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

Although histologically benign, one-third of all pituitary tumors will be invasive of surrounding structures. In this study, the relationship between the proliferative activity in pituitary adenomas and their invasiveness was investigated. Invasion was defined as gross, operatively or radiologically apparent infiltration of dura or bone. Using the recently developed MIB-1 monoclonal antibody, which recognizes the Ki-67 cell cycle-specific nuclear antigen, the growth fractions of 37 noninvasive adenomas, 33 invasive adenomas, and 7 primary pituitary carcinomas were determined. All tumors were fully classified by histology, immunohistochemistry, and electron microscopy. The mean Ki-67 -derived growth fractions for noninvasive adenomas, invasive adenomas, and pituitary carcinomas were 1.37 +/- 0.15%, 4.66 +/- 0.57%, and 11.91 +/- 3.41%, respectively (mean +/- standard error of the mean). An analysis of variance and then individual pairwise comparisons confirmed significant differences in the mean Ki-67 labeling index between each of the three tumor groups (P < 0.01). The mean growth fraction of hormonally active pituitary adenomas (3.25 +/- 0.26%) was significantly higher than that for nonfunctioning adenomas (2.06 +/- 0.23%) (P = 0.03). Establishing a threshold labeling index of 3% served to distinguish invasive from noninvasive adenomas with 97% specificity and 73% sensitivity and was associated with positive and negative predictive values of 96 and 80%, respectively. Although invasive pituitary tumors exhibited significantly higher growth fractions than did noninvasive tumors, there were individual exceptions, indicating that in a subpopulation of invasive pituitary tumors, factors other than proliferative activity determine invasive potential.
 ...
PMID:Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. 874 57

In a series of 205 node-negative breast cancers (NNBC), we determined staining by the novel antibody Ki-S1, a marker of tumor cell proliferation, in order to test its association with other prognostic variables and its prognostic significance. Ki-S1 was determined in routinely formalin-fixed paraffin-embedded tumor samples. Ki-S1 gave a nuclear staining in the majority of the carcinomas (188 of 205), with percentages of reacting nuclei ranging from 2% to 90% (median value of 7%). In 107 tumors frozen sections were available to also assess the Ki-67 antibody. Among these, 94 had a nuclear staining of cancer cells ranging from 5% to 80% (median value of 7%). In 46 tumors we also determined the MIB-1 antibody. The percentage of MIB-1 nuclear staining ranged from 1% to 50% (median value of 20%). There was no significant relationship between Ki-S1 and the other two cell kinetic markers. Ki-S1 labeling was significantly associated only with tumor size (p = 0.03). With a median follow-up of 6 years, Ki-S1 had no significant prognostic value for either relapse-free survival (RFS) or overall survival (OS) (Ki-S1 as continuous logarithmic variable; p = 0.86 and p = 0.23, respectively). For RFS the following variables had a significant prognostic value: Ki-67 (< or = 10% vs > 10%; p = 0.037); progesterone receptor (PgR) expression (- vs+/++; p = 0.041); tumor size (pT1 vs pT2-3; p = 0.042) and grading (GI vs GII-III; p = 0.047). For OS, tumor size (p = 0.0044), age (continuous variable; p = 0.0060), and Ki-67 (p = 0.043) were significantly prognostic. In multivariate analysis (final model), only tumor size retained a significant and independent prognostic value for RFS (p = 0.0042). For OS, both tumor size (p = 0.0029) and age (< or = 55 years vs > 55 years; p = 0.041) retained significance in the multivariate model. In conclusion, Ki-S1 does not seem to have prognostic relevance in this series of NNBC. Possible hypotheses to explain this observation are discussed.
 ...
PMID:Lack of prognostic significance of the monoclonal antibody Ki-S1, a novel marker of proliferative activity, in node-negative breast carcinoma. 875 May 80

