UMLS:C0027651 - FACTA Search

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Query: UMLS:C0027651 (tumor)
685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulosa cell tumors with bizarre nuclei (GCT-BN) are rare lesions with a prognosis apparently similar to that of conventional granulosa cell tumors (GCT-NOS). The immunohistochemical features of GCT-BN have not been described, and the exact nature of the bizarre nuclei (BN) is unclear. Thirteen GCT-BN were studied with antibodies to cytokeratin, vimentin, epithelial membrane antigen, muscle-specific actin, alpha smooth muscle actin, desmin, and S-100 protein. Six cases were also examined by fluorescence in situ hybridization for trisomy 12, a nonrandom chromosomal aberration found in a proportion of ovarian sex-cord stromal tumors. Histologically, 12 tumors (86%) contained BN areas interspersed with large areas of GCT-NOS. The remaining tumor contained only microscopic foci of GCT-NOS. Immunohistochemically, the tumors stained for vimentin (13 tumors), S-100 protein (11 tumors), muscle-specific actin (10 tumors), cytokeratin (eight tumors), alpha smooth muscle actin (eight tumors), and desmin (one tumor), but none stained for epithelial membrane antigen. Immunostaining results for the BN and GCT-NOS areas were concordant in eight (73%) of the 11 tumors in which both areas could be independently assessed. The remaining three tumors (27%) showed discordant results for only one of the eight markers used. In five patients, trisomy 12 was detected by fluorescence in situ hybridization in areas of BN but not in areas of GCT-NOS present in the same tumor. Trisomy 12 was also present in another BN tumor in which the foci of GCT-NOS were too small to be evaluated. We conclude that within GCT-BN, areas with BN are immunohistochemically similar to areas of GCT-NOS present in the same tumor. The finding of trisomy 12 in areas with BN but not GCT-NOS in the same tumor, however, suggests that cells with BN represent a genetically distinct clone of tumor cells arising within GCT-NOS.
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PMID:Ovarian granulosa cell tumors with bizarre nuclei: an immunohistochemical analysis with fluorescence in situ hybridization documenting trisomy 12 in the bizarre component [corrected]. 868 33

Nitric oxide (NO) is a short-lived pleiotropic mediator with a multitude of biologic functions. The inducible form of NO synthase (iNOS) is responsible for the discontinuous production of high amounts of NO and is important for the cytotoxic capacity of macrophages in rodents, whereas NO production by human macrophages or monocytes (MO) is under debate. Here we report that high amounts of NO are synthesized in cocultures of human MO with the human carcinoma cell line RT4 without further stimulation. Both cell types have to be viable and metabolically active for NO production. However, in contrast to reports by others, we could demonstrate that tumor cells and not MO are the producers of NO by the following findings: 1) NO release was induced in RT4 cells, but not in MO, by diluted supernatants (SN) of RT4/MO cocultures; 2) SN of MO stimulated with tumor cell membrane preparations were sufficient to induce NO release by tumor cells; and 3) NOS mRNA expression could be detected only in tumor cells, not in MO. Separating both cells by a cell-impermeable membrane resulted in NO amounts comparable to those in cocultures with direct cell contact, indicating one or more soluble NO-inducing factors. Considerable amounts of IL-1 beta and TNF-alpha were present in cocultures. IL-1 beta and TNF-alpha, mediators produced by activated MO, in combination induce NO release in RT4 cells. Blocking of TNF-alpha or IL-1 in SN inhibited NO release in RT4 cells. This indicates that IL-1 beta and TNF-alpha play prominent roles in iNOS induction by MO in RT4 tumor cells.
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PMID:Human monocytes induce a carcinoma cell line to secrete high amounts of nitric oxide. 875 34

