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

Tumor growth is dependent on the balance between cell proliferation and cell death, and these events occur heterogenously within an individual tumor. We present a methodology that provides integrative information about cell kinetics, cell death, and cell growth within individual tumors in animals treated with cytotoxic chemotherapeutic agents. Using HCT-116 and NCI-H460 cells, human colonic adenocarcinoma and non-small cell lung cells, respectively, traditional xenograft studies were performed. The tumor-bearing animals were treated with cyclophosphamide (Cytoxan), gemcitabine (Gemzar), or mitomycin C, and extensive analysis of the tumors was studied. Cell kinetics were evaluated by measuring the apoptotic and proliferation indices. The ability to image an entire tumor section using "tiling" by creating a large montage from many high-resolution images makes it possible to identify regional differences within areas of tumor and to demonstrate differences in these tumor regions after treatment with selected chemotherapeutic agents. Two specific areas within tumors have been identified: (a) areas of viable cells within the cell cycle, determined by bromodeoxyuridine and/or morphological characteristics determined by hematoxylin staining; and (b) areas of necrosis determined by the absence of bromodeoxyuridine and proliferating cell nuclear antigen-labeled cells coupled with morphological changes. By standardizing the tumor size to 100 mm2, different patterns of tumor responses to chemotherapeutic agents were determined. By creating such tiled images and by quantitating cell cycle kinetics, it is possible to gain a more complete understanding of tumor growth and response to treatment, leading to the development of more reliable methods for assessing the clinical behavior of anticancer drugs.
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PMID:Tumor biology: use of tiled images in conjunction with measurements of cellular proliferation and death in response to drug treatments. 1095 24

Transitional cell carcinoma of the upper urinary tract is an uncommon neoplasm. Relatively little information is available regarding the clinical relevance of molecular markers. This study was performed to examine the importance of nm23-H1 gene expression (NM23-H1) in this type of tumors. Immunohistochemical expression of NM23-H1 was analyzed in 90 cases of upper urinary tract cancer, and was compared for its prognostic significance with conventional biological indicators. High expression of NM23-H1 was found in 7 cases (8%), intermediate expression in 32 cases (36%), and low expression in 51 cases (57%). Reduced NM23-H1 (defined as intermediate or low level of expression) was associated with a higher histological grading (p=0.002), invasive tumor growth (p=0. 002), or an increased proliferating cell nuclear antigen labeling index (p=0.004). NM23-H1 tended to inversely relate to later recurrence or long-term survival (p=0.06), but, only tumor staging was found to be significant in predicting clinical outcome (p=0.002). nm23-H1 appears to function as a tumor suppressor for upper urinary tract cancer, however, evaluation of NM23-H1 provides limited prognostic information.
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PMID:Expression of nm23-H1 in transitional cell carcinoma of the upper urinary tract. 1111 97

We have reported that thymidine phosphorylase (dThdPase) is identical to platelet derived-endothelial cell growth factor and that it has an angiogenic activity in vitro and in human carcinoma tissues as well as gastric carcinoma. Recently, we revealed that dThdPase may have an another function(s) besides angiogenesis in vitro and in human solid tumors. Using immunohistochemistry, we examined retrospectively whether the expression of dThdPase was correlated with tumor growth, comparing it with the proliferating cell nuclear antigen labeling index (PCNA LI) and examining their prognostic significance in 116 patients with gastric carcinoma. A direct correlation of these two factors was observed (R=0.659, P<0.001). A multivariate Cox regression analysis showed that both dThdPase positivity and PCNA LI were independent prognostic factors, as were depth of invasion and lymph node metastasis. Furthermore, the patients with dThdPase-positive/high PCNA LI tumors had the worst prognoses. The combination of dThdPase and PCNA expression is a better tool for predicting the prognosis of patients with gastric carcinoma than the expression of either of them alone. These results raise the possibility that dThdPase may have a function(s) involved in tumor growth besides angiogenesis.
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PMID:Clinicopathological and prognostic significance of thymidine phosphorylase and proliferating cell nuclear antigen in gastric carcinoma. 1129 93

Cellular proliferation with altered control is one of the 1st characteristics of a neoplastic cell population. Although tumor growth reflects both tumor cell replication and cell loss (opposing growth and antigrowth factors), most studies published in veterinary literature used immunohistochemistry (proliferating cell nuclear antigen [PCNA]; Ki-67 [MIB-1]) or staining for argyrophilic nucleolar organizer regions (AgNORs) to measure proliferation. These studies have appeared in the veterinary literature for more than a decade, describing associations between proliferation indices and histologic grade, biological behavior, and clinical outcome for some tumor types but no clinically relevant associations for other tumors. The results of these studies are summarized here. Methods for evaluation of the numerous regulatory proteins that direct the cell throughout its cycle are now available and should allow more precise identification of cellular aberrations in cancer.
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PMID:Cellular proliferation in tumors: a review of methods, interpretation, and clinical applications. 1146 90

