Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An antigen, immunologically related to the external domain of the c-erbB-2 (HER-2/neu) protein, was found shed into the serum of nude mice bearing tumors that overexpress the c-erbB-2 protein (gp185). Utilizing paired combinations from a panel of monoclonal antibodies (TAbs 250-265), with specificity for extracellular epitopes of gp185, an immunoradiometric assay was developed to quantitate this shed antigen. The immunoradiometric assay detected membrane-bound and soluble gp185 as well as a soluble derivative corresponding in sequence to the extracellular domain of gp185 (designated gp75). This recombinantly expressed gp75 was immunoaffinity purified and used to generate a standard curve from which serum samples were quantitated. Increases in antigen levels measured in the sera of tumor-bearing nude mice correlated with both overexpression of the c-erbB-2 protein and increased tumor volume. Positive sera were obtained from mice given implants of NIH3T3 cells transfected with c-erbB-2 complementary DNA (NIH3T3t), or ovarian (SK-OV-3) or breast (MDA-MB-361) tumor cell lines overexpressing the c-erbB-2 protein. In mice bearing NIH3T3t tumors, increases in tumor volume from 80 to 9000 mm3 resulted in levels of shed antigen from 8 to greater than 1000 ng/ml gp75 equivalents. Sera from mice with c-erbB-2-negative tumors or tumors overexpressing the epidermal growth factor receptor were negative in the assay. This assay, and the quantitation of shed antigen levels, may have diagnostic or monitoring utility in cancers, such as breast and ovarian, in which the c-erbB-2 protein is overexpressed.
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PMID:An antigen immunologically related to the external domain of gp185 is shed from nude mouse tumors overexpressing the c-erbB-2 (HER-2/neu) oncogene. 167 37

Multidrug resistance for many types of cancer outside the central nervous system (CNS) has been found to be due to the overexpression of the multidrug resistance gene MDR1, of which the gene-product P-glycoprotein acts as a membrane-bound efflux pump for many anticancer drugs. To examine whether brain tumors overexpress the MDR1 gene, 25 brain-tumor specimens were subjected to Northern blot analysis: 10 gliomas, eight meningiomas, three schwannomas, one malignant lymphoma, and three tumors metastatic to the brain. Ten fresh-frozen autopsy specimens of various parts of normal brain were also analyzed. Blots were hybridized with 32P-labeled Chinese hamster complementary deoxyribonucleic acid (cDNA) and 32P-labeled human MDR1 cDNA. The MDR1 gene messenger ribonucleic acid (mRNA) was detected in two tumors using the Chinese hamster probe (one sphenoid wing meningioma and one metastatic prostate tumor) and in one CNS lymphoma using the human probe. Intact mRNA could not be extracted from the fresh-frozen autopsy specimens of normal brain. Seventeen tumors were examined for P-glycoprotein by immunohistochemical staining using murine monoclonal antibody C219: eight gliomas, eight meningiomas, and one craniopharyngioma. The neoplastic cells from two gliomas and three meningiomas and the blood vessels within six gliomas and two meningiomas stained positively for P-glycoprotein. Seven of 10 normal brain specimens stained positively for P-glycoprotein in blood vessels but no specimen demonstrated staining of parenchymal cells. This study demonstrates that the MDR1 gene can be detected in normal brain, and in malignant, benign, and metastatic lesions. P-glycoprotein can be present in tumor blood vessels even when it is not seen in neoplastic cells. Although the role of P-glycoprotein in tumor blood vessels needs to be further examined and more clearly defined, drug resistance in malignant primary brain tumors may result from characteristics not solely of neoplastic cells but also tumor vasculature.
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PMID:Multidrug resistance gene (MDR1) expression in human brain tumors. 168 28

Primary neuroendocrine carcinomas of the skin were recognized as distinctive neoplasms and clinicopathologic information on their location on the eyelids have been reported. The authors present one case of primary neuroendocrine carcinoma occurring on the right lower lid in a 73-year-old woman. The clinical history, light and electron microscopic findings as well the results of an immunohistochemical study are described. The ultrastructural study demonstrated the characteristic membrane-bound dense-core neurosecretory granules. Immunoreactivity for neuron-specific enolase, keratin filaments, epithelial membrane antigen and calcitonin were observed and are strongly suggestive of a neuroendocrine differentiation in a neoplasm of epithelial origin. Various hypothesis concerning the origin of this tumor are discussed on the basis of the immunohistochemical findings. The authors also provide a brief review of the literature.
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PMID:Primary neuroendocrine carcinoma of the eyelid, immunohistochemical and ultrastructural study. 169 12