A key prognostic parameter for vulvar carcinoma is the presence of lymph node metastases. Determination of proliferation markers has been suggested as a method to predict lymph node metastases in several tumor types. If this were true in vulvar carcinomas, reduced surgical therapy for patients with low-risk vulvar carcinoma could be considered. The authors analyzed whether the proliferation-associated markers silver nucleolar organizer region (Ag-NOR) and Ki-67 are predictors for inguinofemoral lymph node metastases in women with vulvar carcinoma. The authors also analyzed whether these proliferation markers are interrelated. Data were obtained from samples of 145 patients with T1/T2 squamous cell carcinoma of the vulva who were treated with vulvectomy and bilateral lymphadenectomy. None of these patients received preoperative therapy, and the invasion depth of the tumors was more than 1 mm. The median age was 71 years. The group consisted of 67 patients with differentiation grade 1, 64 with grade 2, and 18 with grade 3; 22% (15 of 67) of the patients with grade 1, 45% (29 of 64) with grade 2, and 43% (six of 14) with grade 3 had lymph node metastases. Formalin-fixed, paraffin-embedded sections were stained for proliferation markers Ag-NOR and MIB-1 (an equivalent of Ki-67 for fixed material). Both parameters were scored at the tumor stroma interface. Ag-NOR number and areas were quantified by interactive image analysis and Ki-67 index was scored microscopically with a grid. No relation was found between Ki-67 or Ag-NOR and lymph node metastases. A relation was found between Ki-67 and mitotic index (MI), but not between Ag-NOR and MI or Ki-67 index. Therefore, it is questionable whether Ag-NOR is, indeed, a marker for proliferation. The authors conclude that quantitation of Ki-67 and Ag-NOR does not contribute to the prediction of inguinofemoral lymph node metastases in squamous cell carcinoma of the vulva.
 ...
PMID:Quantitation of proliferation-associated markers Ag-NOR and Ki-67 does not contribute to the prediction of lymph node metastases in squamous cell carcinoma of the vulva. 876 14

Astrocytomas often show high rates of local invasion that lead to local recurrence of the disease. Histologically, the most highly invasive astrocytoma cells are detected in isolation rather than as nests of tumor. Our study attempted to determine whether the migratory response to extracellular substrates influences the proliferative behavior of these highly invasive cells. The preferential and specific migratory response of human astrocytoma cells to extracellular matrix proteins was assessed by a microliter scale migration assay. Growth curve studies on protein ligands permissive (merosin) for cell migration indicated that the lag phase was protracted compared with cells seeded on non-permissive proteins (vitronectin). Once a certain cell density was reached, logarithmic proliferation was indistinguishable on the different proteins. The proliferation index of populations of cells migrating on merosin and vitronectin was measured by both BrdU incorporation and MIB-1 immunocytochemistry labeling. Cells seeded on vitronectin showed higher proliferation throughout the population than cells seeded on merosin. On merosin, the more migratory cells at the periphery were less proliferative than non-migratory cells in the central region of that population. The integrin-associated signal transduction protein, p125FAK, was heavily localized in the membrane of non-migrating cells and largely absent in migrating astrocytoma cells. We conclude that temporally, proliferation and migration are mutually exclusive behaviors. Cell density or non-permissive substrates that inhibit cell motility favor a more proliferative phenotype. Conversely, active migration suppresses cell proliferation.
 ...
PMID:Dichotomy of astrocytoma migration and proliferation. 876 May 99

The aim of this report was to investigate the expression of the p53 and mdm-2 oncoproteins in astrocytic gliomas and to assess their interrelation to proliferating activities. Using monoclonal antibodies directed against p53 and mdm-2, these proteins were stained immunohistochemically in 60 astrocytic brain tumors with different histologic grade. Positive p53 stained nuclei were detected in 25.4% of the tumor cases. Mdm-2 staining products were only localized in 10.5% of specimens. Significant correlations could be found between p53, MIB-1, PCNA and mitotic index on the one hand, and tumor grade on the other hand. There were no clear relations between mdm-2 expression and proliferation markers. The grade of ploidy has a lower priority for the proliferating activity. In most cases mdm-2 immunoreactivity was strongly associated with a low or negative p53 expression.
 ...
PMID:Immunohistochemically detectable p53 and mdm-2 oncoprotein expression in astrocytic gliomas and their correlation to cell proliferation. 878 Sep 33

