Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case history of a 16-year-old boy with hepatocellular carcinoma and an intermediate deficiency of alpha1-antitrypsin (MZ phenotype) is presented. Previous reports have suggested that hepatocellular carcinoma may be associated with the Z variant of antitrypsin and either a severe or intermediate antitrypsin deficiency. The present case is unusual because of the rather high level of the serum trypsin inhibitory capacity for an MZ heterozygote (1.633 units), which may be due to involvement of the liver by the tumor or to a recent partial hepatectomy. PAS-positive antitrypsin globules were seen in the primary tumor and in nodules metastatic to the mesentery, as well as in nonneoplastic portions of the liver. Hepatocellular carcinoma is another disease state that may occur preferentially in individuals with either severe or intermediate deficiencies of alpha1-antitrypsin.
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PMID:Hepatocellular carcinoma and intermediate alpha1-antitrypsin deficiency (MZ phenotype). 16 86

Glycopeptides suggesting a complex oligosaccharide composition are present on the surface of cells from human neuroblastoma tumors and several cell lines derived from the tumors. The glycopeptides, labeled with radioactive L-fucose, were removed from the cell surface with trypsin, digested with Pronase, and examined by chromatography on Sephadex G-50. Human skin fibroblasts, brain cells, and a fibroblast line derived from neuroblastoma tumor tissue show less complex glycopeptides. Although some differences exist between the cell lines and the primary tumor cells, the similarities between these human tumors and animal tumors examined previously are striking.
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PMID:Glycopeptides from the surgace of human neuroblastoma cells. 100 Apr 97

Platelet function following inoculation of chemically induced carcinoma was evaluated in the rat. The original line of tumor (NGW1) was obtained using N-methyl-N-nitrosoguanidine. After trypsin homogenation a cell suspension of 0.3 X 10(6) viable tumor cells was injected subserosally in the cecum of each animal. Controls received injections of equal volumes of 0.9% NaCl solution or trypsin. The animals were subjected to laparotomy 2, 4, and 6 weeks after inoculation. Platelet function was assessed in vivo by measuring bleeding time and blood loss during mesenteric vessel transection or liver resection upon laparotomy. Hemoglobin, hematocrit, platelet count, activated partial thromboplastin time, platelet aggregation, thromboxane B2, platelet factor 4, and fibrinogen levels were evaluated after sacrifice by exsanguination. Significant decrease in bleeding time and blood loss was observed in animals with local primary tumors as well as in rats with lymph node metastases. Hemoglobin and hematocrit were decreased in the presence of metastases. Platelet count was not changed. Activated partial thromboplastin time was not affected by the presence of tumor. Platelet aggregation in vitro was accelerated in the presence of primary tumor or lymph node metastases, as well as following addition of tumor cells to platelet suspensions. No changes in thromboxane B2 or platelet factor 4 could be registered. Fibrinogen levels were decreased in the presence of liver metastases. Enhancement of primary hemostasis and platelet function in the presence of colon carcinoma in the rat was demonstrated both in vivo and in vitro. Direct or indirect interaction of the tumor cell with thrombocytes may play a role in determining the metastatic potential of the neoplasm.
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PMID:Hemostasis following inoculation and during spreading of colon carcinoma in the rat. 375 13

Trypsinogen (TRY), the precursor to the serine protease trypsin, is found in the pancreas and mediates digestive proteolysis in the small intestine. Differential display of cDNAs expressed by human colorectal tumor tissues compared with adjacent normal colonic mucosa identified an isoform of TRY (TRY2) up-regulated in colorectal cancers. Northern blot analysis of RNA isolated from a series of 28 malignant colon tumors and corresponding normal mucosa showed that TRY transcripts were up-regulated 2- to 33-fold in 29% of tumors. Further, TRY mRNA was expressed in 6 colorectal cancer cell lines, with highest levels detected in the metastatic tumor lines SW620 and HT29. Immunostaining for TRY protein expression showed intense immunoreactivity in the supranuclear cytoplasm of colon tumors in 16% of tissue specimens. To evaluate the relative contributions of 2 isoforms of TRY, TRY1 and TRY2, to total TRY mRNA expression, a semi-quantitative multiplex RT-PCR assay was developed. TRY2 mRNA was detected in all 6 colorectal tumor cell lines, whereas TRY1 mRNA was expressed only in the metastatic tumor lines, showing that the high levels of TRY expression in the metastatic tumor lines are likely due to up-regulation of TRY1. Evaluation of TRY1 and TRY2 mRNA expression by multiplex RT-PCR in a series of 20 colon tumor tissues representative of the range of tumor progression showed that TRY2 mRNA was expressed much more commonly than TRY1 mRNA in normal mucosa (26% vs. 6%) as well as in primary tumor tissues (65% vs. 15%). These data demonstrate that TRY2 is the dominant TRY in colon tissue and suggest that up-regulation of TRY1 expression in colon tumors may be associated with a metastatic phenotype.
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PMID:Human trypsinogen in colorectal cancer. 1139 23