In order to investigate the expression of androgen receptor (AR) in meningiomas and its relation to tumor proliferative potential, we examined the expression of AR and proliferating cell nuclear antigen (PCNA) by avidine-biotin complex immunohistochemistry in 39 cases of meningiomas. Of the 39 cases of meningiomas, 20(51%) showed positive AR immunoreactivity. The AR expression positivity rates were 31% (6/19) in benign meningiomas, 58% (7/12) in atypical meningiomas, 87.5% (7/8) in malignant meningiomas, respectively. In addition to the tumor cells, cells of microvascular endothelial proliferation were frequently AR positive. Malignant meningiomas had a significantly higher percentage of AR positive cells compared with atypical and benign meningiomas (P < 0.05). The mean proliferating cell nuclear antigen labeling index (PCNA LI) was significantly higher in the malignant meningiomas when compared with atypical meningiomas (P < 0.05) and benign meningiomas (P < 0.05). AR positive meningiomas had higher PCNA LI than AR negative meningiomas (P < 0.05). The expression of AR in tumor tissues was significantly related with PCNA LI. These data indicated that AR in the meningiomas was correlated with histological grade and AR might participate in the growth of these tumors and tumor angiogenesis. The measurement of AR in these tumors may indirectly represent tumor growth potential.
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PMID:Expression of androgen receptor in meningiomas. 1152 20

The study was concerned with growth of sarcoma M-1 and basic morphological characteristics of proliferative activity of cells of this strain as well as apoptosis of cells at different stages of tumor progression in rats before and after a single gamma irradiation at 30 Gy. At the parenchymal periphery which determines tumor growth, the PCNA index of proliferating cells was 76.5%; spontaneous cell death--0.28%. During post-irradiation period, the sarcoma PCNA index fell to 62.3% while the apoptotic index rose five-fold. These findings support the concept of radiation-induced apoptosis being a major pathogenetic factor responsible for effectiveness of radiotherapy of tumors. Indirect evidence on PCNA immunostaining suggested that synthesis of this cyclin is sensitive to the level of oxygen input in the cell, yet it offers sufficient resistance to gamma-radiation.
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PMID:[Growth kinetics and functional morphology of M-1 sarcoma in rats before and after gamma-irradiation]. 1154 33

The thiol N-acetyl-L-cysteine (NAC), an analogue and precursor of reduced glutathione, has cancer chemopreventive properties attributable to its nucleophilicity, antioxidant activity, and a variety of other mechanisms. We demonstrated recently that NAC has anti-invasive, antimetastatic, and antiangiogenic effects in in vitro and in vivo test systems. In the present study, s.c. transplantation of KS-Imm cells in (CD-1)BR nude mice resulted in the local growth of Kaposi's sarcoma, a highly vascularized human tumor. The daily administration of NAC with drinking water, initiated after the tumor mass had become established and detectable, produced a sharp inhibition of tumor growth, with regression of tumors in half of the treated mice along with a markedly prolonged median survival time. The production of vascular endothelial growth factor (VEGF) and certain proliferation markers (proliferating cell nuclear antigen and Ki-67) were significantly lower in Kaposi's sarcomas from NAC-treated mice than from control mice. Treatment of KS-Imm cells with NAC in vitro resulted in a dose-dependent inhibition of chemotaxis and invasion through inhibition of gelatinase-A (matrix metalloproteinase-2, MMP-2) activity without altering MMP-2 or MMP-9 mRNA levels. NAC also significantly inhibited VEGF production but did not affect proliferation markers in vitro. Reverse transcription-PCR analysis indicated that total VEGF mRNAs were reduced by 10 mM NAC. Taken together, these findings provide evidence that NAC, the safety of which even at high doses has been established in almost 40 years of clinical use, in addition to its chemopreventive action, has a strong antiangiogenic potential that could be exploited for preventing cancer progression as well as used in cancer adjuvant therapy.
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PMID:Inhibition of angiogenesis-driven Kaposi's sarcoma tumor growth in nude mice by oral N-acetylcysteine. 1171 47

