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)

Neuroblastoma is the most common extracranial solid tumor of childhood. It commonly presents in children younger than 2 years of age, with 90% being younger than 5 years of age. There is marked variability in clinical behavior ranging from spontaneous regression or differentiation into benign tumors to rapid and progressive fatal disease. Approximately 50% of patients will have metastases at presentation. The management is dependent on age, stage of disease, and biological and biochemical markers. Nuclear medicine plays an important role in the initial staging, as a prognostic indicator, for assessment of response to treatment, and also in therapy. The most common nuclear medicine diagnostic studies are (99m)Tc-disphosphonate bone scintigraphy and (123)I-MIBG (metaiodobenzylguanidine) scintigraphy. Bone scintigraphy has been the main investigational modality to diagnose skeletal metastases. Whole body imaging with (123)I-MIBG has become the preferred diagnostic test because this agent accumulates in neuroblastoma in 90% to 95% of cases and will accumulate in the primary tumor and metastases particularly in bone, bone marrow, lymph nodes, and soft tissues. MIBG can be used to assess therapy response and is a significant prognostic indicator. Other diagnostic techniques include positron emission tomography (PET)/computed tomography, mainly using (18)F-fluorodeoxyglucose. Other more experimental PET agents, as well as radiolabeled antibodies and octreotide, also are being investigated. Therapy has mainly focused on palliation and has been used alone or in combination with chemotherapy in high-risk refractory or relapsed patients. Major attention is being placed on stratification of patients to try and reduce the side effects associated with intensive megatherapy in the low to intermediate risk patients. Neuroendocrine tumors (NETs) are rare in childhood, but nuclear medicine techniques, mainly using MIBG and somatostatin receptor agents, have a role in diagnosis, staging, and a limited role in therapy. Newer radiopharmaceuticals, including PET agents, are being evaluated for the assessment of NET. Nuclear medicine techniques play a major role in the management of neuroblastoma and NET.
 ...
PMID:Neuroblastoma and other neuroendocrine tumors. 1754 28

Neuroendocrine tumor metastases to the pituitary gland are very rare. There are few case reports of carcinoid tumor metastases to the pituitary, but no cases of pancreatic neuroendocrine pituitary metastases have been reported. In this report we present a 55-year-old female with a sellar mass, ophthalmoplegia and headaches initially thought to represent an invasive null cell pituitary adenoma. However a histological (trans-sphenoidal and liver biopsies) and systemic investigation proved it to be a metastasis of an undiagnosed pancreatic neuroendocrine tumor. Our patient was unique in respect to the location of the metastasis and the uncharacteristically high proliferative index of her tumor. She received conventional therapy consisting of Sandostatin, chemotherapy and radiotherapy as well as labeled somatostatin following an avid uptake on octreotide scanning. Despite a radiological improvement the patient suffered progressive clinical deterioration and died.
 ...
PMID:Metastatic pancreatic neuroendocrine tumor presenting as a pituitary space occupying lesion: a case report. 1763 85

Elevated circulating chromogranin A (CgA) levels are found in neuroendocrine tumors (NETs), but the diagnostic usefulness of this marker is still debatable. To assess the role of CgA for the diagnosis of gastroenteropancreatic (GEP) NETs and the identification of metastatic patients, an Italian multicenter observational study has been performed. CgA was evaluated in 202 GEP NET patients by IRMA and ELISA. The cutoffs for diagnosis and presence of metastases were identified by receiver-operating characteristic (ROC) curve. We found good correlation between IRMA and ELISA. The ROC analysis identified a cutoff of 53 ng/ml for IRMA and 16 U/l for ELISA as discriminating between controls and patients with active disease (sensitivity 71.3 and 84%; specificity 71 and 85% respectively). Metastases were present in 123 patients, having significantly higher CgA levels than patients without metastases. ROC analysis identified a cutoff of 146 ng/ml for IRMA and 67.3 U/l for ELISA as discriminating between patients with and without metastases (sensitivity 57 and 63.3%; specificity 55.6 and 71.4% respectively). For pancreatic NETs positive and negative predictive values were 84 and 78% respectively (90% specificity and 68% sensitivity). We found lower CgA levels in patients with extensive metastatic spread than in those with liver metastases only. These data assess the role of CgA evaluation in GEP NETs, and demonstrate that higher CgA levels associate with metastatic disease, confirming that CgA levels can provide a helpful practical biochemical marker for the clinical management of NETs, but with low sensitivity and specificity.
 ...
PMID:Chromogranin A as a marker of neuroendocrine neoplasia: an Italian Multicenter Study. 1763 60

