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

The pattern of vascularization of papillary carcinoma was investigated in tumour sections from 31 cases and in primary cultures from 12 cases. Tumour sections were immunostained for von Willebrand Factor (vWF) to visualize blood vessels; for endothelial-specific nitric-oxide-synthase (EC-NOS), as a marker of endothelial cell activation; and for Ki-67 to evaluate endothelial cell proliferation. It was found that endothelial cells lining venous vessels located in peritumoural fibrous tissue were intensely EC-NOS-positive and occasionally Ki-67-positive. Capillary vessels of tumour papillae were not stained for Ki-67 and were weakly EC-NOS-positive. Primary cultures of papillary carcinoma cells were used as a potential source of factors active on endothelial cells. It was found that thyroid tumour cells contain RNAs for angiopoietin, vascular endothelial growth factor (VEGF), and VEGF-C; moreover, they release large amounts of VEGF into culture supernatants and exert chemotactic activity in vitro for the endothelial cell line SIEC. The ability of papillary carcinoma cells to release angiogenic factors could be stimulated in vitro. Hepatocyte growth factor (HGF; 25 ng/ml) induced a 1.2- to 5-fold increase in the amount of VEGF released by tumour cells and a 1.2- to 4.2-fold increase in the amount of chemotactic activity present in culture supernatants. Met protein, the high affinity HGF-receptor, is overexpressed in a large proportion of cases of papillary carcinoma. These findings are consistent with the possibility that HGF-Met protein interaction is one of the molecular mechanisms promoting the vascularization of papillary carcinoma of the thyroid.
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PMID:Papillary carcinoma of the thyroid: evidence for a role for hepatocyte growth factor (HGF) in promoting tumour angiogenesis. 1253 38

A correct histologic differential diagnosis between salivary acinic cell carcinoma (ACC) and adenocarcinoma not otherwise specified (AC-NOS) is highly relevant because of the strikingly different biologic behavior and related therapeutical strategies. The distinction between both tumor types can be difficult because of an enormous variation in histologic appearance, with either type showing partially overlapping morphologic features. Owing to a lack of approved markers, the expression of PAS-staining, alpha-Amylase, alpha-1 Anti-trypsin, cytokeratin (CK)-subtypes 7/18 and Ki-67 was evaluated in 16 cases of ACC and 16 cases of AC-NOS. CK 7 is identified as the most reliable marker with strong positivity in AC-NOS, and complete or preponderant negativity in ACC. The characteristic membranous staining pattern of CK 18 in ACC, in contrast to a diffuse cytoplasmic pattern in AC-NOS, proved to be an additional valuable criterion. PAS and alpha-Amylase are only of little value when ACC is diagnosed, as many cases are only faintly positive or completely negative. The proliferation index (Ki-67) proved to be significantly higher in AC-NOS; however, the diagnostic usefulness is limited by a relevant overlap. In conclusion, we recommend CK 7 and 18 as the most valuable markers in cases with difficult differential diagnosis between ACC and AC-NOS.
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PMID:Differential diagnosis of salivary acinic cell carcinoma and adenocarcinoma (NOS). A comparison of (immuno-)histochemical markers. 1260 54

