Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Due to the increased costs of medical care, a cost-benefit analysis is needed when trying for the 'ultimate' biochemical diagnosis of gastro-enteropancreatic (GEP) tumours. The glycoprotein chromogranin family has proved useful in screening for neuroendocrine tumours. In patients with midgut carcinoid tumours, chromogranin A is more sensitive than urinary 5-hydroxyindoleacetic acid but by combining these two biochemical markers most GEP tumours can be diagnosed. Chromogranin A is also a prognostic marker for survival in patients with midgut carcinoid tumours. Pancreastatin constitutes a part of the chromogranin A molecule and is a less sensitive general screening marker for neuroendocrine gut and pancreatic tumours, but levels, in combination with chromogranin A, might give some insight into tumour biology. Specific markers such as gastrin, glucagon, vasoactive intestinal peptide, insulin, neuropeptide K and substance P should be used to further characterise hormone production in neuroendocrine tumours. However, in some patients, confirmation of diagnosis requires provocation tests, such as the secretin or meal provocation tests. Staging information can be obtained by new investigations such as intra-operative or endoscopic ultrasound, octreoscan, and positron emission tomography. We combine the biochemical characterisation of neuroendocrine tumours with studies of growth factors/receptors, adhesion molecules, proliferation markers, somatostatin receptor content, induction of the enzymes p68 kinase and 2'5'-A-synthetase, and apoptosis, to establish a sound rationale for therapeutic decisions, enabling every patient to receive individualised treatment.
 ...
PMID:The ultimate biochemical diagnosis of gastro-enteropancreatic tumours. 881 68

Neuroendocrine gut and pancreatic tumours have provided a diagnostic and therapeutic challenge over the years. These rather slowly growing neoplasms have been assigned a good prognosis but when liver metastases are present the prognosis is not better than that of most other malignant tumours. Despite the development of improved diagnostic procedures many patients are still referred at a stage of the disease too late for surgical cure, at which time medical treatment is warranted. The diagnosis is based on histopathological diagnosis including silver stainings (Grimelius, Masson) and immunohistochemistry for chromogranin A and synaptophysin. Analysis of chromogranin A in the plasma is an important adjunct in the screening for various types of neuroendocrine gut and pancreatic tumours. About 80%-100% of patients with verified neuroendocrine gastrointestinal tumours have elevated circulating levels of this glycoprotein. Depending on clinical symptoms the chromogranin A analysis is supplemented by other peptide hormone analyses as well as urinary 5-HIAA for patients with midgut carcinoid tumours. In the past the localization procedures were based on CT, MRI and ultrasound investigations but in recent years somatostatin receptor scintigraphy (octreoscan) and endoscopic ultrasonography have significantly improved the diagnostic potential. Almost 80% of neuroendocrine gastrointestinal tumours present somatostatin receptor subtype 2 binding 111Indium-labelled octreotide which can be used for staging of the disease, and which also indicates whether or not somatostatin analogues can be used in the treatment of these tumours. Surgery is still a cornerstone in the treatment of neuroendocrine gastrointestinal tumours, even if the patients are beyond cure. Debulking procedures and bypassing operations are important for improving clinical condition and facilitating impending medical treatment, and during the past decade a more aggressive surgical approach has emerged. The medical treatment is based on chemotherapy, and the use of somatostatin analogues and alpha-interferons. Chemotherapy, in particular the combination of streptozotocin with 5-FU or doxorubicin, is still first-line treatment for most endocrine pancreatic tumours, while somatostatin analogues and alpha-interferons are considered first-line for classical midgut carcinoids. Chemotherapy and biotherapy can be combined in many patients, and changes from one medical treatment to another during the course of the disease is mandatory for control of the disease. It is important to realise that most patients with malignant tumours are not cured by medical treatment but that the disease can be controlled for extended periods of time. In the future it will be possible to individualize treatments on the basis of new information about such features of tumour biology as proliferation capacity, expression of adhesion molecules, and growth factors and their receptors.
 ...
PMID:Neuroendocrine gastrointestinal tumours. 883 99

Chromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other neuroendocrine markers, have not clearly been defined, however. The objectives of this study were to evaluate the clinical usefulness of CgA as neuroendocrine serum marker. Serum levels of CgA, neuron-specific enolase (NSE), and the alpha-subunit of glycoprotein hormones (alpha-SU) were determined in 211 patients with neuroendocrine tumors and 180 control subjects with nonendocrine tumors. The concentrations of CgA, NSE, and alpha-SU were elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors, respectively. Serum CgA was most frequently increased in subjects with gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%), nonfunctioning tumors of the endocrine pancreas (69%), and medullary thyroid carcinomas (50%). The highest levels were observed in subjects with carcinoid tumors. NSE was most frequently elevated in patients with small cell lung carcinoma (74%), and alpha-SU was most frequently elevated in patients with carcinoid tumors (39%). Most subjects with elevated alpha-SU levels also had elevated CgA concentrations. A significant positive relationship was demonstrated between the tumor load and serum CgA levels (P < 0.01, by chi 2 test). Elevated concentrations of CgA, NSE, and alpha-SU were present in, respectively, 7%, 35%, and 15% of control subjects. Markedly elevated serum levels of CgA, exceeding 300 micrograms/L, were observed in only 2% of control patients (n = 3) compared to 40% of patients with neuroendocrine tumors (n = 76). We conclude that CgA is the best general neuroendocrine serum marker available. It has the highest specificity for the detection of neuroendocrine tumors compared to the other neuroendocrine markers, NSE and alpha-SU. Elevated levels are strongly correlated with tumor volume; therefore, small tumors may go undetected. Although its specificity cannot compete with that of the specific hormonal secretion products of most neuroendocrine tumors, it can have useful clinical applications in subjects with neuroendocrine tumors for whom either no marker is available or the marker is inconvenient for routine clinical use.
 ...
PMID:Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones. 925 44

Neuroendocrine gut and pancreatic tumors are known to contain and secret different peptide hormones and amines. During the last two decades, many radioimmunoassays and Elizas have been developed to analyze these substances in blood and urine, which has enabled clinicians to improve the diagnosis and monitoring of patients with various neuroendocrine tumors. Due to cost constraints in medical care, it is important to try to define the most useful biochemical markers from the clinical point of view. The glycoprotein chromogranin A has been shown to be a useful marker for diagnosing various neuroendocrine tumors, both by histopathology and circulating tumor markers. In patients with demonstrable endocrine tumors, about 90 percent of the patients present high circulating levels of chromogranin A. A hundred-fold increase of plasma chromogranin is seen in patients with midgut carcinoid tumors and liver metastases. The plasma levels of chromogranin A reflect the tumor mass and can be used for monitoring the patient during treatment and follow-up, although the day-to-day variation might be 30-40 percent. High circulating levels of the chromogranin A might be an indicator of bad prognosis in patients with malignant carcinoid tumors. Besides analyzing plasma chromogranin A, specific analyses such as urinary 5-HIAA in midgut carcinoid patients, serum gastrin in patients with Zollinger-Ellison syndrome and insulin/proinsulin in patients with hypoglycemia should be performed. In patients with small tumor masses or intermittent symptoms, provocative tests such as a meal stimulation test, secretin test or pentagastrin stimulation of tachykinin release can supplement the basal measurements of peptides and amines. To fully evaluate the growth potential in neuroendocrine tumors, traditional biochemical markers should be supplemented with indicators of growth proliferation (Ki-67, PCNA) and immunohistochemical staining for the adhesion molecule CD44 and the PDGF-alpha receptor. Finally, analysis of somatostatin receptor subtypes and induction of the enzymes 2-5A syntethase and PKR are of clinical value.
 ...
PMID:Biochemical diagnosis of neuroendocrine GEP tumor. 982 77

Neuroendocrine gut and pancreatic tumors are rather rare malignant diseases which has gained increased attraction through the last decennium, possibly through development of new diagnostic and therapeutic methods. Histopathology demonstrating the common neuroendocrine features of these tumors has been the diagnostic corner stone for long, but today it should be supplemented with information about the tumor biology. An excellent biochemical marker which is easy to analyze in serum or plasma is chromogranin A, which is a glycoprotein that is stored and released from neuroendocrine cells. This marker can be used for diagnosis and follow-up of the patients. Somatostatin receptor scintigraphy has been one of the most important diagnostic tools for staging of the disease and also indicating sensitivity to treatment with somatostatin analogues. It is a general agreement that almost every patient should be subjected to this procedure before or during the treatment course. From the therapeutic point of view, surgery is nowadays more extensive aiming at reducing the tumor mass in patients who could not be cured by surgery alone. Other means of tumor reduction is liver dearterialization by embolization with starch spheres. The medical treatment of neuroendocrine tumors has made a real break through with the introduction of somatostatin analogues, particularly octreotide, and today most of the hormonally related symptoms can be controlled by this kind of treatment. Somatostatin analogues have also shown to be inhibitors of tumor growth and the latest development is tumor targeted radioactive treatment with Ytrium or Indium labelled octreotide. Long-acting formulation of somatostatin analogues have come into clinical use and significantly improved quality of life for patients with neuroendocrine tumors. Other means of medical treatment are alpha interferons, which have shown particular effect in patients with midgut carcinoid tumors giving both biochemical and tumor responses. Chemotherapy such as streptozotocin plus 5-fluorouracil (5-FU) or doxorubicin is still considered as first-line treatment in malignant endocrine pancreatic tumors but is combined with concomitant somatostatin analogue treatment. In the future a multimodal treatment will further develop combining different agents and also somatostatin receptor subtype specific analogues will come into clinical use.
 ...
PMID:Neuroendocrine gastrointestinal tumors--a condensed overview of diagnosis and treatment. 1039 26

