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)

We performed combination therapy with cyclophosphamide, Vincristine and Dacarbazine (CVD) regimen and transarterial embolization (TAE) in 2 cases of malignant pheochromocytoma with metastases. Case 1: 59-year-old female. After primary left adrenal lesion had been removed, recurrence at the left renal hilar region and metastases to the right iliac bone and 5th cervical vertebra occurred. We took 3 courses of CVD regimen after TAE for the lesions in the right iliac bone. Her endocrinological data has been normal for more than 1 year after treatment. Case 2: 29-year-old male. Total cystectomy, ileal conduit and pelvic lymphadenectomy had been performed for the primary lesion of the urinary bladder. 2 years after the 1st operation, metastases to the right obturator nodes and multiple bones occurred. We gave 3 courses of CVD regimen followed by TAE for the lesions in the right obturator nodes. Just after treatment, we could stop insulin and reduce anti-hypertension drugs, but the effect of treatment was temporary. In conclusion, combination of CVD regimen and TAE is effective for malignant pheochromocytoma with metastases.
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PMID:[Treatment of malignant pheochromocytoma by combination of CVD regimen and transarterial embolization]. 187 77

Serotonin-producing pancreatic endocrine tumours are rare neoplasms which in most cases exhibit malignant biological behaviour. These tumours, in the majority of the well-documented cases, are composed of argyrophil- and argentaffin-positive cells which contain large pleomorphic neurosecretory granules. In contrast, argyrophilic non-argentaffin pancreatic endocrine tumours with tumour cells containing round neurosecretory granules are exceptional. In this study we describe such a tumour not associated with clinical evidence of carcinoid syndrome in a 60-year-old woman. Histological examination revealed tumour extension in pancreatic lymphatic vessels and veins but no evidence of locoregional or distant metastases. Ten months after surgery the patient showed no recurrence of the disease. Immunohistochemistry revealed cytoplasmic serotonin production in the tumour cells which were negative for anti-gastrin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and ACTH. This study emphasizes the usefulness of combined ultrastructural and immunohistochemical investigations in order to identify and characterize the rare pancreatic endocrine tumours with serotonin production.
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PMID:Serotonin-producing pancreatic endocrine tumour. Histological, ultrastructural and immunohistochemical study of a case. 196 80

In 15 patients with insulinoma, six patients after successful removal of this tumour, two patients with previous pancreas resection because of hypoglycaemia elsewhere, and 10 control subjects, the diagnostic usefulness of euglycaemic clamp procedures (without exogenous insulin) was assessed in comparison with prolonged starvation. Only insulinoma patients developed sustained hypoglycaemia (less than or equal to 2.3 mmol l-1) within 2-44 h without caloric intake, because of inappropriately elevated immunoreactive insulin (IR-insulin) concentrations. IR-proinsulin values were elevated in most (7 out of 10), but not in all insulinoma patients. The steady-state glucose infusion rate necessary to maintain a stable plasma glucose concentration of 4.4-5.0 mmol l-1 was significantly (P less than or equal to 0.001) higher in insulinoma patients (2.5 +/- 0.6 mg kg-1 min-1) than in pancreas resected patients (0.6 +/- 0.2 mg kg-1 min-1), or in control subjects (0.5 +/- 0.1 mg kg-1 min-1). Due to a considerable degree of overlap, sensitivity (0.44) and specificity (0.95) were too low for such a procedure to qualify as a diagnostic test. There was no correlation of glucose infusion rates to IR-insulin values (r = 0.024, P = 0.461). One reason for this was the development of insulin resistance in some, but not in all insulinoma patients. When, in analogy to insulin/glucose ratios, a diagnostic index was derived by multiplying the steady state glucose infusion rate by the steady state IR-insulin concentration, the diagnostic accuracy was greatly increased (sensitivity and specificity 0.94, respectively), but still lower than that of 'amended' insulin/glucose ratios in fasting plasma or at the time of discontinuation of prolonged fasts (1.00). Somatostatin infusions inhibited insulin secretion (IR-C-peptide plasma concentrations) by 52-88% in subjects without insulinoma and in those insulinoma patients whose tumour cells ultrastructurally contained plenty of normal secretory granules, and to a lesser degree when only abnormal or virtually no secretory granules were present, i.e. in more de-differentiated tumours. In contrast to this significant (P = 0.036) association, malignancy, i.e. the presence of metastases, could not be predicted from whether or not insulin secretion was resistant to the inhibitory action of somatostatin. In conclusion, euglycaemic clamp experiments are less reliable for detecting or excluding a functioning insulinoma than the relation of glucose and insulin values during starvation. The inhibition of insulin secretion by somatostatin depends on the presence of normal beta-granules, and does not distinguish adenomas from carcinomas.
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PMID:Evaluation of a euglycaemic clamp procedure as a diagnostic test in insulinoma patients. 196 48

