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

Tumor cells are characterized by abnormalities in growth and metabolism, including the autocrine secretion of certain growth factors. On the basis of our previous demonstration of the production of insulin-like growth factors (IGFs) and their binding proteins by central nervous system (CNS) tumors, we asked whether the levels of IGFs in the CSF may be altered in patients with pituitary and other CNS tumors and may reflect autocrine secretion. We used specific radioimmuoassays for IGF-I and -II and measured these growth factors in the cerebrospinal fluid (CSF) from 26 patients with tumors located adjacent to the ventricular system. The tumors included were eight pituitary tumors (five nonsecreting, three growth hormone secreting), five gliomas, two meningiomas, five medulloblastomas, three metastases, and three other tumors. CSF from patients without tumors served as controls. For radioimmunoassay, CSF was treated with acetic acid overnight and IGF-binding proteins were separated from IGFs by C-2 solid phase cartridge extraction. The pituitary tumors were characterized by significantly elevated levels of IGFs in the CSF. In nonseceting pituitary tumors, the levels of IGF-I in the CSF were similar to normal levels, whereas IGF-II levels were significantly elevated. In acromegalic patients, levels of both IGF-I and -II in the CSF were significantly elevated compared with normal levels and compared with levels in patients with nonsecreting tumors. In contrast, the levels of IGFs in the CSF from most of the primary and metastatic CNS CNS tumors did not significantly differ from normal values. In summary, although IGFs may contribute to the regulation of cell growth in primary CNS tumors, CSF levels are not elevated.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Radioimmunoassay of insulin-like growth factors I and II in the cerebrospinal fluid of patients with pituitary and other central nervous system tumors. 775 56

Organ cultures were established from 2-mm punch biopsies of human skin and maintained for 12 days in either serum-free, growth-factor-free basal medium or in medium supplemented with a number of epithelial cell growth factors including epidermal growth factor, insulin, hydrocortisone and pituitary extract. Normal histological architecture was preserved in growth-factor-free basal medium. However, in the presence of exogenous growth factors, the epidermis was thickened and hypertrophied. There was focal loss of the usual maturation progression, accompanied by abnormal keratinization patterns. In some areas, basement membrane disruption occurred and epithelial cells penetrated into the dermis in these areas. Isolated squamous epithelial cells and nests of cells could be clearly seen within the dermal stroma. In additional studies, an enzyme-linked immunosorbent assay was used to assess fibronectin and laminin production. Increased levels of both matrix components were seen in the culture fluids from tissues maintained under conditions which promote invasion. Taken together these findings indicate that growth-factor-stimulated normal squamous epithelial cells have the capacity to carry out functions that lead to concomitant synthesis and break-down of the underlying basement membrane and to invasion of mesenchymal tissue. This organ culture system may help to elucidate mechanisms of in situ invasion by squamous epithelial cells.
Invasion Metastasis 1993
PMID:In situ epithelial cell invasion in organ culture. 796 May 75

An unusual case of insulin producing islet cell tumor is reported which recurred after a 16 yr interval. In most instances malignancy of islet cell tumors is impossible to assess morphologically or functionally but depends on the recognition of metastases. Nuclear DNA analysis provides significant prognostic and biological information in a number of solid human tumors. Retrospective computerized nuclear image analysis of the primary tumor in the present case showed an aneuploid DNA profile similar to that seen in the metastasis. It appears that ploidy studies may be useful in predicting malignant potential of islet cell tumors.
 ...
PMID:Aneuploid islet cell tumor with late metastasis. 799 Dec 94

Three stable carcinoma cell lines, designated RM22-F5, RM17-5R, and RM1-4, were established from spontaneously occurring mammary carcinomas in old, outbred, female Wistar rats. The RM22-F5 and RM17-5R cells were keratin-positive and formed epithelial monolayers, whereas RM1-4 cells exhibited a spindle-like morphology and intense vimentin staining. When injected into nude mice, RM22-F5, RM17-5R and RM1-4 cells formed well-differentiated, poorly differentiated and undifferentiated carcinomas, respectively. The relative growth rates of the tumor cells in vitro were RM1-4 > RM22-F5 > RM17-5R. The growth of RM22-F5, but not of RM17-5R and RM1-4 cells, was significantly stimulated by insulin, epidermal growth factor, dexamethasone, 17 beta-estradiol and progesterone in vitro. Ovariectomy reduced the growth of RM22-F5 cells in vivo and these cells (but not RM1-4 or RM17-5R) were estrogen-receptor (ER)-positive. None of the lines were positive for the progesterone receptor (PR). Spontaneous lung and lymph-node metastases were observed in nude mice injected with RM22-F5 or RM17-5R cells, respectively. In contrast, RM1-4 cells were non-metastatic but invasive. Karyotype analysis revealed that RM22-F5 cells were hyperdiploid, RM17-5R were hypotetraploid, and RM1-4 were diploid with a sizeable insertion in chromosome 1. A point mutation in codon 12 (G to A transition) and loss of the normal allele of the H-ras-1 gene was detected in the DNA from RM22-F5 cells. No p53 mutations were apparent in any of the cell lines. The results indicate that RM22-F5 cells are hormone-dependent with an ER+/PR- phenotype, while the RM17-5R and RM1-4 lines are hormone-independent and ER-/PR-. These cell lines exhibit the spectrum of biological properties and genetic alterations observed in human breast cancers and may, therefore, be novel and useful models for understanding sporadic breast cancer in post-menopausal women.
 ...
PMID:Establishment of hormone-dependent and hormone-independent carcinoma cell lines with different metastatic potentials from spontaneous mammary tumors in aged Wistar rats. 805 57