Inducible cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS/NOS-2) play pivotal roles as mediators of inflammation involved in early steps of carcinogenesis in certain organs. Therefore, chemoprevention is theoretically possible through inhibition of COX-2 and/or iNOS. In the present study, we examined the chemopreventive effects of indole-3-carbinol (I3C), a constituent of cruciferous vegetables (the family of Cruciferae) such as cabbages, cauliflowers and broccoli on the multiple intestinal neoplasia (Min) genetic mouse model, and on mouse colon carcinogenesis induced by azoxymethane (AOM). The consumption of cruciferous vegetables such as cabbage, broccoli, and Brussels sprouts has been shown to have cancer chemopreventive effects in humans and experimental animals. I3C has been shown to exert a cancer chemopreventive influence in liver, colon, and mammary tissue when given before or concurrent with exposure to a carcinogen. Powdered AIN-76A diets (Harlan Teklad Research Diet, Madison, USA) containing 100 or 300 ppm I3C (group 1 or 2) or the same pellet diets without supplement (group 3) were fed to 6-week-old male C57BL/6J-Apc(Min)(/+) (Min/+) mice (The Jackson Laboratory, Bar Harbor, ME, USA) for 10 weeks. In addition the same diets were given to wild-type normal C57BL/6J-Apc(Min)(/+) littermates after AOM initiation (groups 4-7: 10 mice in each group) for 32 weeks from week 4. At 16 weeks of age, all Min/+ mice (groups 1-3) were sacrificed for assessment of intestinal polyp development. The incidences of the colonic adenomatous polyps in the groups 1-3 were 60% (12/20), 60% (15/25) and 84% (21/25), respectively. A decreasing tendency in multiplicities of the colonic adenomatous polyps in group 1 (I3C 100 ppm; 0.85 +/- 0.22; 61%) and group 2 (I3C 300 ppm; 1.32 +/- 0.28; 94%) was observed when compared with group 3 (control; 1.40 +/- 0.21; 100%). Total number of aberrant crypt foci (ACF)/colon or aberrant crypts (AC)/colon in wild-type mice of group 4 or 5 were decreased significantly compared with those of the AOM alone group (group 6) (P < 0.01). These results suggest that I3C may be a potential chemopreventive agent for colon cancer.
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PMID:Chemoprevention of colon cancer by Korean food plant components. 1262 7

Ovarian steroid cell tumors, not otherwise specified (SCTs, NOS) are uncommon sex cord-stromal tumors that may be difficult to distinguish from other oxyphilic or clear-cell neoplasms. Immunohistochemical staining for inhibin, although generally useful in the diagnosis of SCTs, NOS, is not positive in every case and not all laboratories have this marker available. Recently, it has been reported that calretinin is expressed by sex cord-stromal tumors. We studied six SCTs, NOS for both calretinin and inhibin expression to evaluate the sensitivity of calretinin in comparison to inhibin. We also tested for CD99, Melan-A (A103), and S-100, other markers reported to be positive in these tumors. HMB-45 and MART-1 (Ab3) completed our panel of markers. All six tumors were positive for both calretinin and inhibin. Calretinin positivity was present in 60% to >90% of tumor cells, whereas inhibin reactivity ranged from <5% to >90% of tumor cells. Membranous staining for CD99 was present in one tumor. S-100-positive cells were seen in two tumors, whereas four tumors were immunoreactive for HMB-45. All six tumors were positive for Melan-A (A103), but in general the staining was less diffuse than with calretinin. All of the tumors were essentially negative for MART-1 (Ab3). The consistent diffuse staining of the tumors in this study for calretinin, in comparison to inhibin and Melan-A (A103), suggests that it is a sensitive marker for SCTs, NOS. MART-1 (Ab3) immunostaining may be useful for cases in which melanoma is considered in the differential diagnosis.
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PMID:Ovarian steroid cell tumors: an immunohistochemical study including a comparison of calretinin with inhibin. 1264 71

In the present study, a model system for studying the role of nitric oxide (NO) in tumor growth and metastasis was reported. Incubation of Panc02 murine pancreatic adenocarcinoma cells in vitro with cytokines and interferon led to heterogeneous expression of NO synthase II (NOS II) protein. Clonal sublines expressing different levels of NOS II were then established using a limited dilution technique. After orthotopical implantation into the pancreas of syngeneic C57BL/6 mice, clones with a low level of NOS II expression produced tumors in pancreas, metastasized to the liver, and formed ascites, whereas those having a high level of NOS II expression did not. Liver-metastasis variants having low to high metastatic ability were also established using in vivo/in vitro passage. Compared with parental Panc02 cells exhibiting a high level of NOS II expression, these variants had a decreased level of NOS II expression. Furthermore, the heterogeneous Panc02 cells were injected intravenously into a large number of syngeneic mice. Variants that metastasized to the liver, lung, skin, peritoneum, ovary, and lymph nodes were established. All of the metastatic variants exhibited a lower level of NOS II expression than the parental Panc02 cell line did. However, the phenotypes of NOS II induction and metastatic ability were unstable. Multiple in vitro/in vivo selection led to stable low NOS II expression and high metastatic potential. Finally, to further confirm the role of NOS II expression derived from tumor cells in metastasis, poorly metastatic Panc02-H0 and highly metastatic Panc02-H7 cells were injected into the pancreas of syngeneic NOS II(-/-) mice, and groups of mice received i.p. injections of either phosphate-buffered saline or L-N(6)-(1-iminoethyl) lysine. Inhibition of NOS II activity in vivo significantly promoted distant liver metastasis. Collectively, these data show that NOS II expression is highly heterogeneous and dynamically regulated, which can directly influence tumor growth and metastasis.
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PMID:A novel model system for studying the double-edged roles of nitric oxide production in pancreatic cancer growth and metastasis. 1266 Aug 13

