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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemical detection of cell cycle-related markers for estimation of tumor growth fractions using paraffin-embedded tissue sections would have applications in experimental and clinical pathology as an in situ histologic alternative to flow cytometry. The monoclonal antibodies 19A2 and PC10 detect the proliferating cell nuclear antigen (PCNA/Cyclin), an auxiliary protein to DNA polymerase-delta. In a prospective group of uniformly handled, formalin-fixed malignant lymphomas we previously demonstrated 19A2 to be a reliable marker of proliferative activity similar to Ki-67 in frozen tissue. The present study examines the applicability of this technique in archival formalin-fixed material. Studies on tonsilar tissue revealed that formalin fixation beyond 30 hours adversely affected reactivity of 19A2, possibly explaining the variable results in nonuniformly fixed archival material. We found that only 27 (56%) of 48 archival cases of infiltrating ductal carcinoma showed sufficient reactivity with 19A2 to permit reliable quantification of the tumor growth fraction. Acid pretreatment with 2N HCl had no apparent effect on 19A2 reactivity. Using both antibodies on a group of 32 archival lymphomas, carcinomas, and sarcomas, significantly more biopsies stained reliably for PC10 (84%) than for 19A2 (72%; P < 0.036). Further, none of the cases that did not react with PC10 reacted with 19A2. PC10 may recognize a different epitope of PCNA/Cyclin which may be more resistant to alterations by fixation. In the 23 cases that reliably stained for both markers, largely carcinomas, there was excellent correlation between estimated growth fractions (r = 0.96). Although immunostaining provides a useful way to estimate tumor growth fractions in paraffin-embedded tissues, modifications of technique and cautious interpretation of results are advisable when using archival material.
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PMID:Estimation of tumor growth fractions in archival formalin-fixed, paraffin-embedded tissues using two anti-PCNA/Cyclin monoclonal antibodies. Factors affecting reactivity. 128 22

BACKGROUND Understanding the tumor growth rate is very important when considering strategies for the treatment of an acoustic neuroma, although the natural course of acoustic neuromas has not been reviewed in detail. METHODS The clinicopathologic features and the postoperative growth of tumors were evaluated in 32 patients with acoustic neuromas. This study was undertaken to assess the variability of the growth potential of cells within an acoustic tumor and to determine the relationships between the growth rate and the clinicopathologic characteristics of the patients with acoustic neuromas, including age at surgery, gender, tumor location and preoperative size, the duration of the symptoms, the presence of cystic regions, the presence of Antoni type A and B cells, the tumor cell density, tumor vascularity, mitotic rate, the presence of hyaline degeneration and hemosiderin deposition, nucleolar organizer regions (NORs), and the level of proliferating cell nuclear antigen (PCNA). RESULTS The growth patterns of the tumors were divided into three groups according to their growth rate: a regression group, a "no-growth" group (growth rates from 0-0.11 cm/year) and a progression group (growth rates from 0.19-1.72 cm/year). An additional operation was required in all patients whose growth rate was more than 0.38 cm/year. A statistical study on the factors associated with an increased growth rate showed that the three histopathologic factors most significantly associated with a postoperative growth rate were hyaline degeneration (p < 0.05), cell density (p < 0.005), and PCNA labeling index (p < 0.005). CONCLUSIONS These results strongly suggest that acoustic tumors can be subdivided into several groups, based upon different biologic activities and tumor growth rates.
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PMID:Clinicopathologic growth factors of acoustic neuromas. 748 32

Immunohistochemical detection of proliferating cell nuclear antigen (PCNA), a cell cycle-related protein used to estimate tumor growth fraction, is variable in formalin-fixed compared with methanol-fixed tissue specimens. This is assumed to result from conformational changes in the antigenic epitope induced by formaldehyde; therefore, to be susceptible to retrieval in archival specimens. In this study, formalin fixation reduced the intensity of staining and the number of positive cells to approximately 25% of those in methanol-fixed material. The washing of tissue specimens prior to methacarn fixation also reduced PCNA staining. Loss of staining was not restored after use of a commercial retrieval kit recommended for PCNA immunohistochemistry. Immunoblotting of formalin fixatives and saline washings after removal of tissue specimens consistently demonstrated the presence of PCNA-like activity in solution. We conclude that the exceptional solubility of PCNA is responsible for reduced immunostaining in formalin-fixed material, that the loss is irreversible, and that methanol or methacarn is the fixative of choice for PCNA immunohistochemistry.
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PMID:Detection of proliferating cell nuclear antigen in paraffin-embedded specimens is dependent on preembedding tissue handling and fixation. 752 64

