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)

The antitumor effect of recombinant human interleukin-2 (rIL-2) on murine hemangioendothelioma D14 (D14) in female BALB/c-nu/nu mice was examined histologically. D14 cells which had been maintained in vitro were transplanted subcutaneously into nude mice on day 0 (1 x 10(7) cells/mouse). The mice with established tumor on day 28 received rIL-2 subcutaneously at a dose of 20 micrograms/mouse/day for 35 days. On day 63, the mice were killed, and the tumor, spleen and bone marrow were examined histologically. In the mice that had received rIL-2, tumor growth was significantly suppressed. Histologically, there was marked infiltration of large granular cells (about 15-30 microns in diameter) in the tumors. In the adjacent areas, there was a significant increase in the number of tumor cells showing karyorrhexis. The large granular cells (LGC) contained periodic acid Schiff-positive round granules in the cytoplasm and were stained positively for Thy-1.2 surface antigen. The LGC were also positive for asialo GM1 surface antigen but not for Lyt-1, Lyt-2 or IgG surface antigens. This evidence suggests that the LGC are lymphokine-activated killer-like cells which were derived from a natural killer cell lineage. The concomitant increases in the number of LGC and the number of cells showing karyorrhexis in the tumors of the mice treated with rIL-2 suggest that LGC play an important role in the destruction of tumor cells.
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PMID:Antitumor effect of recombinant human interleukin-2 on the growth of murine hemangioendothelioma D14 in nude mice: occurrence of large granular cells in the tumor. 191 31

A 45-year-old woman whose x-ray film revealed multiple widespread bilateral small nodules was diagnosed as having pulmonary tuberculosis or metastatic pulmonary cancer. A conclusive histological diagnosis of pulmonary epithelioid hemangioendothelioma (PEH) was made following an open-lung biopsy. PEH is a progressive disease that probably originates from an endothelial cell. However, there is still no effective therapeutic modality for PEH. The postoperative course of our patient has been uneventful with no evidence of tumor growth for four and a half years after initial x-ray detection of the lesions.
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PMID:Pulmonary epithelioid hemangioendothelioma: a case report. 852 26

Malignant endothelial neoplasms involving the serous membranes are rare, and only a few cases have been documented. We report 14 patients with epithelioid hemangioendothelioma (EHE) or epithelioid angiosarcoma (EA) diffusely involving the pleural, peritoneal, or pericardial cavities, resulting in a picture closely resembling mesothelioma. The mean age at diagnosis was 52 (range, 34-85). The patients included two women and one man with peritoneal tumors, eight men with pleural tumors, and three men with pericardial tumors. A shared histological appearance was a diffuse sheet-like and clustered pattern of tumor growth with variable degrees of vascular differentiation. A tubulopapillary growth pattern, often seen in mesothelioma, was prominent in four cases. Nine cases showed a variable number of spindle cells, some neoplastic, others reactive, focally producing a biphasic growth pattern, further suggesting mesothelioma. Initial interpretations included mesothelioma, adenocarcinoma, and, in one case with prominent spindle-cell components, leiomyosarcoma. Immunohistochemically, strong vimentin staining and negative or weak to moderate cytokeratin staining were observed in all 14 cases. The tumor cells coexpressed at least two of the four endothelial markers used in the study (CD31, CD34, von Willebrand factor, and Ulex europaeus agglutinin-I [UEA-I)]. Detection of abortive vessel formation was facilitated by staining for collagen type IV. Markers of mesothelial, epithelial, muscular, and neuronal differentiation were all negative in the subset of cases studied. As a control group, 39 mesotheliomas and more than 60 adenocarcinomas of various origins were studied using the same antibody panel. This group revealed strong keratin staining, moderate or negative vimentin staining, and no expression of any of the endothelial-lineage markers, with the exception of positive staining for UEA-I in occasional adenocarcinomas. Clinically, these endothelial tumors were highly aggressive; 12 patients presented with disseminated disease, and most died within months of the initial presentation. These findings indicate that, although uncommon, EHE/EA should be included in the differential diagnosis of serous membrane neoplasms with histological and clinical features of malignant mesothelioma. The diagnosis of an endothelial neoplasm can be suspected by the presence of abortive vessel formation and by the strong expression of vimentin, with absent or low-level expression of cytokeratin. The demonstration of immunoreactivity for two or more endothelial-associated markers is essential in confirming the diagnosis.
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PMID:Malignant vascular tumors of the serous membranes mimicking mesothelioma. A report of 14 cases. 894 35

We previously identified the angiogenesis inhibitor angiostatin. Using a similar strategy, we have identified endostatin, an angiogenesis inhibitor produced by hemangioendothelioma. Endostatin is a 20 kDa C-terminal fragment of collagen XVIII. Endostatin specifically inhibits endothelial proliferation and potently inhibits angiogenesis and tumor growth. By a novel method of sustained release, E. coli-derived endostatin was administered as a nonrefolded suspension. Primary tumors were regressed to dormant microscopic lesions. Immunohistochemistry revealed blocked angiogenesis accompanied by high proliferation balanced by apoptosis in tumor cells. There was no toxicity. Together with angiostatin data, these findings validate a strategy for identifying endogenous angiogenesis inhibitors, suggest a theme of fragments of proteins as angiogenesis inhibitors, and demonstrate dormancy therapy.
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PMID:Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. 900 68