Both enhanced vascular permeability and angiogenesis of tumor sustain rapid growth of tumor involving many vascular mediators and high vascular density. On the contrary, however, they can be utilized for macromolecular drug delivery to tumor. Impaired reticuloendothelial/lymphatic clearance of macromolecules from the tumor, or lack of such clearance, is another unique characteristic of tumor tissue, which results intratumor retention of macromolecular drugs thus delivered (Figure 1). Consequently, enhanced permeability and retention (EPR) effect is the basis for the selective targeting of macromolecular drugs to tumor, and the EPR concept is now utilized for selective delivery of many macromolecular anticancer agents in aqueous formation for i.v. or i.a. as well as oily formation for i.a. dosing, which is not possible for low-molecular-weight drugs because of rapid washout by capillary vascular blood flow. This EPR concept has been validated in clinical settings with hepatoma and other solid tumors. In our laboratories, several promising macromolecular anticancer drugs after SMANCS, such as PEG-XO, PEG-DAO, PEG-ZnPP, were developed, warranting further investigation for clinical application. More efficient drug delivery to tumor, especially of macromolecular drugs, may be possible by enhancing the EPR effect with the use of various vascular permeability mediators or potentiators. Suppression of the EPR effect by the use of appropriate inhibitors or antidotes, such as the bradykinin antagonist HOE 140 and protease inhibitors or NOS inhibitors, may also be possible. Thus, one may be able to suppress or retard tumor growth and tumor metastasis. Also, by suppressing vascular permeability with antidotes such as the bradykinin antagonist HOE 140, pleural fluid in lung cancer and ascitic fluid in abdominal carcinomatosis may be controlled and the clinical course of cancer patients may be improved. In summary, tumor vasculature can be an excellent target for delivery of macromolecular anticancer drugs; the most beneficial class of drugs in view of tumor-selective targeting based on the EPR effect in solid tumor as well as compliance of patients and ultimate therapeutic efficacy.
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PMID:Factors and mechanism of "EPR" effect and the enhanced antitumor effects of macromolecular drugs including SMANCS. 1267 6

Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has indicated this polyphenol can both prevent and treat cancer. The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells, down-regulate transcription factors NF-kappa B, AP-1 and Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinases and protein serine/threonine kinases. In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. All of these studies suggest that curcumin has enormous potential in the prevention and therapy of cancer. The current review describes in detail the data supporting these studies.
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PMID:Anticancer potential of curcumin: preclinical and clinical studies. 1268 Feb 38

Arsenic (As) is widely distributed in nature, and its contamination in drinking water remains a major public health problem. Exposure to As may lead to degenerative peripheral vascular diseases. The purpose of this study is to clarify the role of As in modulating cell proliferation and in vitro angiogenesis in human umbilical vein endothelial cells (HUVECs) and to scrutinize the contributing factors of these events. The results revealed that lower concentrations (up to 1 microM) of sodium arsenite stimulated HUVEC cell growth. An in vitro angiogenesis assay indicated that low concentrations of As increased vascular tubular formation, which was abrogated by hemoglobin, a potent nitric oxide scavenger. In contrast, higher concentrations of As (>5 micro M) revealed cytotoxicity and inhibition to angiogenesis. We also demonstrated that lower concentrations of As upregulated the expression of constitutive nitric oxide synthase (NOS3) at both transcriptional and translational levels and that lower concentrations of As implicated a modulatory role in vascular endothelial growth factor (VEGF) expression. In addition, low concentrations of As (<1 micro M) increased von Willebrand Factor (vWF) antigen expression, whose elevation paralleled the onset of angiogenesis and was considered an early indicator of endothelial activation in tumor metastasis. VEGF and basic fibroblast growth factor can synergistically upregulate the vWF gene expression. Therefore, we conclude that the treatment of HUVECs with As leads to cell proliferation and activation, which preferentially enhances angiogenesis in vitro, possibly via the VEGF-NOS signaling pathway. The molecular mechanism(s) by which As facilitates angiogenesis remains to be elucidated.
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PMID:Low concentrations of arsenic induce vascular endothelial growth factor and nitric oxide release and stimulate angiogenesis in vitro. 1270 62