Recent studies suggest that drug induced apoptosis relates to the sensitivity. p53 gene, which has a pivotal role in inducing apoptosis, frequently mutates in ovarian cancer. Therefore, p53 gene status and chemosensitivity in epithelial ovarian cancer is discussed. Nonresponders to chemotherapy had mutations of the p53 gene more frequently (83% for nonresponders vs. 16% for responders) in patients with epithelial ovarian cancer undergoing platinum-base chemotherapy. Apoptotic index was significantly greater in tumors with wild-type p53 gene than those without the gene. p53 gene transduction markedly enhanced the sensitivity to cisplatin (CDDP) and CDDP-induced apoptosis, but did not affect the sensitivity to paclitaxel (PTX) nor PTX-induced apoptosis in ovarian cancer cells without p53 gene. The combination treatment with a recombinant adenovirus carrying a wild-type p53 gene (AxCAp53) and CDDP significantly suppressed tumor growth of ovarian cancer cells with and without p53 gene, compared with a single treatment of either AxCAp53 or CDDP in ovarian cancer xenograft. Apoptotic index was significantly higher and proliferating cell nuclear antigen labeling index was relatively lower in an ovarian cancer xenograft without p53 gene receiving combination treatment, compared with a single treatment of either CDDP or AxCAp53, suggesting that the transduction of p53 gene induces apoptosis, but does not enhance the DNA repair system. A significant survival advantage was observed in the combination treatment compared with other treatments in carcinoma peritonitis models. In conclusion, p53 gene status contributes the sensitivity to CDDP in ovarian cancer. Additionally, combination treatment of p53 gene transduction and CDDP may be an effective therapeutic modality for ovarian cancer without wild-type p53 gene.
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PMID:p53 gene status and chemosensitivity in ovarian cancer. 1177 36

Precise quantitation of apoptotic cells in meningiomas is necessary to determine the role of apoptosis in tumor growth and recurrence. In this study, we investigated the incidence of baseline apoptosis in relation to p53 and bcl-2 protein expression, proliferation status as expressed by Ki-67, PCNA and mitotic counts, standard clinicopathological parameters and patients' outcome, in a series of 59 patients with primary intracranial benign and atypical meningiomas. Seven tumors recurred (11.9%) following complete surgical resection, within a follow-up period ranging from 21 to 108 months. Apoptotic fractions were quantified immunohistochemically by means of a novel monoclonal antibody recognizing exposed single-stranded (ss) regions in the DNA of apoptotic cells during heating. Tissues consisted of archival formalin-fixed paraffin-embedded meningioma specimens. The apoptotic index (AI) ranged from 0% to 2.90% (mean: 0.50%), increased with proliferative activity (p = 0.014), had lower values in transitional meningiomas (p = 0.001) and was unrelated to grade and p53 expression. Increased AI predominated among bcl-2 negative tumors (p = 0.041) and tended to be accompanied by a shortened recurrence-free survival, in univariate (p = 0.0407) as well as in multivariate analysis (p = 0.0405). These results implicate apoptotic rate in meningioma growth and recurrence and denote that assessment of apoptotic potential by means of anti-ssDNA monoclonal antibody provides valid prognostic information irrespective of other parameters.
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PMID:Apoptosis detected with monoclonal antibody to single-stranded DNA is a predictor of recurrence in intracranial meningiomas. 1180 77

We investigated the effect of transfection with connexin (Cx) 26 gene on the malignant potential of PLC/PRF/5 hepatoma cells, observing changes in their morphological features, alpha-fetoprotein (AFP) expression, cell proliferation and apoptosis in vitro, and their tumor growth in vivo. Fluorescence-activated cell sorting (FACS) analysis showed that 10.6% of PLC/PRF/5 hepatoma cells transfected with Cx26 cDNA expressed excessive Cx26, and the spread of lucifer yellow was wider in the colony of stable transfectants (PLC/Cx26) after its microinjection than in control. Nucleo-cytoplasmic (N/C) ratio was significantly lower in PLC/Cx26 (P < 0.0001). Cell proliferation assay showed significantly lower numbers in PLC/Cx26 on day 10 after seeding than in control (P = 0.0039), and AFP level /10(5) cells was significantly lower in medium of PLC/Cx26 (P = 0.0039). The number of proliferating cell nuclear antigen (PCNA)-positive cells was less in PLC/Cx26 in vitro than in control (P = 0.0039), and single-stranded DNA (ssDNA)-positive cells were more abundant in the colony of PLC/Cx26 (P = 0.029). Tumor volume in SCID mice was significantly smaller in the group of PLC/Cx26 than in the control (P < 0.01) throughout the observation period, and tumor weight of PLC/Cx26 was significantly lower (P = 0.0019) week 9 after inoculation. Transfection with Cx26 cDNA inhibited dedifferentiation, suppressed cell proliferation, and apoptosis was induced. Tumor growth of PLC/Cx26 was retarded. These findings suggest that transfection with Cx26 gene into human hepatoma cells reduces their malignant potential.
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PMID:Influence of transfection with connexin 26 gene on malignant potential of human hepatoma cells. 1187 44


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