Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor (VEGF) seems to be essential for angiogenesis and for the growth of colorectal cancer; thus its inhibition can arrest tumor growth and decrease metastatic potential. Octreotide has been shown to inhibit growth of colorectal tumors in vitro and in vivo. Part of the antiproliferative activity of octreotide could be related to its antiangiogenic properties. Effects of octreotide on VEGF expression were evaluated in 35 patients with operable colorectal cancer receiving octreotide for 2 weeks before surgery. Tissue VEGF expression and serum VEGF concentrations were determined before and after treatment with octreotide. There was a statistically significant reduction in the tissue VEGF expression both considering the percentage of VEGF positive cells (P = 0.006) and the intensity of VEGF staining (P = 0.003). A similar significant reduction was observed in serum values of VEGF (P = 0.03). The present study indicates that octreotide inhibits expression of VEGF in colorectal cancer patients, and, furthermore, that serum VEGF expression correlates with tissue VEGF, representing a safe method to monitor the activity of antiangiogenic agents.
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PMID:Inhibition of vascular endothelial growth factor by octreotide in colorectal cancer patients. 1129 60

To investigate the effects of octreotide administration on the growth rate of GH-secreting pituitary adenomas, we measured both the Ki-67 labeling index (LI) and the apoptotic index in tumor specimens from octreotide-treated or matched untreated acromegalic patients. Thirty-nine patients who received octreotide until the day of or the day before surgery and 39 untreated patients matched for sex, age, tumor size, extension, and invasiveness were studied. Immunocytochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick endlabeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. The Ki-67 LI and apoptosis were counted on separate slides in at least 1000 evaluable cells. Octreotide-treated patients showed a lower Ki-67 LI (1.8 +/- 0.3%) than untreated controls (3.8 +/- 0.7%; P < 0.02). Overall, the mean Ki-67 LI of treated patients was 53% lower than that in untreated patients. The antiproliferative effect of octreotide occurred independently of tumor extension and invasiveness. Octreotide-treated and untreated patients showed similar apoptotic indexes (0.6 +/- 0.2% and 0.8 +/- 0.3%, respectively). There was a positive correlation between the Ki-67 LI and the apoptotic index (r = 0.29; P < 0.03). Our study demonstrates that acromegalic patients receiving chronic octreotide treatment have a lower value of the proliferation marker Ki-67, but no significant difference in the apoptotic index compared with matched untreated patients. The antiproliferative effect of octreotide on GH-secreting adenomas should imply a lower risk of tumor growth during long-term chronic treatment with the drug.
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PMID:Effects of octreotide treatment on the proliferation and apoptotic index of GH-secreting pituitary adenomas. 1170 76

Neuroendocrine tumors are rare, occurring in less than 1% of the population. They are divided clinically into functionally active or non-active tumors. Functionally active tumors produce a variety of substances (mainly peptides or serotonin) that are responsible for symptoms and sometimes can lead to the death of the patient independently from tumor proliferation. The most important compounds that can control symptoms in these patients are somatostatin analogs. Native somatostatin is not suitable for long-term clinical application due to its short half-life. Therefore, synthetic drugs were developed with improved pharmacokinetic characteristics. The best-characterized analog, octreotide, has been successfully applied to patients with functioning tumors. Octreotide can ameliorate symptoms in 30%-70% of the patients, mainly through a direct inhibitory effect on hormone production from the tumors. There is little or no effect on tumor growth during octreotide therapy; clinical responses were recorded in only 10%-30% of the patients. Recently, significant improvement in the management of the disease has been demonstrated with long-acting repeatable (LAR) octreotide. This new formulation requires only one monthly intramuscolar injection, and shows better acceptability and patient compliance to therapy. Data available to date show superimposable results of both standard octreotide and LAR octreotide in controlling symptoms, lowering hormone and tumor marker levels, and in reducing tumor growth. The availability of long-acting molecules have permitted the exploration of high-dose therapy in increasing tumor shrinkage and prolonging survival. Although there is a clear dose-response trend, the published data are not conclusive and further investigations are needed. The possible lack of cross-resistance between LAR octreotide and a different analog, Lanreotide, is a very stimulating finding and this might lead to the development of new therapeutical strategies in the management of neuroendocrine tumors.
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PMID:The clinical management of neuroendocrine tumors with long-acting repeatable (LAR) octreotide: comparison with standard subcutaneous octreotide therapy. 1176 34