The tumors produced by transplantation into nude mice of human adenoid squamous carcinoma-forming cell line TYS, presumably derived from a minor salivary gland, were treated with a differentiation-inducing agent, vesnarinone, which was given per o.s. daily at a dose of 200 mg/kg for 35 days. They were then examined morphologically and immunohistochemically. The vesnarinone treatment resulted in a significant suppression of tumor growth. In addition, tumor nests indicating keratinocyte and acinar cell differentiation were often observed in the treated tumors, but not in untreated controls. Tissue sections from vesnarinone-treated and untreated TYS tumors were stained with monoclonal antibody (NAb) directed to carbohydrate antigen LeY or proliferating cell nuclear antigen (PCNA) and with rabbit polyclonal antibody to p53. Antibody staining patterns were compared with morphological characteristics of cells as revealed by hematoxylin and eosin staining, and DNA fragmentation patterns as revealed by 3'-OH nick-end labelling techniques. Tissue sections from vesnarinone-treated TYS tumors showed positive reaction with nick-end labelling and were extensively stained strongly by anti-LeY MAb, whereas the untreated tumors showed negative reaction with nick-end labelling and were infrequently stained by anti-LeY MAb. Within LeY-positive areas of tissue sections from the vesnarinone-treated tumors, keratinocyte and acinar cell differentiation as well as DNA fragmentation were frequently observed, although not all LeY-positive cells showed such signs of apoptosis. LeY-positive cells showed consistent negative staining by anti-PCNA MAb and anti-p53 rabbit serum. From these findings, it can be considered that vesnarinone has differentiation and apoptosis-inducing activity against TYS cells grown in athymic nude mouse.
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PMID:Characteristics of antitumor activity of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]- 2(1H)-quinolinone (vesnarinone) against a human adenoid squamous carcinoma-forming cell line grown in athymic nude mice. 775 82

Castration of rats transplanted with the androgen-sensitive Dunning R3327-PAP prostatic tumor results initially in a reduction of tumor growth, but after some time, some of the tumors start to grow again. The relapsed, androgen-insensitive PAP tumor shows a dedifferentiated morphology. In the present study, we examined whether this androgen-independent tumor regrowth was due to an increased cell proliferation rate or to a reduction of the number of tumor cells dying by apoptosis. Nine rats (with 18 tumors) were castrated and followed for 16 to 20 weeks. Six of the tumors increased their volume markedly (relapsed), while 12 remained relatively stable (nonrelapsed). The mitotic index and apoptotic index for epithelial cells were examined by light microscopy. Tumor growth rate correlated negatively both to the apoptotic index identified by morphological criteria (RS = -0.82; P < 0.0001) and to the apoptotic index identified by in situ end labeling (RS = -0.83; P < 0.0001). The tumor growth rate percentage did not correlate to the mitotic index, and it was negatively correlated (RS = -0.62; P < 0.01) to the number of cells immunostained for proliferating cell nuclear antigen. It is suggested that one initial event during the androgen-independent prostatic tumor regrowth in the PAP relapse model might be a reduction of the number of tumor cells being depleted by apoptosis, rather than an increase of cell proliferation rate.
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PMID:Prostatic tumor regrowth after initially successful castration therapy may be related to a decreased apoptotic cell death rate. 791 74

Immunohistochemical detection of the proliferating cell nuclear antigen (PCNA) represents a potentially useful tool for the study of tumor proliferative activity. To study the intratumor heterogeneity of tumor growth, 88 breast carcinomas were immunostained with the anti-PCNA antibody 19F4 and analyzed with the CAS 200 image analysis system (Cell Analysis System, Inc., Lombard, IL). For each sample, 12 fields from both the central and the peripheral areas of the tumor were measured. The proportion of PCNA-positive nuclear area in the whole tumor (PCNAt score) varied from 0.7% to 45.2% (median, 14.4%). There was considerable intratumor heterogeneity in the staining for PCNA. In 79% of the specimens, the PCNA score was higher in peripheral areas than in the center of the tumor, the average difference being +3.4% (range, -9.2- +15.1%; P < 0.0001, Student's t-test). The S-phase fraction, determined by DNA flow cytometry of the same tumors, varied from 2.0% to 32.6% (median, 10.0%). The PCNA score showed a significant correlation with the S-phase fraction (r = 0.469, P < 0.001). Most divergent results were those with high PCNA scores and low S-phase fraction; possible explanations for this are discussed. The PCNA score also was related to the histologic grade of the tumors (P = 0.03, analysis of variance). In conclusion, proliferation indices obtained from different areas of a tumor can differ significantly because of intratumor heterogeneity in growth fractions. The PCNA immunostaining correlates with well-known prognostic factors (S-phase fraction and histologic tumor grade) in breast carcinoma.
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PMID:Intratumor variation in cell proliferation in breast carcinoma as determined by antiproliferating cell nuclear antigen monoclonal antibody and automated image analysis. 844 82