Somatostatin is a regulatory hormone or tissue factor which plays an inhibitory role in the normal regulation of several organ systems, including the central nervous system, hypothalamus and pituitary gland, the gastrointestinal tract and the exocrine and endocrine pancreas. Sandostatin is an analogue of somatostatin which has characteristics which makes it a better compound for clinical use than native somatostatin: it inhibits GH preferentially over insulin. It has a long half-life in the circulation, causing a prolonged inhibitory effect in somatostatin-responsive target organs. It is active after subcutaneous administration and rebound hypersecretion does not occur. Sandostatin is very well tolerated by most patients. Somatostatin receptors remain present on a variety of tumours which arise in tissues that contain these receptors normally. High numbers of somatostatin receptors have been found on GH-secreting pituitary tumours and on most metastatic endocrine pancreatic tumours and carcinoids. Sandostatin treatment ameliorates clinical symptoms in most acromegalic patients while GH hypersecretion and elevated concentrations of circulating IGF-I are well controlled. In most patients hormonal hypersecretion from endocrine pancreatic tumours and carcinoids is also suppressed during Sandostatin therapy. This results in an instant improvement in the quality of life. There is preliminary evidence of control of tumour growth. The presence of high numbers of somatostatin receptors on tumours enables in vivo receptor-imaging, with 123iodine coupled to a somatostatin analogue. This newly developed technique provides for the first time the possibility of localization of the primary tumours and their metastases and a prediction of which patients may respond to treatment with Sandostatin. Theoretically this somatostatin-receptor imaging technique represents a new approach which may be extended to other receptor-containing tumours. Therefore it may provide a new, powerful alternative to tumour localization performed with monoclonal antibody technology. Another potential development is the use of beta-emitting isotopes coupled to somatostatin analogues for therapeutic irradiation. Somatostatin analogues exert potent inhibitory effects on the growth of a variety of experimental tumour models in animals. Several mechanisms of action have been proposed including the direct antiproliferative effects of somatostatin and its analogues in a variety of tumour cell cultures. Most well-differentiated human brain tumours like meningiomas and low-grade astrocytomas contain somatostatin receptors, while undifferentiated brain tumours mainly contain EGF receptors. Fifteen percent of human breast carcinomas contain somatostatin receptors; those which do have a better prognosis. It can be concluded that somatostatin is an endogenous, naturally occurring inhibitory growth factor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The clinical use of somatostatin analogues in the treatment of cancer. 197 66

A 58-year-old male patient with rectal carcinoid tumor is presented. The tumor extensively involved the lymph nodes and liver, and multiple tumors were also recognized in the pancreas and thyroid. Grossly, it was uncertain whether the latter were metastases from the rectal carcinoid or all were coincident primary tumors involving multiple endocrine organs, so-called multiple endocrine neoplasia (MEN) syndrome. Histologic, histochemical and electron microscopic examinations of the tumors in both the pancreas and thyroid showed similar features to those of the rectal carcinoid. The neoplastic cells in all involved organs commonly expressed positive immunoreactivity for somatostatin, but negativity for carcinoembryonic antigen, calcitonin, calcitonin gene-related peptide, thyroglobulin, insulin, glucagon and pancreatic polypeptide. These immunohistochemical results confirmed that the tumors observed in multiple endocrine organs were indeed metastatic from the rectal carcinoid, rather than being a new combination of MEN syndrome. Some neuroendocrine tumors may develop widespread metastasis, sometimes creating problems with differentiation from multiple primary endocrine tumors. Immunohistochemistry may be of great help in setting this issue.
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PMID:Rectal carcinoid tumor metastasizing to the thyroid and pancreas. An autopsy case exploiting immunohistochemistry for differentiation from tumors involving multiple endocrine organs. 197 68