Carcinoid tumors are neuroendocrine malignancies that frequently metastasize and secrete hormones that cause debilitating symptoms in patients. In this study we report the effects of valproic acid (VPA), a drug long used for the treatment of epilepsy, on the growth and neuroendocrine phenotype of human carcinoid cancer cells. VPA treatment of gastrointestinal and pulmonary carcinoid cells resulted in a dose-dependent inhibition of cancer cell growth. Western blot analysis revealed degradation of cyclin D1 and an increase in cyclin-dependent kinases p21 and p27 with VPA treatment. Flow cytometry confirmed that the mechanism of VPA-induced growth inhibition is G(1) phase cell cycle arrest. Furthermore, VPA suppressed expression of the neuroendocrine tumor marker chromogranin A. In addition to these effects, VPA also increased levels of full-length Notch-1 and the active Notch-1 intracellular domain. Luciferase reporter assays incorporating the centromere-binding factor 1 (CBF-1) binding site and the achaete-scute complex-like 1 (ASCL-1) promoter confirmed the functional activity of VPA-induced Notch-1. Transfection of Notch-1 small-interfering RNA into carcinoid tumor cells blocked the effects of VPA on Notch-1 activation, ASCL-1 suppression, p21 induction, and cell growth inhibition. VPA also suppressed growth of carcinoid tumors in vivo in a mouse tumor xenograft experiment. These findings confirm the important role of Notch-1 in regulating the growth and neuroendocrine phenotype of carcinoid tumor cells. On the basis of this study, a clinical trial of VPA for patients with advanced carcinoid cancer will be conducted. Disclosure of potential conflicts of interest is found at the end of this article.
 ...
PMID:Valproic acid activates notch-1 signaling and regulates the neuroendocrine phenotype in carcinoid cancer cells. 1776 53

Neuroendocrine tumor consisting of pancreatic alpha-cells -- glucagonoma -- is a very rare finding (one case per two million people a year). This functionally active, usually malignant tumor has typical clinical manifestations. Glucagonoma syndrome is a disease that has an original clinical picture that includes necrolytic migrating erythema with secondary bullous dermatitis, glucose tolerance disorder or diabetes mellitus, weight loss, anemia, hypoaminoacidemia, venous thrombosis, and alimentary and mental disturbances. By the time diagnosis is made, 60 to 70% of glucagonomas already give metastases, and even small glucagonomas should be considered tumors with unknown malignant potential or malignant tumors. Glucagonomas grow slowly, and patients live long (the survival median is approximately 15 years). The authors describe their own observation.
 ...
PMID:[A case of pancreatic glucagonoma]. 1792 96