The present studies examined the temporal sequence of inducible nitric oxide synthase (iNOS) gene expression and the cellular sources of iNOS protein and of 3-nitrotyrosine, as a marker of production of nitric oxide-derived reactive nitrogen intermediates during murine multi-stage carcinogenesis. Levels of iNOS mRNA in dorsal skin isolated from acetone-treated female Sencar mice were 2.5-fold higher than iNOS gene expression detected in cutaneous tissue isolated from Sencar mice at 1, 3, 6, 10, 16 and 22 weeks after exposure to a single topical application of 25 nmol 7,12-dimethylbenz[a]anthracene (DMBA) followed by repetitive applications of 2 microgram 17-O-tetradecanoylphorbol-13-acetate (TPA). Papillomas isolated at 16 and 22 weeks of a tumor promotion protocol also had low levels of iNOS mRNA. The diminished levels of iNOS mRNA inversely correlated with the extent of TPA-induced epidermal hyperplasia. In acetone-treated mouse skin, iNOS immunospecific antibody binding was localized to the stratum corneum and suprabasal keratinocytes. In contrast, iNOS protein was present in lower amounts and was localized to the upper-most suprabasal keratinocytes in cutaneous tissue isolated at 22 weeks following a single exposure to either 25 nmol DMBA or acetone and repetitive applications of 2 microgram TPA. At all time points examined over the 22 week time period of papilloma growth, infiltrating neutrophils within the dermis bound significant levels of anti-iNOS antibodies. The production of iNOS by neutrophils within the dermis correlated with the formation of protein nitrotyrosination within the dermal tissue, as detected by 3-nitrotyrosine-specific antibodies. The present studies indicate that NOS and reactive nitrogen intermediates, including peroxynitrite, are produced specifically by dermal neutrophils during the tumor promotion process at time points that correspond to simultaneous production of reactive oxygen intermediates. Conversely, iNOS is simultaneously down-regulated in hyperplastic epidermis and in papillomas.
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PMID:Gene expression and cellular sources of inducible nitric oxide synthase during tumor promotion. 882 34

The Ca(2+)-binding S-100 proteins are involved in the regulation of a number of cellular processes and an altered expression has been reported in several neoplastic tissues. Tissue specimens of normal salivary glands (n = 23), pleomorphic adenomas (n = 60), basal cell adenomas (n = 6), canalicular ademomas (n = 2), myoepitheliomas (n = 2), adenoid cystic carcinomas (n = 26) and adenocarcinomas NOS (n = 11) were evaluated for the expression of S-100A1, S-100A2, A-100A4, S-100A6 and S-100B by using highly specific polyclonal and monoclonal antibodies generated against the recombinant human protein. In normal salivary glands, the ductal cells showed mild to intense immunoreactivity for S-100A1, S-100A2, S-100A4 and S-100A6, while S-100B was observed in nerve fibers in the connective tissue. The normal myoepithelial cells were unreactive. In pleomorphic adenoma, the luminal tumor cells of the duct-like structures showed moderate to intense immunoreactivity for S-100A2, while reactivity for S-100A1, S-100A4 and S-100A6 was relatively weak. The non-luminal cells, also termed neoplastic myoepithelial cells, showed immunoreactivity for S-100B, while tumor cells in the solid, myxoid and chondroid areas were immunoreactive for S-100A1, S-100A4, S-100A6 and S-100B. The non-luminally located tumor cells in basal cell adenomas and canalicular adenomas, and numerous tumor cells in clusters in myoepitheliomas were intensely reactive for S-100A2. In adenoid cystic carcinomas and in adenocarcinomas not otherwise specified, the luminal cells forming the tubular or cribriform structures were markedly positive for S-100A2 and/or S-100A6. Squamous metaplastic cells in salivary tumors showed intense immunoreactivity for S-100A2. The results of the present study suggest that the majority of the tumor cells in salivary neoplasms, despite the most heterogeneous tumor cell differentiation, express S-100 proteins more heterogeneously than the normal glandular ducts. The salivary ducts in normal glands, the luminal tumor cells and squamous metaplastic cells in the neoplastic lesions were intensely immunoreactive for S-100A2 as compared to S-100A1, S-100A4 or S-100A6. In contrast, the non-luminal tumor cells showed a rather heterogeneous expression of the S-100 proteins.
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PMID:Immunohistochemical evaluation of the Ca(2+)-binding S-100 proteins S-100A1, S-100A2, S-100A4, S-100A6 and S-100B in salivary gland tumors. 898 67

MIB-1 Ki-67 and PCNA scores in infiltrating ductal NOS breast carcinomas were compared. The correlation between MIB-1, Ki-67 and PCNA indices and several clinicopathological factors that have prognostic significance in breast cancer was also assessed. The mean Ki-67, MIB-1 and PCNA indices were 13.4%, 19.4%, 27.6%, respectively. Significant positive linear correlation was found only between Ki-67 and MIB-1 indices. PCNA score did not correlate with Ki-67 and MIB-1 indices. The significant correlation between Ki-67 and MIB-1 scores and histological grade was found. There was no correlation between Ki-67 and MIB-1 indices and axillary lymph node status or tumor diameter. The results suggest that MIB-1 antibody is an excellent tool for assessment of proliferative rate of breast cancer cells in paraffin sections.
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PMID:Immunohistochemical assessment of proliferation rate of breast carcinoma cells using Ki-67, MIB-1 and anti-PCNA monoclonal antibodies. 909 11