Insulinomas in dogs have been described frequently. The clinical signs of this tumor result from neuroglycopenia and increased concentrations of plasma catecholamines. Laboratory confirmation of hypoglycemia in association with an inappropriately high serum insulin concentration helps establish a tentative diagnosis of insulinoma. Surgical exploration of the pancreas and histologic evaluation is required for definitive diagnosis of insulinoma. Whenever possible, surgical excision of the primary lesion and associated metastases should be performed. The distinction between benign and malignant insulinomas is based on the presence or absence of metastases and clinical course of disease. Histologically, it is difficult to determine the malignant potential of these tumors. Careful medical management is essential to the dog with signs referable to an insulinoma, whether the patient is awaiting surgery, is not a surgical candidate, or has a relapse of signs after surgical resection. This chapter will review the clinical and diagnostic features of insulinoma in dogs and address the problem of refractory hypoglycemia and its management.
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PMID:Management of insuloma patients with refractory hypoglycemia. 198 99

Tumor metastasis requires highly motile cells that can respond to appropriate stimuli. A2058 human melanoma cells were shown previously to secrete a highly potent autocrine motility factor (AMF) that stimulates chemokinetic movement. We have shown that the insulin polypeptides (IPs; insulin-like growth factors I and II [IGF-I, -II] and insulin) stimulated A2058 cell chemotaxis and chemokinesis. We now report that the IPs and AMF stimulate locomotion in other human malignant cell lines. Insulin (100 nM) induced motility of up to 50% of the magnitude of the AMF response in human carcinoma lines MDA-231 (breast), T24 (bladder), and OVCAR3 (ovarian). The tumorigenic and metastatic 5R Haras-transfected rat embryo fibroblast cell line responded to insulin with both chemotaxis and chemokinesis and was 100% of that seen for AMF. The ED50 for IGF-I in the carcinoma cell lines was in the order of I nM, but the magnitude of the responses at this concentration was 40% of the AMF-stimulated response, with the exception of the A2058 cells, which were maximally stimulated at I nM. IGF-II induced maximal motility of 75 to 130% of the AMF-stimulated response in the carcinoma lines with ED50 of less than or equal to 10 nM. IGF-II-stimulated motility in the carcinoma lines was predominantly chemotactic by modified checkerboard analysis. Cell pretreatment with pertussis toxin inhibited 90-100% of AMF-induced motility, whereas migration to the IPs was not pertussis toxinsusceptible. In growth studies, IGF-I induced mitogenesis up to 140% of basal media control growth. In general, maximal growth stimulation was seen at 100 nM IGF-I, and optimal migration was seen at 10 nM IGF-I. The IGFs are secreted by normal stroma in a number of organs that are common sites for primary and metastatic disease. Therefore, we suggest that IPs may be important homing and mitogenic signals for tumor cells in the process of invasion and metastasis and that the differential motility stimulation and respective mechanisms of action by these physiologically important agents may underlie the diversity of the metastatic process.
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PMID:Heterogeneity of the motility responses in malignant tumor cells: a biological basis for the diversity and homing of metastatic cells. 211 98