The preproglucagon gene encodes, in addition to glucagon, two smaller peptides with structural similarity: glucagon-like peptides 1 and 2. Glucagon-like peptide 1 (GLP-1) 7-36 amide is the most powerful incretin candidate. In the present study, GLP-1 immunoreactivity was investigated in tissue specimens of various types of gastroenteropancreatic tumors, and the serum-levels of GLP-1 were assayed. Immunohistochemical staining of 88 tumors revealed GLP-1 immunoreactivity in 17 neoplasias (19.3%), viz., in 7 out of 33 non-functioning tumors, 4 out of 20 gastrinomas, 4 out of 13 insulinomas, 1 out of 3 vasoactive-intestinal-polypeptide (VIP)omas and 1 adrenocorticotropic-hormone (ACTH)-producing tumor. In these tumors, GLP-1-immunoreactive cells were distributed either diffusely, arranged in clusters, or as single cells. All GLP-1-positive tumors were immunoreactive for glucagon or glicentin, 10 tumors were immunoreactive for pancreatic polypeptide, and 8 tumors for insulin. Ultrastructural analysis of 8 GLP-1-positive tumors, with the immunogold technique, demonstrated GLP-1 immunoreactivity mainly in cells resembling the A-cells of the pancreas or the L-cells of the gut. Of the 17 GLP-1-immunoreactive tumors, 15 were primarily located in the pancreas. Additionally, 2 non-functioning tumors of the rectum were GLP-1 immunoreactive. Five tumors were GLP-1 immunoreactive from 9 patients with multiple endocrine neoplasia I syndrome. Patients with GLP-1-immunoreactive tumors were characterized by a significantly lower rate of distant metastases (P < 0.01) and a higher rate of curative resections (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Glucagon-like peptide 1 immunoreactivity in gastroentero-pancreatic endocrine tumors: a light- and electron-microscopic study. 806 45

Primary meningeal hemangiopericytomas (formerly referred to as angioblastic meningiomas) are by most authors no longer considered to be actual meningiomas but rather thought to be intracranial hemangiopericytomas. Their biological behavior is usually malignant, with recurrences and metastases, often at intervals of years. Both intracranial and extracranial hemangiopericytomas may, however rarely, be accompanied by paraneoplastic hypoglycemias. Our own characteristic observations are based on a female patient aged 67 at the time of her death, in whom a meningeal tumor was resected first at the age of 41. Later recurrencies were removed at the age of 52 and 58 respectively. Three years prior to her death liver metastases had developed followed by increasingly frequent attacks of early morning hypoglycemia with blood sugar levels ranging between 1.4-2.3 mmol/l. Specific examinations revealed low endocrine production of insulin and a distinctly decreased insulin-like growth factor (IGF) I of 25 ng/mb (normal 120-130) and a normal value of total IGF II of 724 ng/ml (normal 400-900), though with a big macromolecular share. The observed paraneoplastic hypoglycemia is probably brought about by coincidence of blocked hepatic glucose production, suppressed lipolysis and increased peripheral glucose uptake. Autopsy revealed a third intracranial recurrence of meningeal hemangiopericytoma and a large metastatic liver. No other sites of metastases were found. Histologic, immunohistologic and electron microscopic findings showed the characteristics features of a hemangiopericytoma. Light microscopic pictures of the primary tumor, recurrences and metastases were identical. Additional autopsy findings were a papillary carcinoma of the right kidney, an angiomyolipoma of the left kidney and a thecoma of the left ovary.
 ...
PMID:[Recurrent and metastasizing hemangiopericytoma of the meninges with paraneoplastic hypoglycemia]. 812 96