Breast cancer is the most frequent malignant tumor in women, whereas it is rare in men. In our own case series the ratio is 175:1. The present paper deals with an evaluation of clinical and morphological findings from a series of 54 de novo male breast cancers observed in our institution from 1978 to 1996 and a comparative discussion of 528 female breast cancers from the same geographic area. We should like to focus on the following observations: At the time of histopathological diagnosis, male patients with breast cancer were on average 67 (34-87) years old and thus 5 years older than women. Below the age of 40, breast cancer is very rare in men. The lag time between first symptoms and surgery was on average 42 weeks, i.e. twice as long as in women. In the vast majority of cases palpation of a retromamillary nodule was the leading diagnostic symptom. Mamillary secretion appeared to be an early symptom with favorable relation to prognosis by tumor size whereas diffuse breast swelling was an unfavorable late symptom. Bilateral carcinoma and double cancer (breast and prostatic cancer) was observed in one case each. Three patients (3/51 = 6%) had a positive family history (breast cancer in 1st and 2nd degree relatives). The average invasive tumor size was nearly identical with 23 mm (s11.02) in men and 25 mm (s13.48) in women. Men presented more frequently with regional lymph node metastases (53% versus 45%), which tended to develop earlier. pT4 cancers were twice as frequent in men compared to women. In situ cancers were found in 2% (1/54) in men and 4% in women. Similar to females, male breast cancers are predominantly of ductal histological type (NOS-cancers), classical lobular carcinoma with LCIS-components were not observed; special forms (tubular, papillary, mucinous) are slightly more common in men. When reviewing our series, need for revision of the origin of tumor was not found in any of the cases. Metastases of prostatic cancer were never misinterpreted as primary breast cancer. In case of isolated NSE-reaction, cancers with carinoid differentiation pattern are to be found in nearly every second tumor. However, when multiple markers were used (chromogranin A or synaptophysin) only 10% displayed such pattern, which corresponded to a positive hormone receptor status in each case. Quantitative (enzyme immunoassay) and semiquantitative (immunohistochemistry) analysis of steroid hormone receptor status was positive in 86% of 35 cases in men and in 75% in women. In contrast to female breast cancer, hormone status proved to be independent of age in males. The average levels of estrogen and progesterone were higher in men. Overlapping results were found only when cases were compared with postmenopausal women. The Nottingham prognostic index, a product of primary tumor size, axillary lymph node status and grading allows an approximative estimate of the course of the disease; its predictive value is higher than that of isolated tumor markers.
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PMID:[Breast carcinoma in the man. Current results from the viewpoint of clinic and pathology]. 915 4

We have investigated the effect of N-(3-(aminomethyl)benzyl)acetamidine (1400W), a novel and highly selective inhibitor for inducible NOS (iNOS), on in vivo growth of solid tumors expressing iNOS. For the EMT6 murine mammary adenocarcinoma, in which iNOS is expressed in the tumor cells, continuous infusion of 1400W for 6 days at 10 or 12 mg/kg(-1)/h(-1) resulted in significant reduction in tumor weight (357 +/- 46 and 466 +/- 70 mg, respectively) compared with that of controls [726 +/- 65 (P < 0.001) and 796 +/- 88 mg (P < 0.02), respectively]. Reduced growth was also observed for a human tumor xenograft (colon adenocarcinoma DLD-1) genetically engineered to express iNOS constitutively and treated for 13 days with 6 mg/kg(-1)/h(-1) 1400W compared with controls (tumor weights 340 +/- 50 and 580 +/- 90 mg, respectively; P < 0.03). Growth of the parental DLD-1 clone was not altered with this treatment compared with that of controls (tumor weights 170 +/- 10 and 240 +/- 50 mg, respectively). Inhibition of iNOS in vivo was confirmed by decreases in plasma nitrite + nitrate concentrations in treated animals compared with that of controls (63-83% decreases for all experiments) and was supported by plasma and tumor concentrations of 1400W that were equivalent and 2.6-4.9 times higher than the EC50 previously reported for iNOS in a tissue assay. For the murine colon adenocarcinoma Colon 38, in which intratumoral macrophages are the predominant source of iNOS and which had high intratumoral arginine concentrations, 1400W treatment had no effect on growth or plasma nitrate + nitrate. Future studies with more potent selective iNOS inhibitors and a wider range of tumors may determine whether iNOS inhibitors could represent a novel approach to the treatment of cancer. These studies confirm that nitric oxide production in tumors plays a role in promoting their growth, rather than a role as a host defense mechanism in inhibiting growth.
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PMID:Selective inhibition of inducible nitric oxide synthase inhibits tumor growth in vivo: studies with 1400W, a novel inhibitor. 924 64