Paragangliomas of the head and neck are uncommon neoplasms. They are usually benign, but tend to be locally invasive. Although surgical resection remains the definitive treatment, important issues about management arise when such lesions are inoperable. Beneficial effects of octreotide treatment have already been reported in a malign paraganglioma case. Here we report a 24 year old female with familial, bilateral, multiple paraganglioma in the head and neck region, who firstly presented with pulsatile tinnitus and hearing loss in her left ear. After embolization was performed, she underwent operation twice because of the gross tumor mass. No significant change in tumor size was determined after the operations, however there were no distant metastases. Although she experienced hypertension attacks, no hormonal overproduction was found in repeated measurements. As the tumor was unresectable, new alternative therapies were sought. Octreotide scintigraphy was positive in the tumoral tissue, so we began to treat her with somatostatin analogue octreotide. After a 16 month follow up period, an improvement of the performance status, the near normalisation of attacks and stabilization of tumor growth were achieved. However, in the last three visits, she began to experience symptoms more frequently and it had been necessary to increase the octreotide dose. She is now well and being followed up. In conclusion, the beneficial effects of octreotide treatment could be quantified by clinical, tumor and scintigraphic criteria. These data suggest that octreotide can be useful in the treatment of inoperable paragangliomas.
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PMID:Case report: patient with multiple paragangliomas treated with long acting somatostatin analogue. 1461 6

A 64-year-old nondiabetic woman presented with spells of lightheadedness and diaphoresis associated with lethargy and hunger of 2 weeks' duration. Physical examination was unremarkable; however, her fasting plasma glucose was 66 mg/dl, with concurrent plasma insulin of 171 microIU/ml (normal, 5-27 microIU/ml). Her C-peptide and pro-insulin levels were elevated, with negative insulin antibody and negative urinary sulfonylurea levels. Abdominal computed tomographic scan demonstrated a 5 x 4-cm mass in the tail of the pancreas and many liver metastases. She underwent resection of the pancreatic mass, radiofrequency ablation, and cauterization of hepatic lesions. Histology confirmed pancreatic insulinoma. Ten months later, she was free of hypoglycemic symptoms, with normal plasma insulin C-peptide and significantly decreased proinsulin levels. Insulinomas are rare, predominantly benign tumors. Surgery is the only curative treatment. Octreotide can be used to control hormone secretion and tumor growth. Other treatments include hepatic embolization, radiotherapy, chemotherapy, and liver transplantation.
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PMID:Metastatic insulinoma: case report and review of the literature. 1498 75

Octreotide is one of the somatostatin analogue used for the treatment of endocrine tumors principally to suppress hormone secretion and to inhibit tumor growth. We experienced a case with multiple endocrine neoplasia type 1 who small amount of octreotide dramatically relieved the lumber pain caused by metastatic bone tumor. He had recurrent bronchial carcinoid tumors that metastasized to liver and bones. The spontaneous and radiated pain by bone tumors subsided within a few minutes after the initial injection of octreotide and the effect persisted for several hours. Combination therapy of octreotide and interferon alpha-2b significantly reduced the size of metastatic liver tumors and inhibited further growth of metastatic bone tumors for the last 27 months. The use of octreotide may be a good option for controlling pain by metastatic bone disease and combination therapy of octreotide and interferon alpha-2b is worth to try for patients with inoperable metastatic carcinoid tumor.
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PMID:Octreotide as a rapid and effective painkiller for metastatic carcinoid tumor. 1586 61

Consensus statement of the Polish Society of Endocrinology, regarding presurgical somatostatin analogs in acromegaly has been presented. It is suggested to administer depot somatostatin analog (Octreotide LAR at the dose 20 mg and then 30 mg or equivalent doses of Lanreotide Autogel 90/120 mg every 4 weeks) in order to normalize or suppress to a maximal extent GH and IGF-1 concentrations. The period of therapy in case of microadenoma would be at least 3 months (targets: biochemical improvement, reduced risk of disease's complications, perioperative risk reduction, inhibition of tumor growth). The period of therapy in case of macroadenoma would be at least 6 months, until maximal possible reduction of GH and IGF-1 concentrations (targets: tumor shrinkage, biochemical improvement, reduced risk of disease's complications, perioperative risk reduction). Using an uniform approach in a group, as numerous as possible, of treated patients would allow objective evaluation of long-term efficacy of the treatment.
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PMID:[Consensus of the Polish Society of Endocrinology. Presurgical somatostatin analogs therapy in acromegaly]. 1805 27