The Zollinger-Ellison syndrome is characterized pathophysiologically by a significant hypergastrinemia derived from a gastrin-secreting neuroendocrine tumor with a primary location in the pancreas or duodenum. Chronic hypergastrinemia in turn triggers gastric acid hypersecretion yielding in chronic or recurrent or refractory peptic ulcer disease and/or chronic diarrhea. One half of patients with ZES will have distant metastases in the liver by the time the diagnosis is established and one half of all patients with ZES will experience chronic diarrhea as chief complaint rather than peptic ulcer-related symptoms and signs. Gastrinomas have been reported to either manifest sporadically or to occur in conjunction with the genetic background of the MEN-I syndrome. Diagnosis is based on the patients history which is typically characterized by recurrent episodes of peptic ulcer disease or by severe reflux esophagitis and/or diarrhea or by acid-related symptoms which fail to respond to standard treatment regimens. Upper gastrointestinal tract endoscopy will provide evidence for peptic ulcer disease in anatomical regions located aborally the duodenal bulb within the descending part of the duodenum or even farther distally within the jejunum. Peptic ulcers frequently occur in groups indicating some substantial acid hypersecretion. A gastric pH > 2 is mutually exclusive for ZES. Increased serum gastrin levels confirm the diagnosis biochemically. Gastrin secretion can be determined in the basal state or following stimulation with secretin or calcium. High sensitivity and specificity for the diagnosis of ZES is provided by determining the ratio of basal versus pentagastrin-stimulated gastric acid secretion: The ratio of BAO / MAO > 0.6 is highly specific for gastrinoma. To localize the gastrin-secreting tumor computer-assisted tomography, endoscopic ultrasound, and somatostatin receptor scintigraphy provide useful help but most recently, endoscopic ultrasound with high resolution transducers appear to improve preoperative site localization. If modern imaging techniques fail to elucidate the site of the tumor, intraoperative diaphany may help to detect gastrinomas within the duodenal wall. Definitive treatment will only be achieved by total surgical resection of the gastrin-producing tumor in the pancreas or duodenum including dissection of the regional lymph nodes. Control of symptoms will have to be achieved by administration of highly potent proton pump inhibitors in up to 2-3-fold increased standard doses to inhibit gastric acid hypersecretion. Elevation of gastric pH > 4 will be the therapeutic target to protect the mucosa of the upper gastrointestinal tract. Basal acid output should be reduced to less than 10 mEq H(+) per hour which requires administration of highly potent proton pump inhibitors with a recommended starting dose of 60 mg omeprazole equivalents per day.
 ...
PMID:Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors. 1798 90

Somatostatin receptor (SSTR) scintigraphy is currently used as one standard imaging modality in neuroendocrine tumors (NETs). However, future optimization of NET imaging may be achieved with positron emission tomography based methods utilizing more sensitive and specific tracers in combination with computed tomography or magnetic resonance imaging. Here we established an orthotopic mouse model that reflects relevant aspects of human pancreatic NETs such as SSTR expression, dense vascularization and metastatic disease. This model was then utilized to test the feasibility of combined magnetic resonance imaging and animal positron emission tomography. Orthotopic implantation of amphicrine, SSTR-positive pancreatic AR42J cells resulted in rapidly growing tumors, with concomitant metastatic spread into abdominal lymph nodes and peritoneal cavity. Primary tumors as well as their metastases expressed the neuroendocrine markers chromogranin A and synaptophysin. For imaging experiments, the SSTR ligands (68)Ga-DOTATOC or (68)Ga-DOTANOC were injected intravenously, and animals were subsequently examined in an animal positron emission tomography scanner and a clinical 3T (tesla) magnetic resonance imager. All animals showed radionuclide accumulation in the primary tumor. Definite anatomical correlation was achieved using digital image fusion of the positron emission tomography and magnetic resonance imaging data. (68)Ga-DOTANOC strongly accumulated in the tumor tissue (mean 6.6-fold vs. control tissues) when compared to (68)Ga-DOTATOC, which showed a higher renal clearance. In good agreement with the biodistribution data, the kidney-to-tumor ratio was higher for (68)Ga-DOTATOC (2.43-fold vs. 1.75-fold). Consequently, (68)Ga-DOTANOC achieved better signal enhancement in the primary tumor and allowed for detection of metastatic lesions. In summary, we established a novel orthotopic pancreatic SSTR-positive tumor model and used this model to provide proof of principle for the diagnostic combination of SSTR-based molecular imaging and magnetic resonance imaging. Specifically, the animal model allowed the comparative evaluation of (68)Ga-DOTANOC and (68)Ga-DOTATOC, with (68)Ga-DOTANOC providing better tumor-specific accumulation and renal activity. We conclude that this animal model will be of innovative value for further investigation in the imaging of NETs.
 ...
PMID:An orthotopic model of pancreatic somatostatin receptor (SSTR)-positive tumors allows bimodal imaging studies using 3T MRI and animal PET-based molecular imaging of SSTR expression. 1802 11