Despite improvements in treatment of patients with head and neck squamous cell carcinoma (HNSCC) over the last two decades, the survival rate of these patients has not increased significantly. One of the major factors in the poor outcome of the disease is regional metastasis. To better understand the mechanisms of this process at the protein level, we performed two-dimensional electrophoresis (2-DE) and mass spectrometry using SELDI ProteinChip technology to identify proteins differentially expressed in two HNSCC cell lines, UMSCC10A and UMSCC10B, from the same patient. UMSCC10A was derived from the primary tumor and UMSCC10B from a metastatic lymph node. The differentially expressed proteins were excised from the gels. Following in-gel digestion by trypsin, mass profiles of the peptides were generated. Proteins were identified by submitting the peptide mass profiles to a public available NCBInr databases (www.proteometrics.com). Two membrane-associated proteins, annexin I and annexin II and glycolytic protein enolase-alpha were found to be upregulated, and calumenin precursor down-regulated, in metastatic cell line UMSCC10B. The identity of these proteins was confirmed by analyzing additional peptide mass fingerprints obtained by endoproteinase lysine-C digestion. The results were also validated by Western blotting analysis. Our results showed that enolase-alpha, annexin-I and annexin-II might be important molecules in head and neck cancer invasion and metastasis. The results also suggest an important complementary role for proteomics in identification of molecular abnormalities important in cancer development and progression.
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PMID:Identification and validation of metastasis-associated proteins in head and neck cancer cell lines by two-dimensional electrophoresis and mass spectrometry. 1209 Apr 72

Hemangioma is a primary tumor of the microvasculature in which angiogenesis is initially excessive, followed by spontaneous regression of the newly formed vessels, with the cellular parenchyma gradually being replaced with fibrofatty tissue. Mast cells, which are highly heterogenous in terms of their morphology, function, and metabolic products, have been implicated in the pathophysiology of hemangioma. Csaba stain shows that mast cells are predominantly of the biogenic amine phenotype throughout the development of hemangioma. The predominance of this phenotype remains unaltered following successful steroid therapy, although their number increases fourfold. Mast cells, all of which stain positive for tryptase, and those that stain positive for chymase as well, have been identified in hemangioma biopsy specimens throughout the three developmental phases. The total number of mast cells is highest during the involuting phase, less in the involuted phase, and least in the proliferative phase. The proportion of mast cells that contain both tryptase and chymase decreases from the proliferative through involuting to the involuted phase. This decreasing proportion of mast cells that contain both tryptase and chymase with ongoing involution parallels that of progressive deposition of the extracellular matrix as indicated by increasing fibrosis and fatty deposition. The short-chain type VIII collagen, thought to play a key role in angiogenesis, has been detected throughout the developmental phases of hemangioma. It has been postulated that this collagen, which is produced early in new vessel development, provides a substratum to facilitate the migration of endothelial cells. It may also facilitate the deposition of other extracellular constituents and influence cell movement and the maintenance of cell phenotypes. The intracellular localization of type VIII collagen in mast cells only in the early proliferative phase suggests that there is an active synthesis by mast cells during this phase. The increasing extracellular localization during hemangioma development may be caused by an increased secretion of protein from intracellular stores. The increased number of mast cells during the involuting phase indicates that these cells may play a role in the regression of hemangioma. This is in contrast to the large body of evidence showing the proangiogenic role of mast cells. The proportion of proliferating mast cells decreases, whereas the proportion of mast cells positive for clusterin/apolipoprotein J increases with ongoing involution of hemangioma. Clusterin/apolipoprotein J expression has been considered as a prominent marker of apoptotic cell loss. The presence of clusterin/apolipoprotein J granules both in the adjacent endothelial cells and in capillary lumens suggests that mast cells may be secreting this apoptotic modulator to promote the regression of hemangioma. Certain effectors produced by mast cells may participate in the development of hemangioma. It has been proposed that one of the functions of mast cells is to release factors leading to the regression of hemangioma. The evidence suggests that although mast cells may have a function in the endothelial proliferation in hemangioma, they also play a crucial role in the regression of this tumor. However, the roles of mast cells in the life cycle of hemangioma are likely to be complex and may involve stimulators of angiogenesis in the proliferative phase but inhibitors in later phases.
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PMID:Mast cells and hemangioma. 1510 98