Carcinoids of the intestine are the most common gastrointestinal carcinoid tumors. Therapeutic options to treat patients with these tumors are limited. There are very few ileal carcinoid cell lines available for in vitro studies to analyze new drugs that could be effective in treating patients with metastatic tumors. A replication defective recombinant adenovirus with an SV40 early T-antigen insert was used to infect two intestinal carcinoid tumors to create carcinoid cell lines. The cell lines were studied by cell culture, reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry. Both cell lines expressed SV40 large T antigen and receptors for TGFbeta1, TGFbeta2, EGFR, and somatostatin receptors. Treatment with TGFbeta1 led to growth inhibition and increased apoptosis in the cultured cells. Octreotide inhibited cell growth of both cell lines while stimulating apoptosis. Treatment of the HC45 cells with gefitinib also inhibited cell growth in a concentration-dependent manner. TGFbeta treatment stimulated chromogranin A expression while expression of two other granins, chromogranin B and 7B2, did not change significantly. RNA profiling of cells treated with TGFbeta1 showed increased expression of vitamin D3 receptor. This finding was validated by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. These results indicate that these carcinoid cell lines can be used to study the proliferative and apoptotic mechanisms involved in intestinal carcinoid tumor growth regulation.
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PMID:Characterization of the functional and growth properties of cell lines established from ileal and rectal carcinoid tumors. 1824 65

Consensus statement of the Polish Society for Endocrinology, regarding presurgical somatostatin analogs in acromegaly has been presented. It is suggested to administer depot somatostatin analog (Octreotide LAR at the dose 20 mg and then 30 mg or equivalent doses of Lanreotide Autogel 90/120 mg every 4 weeks) in order to normalize or suppress to a maximal extent GH and IGF-1 concentrations. The period of therapy in case of microadenoma would be at least 3 months (targets: biochemical improvement, reduced risk of disease's complications, perioperative risk reduction, inhibition of tumor growth). The period of therapy in case of macroadenoma would be at least 6 months, until maximal possible reduction of GH and IGF-1 concentrations (targets: tumor shrinkage, biochemical improvement, reduced risk of disease's complications, perioperative risk reduction). Using an uniform approach in a group, as numerous as possible, of treated patients would allow objective evaluation of long-term efficacy of the treatment.
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PMID:Consensus statement of the Polish Society for Endocrinology: presurgical somatostatin analogs therapy in acromegaly. 1828 67

The mammalian target of rapamycin (mTOR) signaling pathway has emerged as a promising target for cancer therapy. Rapamycin inhibits mTOR activity but induces upstream signaling, leading to Akt activation, potentially limiting antitumor activity. Octreotide, a somatostatin analog, decreases phosphatidylinositol-3-kinase/Akt signaling in some models, and thus theoretically may enhance rapamycin's antitumor activity. The aim of this study was to determine the antitumor activity of rapamycin and octreotide as single agents and in combination in neuroendocrine tumors. In carcinoid cell lines BON-1 and NCI-H727, cell proliferation was significantly inhibited by rapamycin in vitro, although rapamycin treatment did lead to Akt phosphorylation. Octreotide had limited antiproliferative effects alone, and did not demonstrate synergistic or additive interactions with rapamycin. Furthermore, octreotide did not overcome rapamycin-induced Akt phosphorylation. In vivo, rapamycin alone caused significant tumor suppression. Octreotide alone did not inhibit in vivo tumor growth and did not enhance rapamycin-mediated growth inhibition. In conclusion, rapamycin causes significant growth inhibition in carcinoid tumor cell lines in vitro and in vivo, thus mTOR is a promising therapeutic target for neuroendocrine tumors. Octreotide does not enhance the efficacy of rapamycin's antiproliferative effects in the models tested, and does not inhibit rapamycin-mediated feedback activation of Akt. Further study is needed in order to determine whether octreotide or other somatostatin analogs enhance the efficacy of mTOR inhibitors in other models.
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PMID:Antitumor activity of rapamycin and octreotide as single agents or in combination in neuroendocrine tumors. 1831 Feb 92


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