Carcinoid tumors are the most common type of neuroendocrine tumors with an incidence of 1.5 per 100 000 of the population. Skin manifestations of carcinoid tumors include those associated with the carcinoid syndrome and sequelae from metastatic disease. Carcinoid tumors in the breast, which were first described in 1977, are rare and may present either as primary or metastatic lesions. The existence of primary breast carcinoid tumors is controversial, however, and, if they do exist, would account for <1% of primary breast cancers. We report the case of a 76-year-old woman who presented to the M.D. Anderson Cancer Center with a long-standing history of a breast lump. Core biopsy of the mass and left axillary lymph node aspiration revealed neuroendocrine tumor of the breast, which stained positive for synaptophysin and chromogranin. Subsequently, the patient developed a left-sided pleural effusion, and a further work-up revealed metastases to the lung parenchyma and pleural space. Three years after her diagnosis, she complained of a persistent, erythematous thickening of skin over the surface of her left inferior breast, which had been present for 1 year. On examination, multiple erythematous grouped nodules arranged in an oval pattern were present. A punch biopsy from one of the nodules revealed invasive low-grade carcinoma with neuroendocrine features similar to those in her prior breast core biopsy. The tumor was seen to be infiltrating the dermis. This is a unique case of a neuroendocrine tumor of the breast with cutaneous spread. The number of reported cases of neuroendocrine tumors with cutaneous involvement remains small.
 ...
PMID:Multinodular cutaneous spread in neuroendocrine tumor of the breast : an unusual presentation. 1803 21

A 71-year-old man with duodenal gastrin cell tumor was being evaluated for residual/metastatic disease. Somatostatin receptor scintigraphy (SRS) identified a 2-cm area of focal uptake within the head of the pancreas, consistent with a pancreatic neuroendocrine tumor. Pathological examination did not reveal any malignancy within the pancreas. Instead, the pancreatic head showed pancreatic polypeptide cell hyperplasia. Strong and diffuse immunoreactivity to somatostatin receptor 2A antibody by immunoperoxidase staining confirmed that the lesion correlated with the site of radioactive tracer (Indium-111 pentetreotide) uptake seen on SRS. The current report therefore presents pancreatic polypeptide cell hyperplasia as a new pitfall in SRS.
 ...
PMID:Indium-111 pentetreotide uptake by pancreatic polypeptide cell hyperplasia: potential pitfall in somatostatin receptor scintigraphy. 1809 Feb 46

Merkel cell carcinoma (MCC) of the skin is a neuroendocrine tumor with characteristic histological and immunohistochemical features. Among various cytogenetic changes, trisomy of chromosome 6 has been reported in 47% of cases using in situ hybridization. Primary tumors, morphologically and immunohistochemically identical to MCCs of the skin, have been described in other organs, including lymph nodes. Here, a cytogenetic study of four cases of MCC of lymph nodes is presented. Four cases of primary MCCs of lymph nodes and ten cases of cutaneous MCCs were studied for chromosome 6 using fluorescent in situ hybridization (FISH). All cases showed typical features of MCC both at hematoxylin and eosin (H&E) and immunohistochemistry. FISH showed trisomy 6 in two out of the four cases ofMCCs of lymph node as well as in 6 out 10 cases of MCCs of skin. Lymph nodal and cutaneous MCCs share same histological and immunohistochemical features, as well as same cytogenetic alteration for chromosome 6. It seems that there are more similarities than differences between cutaneous and lymph nodal MCCs. Whether lymph nodal MCCs are primary tumors or metastases from regressed skin lesions is still questionable, although several findings indicate a primary origin.
 ...
PMID:Trisomy of chromosome 6 in Merkel cell carcinoma within lymph nodes. 1838 54


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