Transmission electron microscopy (TEM) was used to study ultrastructural changes that accompanied the tumorous transformation of the descending rat colon epithelial cells, following short treatment with a direct carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), with subsequent prolonged treatment with secondary bile acids, lithocholic (LCA) and deoxycholic (DCA), which enhanced tumor formation. Colon epithelial cells after long treatment with bile acids alone were characterized by the presence of an irregular nuclear membrane, ring-shaped rough endoplasmic reticulum (RER), collagen-like tonofilaments and membrane-bound mucous vacuoles. Tumor cells which developed following treatment with MNNG alone were characterized by the irregular shape of the nuclear membrane and, sometimes, by polynuclei, accumulation of large amounts of mitochondria, loss of cell-cell contacts and by endocytosis of the cell membrane. After combined treatment with MNNG and LCA, many mitochondria lost their membranous envelope; in the cytoplasm many collagen-like tonofilaments, ring-shaped RER and many free ribosomes were present. After treatment with MNNG and DCA, many polysomes were found in the cytoplasm. It was apparent that treatment with MNNG alone caused the development of adenocarcinoma-like tumors, while additional treatment with secondary bile acids significantly enhanced these changes, which were accompanied by the development of atypia and anaplasia of epithelial cells, with many irregularities in intracellular organization.
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PMID:Ultrastructural changes in rat colorectal epithelium and tumors after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and secondary bile acids. 175 92

DMN exposure has been shown to increase macrophage cytotoxic activity against tumor targets both in vitro and in vivo. Since the production and expression of the macrophage-derived cytokine tumor necrosis factor-alpha (TNF-alpha) is associated with such anti-tumor activity, studies were performed to determine whether changes in TNF-alpha gene transcription and biosynthesis resulted following DMN exposure. Thioglycollate-elicited macrophages obtained from DMN-exposed animals displayed enhanced levels of constitutively expressed TNF-alpha transcripts compared to vehicle controls. Northern blot analysis of the time course expression of TNF-alpha following endotoxin (1 microgram/ml) stimulation in vitro showed a significantly greater induction of TNF-alpha transcripts in macrophages from DMN-exposed than control animals, with peak levels detected between 30 and 120 min. Maximum endotoxin-induced TNF-alpha secretion occurred later than the accumulation of the transcripts, with greater secretion observed between 120 and 360 min. In contrast to endotoxin, stimulation with IFN-gamma (100 U/ml) produced no changes in the level of TNF-alpha transcripts. However, stimulation of macrophages with IFN-gamma did greatly enhance the surface expression of membrane-bound TNF-alpha in cells from the DMN-treated animals. Supernatants from media and endotoxin stimulated macrophage were tested for TNF-alpha activity against WEHI-164 cells. In media alone, a five-fold increase in TNF-alpha activity was observed at 6 h in supernatants from macrophage obtained from DMN-exposed animals compared to the vehicle group. Treatment of supernatants with either superoxide dismutase (SOD) or catalase to remove reactive oxygen products did not alter their lytic capacity. However, addition of a neutralizing murine-anti-TNF-alpha antibody reduced the lytic capacity of the supernatants by 90% in both treatment groups. Accumulation of IL-1 beta transcripts gradually increased over the 6 h with a concomitant increase in secreted IL-1 beta that was identical in both DMN and vehicle groups. These results demonstrate that DMN exposure: (1) enhances the expression of TNF-alpha in peripheral macrophages by transcriptional regulatory mechanism(s) and, (2) does not alter the expression or secretion of IL-1 beta.
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PMID:Transcriptional changes in macrophage TNF-alpha expression following dimethylnitrosamine exposure in vivo. 179 Nov 40

Alveolar soft part sarcoma of the lung seen in a 42-year-old female is reported. In the partial pneumonectomy specimen, there was a 3 x 2.5 cm tumor arising from the pulmonary vein at the level of the right lung hilus, with tumor thrombus formation. The transition between the tumor and venous smooth muscle layer was microscopically confirmed. At autopsy, performed 18 months after surgery, metastases were noted in the left lung and brain. No primary focus was identified in the soft tissue. The alveolus-forming clear tumor cells contained diastase-resistant periodic acid-Schiff-reactive granules. Immunohistochemically, granular cytoplasmic reactivities with monoclonal antibodies against pan-actin and alpha-sarcomeric actin were demonstrated, whereas other muscle markers such as desmin, alpha-smooth muscle actin, myoglobin, fast skeletal myosin, and the mm-isozyme of creatine kinase were negative. Ultrastructurally, crystallized structures were occasionally identified in the membrane-bound, electron lucent granules, which often filled the tumor cell cytoplasm. The muscle cell nature of the neoplasm is discussed.
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PMID:Alveolar soft part sarcoma of the pulmonary vein. 150 8