Most of the neuroendocrine tumours produce and secrete a large number of peptide hormones and amines. Each of these substances cause a specific clinical syndrome: carcinoid, Zollinger-Ellison, hyperglycaemic, glucagonoma and WDHA syndrome. Specific markers for these syndromes are basal and/or stimulated levels of: urinary-5-HIAA, serum or plasma gastrin, insulin, glucagon, and VIP, respectively. About 1/3 of neuroendocrine tumours belong to the so-called "non-functioning" tumours. Therefore, general markers such as chromogranin A, pancreatic polypeptide, serum neuronspecific enolase and subunit of glycoprotein hormones have been used for screening purposes in patients without distinct clinical hormone related syndromes. Among these general tumour markers chromogranin A, although its precise function is not yet established, has been shown to be a very sensitive and specific serum marker for various types of neuroendocrine tumours. This is because it may also be increased in many cases of less well differentiated tumours of neuroendocrine origin that do not secrete known hormones. Then chromogranin A is considered the best general neuroendocrine serum or plasma marker available at the moment and is increased in 50-100% of patients with various neuroendocrine tumours. Chromogranin A serum or plasma levels reflect tumour load and may be an independent marker of prognosis in patients with midgut carcinoids.
 ...
PMID:Tumour markers in neuroendocrine tumours. 1060 22

Most neuroendocrine tumors produce and secrete a multitude of peptide hormones and amines. Some of these substances cause a specific clinical syndrome: carcinoid, Zollinger-Ellison, hyperglycemic, glucagonoma and WDHA syndrome. Specific markers for these syndromes are basal and/or stimulated levels of urinary 5-HIAA, serum or plasma gastrin, insulin, glucagon and vasoactive intestinal polypeptide, respectively. Some carcinoid tumors and about one third of endocrine pancreatic tumors do not present any clinical symptoms and are called 'nonfunctioning' tumors. Therefore, general tumor markers such as chromogranin A, pancreatic polypeptide, serum neuron-specific enolase and subunits of glycoprotein hormones have been used for screening purposes in patients without distinct clinical hormone-related symptoms. Among these general tumor markers chromogranin A, although its precise function is not yet established, has been shown to be a very sensitive and specific serum marker for various types of neuroendocrine tumors. This is because it may also be elevated in many cases of less well-differentiated tumors of neuroendocrine origin that do not secrete known hormones. At the moment, chromogranin A is considered the best general neuroendocrine serum or plasma marker available both for diagnosis and therapeutic evaluation and is increased in 50-100% of patients with various neuroendocrine tumors. Chromogranin A serum or plasma levels reflect tumor load, and it may be an independent marker of prognosis in patients with midgut carcinoids.
 ...
PMID:Tumor markers in neuroendocrine tumors. 1094 Jun 85