We showed previously that insulin-like growth factor I (IGF-I) is detectable in small cell lung cancer (SCLC) tumor biopsies and cell lines and that recombinant human IGF-I stimulates DNA synthesis in SCLC cells. Here we report further studies on the role of IGF-I in 2 SCLC cell lines: HC12, classic; and ICR-SC17, variant. Immunoreactive IGF-I was detected in medium conditioned by HC12 but not ICR-SC17. Both HC12 and ICR-SC17 bound IGF-I with 100-fold greater affinity than insulin. Scatchard analysis revealed two classes of IGF-I binding site of high (Kd 0.1 nM, n = 2,300) and lower (Kd 3 nM, n = 28,000) affinity. In both cell lines [3H]thymidine incorporation was enhanced by recombinant human IGF-I, 100-1000 ng/ml. ICR-SC17 also showed growth enhancement as measured by increase in cell numbers. There was no response in HC12, probably due to endogenous IGF-I production. 125I-IGF-I binding and basal and IGF-I-stimulated mitogenesis were inhibited by monoclonal antibodies to IGF-I (SM1.20B, SM1.25) or the type I IGF receptor alpha IR3 but not an isotypic control monoclonal antibody. Antiproliferative effects were manifest in [3H]thymidine incorporation assays in serum-free conditions and growth of serum-supplemented liquid cultures. We also tested fresh or newly cultured tumor cells obtained by fine needle aspiration of metastases in three previously untreated and four relapsed patients with SCLC. IGF-I binding sites were demonstrable on fresh SCLC cells, and specific binding was inhibited by SM1.20B. All seven samples showed stimulation of [3H]thymidine incorporation in the presence of recombinant human IGF-I, 100-500 ng/ml. As in cultured cells, basal and IGF-I-stimulated DNA synthesis was inhibited by monoclonal antibodies SM1.20B, SM1.25, and alpha IR3 but not the isotypic control. These results confirm the findings of previous studies and suggest that IGF-I can function as an autocrine growth factor in SCLC in vitro and possibly also in vivo.
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PMID:Autocrine function for insulin-like growth factor I in human small cell lung cancer cell lines and fresh tumor cells. 215 21

The effects of octreotide in vivo and in vitro on hormone release, in vivo [123I]Tyr3-octreotide scanning, and in vitro [125I]Tyr3-octreotide autoradiography were compared in five patients with endocrine pancreatic tumors. [123I]Tyr3-octreotide scanning localized the primary tumor and/or previously unknown metastases in four of the five patients. The patient with a negative scan had an insulinoma that did not respond to octreotide in vivo. No Tyr3-octreotide-binding sites were subsequently found at autoradiography of the tumor, whereas somatostatin-14 receptors were present at a high density. In parallel, culture studies with the cells prepared from this adenoma showed that insulin release was not affected by octreotide, while both somatostatin-14 and -28 significantly suppressed hormone release. Culture studies of the tumor cells from two gastrinomas showed a dose-dependent inhibition of gastrin release by octreotide. Octreotide exerted direct antiproliferative effects in one of these gastrinomas, which had been shown to be rapidly growing in vivo. Both gastrinomas had specific somatostatin receptors, as measured by in vitro receptor autoradiography. Somatostatin release by the cultured somatostatinoma cells from one of these patients was suppressed by octreotide. In conclusion, 1) the [123I]Tyr3-octreotide scanning procedure is valuable in the localization of primary endocrine pancreatic tumors as well their often clinically not yet recognized metastases; 2) the in vitro detection of somatostatin receptors in those tumors that were also visualized in vivo after injection of [123I] Tyr3-octreotide indicates that the ligand binding to the tumor in vivo indeed represents binding to specific somatostatin receptors; and 3) the parallel between the presence of somatostatin receptors on tumors and in in vivo and in vitro effects of octreotide on hormonal release from these tumors indicate that a positive scan predicts a good suppressive effect of octreotide on hormonal hypersecretion by these tumors.
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PMID:Parallel in vivo and in vitro detection of functional somatostatin receptors in human endocrine pancreatic tumors: consequences with regard to diagnosis, localization, and therapy. 216 29

Forty-five primary human lung carcinomas were evaluated for the loss of heterozygosity for genes on the short end of chromosome 11. Of 40 evaluable heterozygous cases, loss of the 11p genes c-H-ras and insulin was documented in nine cases (22%). The clinical parameters investigated for each patient included the disease stage at presentation, the presence of metastatic disease in either bronchial or mediastinal lymph nodes, and the presence of positive parietal pleural margins in the surgically resected specimen. There were no differences found with respect to these indicators when patients exhibiting the loss of heterozygosity were compared with those who did not have such genetic loss. In addition, when the clinical courses of the two patient groups were compared, there was no difference in survival. We conclude that the loss of heterozygosity for c-H-ras and insulin on 11p is a common finding in primary non-small cell human lung carcinomas but does not confer a more aggressive phenotype on these tumors. Although this genetic lesion may be important in the initial transformation of the cells to carcinoma, the available data for lung carcinoma are insufficient to prove causality.
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PMID:Loss of heterozygosity for genes on 11p and the clinical course of patients with lung carcinoma. 218 May 65


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