In tumor metastasis, multicellular aggregates of tumor cells form and disseminate into the blood or lymph vessels from the tumor mass, following the formation of tumor cell emboli in distant vessels. However, the mechanism by which aggregates form in the tumor mass is unknown. Neutrophils often exist in tumors and are considered to affect tumor development. We observed that neutrophils had the capacity to induce the aggregation of MCF-7 human breast carcinoma cells adhering to culture substrates. When MCF-7 cells were cultured with rat inflammatory neutrophils, the soluble fraction of their lysate, and the conditioned medium of neutrophils stimulated with N-formyl-Met-Leu-Phe plus cytochalasin B, multicellular aggregates formed within 16 h, and tightly aggregated 3-D spheroids formed when the cultures were prolonged. The spheroid-inducing reaction was reversible and energy-dependent. The MCF-7 cells induced to aggregate by the neutrophil extract showed growth potential, although the growth rate of the cells was slightly reduced. The aggregation was dependent on E-cadherin, because the spheroids dispersed into isolated cells on incubation with EGTA or anti-E-cadherin antibody following pipetting. The aggregation-inducing activity in neutrophils was completely inhibited by soybean trypsin-chymotrypsin inhibitor. Moreover, the commercially available human neutrophil elastase and cathepsin G induced the aggregation of MCF-7 cells and formation of spheroids. The proteases secreted by infiltrated neutrophils in tumors are implicated in the dissemination of tumor aggregates from primary tumor sites.
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PMID:Induction of multicellular 3-D spheroids of MCF-7 breast carcinoma cells by neutrophil-derived cathepsin G and elastase. 1612 41

Composite tumors of the stomach consisting of mixed glandular and endocrine components are rare. We report 3 cases of composite glandular and endocrine tumors with pancreatic acinar differentiation in the stomach with their clinicopathologic findings. The patients' presenting symptoms were variable and included abdominal pain, gastrointestinal hemorrhage, and weight loss. One patient with abdominal pain also had an elevated serum lipase level, clinically mimicking acute pancreatitis. The histology of these tumors was similar. They showed admixture of well-differentiated endocrine components with acinar and glandular components. The glandular component consisted of columnar epithelial cells resembling gastric foveolar or intestinal goblet cells, consistent with a well-differentiated adenocarcinoma. A panel of histochemical and immunohistochemical stains was performed, which included PAS, Alcian blue, Mib1, CEA, cytokeratin 7, cytokeratin 20, Muc2, Muc5AC, chromogranin, synaptophysin, trypsin, chymotrypsin, lipase, insulin, gastrin, serotonin, and pancreatic polypeptide. While the immunoreactivity for cytokeratin 7, cytokeratin 20, Muc2, Muc5AC, and CEA was largely restricted to the glandular component, the endocrine and pancreatic acinar markers showed marked variability and overlap. All cases showed immunoreactivity for at least one of the exocrine pancreatic enzymes, and all expressed endocrine differentiation. Some degree of amphicrine differentiation was suggested in all cases. Two cases showed metastases in perigastric lymph nodes, which histologically resembled the primary tumor. In summary, these tumors represent another distinct type of composite glandular and endocrine gastric neoplasm with pancreatic acinar differentiation.
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PMID:Composite glandular and endocrine tumors of the stomach with pancreatic acinar differentiation. 1622 21

Herein is presented the case of a malignant non-functioning endocrine tumor of the pancreas with oncocytic features, and a discussion on the high incidence of malignancy in oncocytic endocrine pancreatic tumors. The patient was a 65-year-old woman who showed no paraneoplastic symptoms produced by functioning pancreatic endocrine tumors. The primary tumor was located in the body and tail of the pancreas, and had metastasized to the liver. Tumor cells were arranged in a ribbon-like or trabecular pattern and had an abundant eosinophilic cytoplasm containing numerous mitochondria and neurosecretory granules. The cytoplasm of the tumor cells was intensely stained with an antimitochondrial antigen antibody. Most tumor cells stained positively with Grimelius stain and for chromogranin A. Some tumor cells also stained for synaptophysin. However, the tumor cells negatively stained for hormones such as insulin, glucagon, somatostatin, gastrin, vasoactive intestinal peptide and pancreatic polypeptide, for serotonin, and for pancreatic enzymes such as amylase and trypsin. Analysis of 18 oncocytic pancreatic endocrine tumors, consisting of those reported previously and that in the present case, suggests that the high incidence of malignancy in oncocytic endocrine tumors is associated with the high incidence of non-functioning endocrine tumors among them, most of which are malignant.
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PMID:Oncocytic non-functioning endocrine tumor of the pancreas. 1709 34

In this monograph, the chemopreventive effects of enterally administered proteases (trypsin, chymotrypsin, and papain) have been documented in a series of animal experimental tumor models. The experimental evidence demonstrates a significant inhibition of growth of both the primary tumor and the metastatic disseminations. Survival in animals treated with proteases is significantly longer than in untreated animals. The results confirm the fundamental correlation between early initiation of therapy and consequent growth of the tumorous disease. Comparable results have been shown in solid tumors in animal models (melanoma and Lewis lung carcinoma) and in human tumors (pancreatic and breast cancers). In this article, details of the known mechanisms of systemic actions of enterally administered proteases are documented and their relationship with cancerogenesis is discussed.
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PMID:Exogenous proteases confer a significant chemopreventive effect in experimental tumor models. 1911 25


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