We performed an immunohistochemical cell kinetic study with monoclonal antibodies to proliferating cell nuclear antigen (PCNA)-PC10-and Ki-67-MIB-1-on 62 thymic epithelial tumors, to evaluate whether there is correlation between the proliferation indices of the neoplastic epithelial cells and histological subtype, stage, and risk of relapse. The 62 cases of thymic epithelial tumors were classified as medullary thymoma (4 cases), composite (mixed) thymoma (17 cases), organoid thymoma (predominantly cortical) (11 cases), cortical thymoma (10 cases), well-differentiated thymic carcinoma (18 cases), and poorly differentiated thymic carcinoma (2 cases). Labeling indices were expressed as percentage of epithelial cells with positive nuclear immunostaining by random counting of 1,000 epithelial tumor cells, using an oil immersion 100 x objective. PCNA labeling indices were consistently higher than those of Ki-67, and they correlated with each other. Well-differentiated thymic carcinoma showed higher labeling indices (3.11% +/- 3.53%) by Ki-67 antibody compared with the medullary type (0.60% +/- 0.07%) (P < .05) but there were no statistically significant differences between the other histological subtypes. Stage IV cases showed higher PCNA labeling indices (PCNA: 11.07% +/- 7.35%, Ki-67: 6.86% +/- 5.87%) than cases of the other stages (P < .05), but there were no statistically significant differences in either labeling index between the other stages. The number of patients who relapsed was too small to permit meaningful correlation between labeling indices and relapse. Our results indicate that the differences in biological behavior of the different histological subtypes of thymic epithelial tumors may be in part explained by differences in tumor growth fraction. Analysis of a larger group of patients will be required to determine whether proliferation fraction as determined by this method can be used to predict outcome in individual cases.
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PMID:Cell kinetic study of thymic epithelial tumors using PCNA (PC10) and Ki-67 (MIB-1) antibodies. 854 14

We have shown previously that human prolactinomas express transforming sequences of the heparin-binding secretory transforming gene (hst) which encodes fibroblast growth factor-4 (FGF-4). To elucidate the role of hst in pituitary tumorigenesis we treated primary rat pituitary and pituitary tumor cell cultures with recombinant FGF-4 and also stably transfected pituitary cell lines with full-length human hst cDNA. Transfectants were screened for hst mRNA expression and FGF-4 production. FGF-4 (0.1-50 ng/ml) caused a dose-dependent 2.5-fold increase of prolactin (PRL) secretion (P < 0.001) in GH4 cells and up to 60% (P < 0.05) in primary cultures, while decreasing growth hormone release (P < 0.001). GH4 hst transfectants displayed markedly enhanced basal PRL secretion (threefold, P < 0.001) and also proliferated faster (P < 0.001). FGF-4 treatment of wild-type GH4 cells, transiently transfected with an expression construct (rPRL.luc) containing a luciferase reporter driven by the rPRL promoter, resulted in a dose-dependent increase of up to 3.3-fold in PRL transcriptional activity. Tumors derived from in vivo subcutaneous injection of GH4 hst-transfected cells strongly expressing FGF-4 grew more aggressively as assessed by histologic invasiveness and proliferating cell nuclear antigen staining (P < 0.01). The results indicate that hst overexpression mediates lactotrope tumor growth and potently stimulates PRL synthesis. Thus, hst may directly facilitate prolactinoma development via paracrine or autocrine action of its secreted protein, FGF-4.
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PMID:Heparin-binding secretory transforming gene (hst) facilitates rat lactotrope cell tumorigenesis and induces prolactin gene transcription. 855 Aug 32

Two immunohistologic demonstrations of markers of proliferating cells, Ki-67 and proliferating cell nuclear antigen, were applied to tissues from 10 vestibular schwannomas. Each method demonstrated three distinct rates of positively stained cells (p < .01 and p < .015, respectively, for each method). There was a one-to-one correspondence between the two immunohistologic methods in the assignment of cases to each growth rate category except for two cases (Spearman rank correlation r = 0.76, p < .05). These data support the concept of distinct growth rates in vestibular schwannoma. Tissues were also sampled from different areas of the same tumor within nine samples. The results suggest that tumor growth is not homogeneous within a tumor, but that proliferation may be more active near the surface.
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PMID:Proliferation indices of vestibular schwannomas by Ki-67 and proliferating cell nuclear antigen. 858 66

The tumor growth suppressor p21 has been shown to be induced by wild-type p53 (wt-p53) and to be a potent inhibitor of cyclin-dependent kinases and PCNA/DNA polymerase delta. Although wt-p53 is reported to be phosphorylated by several protein kinases, the function and significance of the phosphorylation of wt-p53 are not yet fully understood. Using OK-1035, a selective inhibitor of DNA-dependent protein kinase (DNA-PK), we demonstrated the importance of the phosphorylation of wt-p53 by DNA-PK in the DNA damage-mediated expression of the p21 gene. Treatment of HCT116, a human colon carcinoma cell line, with adriamycin induced the expression of wt-p53 and p21. By addition of OK-1035 to this culture, the induction of p21 protein was significantly decreased in a dose-dependent manner, whereas wt-p53 induction was not affected. Northern blot analysis revealed that suppression of p21 protein expression by OK-1035 resulted from reduction in the level of p21 mRNA. OK-1035 did not directly affect the binding ability of wt-p53 to its consensus DNA sequence. Our observations support the idea that wt-p53 induces the transcriptional activation of the p21 gene only after it is phosphorylated by DNA-PK.
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PMID:DNA-dependent protein kinase inhibitor (OK-1035) suppresses p21 expression in HCT116 cells containing wild-type p53 induced by adriamycin. 861 35


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