T lymphocyte activation is initiated as a result of the interaction between the TCR complex and Ag as seen in the framework of a membrane-bound MHC molecule. Receptor stimulation results in a rise in free intracellular Ca2+ and the activation of protein kinase C (PKC). Bryostatin (Bryo) and phorbol esters (e.g., 12-O-tetradecanoylphorbol 13-acetate (TPA] are PKC activators with somewhat different immunologic effects. We compared the effect of Bryo and TPA on the T cell tumor line Jurkat and derivatives of Jurkat cells grown in media supplemented with 100 nM Bryo ("BR100" cells) or 100 nM TPA ("TP100" cells). In untreated Jurkat cells, there is a dose- and time-dependent decrease in proliferation, compared to media controls, after the administration of as little as 10 nM TPA. This can be reversed in a dose- and time-dependent manner by Bryo. Interestingly, the expression of the transferrin receptor parallelled this effect on proliferation. Furthermore, Jurkat cells grown continuously in 100 nM TPA regained full proliferative capacity after several weeks in culture and transferrin receptor expression returned to near the level seen in untreated Jurkat cells. The chromatographic separation of PKC activity in these three cell lines showed that total PKC activity was dramatically decreased in both the TP100 and BR100 cells when compared to untreated Jurkat cells. However, in the TP100 cells there exists a peak of activity that is activated by Bryo, but not TPA. Western blots of whole cell lysates of the three cell lines showed that PKC-alpha and PKC-beta II were both down-regulated in BR100 and TP100 cells compared to untreated Jurkat cells. PKC-gamma was not detected in any of the cell lines. Therefore, the Bryo-specific peak seen in TP100 cells may be PKC-delta, -epsilon, -zeta, -eta, or a novel PKC isoform. This could provide the basis for a molecular characterization of the differences in PKC activation between phorbol esters and Bryo.
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PMID:Response of Jurkat T cells to phorbol ester and bryostatin. Development of sublines with distinct functional responses and changes in protein kinase C activity. 183 42

A soluble (cell-free) oncofetal antigen (OFA) was detected in murine and human amniotic fluids by immunostaining with the murine monoclonal antibody (MAb 115) produced by syngeneic immunization with mid-gestational mouse fetal cells. OFA was purified from the amniotic fluids by ammonium sulfate precipitation at 30-70% saturation, followed by successive gel chromatography of the OFA-containing fraction on Sephacryl-S300 HR, Q- and S-Sepharoses and lentil lectin agarose. The fraction eluted from the lentil lectin column gave a single band on SDS-PAGE of the same molecular weight as the membrane-bound OFA found on both fetal and tumor tissues of humans and several rodents. Both soluble and membrane-bound OFAs share several chemical characteristics, including binding to lentil lectin and wheat-germ agglutinin, molecular weight (44 kDa) and pI (6.8). Mild periodate oxidation of OFA did not affect its binding to MAb 115 in an enzyme-linked immunosorbent assay, indicating that the reactive epitope is a peptide.
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PMID:Isolation and partial characterization of a soluble oncofetal antigen from murine and human amniotic fluids. 185 Mar 86

Giant cell carcinomas of the lung have been notorious in fulminant clinical courses. Thus, this report describes two exceptionally favorable cases among six cases of giant cell carcinoma of the lung. Their histopathological features are a sharply-demarcated tumor of Stage I, absence of vascular permeation of the cancer cells, prominent lymphoid and plasma cell infiltration in the tumor tissue, and lymph follicle formation in the surrounding tissues. Another case with a Stage II tumor showed the same histopathological findings as the above two cases with the exception of lymphatic permeation of the cancer cells. This patient expired about one year after undergoing an operation. As conventional controls, the remaining three cases with Stage III tumors showed an alveolar extension of tumor cells and vascular permeation. There was a fulminant course after the operation. Notwithstanding similar intervals from their clinical onset to operation in the 4 cases other than Cases 4 and 6, their stages showed considerable variations. Hence, each histopathological feature might have substantiated the different clinical courses following the operation. Electron microscopy of three of the cases indicated double-membrane-bound blisters with intermediate junctions in the bizarre giant cells, and cancer cell differentiation toward both glandular and squamous directions.
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PMID:Clinicopathological study of pulmonary giant cell carcinomas with reference to prognosis of patients. 187 56

Neuroendocrine carcinoma of the skin usually occurs in elderly individuals. Head and neck are the most common primary sites followed by the extremities and trunk. As this tumor represents a remarkable rarity in younger people, we report the case of a 33-year-old woman with a neuroendocrine carcinoma in an unusual localization. Diagnosis was based on the results of the examination of a metastasis in the inguinal lymph nodes. The lesion at the Labium minus pudendi which is to be considered the primary tumor was detected several months later. Diagnosis of Merkel cell tumor until recently had depended on ultrastructural demonstration of dense-core membrane-bound granules. Today, diagnosis can be secured also by optical light microscopy, on the basis of a certain constellation of immunohistochemical and lectin histochemical findings.
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PMID:[Merkel cell tumor (neuroendocrine carcinoma of the skin) in an unusual location. Immunohistochemical and lectin histochemical findings]. 191 29


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