Small cell lung cancer (SCLC) is an aggressive form of lung cancer associated with cigarette smoking and presently accounts for approximately 20% of all lung cancer cases. SCLC cells derive from a neuroendocrine origin and therefore their antigenic profile coincides, to a great extent, with that of neuroendocrine cells. Multiple attempts to generate SCLC-specific MoAbs during the past decade have failed because all SCLC-specific MoAbs isolated also react against neuroendocrine tissues or normal immune cells. Cross-reactivity with normal antigens raises safety concerns due to the inevitable toxicity of such interactions and the dreaded effects. The concept of DIAAD trade mark ( Differential Immunization for Antigen and Antibody Discovery) provides for an immune response that can be effectively focused on cancer antigens. The object is to overcome obstacles resulting from an antigenic hierarchical pattern biased towards a response to dominant antigens in order to induce a robust immune response to cancer antigens. Cancer antigens are weak or nonimmunogenic molecules. Due to the fact that the immune system responds more strongly to immunodominant antigens than to weak immunogenic antigens, cancer cell proliferation is unencumbered. DIAAD employs protocols of induction of tolerance and immunity, conducted in sequential order to "biologically subtract" the immune response of dominant antigens expressed by normal cells. This biological subtraction is achieved in a laboratory animal by first eliminating the immune response to the normal cells or closely related cancer cells, followed by immunization of the same laboratory animal with diseased cells. This procedure directs the immune response exclusively towards antigens expressed by the diseased and not the normal cells. Our objective was to use DIAAD to generate monoclonal antibodies specific to SCLC antigens that are not shared by neuroendocrine cells by contrasting a pool of human SCLC cell lines with a pool of human neuroendocrine cancer cell lines. Four monoclonal antibodies reacted strongly and exclusively with SCLC cells and identified a membrane molecule comprising a single chain glycoprotein. Two of four antibodies were selected for a detailed analysis that revealed a narrow tissue specificity of antigen expressed by colon, lung, and pancreatic cancers (less than 20% staining was found on breast, ovarian and prostate cancer). These antibodies did not bind to various other cancers such as kidney, carcinoid, lymphoma, sarcoma, adrenal, liver, melanoma, seminoma, leiomyoma, basal cell cancer, or undifferentiated cancer. The epitope recognized by the selected MoAbs was destroyed with the removal of carbohydrates from SCLC cells. This result does not exclude the possibility of protein-carbohydrate cooperation in epitope recognition. However, it strongly suggests the pivotal role of carbohydrates in antibody binding to this molecule. Upon binding to the extracellular molecule on SCLC cells, the antibodies were shown to internalize. A low or insignificant level of internalization was recorded following incubation of the antibodies with neuroendocrine-derived tumors. The capacity of these antibodies to internalize upon binding the extracellular receptors renders them potential candidates for prodrug or immunotoxin-targeted therapeutics. In a qualitative experiment involving immunoaffinity purification, the SCLC antigen was shown to be differentially detected in sera of SCLC patients. Plans are being generated to explore the possible utility of this novel SCLC-specific antigen recognized by the above MoAbs as a new biomarker for early diagnosis of the disease, as well as for therapeutic intervention for SCLC.
 ...
PMID:A new small cell lung cancer (SCLC)-specific marker discovered through antigenic subtraction of neuroblastoma cells. 1266 43

To extend flow cytometry (FC) to the diagnosis of nonhematopoietic neoplasms, we have developed new flow cytometric assays to identify expression of cytokeratin, epithelial cell adhesion molecule (EpCAM)/epithelial glycoprotein-2, myogenin, and CD99. To validate these assays, we correlated the flow cytometric results with the histologic and immunohistochemical results on paraffin-embedded tissue in a series of 21 cases, including 17 carcinomas, 1 atypical carcinoid, 2 rhabdomyosarcomas, and 1 Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET). Six of 7 assayed carcinomas and the carcinoid were positive for cytoplasmic cytokeratin by the flow cytometric assay. EpCAM was expressed by 11 of 12 carcinomas that were assayed by FC. Both rhabdomyosarcomas expressed myogenin by FC, and the ES/PNET case expressed CD99. Interestingly, the blast-associated antigen CD90 was expressed uniformly on the ES/PNET case and on subsets of cells in the rhabdomyosarcoma and carcinoma cases. Potential applications of the flow cytometric assay to nonhematopoietic neoplasms will include evaluating samples with limited material, monitoring disease persistence and recurrence in patients with previous diagnoses, and making rapid diagnoses in urgent cases.
 ...
PMID:Lineage-specific identification of nonhematopoietic neoplasms by flow cytometry. 1276 Feb 82

Several circulating or urinary tumour markers can be used for the diagnosis and follow-up of functioning and clinically non-functioning neuroendocrine tumours of the pancreatic islet cells and intestinal tract. Among the specific tumour markers are serotonin and its metabolites--e.g. 5-hydroxyindoleacetic acid (5-HIAA)--in carcinoid tumours and the carcinoid syndrome, insulin and its precursors or breakdown products in insulinoma, and gastrin in gastrinoma. Plasma vasointestinal polypeptide (VIP) determinations have been used in the diagnosis of VIPoma, plasma glucagon for glucagonoma, and serum somatostatin for somatostatinoma. Among the tumour-non-specific markers are: chromogranins, neuron-specific enolase (NSE), alpha-subunits of the glycoprotein hormones, catecholamines, pancreatic polypeptide (PP), ghrelin and adrenomedullin.
 ...
PMID:Biochemistry of neuroendocrine tumours. 1738 64


<< Previous 1 2 3