methylation in key specific genes that alter specific oncogenic pathways. Hypermethylation of several gene clusters has been termed CpG island methylator phenotype and appears to define a subgroup of colon cancer distinctly characterized by pathological, clinical, and molecular features. DNA methylation of multiple promoters may serve as a biomarker for early detection in stool and blood DNA and as a tool for monitoring patients with CRC. DNA methylation patterns may also be predictors of metastatic or aggressive CRC. Therefore, the aim of this review is to understand DNA methylation as a driving force in colorectal neoplasia and its emerging value as a molecular marker in the clinic.
Cancer Metastasis Rev 2010 Mar
PMID:DNA methylation markers in colorectal cancer. 2013 98

The deregulation of Met/hepatocyte growth factor (HGF) receptor tyrosine kinase signaling constitutes a common event in colorectal cancers. However, the physiopathological functions of such a deregulation remain poorly understood. In the present study, we investigated the role of the deregulation of Met receptor in the neoplastic transformation of intestinal epithelial cells. To do so, the normal, well-established and characterized rat intestinal epithelial IEC-6 cells were transduced with a retrovirus carrying the oncogenic constitutive active form of Met receptor, Tpr-Met. Herein, we show that compared with control IEC-6 cells, Tpr-Met-IEC-6 cells exhibit enhanced proliferation, loss of growth-contact inhibition, cell morphological alterations, actin cytoskeletal reorganization, loss of E-cadherin expression and anchorage-independent growth. Moreover, Tpr-Met-IEC-6 cells are conferred the capacity to produce the proangiogenic factor VEGF and to reduce the potent antiangiogenic factor thrombospondin-1. Of significance, Tpr-Met-IEC-6 cells are endowed with the ability to elicit angiogenic responses and to form tumors and metastases in vivo. Hence, our study demonstrates for the first time that the sole oncogenic engagement of Met receptor in normal intestinal epithelial cells is sufficient to induce a wide array of cancerous biological processes that are fundamental to the initiation and malignant progression of colorectal cancers.
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PMID:Oncogenic engagement of the Met receptor is sufficient to evoke angiogenic, tumorigenic, and metastatic activities in rat intestinal epithelial cells. 2053 3


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