A bioassay for possible carcinogenicity of p-anisidine hydrochloride was conducted using Fischer 344 rats and B6C3F1 mice. p-Anisidine hydrochloride was administered in the feed, at either of two concentrations, to groups of 55 male and 55 female animals of each species. Fifty-five animals of each sex and species were placed on test as controls. The high and low dietary concentrations of p-anisidine hydrochloride were, respectively, 0.6 and 0.3 percent for rats and 1.0 and 0.5 percent for mice. The compound was administered in the diet for 103 weeks, followed by an observation period of 2 to 3 weeks for rats and 2 weeks for mice. There were no significant positive associations for either species between the concentration of p-anisidine hydrochloride administered and mortality. In addition, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. In male rats there were significant associations between compound administration and the incidences of both squamous-cell carcinomas of the skin and alveolar/bronchiolar adenomas. None of the Fischer exact comparisons, however, supported these findings. When those males having adenomas NOS or carcinomas NOS of the preputial gland were combined and the resulting incidences statistically analyzed, the only test providing a significant result was the Fisher exact comparison of the low dose to the control. There were no significant positive associations between the administration of p-anisidine hydrochloride and the incidence of any tumor in mice of either sex. Although, under the conditions of this bioassay, there appeared to be an association between chemical administration and the increased incidence of preputial gland tumors in low dose male rats, the evidence was insufficient to establish the carcinogenicity of p-anisidine hydrochloride in Fischer 344 rats. The compound was not carcinogenic in B6C3F1 mice.
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PMID:Bioassay of p-Anisidine Hydrochloride for Possible Carcinogenicity (CAS No. 20265-97-8). 1279 75

Fine-needle aspiration cytology (FNAC) is a widely practiced technique in the diagnosis of breast carcinoma, and it is the only diagnostic procedure performed before definitive treatment, at most institutions. While the histological grading of breast carcinoma has become routine in many centers worldwide, the cytopathological grading of breast carcinoma is not commonly used. Grading of breast carcinoma, while the tumor is still in vivo, would be the most ideal and desirable situation, as it would be helpful in the selection of patients for appropriate therapy. The objective of this study, therefore, was to devise a simple system for grading breast carcinoma, based on the cytological features alone. We reviewed 125 cases of breast carcinoma retrospectively, which were initially diagnosed by FNAC, with subsequent histopathological confirmation. These included 105 ductal, 6 lobular, 2 tubular, 1 papillary, and 1 medullary carcinoma. There was 1 ductal carcinoma in situ. Nine cases were rendered insufficient for grading. Thus 105 cases of ductal carcinoma (NOS) were evaluated for final cytological grading. Air-dried Diff-Quik-stained smears were reviewed at least twice independently by four histopathologists and were then compared with the original histological grades. Six cytological features used for grading were found to be statistically significant: cellular pleomorphism, nuclear size, nuclear margin, nucleoli, naked tumor nuclei, and mitoses. A scoring system based on these six essential parameters was used, to classify ductal carcinoma into three cytological grades, which showed close correlation with the established histological grades. In addition, two less consistent, but still important, features were the presence or absence of necrosis and stromal invasion. Another six parameters, including smear cellularity, degree of cell dispersion or clustering, lymphoplasmacytic infiltrate, presence of tubular structures, cytoplasmic appearance of the tumor cells, and smear background, were not statistically significant. However, these additional parameters were found helpful in assigning the correct grade, in cases with borderline scores. The concordance rate with histology was 100% for grade 1, 98% for grade 2, and 93% for grade 3.
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PMID:Cytopathological grading, as a predictor of histopathological grade, in ductal carcinoma (NOS) of breast, on air-dried Diff-Quik smears. 1450 69


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