We compared different means of assaying tumor proliferative activity by either flow cytometric or immunohistologic methods in formalin-fixed, paraffin-embedded blocks. A series of 84 Dukes' stage B colorectal carcinomas were examined to identify high-risk patients who may potentially benefit from adjuvant therapy. Flow cytometric analysis was performed by a modified Hedley method with a combined S+G2/M phase proliferative fraction calculated by means of a rectangular model after debris subtraction. Immunohistologic tumor proliferative activity was analyzed by means of serial step sections from the same blocks used for flow cytometric examination with antibodies to proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1). Mean with standard deviation and (range) tumor proliferative activity measurements were: flow cytometric analysis: proliferative fraction = 14.8% +/- 5.3 (5-27%), PCNA = 43.2% +/- 21.2 (4-90%), and MIB-1 = 16.2% +/- 10.8 (2-47%). No correlation was found between flow cytometric proliferative fraction and immunohistologic tumor proliferation measurement or between PCNA and MIB-1 staining indices. Lack of correlation between flow cytometric and immunohistologic findings may be related to the use of archival formalin-fixed paraffin-embedded tissue for flow cytometric evaluation, with resultant increased debris and decreased accuracy of cell cycle calculations. Discordance between PCNA and MIB-1 may reflect inherent problems with anti-PCNA antibody staining of formalin-fixed tissues whereby anti-PCNA clone PC-10 detects non-replicon associated PCNA in formalin-fixed tissues. Prospective studies using fresh tissue with two-color multiparameter flow cytometric analysis and histogram-dependent background fitting may help to clarify the relationship between findings of tumor proliferation as analyzed by flow cytometric and by immunohistologic techniques.
 ...
PMID:Lack of correlation between flow cytometric and immunohistologic proliferation measurements of tumors. 878 8

In vitro studies have suggested that vitamin A lowers invasive potential of squamous cell carcinoma. Epidemiological data have also indicated that high dose vitamin A may improve survival in patients with previously resected lung carcinoma. To our knowledge, no studies have attempted to test the in vivo effect of vitamin A on the morphology and growth rate of lung and head and neck cancer. Freshly resected tumor cell suspensions were obtained by ex vivo fine needle aspiration and injected subcutaneously in duplicate in athymic male nude mice. Two to six weeks post-engraftment tests and controls were separated for each xenograft. Mice with test xenografts were given water soluble vitamin A (Aquasol ATM, Astra pharmaceutical, Westborough, MA, U.S.A) at a dose of 10,000 U/Kg/day intraperitoneally for 6 to 10 weeks (median 8 weeks). One to two hours prior to sacrifice bromodexouridine (BrdU) was injected intraperitoneally to assess the S-phase fraction in both test and control xenografts. Blood vitamin A levels in test and control animals were measured after sacrifice using high performance liquid chromatography (HPLC). Sections of test and control xenografts were routinely stained to assess morphologic differentiation and mitotic counts. Unstained sections of xenografts were immunostained by the antibody to BrdU to test for BrdU labeling index (BLI) reflecting S-phase fraction (SPF) and also by the MIB-1 antibody to assess proliferative activity. Eighteen tumors were studied. These included 9 squamous cell carcinomas of the lung, 5 squamous cell carcinomas of the head and neck, and 4 adenocarcinomas of the lung. Blood levels of vitamin A in test animals were 7 to 23 times those of the control animals (median 13 times). Neovascularization of the xenografts was seen in all cases. The morphology and mitotic activity of the test and control xenografts showed no significant difference. SPF and proliferative activity measured by BrdU and MIB-1 immunolabelling respectively showed no significant difference between test and control xenografts. Our study suggests that there is no significant in vivo effect of high dose vitamin A on the morphology and growth rate of xenografted non small cell carcinoma of the lung or squamous cell carcinoma of the head and neck.
 ...
PMID:The effect of high dose vitamin A on the morphology and proliferative activity of xenograft lung and head and neck cancer. 879 35