It is now just 10 years since it was first appreciated that NO is endogenously synthesized in mammals. In this period, two constitutive and one inducible isoform of NOS have been isolated, sequenced, and characterized with respect to their protein chemistry and catalytic mechanism. A wide variety of NOS inhibitors, most targeted to the arginine binding site in the oxygenase domain, have been synthesized and used to elucidate the physiological and pathophysiological roles of NO. It is now clear that NO is involved in signal transduction (e.g., in neurotransmission and blood pressure homeostasis), and that these roles are mediated by low concentrations of NO synthesized by nNOS or eNOS. The NO receptor is the heme cofactor of soluble isoform of guanylyl cyclase. Higher amounts of NO, typically but not always synthesized by iNOS, are often cytotoxic. At a minimum, high concentrations of NO derange the signal transduction pathways normally served by nNOS or eNOS. In addition, NO or its nitrosative products (RSNO, N2O3, or ONOO-) inhibit or damage cellular constituents, interfering with DNA synthesis, energy metabolism, and the structural integrity of the cell. Such cytotoxicity can be beneficial to the host if pathogens or tumor cells are destroyed, but is detrimental to the host if it results in inappropriate inflammation, hypotension, or immunosuppression. Therapeutic utility of NOS inhibitors has been demonstrated in sepsis and cytokine-induced hypotension; additional applications are being identified in a treatment of inflammatory and autoimmune disorders.
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PMID:Design of nitric oxide synthase inhibitors and their use to reverse hypotension associated with cancer immunotherapy. 938 71

To evaluate four methods to study cellular proliferation (mitotic count, mitotic index, PCNA and MIB1) in a series of breast ductal invasive cancer NOS, and the possible correlations between these different methods and other pathological variables, we studied 110 ductal invasive carcinomas NOS specimens. Mitoses per 1000 tumor cells and per 10 HPF, and immunostaining for PCNA and MIB1 were evaluated. Other accepted prognostic factors such as tumor size, histologic grade, estrogen and progesterone receptors measured by immunostaining and axillary status were obtained. Correlation between the four methods to evaluate cellular proliferation and these other variables was performed. Mitotic count, mitotic index, PCNA and MIB1 showed a good rate of correlation (r = 0.71-0.53, p < 0.05), with the exception of MIB1-mitotic index which was weak (r = 0.38, p < 0.05). A strong association between cellular proliferation, with independence of the method applied, and histologic grade, ER and PR was obtained. No association was observed with tumor size and lymph node involvement. In conclusion, there was a strong correlation between the four methods to evaluate cellular proliferation. Mitotic count (per 10 HPF) and MIB1 show a better correlation with other morphological variables. None of the evaluated methods are associated with the tumor size and axillary status, suggesting that mitotic count is the most accurate method to analyse cellular proliferation in routine practice.
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PMID:Cellular proliferation in breast ductal infiltrating carcinoma. Correlation with clinical and histopathological variables. 950 60

During the past five years we observed many advances in the study of the polymer drug, "SMANCS". This first polymeric drug was approved by the Japanese Ministry of Health and Welfare in 1994 as a drug for primary liver cancer, in which the arterial injection of oily formulation in Lipiodol (a lipid contrast medium) is the standard procedure. The advantage of this tactic is the most extraordinary cancer targeting efficiency with the least systemic side effect and very prolonged slow release of SMANCS. The mechanism of tumor selective accumulation of SMANCS and polymeric drugs in general is discussed in view of the so called-EPR (enhanced permeability and retention) effect of solid tumor. The mode of action of SMANCS at the cellular level seems to accompany the generation of superoxide radical which damages DNA; strand break and modification of guaninine by 8-hydroxylguanine. Immunological potentiation involves either the cellular (M phi, T-cell, NK-cell) or molecular level (induction of cytokines, including interferon gamma). The in vivo effect of SMANCS is most pronounced in the tumor vessels where more concentrated SMANCS is accessible due to the EPR effect, and perhaps the generation of O2.-. Nitric oxide generated by both inducible form of NO synthase (iNOS) by the infiltrated macrophages and NOS of endothelial cells, and superoxide from SMANCS will readily react to form peroxynitrite (O2- + NO-->ONOO-), which is a very potent cytotoxic molecule and will damage (nitrate and oxidize) DNA and proteins. Thus, tissue damage and vascular injury or collapse will be the principle tumor toxic mechanism of SMANCS at tissue level. The dose of SMANCS (or grade I-IV tumor filling) and tumor regression parallel each other, and a profile of AFP-value and technical issues of SMANCS/Lipiodol administration intraarterially are also discussed.
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PMID:[Recent advances in research on SMANCS]. 951 80

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