Angiostatin inhibits angiogenesis and metastatic tumor growth; however, its usefulness in treating primary nonmetastasizing tumors is less well understood. We now report the effectiveness of human angiostatin administration in a mouse hemangioendothelioma model. Human angiostatin was administered to mice with s.c. hemangioendothelioma and associated disseminated intravascular coagulopathy (Kasabach-Merritt syndrome). Angiostatin significantly reduced tumor volume in comparison to nontreated controls, increased survival, and prevented the profound thrombocytopenia and anemia of Kasabach-Merritt syndrome. Apoptosis of tumor cells was induced by angiostatin, but tumor cell proliferation was not inhibited. These data suggest angiostatin as a novel treatment for nonmetastasizing vascular tumors and for Kasabach-Merritt syndrome.
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PMID:Human angiostatin inhibits murine hemangioendothelioma tumor growth in vivo. 939 49

A hepatic epithelioid hemangioendothelioma leading to almost complete calcification of the right and left liver lobes in a 75-year-old female is reported. Over a period of 16 years the liver progressively calcified, but its function remained normal by compensatory hypertrophy of the caudate lobe. Multiple partially calcified metastases were present in the lungs, peripancreatic region and along the left principal bronchus. Extreme liver calcification has only rarely been reported. The case presented here reflected slow tumor growth and subsequent long disease course. The vascular nature of the tumor was confirmed by immunohistochemical and ultrastructural analysis.
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PMID:Subtotal liver calcification due to epithelioid hemangioendothelioma. 958 38

Kasabach-Merritt Syndrome (KMS) is seen in children with large vascular tumors. KMS is characterized by very low platelet counts and a consumption of coagulation factors causing life-threatening complications. It has been proposed that thrombopenia in these patients is caused by intratumoral trapping of platelets. The truncated form of the cMpl-receptor ligand thrombopoietin, pegylated human megakaryocyte growth and development factor (Peg-rHuMGDF), is an agent that stimulates platelet production. We hypothesized that stimulation of the platelet production would prevent the life-threatening complications of patients with KMS owing to low platelet counts. In a mouse model of KMS, with tumors derived from a hemangioendothelioma cell line, we studied the effect of Peg-rHuMGDF. Treatment with Peg-rHuMGDF (10 microg/kg/day intraperitoneally) increased platelet counts by 7-8-fold compared with control tumor-bearing mice after 11 d of treatment (p < 0.001, n = 8). Survival was significantly increased, with 50% of treated animals alive at 1 mo versus 0% in untreated controls. Interestingly, we also observed an inhibition of tumor growth by 75% (p < 0.001, n = 8). Hematoxylin and eosin staining showed fresh fibrin clots in the treated tumors, suggesting that higher platelet counts caused intravascular thrombosis of tumor vessels. We conclude that increased platelet production in this model of KMS resulted in an antivascular tumor effect via platelet trapping. Further, we propose that thrombopoietin may be of critical value in preventing life-threatening complications from KMS.
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PMID:Treatment of the Kasabach-Merritt syndrome with pegylated recombinant human megakaryocyte growth and development factor in mice: elevated platelet counts, prolonged survival, and tumor growth inhibition. 1054 19

We report on a 12-year old boy suffering from malignant epithelioid hemangioendothelioma of the liver, which is a very rare tumor in childhood. The tumor was detected by ultrasound examination at the age of 10 and appeared at that time as a solitary intrahepatic nodular lesion. During the following 2 years multiple nodular lesions developed in both hepatic lobes. There were neither any suspect anamnestic findings nor abnormal clinical or laboratory data. The tumor showed the typical histomorphological, immunohistochemical, and ultrastructural features of this entity, which is usually seen in older patients. We investigated proliferative activity, apoptotic regulation, and expression of VEGF and VEGF-receptor flk-1 by means of immunohistochemical techniques. According to the known slow growth activity of these tumors we found only a few Ki-67 positive tumor cells. We did not detect any apoptotic cells using TUNEL technique. The positive immunoreaction of the tumor cells with antibodies against VEGF and VEGF-receptor flk-1 may indicate the regulation of tumor growth by angiogenetic factors. We present our findings together with a summary of the most important publications of recent years concerning these tumors.
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PMID:[Malignant epithelioid hemangioendothelioma of the liver - a very rare tumor in children]. 1059 53

Endostatin, a potent inhibitor of angiogenesis and tumor growth, is a COOH-terminal fragment of collagen XVIII derived through cleavage of an Ala-His linkage by an as yet unidentified endostatin-processing enzyme. Endostatin was originally isolated from the conditioned medium of hemangioendothelioma (EOMA) cells. By investigating the processing of collagen XVIII to endostatin by EOMA cells, we show here that the generation of endostatin can be mediated by an elastase activity. We also show that several members of the elastase family can act as an endostatin-processing enzyme by specifically cleaving the Ala-His linkage and releasing endostatin from a precursor molecule. We further suggest that the generation of endostatin from collagen XVIII is at least a two-step process, involving a metal-dependent early step and an elastase activity-dependent final step.
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PMID:The generation of endostatin is mediated by elastase. 1062 89

Endostatin, an inhibitor of angiogenesis and tumor growth, was identified originally in conditioned media of murine hemangioendothelioma (EOMA) cells. N-terminal amino acid sequencing demonstrated that it corresponds to a fragment of basement membrane collagen XVIII. Here we report that cathepsin L is secreted by EOMA cells and is responsible for the generation of endostatin with the predicted N-terminus, while metalloproteases produce larger fragments in a parallel processing pathway. Efficient endostatin generation requires a moderately acidic pH similar to the pericellular milieu of tumors. The secretion of cathepsin L by a tumor cell line of endothelial origin suggests that this cathepsin may play a role in angiogenesis. We propose that cleavage within collagen XVIII's protease-sensitive region evolved to regulate excessive proteolysis in conditions of induced angiogenesis.
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PMID:Secreted cathepsin L generates endostatin from collagen XVIII. 1071 19


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