Evaluation of the p53 gene protein expression and proliferative potential with MIB-1 monoclonal antibody (MBL Co.), a new marker of cellular proliferation that binds Ki67 in paraffin sections, by immunohistochemical studies were made in 10 cases of the non-recurrent meningiomas and the 8 cases (17 samples) of the recurrent meningiomas. Tissue samples were embedded in paraffin after fixation in 10% formalin, and 3-microns sections were activated by microwave heating before being immersed with p53 protein or MIB-1 monoclonal antibody. The positivity of immunostaining for p53 protein and MIB-1 was calculated as the % values of tumor cell nuclei stained to all tumor cell nuclei examined within several fields under a light microscope. The mean % value of the proliferating cell index (PCI) stained with MIB-1 monoclonal antibody was 2.1% in the non-recurrent meningiomas, and high values of 11.9% were obtained for the recurrent meningiomas. High values of PCI exceeding 3% were indicated in most of the cases of recurrent meningiomas. p53 protein was not found in the 10 cases of non-recurrent meningiomas. However, it was positive showing values of 0.5-8.5% (mean; 3.4%) in 5 of the 8 cases of recurrent meningiomas. 2 of 4 cases of recurrent meningiomas with a benign type of histology at both initial discovery and recurrence revealed p53 protein expression in the tumor tissues. 3 of 4 cases of recurrent meningiomas, which were of the benign type at the initial operation but transformed to the malignant (atypical) type on recurrence, demonstrated positive staining for p53 protein in the tumor tissues. Although positivity for p53 protein was observed in the recurrent meningiomas with high values of PCI with MIB-1, no significant correlation between the values of PCI with MIB-1 and those for the p53 protein expression was found. The p53 gene protein may be altered on tumor recurrence and/or malignant transformation in meningiomas. It is concluded that evaluations of the p53 protein expression and proliferative potential with MIB-1 are important as additional factors for the prediction of tumor recurrence in meningiomas.
 ...
PMID:[P53 protein expression and proliferative potential in non-recurrent and recurrent meningiomas]. 879 5

Ependymomas are rare central nervous system (CNS) neoplasms that occasionally disseminate along the neuraxis or to extraneural sites. Definitive criteria predictive of dissemination have yet to be determined. One hundred forty patients with CNS ependymoma (88 primary spinal and 52 primary intracranial tumors) were surgically treated by the senior author (F.J.E.) between 1986 and 1994. Sixteen patients (11.4%) demonstrated tumor dissemination. The disseminated group consisted of 11 (12.5%) of 88 primary spinal and five (9.6%) of 52 primary intracranial ependymomas. The authors retrospectively reviewed the patients with CNS ependymoma and have identified several characteristics associated with dissemination from the primary tumor site. The mean time from diagnosis to dissemination was 6.8 years. The patients with disseminated disease were younger (16.8 vs. 28.3 years old, p = 0.02), had fewer gross-total resections (29% vs. 68%, p = 0.015), and had tumors with higher proliferative indices (MIB-1 staining, 13.14% vs. 2.06%, p = 0.02). High-grade tumors had a mean proliferation index of 21%, versus 2.4% and 1.6% for myxopapillary and low-grade tumors, respectively (p = 0.0003). In contrast to previous studies, tumor histology was the most significant variable for time to dissemination as determined by multivariate analysis (p = 0.008). Myxopapillary and high-grade tumors were 3.6 and 5.6 times more likely to have a shorter time to dissemination than low-grade tumors. In addition, dissemination is associated with a worse prognosis. At follow-up review, 31% of patients with disseminated disease had died compared to 7% of patients without dissemination (p = 0.04). It is concluded that younger patients with subtotal resections, myxopapillary or high-grade histology, and tumors with high proliferative indices are at substantial risk for the development of disseminated disease during their clinical course.
 ...
PMID:Disseminated ependymomas of the central nervous system. 881 65

A retrospective immunohistochemical study of radiosurgically treated brain metastases was performed to determine whether residual tumor has reduced proliferative potential. The monoclonal antibodies MIB-10 and PC-10 were used as markers for proliferation. The experimental group consisted of pathological specimens obtained from five patients in whom brain metastasis previously had been treated with radiosurgery. Pathological specimens obtained from 10 patients with brain metastases, matched in histology to diseases in the experimental group but untreated by radiosurgery, served as controls. A significant decrease in proliferative indices was observed in metastatic brain cancers after radiosurgery (p < 0.001). These results indicate that the persistent tumor that is present at the site of a metastasis previously treated with radiosurgery is less viable and may not in itself be a significant finding.
 ...
PMID:Analysis of the proliferative potential of residual tumor after radiosurgery for intraparenchymal brain metastases. 881 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>