Clinical features, diagnostic accuracy of imaging study, and the outcome of surgical treatment for endocrine tumors of the pancreas were analyzed in 12 patients who underwent surgery for the past 16 years and 11 months. The 12 cases were classified into two groups: functioning tumors in 8 (insulinoma in 7 including one malignant case, and malignant glucagonoma in one), and nonfunctioning tumors in 4 including 3 malignant cases. In functioning tumors, tumor size was 2 cm or less in 6 benign cases, but 5 cm or more in 2 malignant cases. In nonfunctioning tumors, tumor size was larger, ranging from 3.5 to 8.0 cm. Diagnostic accuracy for localization of functioning tumors was 66.7% for US, 75.0% for CT, 66.7% for endoscopic retrograde pancreatography (ERP), and 50.0% for selective angiography, while all nonfunctioning tumors could be detected by any diagnostic imagings. Percutaneous transhepatic portal venous sampling for immunoreactive insulin was very helpful to localize insulinoma. Stenosis or obstruction of the main pancreatic duct on ERP and arterial encasement on angiography highly suggested a malignant tumor. Even for malignant cases with liver metastasis, resection of the primary tumor with debulking of metastatic disease or intraarterial infusion chemotherapy was considered to prolong patient prognosis.
 ...
PMID:[Diagnosis and surgical treatment for endocrine tumors of the pancreas]. 813 24

The raf genes encode for a family of cytoplasmic proteins (A-raf, B-raf and c-raf-1) with associated serine/threonine kinase activities. Raf-1 is an important mediator of signals involving cell growth, transformation and differentiation. It is activated in response to a wide variety of extracellular stimuli such as insulin, nerve growth factor (NGF), platelet derived-growth factor (PDGF), and in response to expression of oncogenes, v-src and v-ras, in a cell-specific manner. Recently, the first physiological substrate for Raf-1 protein kinase was identified. Raf-1 was found to phosphorylate and activate Mitogen-Activated Protein Kinase Kinase (MEK), an activator of MAP kinase, thus linking the Raf-1 signaling pathway with that of MAP kinase. Cell specific differences in signalling pathways involving Raf-1 and MAP kinase have also been discovered. Accumulating evidence indicates that membrane tyrosine kinases, ras, Raf-1, MEK and MAP kinase are interconnected via a complex network rather than via a linear pathway involving multiple substrates and feedback loops.
Cancer Metastasis Rev 1994 Mar
PMID:Signal transduction pathways involving the Raf proto-oncogene. 814 42

Neuroendocrine pancreatic tumors are neoplasms derived from APUD cells, characterized by hyperincretion of several peptides of hormonal activity. The incidence of these tumor is low. They are usually classified according to the predominant secreted peptide: gastrinoma, insulinoma, VIPoma, glucagonoma. Insulinoma is the most frequent endocrine pancreatic tumor, characterized by a peculiar clinical picture due to insulin action. This neoplasm is prevalently benign (90%), and may cause symptoms due to hypo-glycemia such as epilepsy, asthenia, deep coma, dizziness, hunger and epigastric pain. Surgery still constitutes the principal therapy for insulinoma treatment, but an accurate tumor identification is necessary. Selective arteriography of the pancreas and new diagnostic investigations as intraoperative US, selective sampling of pancreatic veins with insulin Quick-RIA, aid the diagnosis and more precise localization of the tumor. When surgical therapy is not practicable, for diffuse metastases, octreotide has an inhibitory effect upon hormone release, and may be combined with chemotherapy for controlling clinical symptoms. We review the clinical records of 2 patients from our Institute, who had hyper-insulinism due to benign insulinomas of the tail of the pancreas. Surgical treatment was performed with enucleation of the neoplasms.
 ...
PMID:[Pancreatic insulinomas]. 817 52

Tumor metastasis is the primary cause of death for cancer patients. The metastatic cascade requires successful tumor cell invasion into and through vascular and parenchymal barriers. We have shown that autocrine motility factor (AMF, autotaxin) and the insulin-like growth factors (IGFs) induce tumor-cell migration. Since granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to prime neutrophils for chemotaxis, we have therefore studied the influence of GM-CSF upon tumor cells and report that GM-CSF stimulates migration of these cells in a dose-dependent fashion. The ED50 for A2058 human melanoma cell line chemotaxis to GM-CSF is approx. 60 pM. The motile response to GM-CSF was additive to that of IGF-I and AMF, both of which are potent attractants for tumor cells. Pre-treatment of cells for 2 hr with non-toxic concentrations of pertussis toxin (PT) or amiloride resulted in a 50% inhibition of chemotaxis to GM-CSF. Therefore, GM-CSF, through PT- and amiloride-sensitive signal pathways, is a potent attractant for melanoma cells, the response to which is additive to that of other attractants. The presence of the GM-CSF receptor in A2058 melanoma cells was indicated by Northern-blot analysis which identified message transcripts of 2.1 and 3.0 kb. These data emphasize the versatility of the melanoma cell migration response to an array of cytokines, including GM-CSF.
 ...
PMID:Granulocyte-macrophage colony-stimulating factor induces human melanoma-cell migration. 847 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>