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)

Tumor growth is dependent on the ability of neoplastic cells to induce angiogenesis. Remodelling of blood vessels requires reconstruction of the collagen (type IV) and non-fibrous protein components of basement membrane. This study assessed the general protease and collagenase (IV) activities of C6 astrocytoma cells in monolayer and spheroid culture and C6 astrocytoma spheroids growing in vivo. Extracellular release of non-specific proteases and collagenase IV was maximal during early exponential cell growth. Increased spheroid size resulted in enhanced extracellular activity of both enzyme groups assessed. The size of the implanted spheroid influenced the activity measured in vivo. General proteolytic activity was significantly greater in tumor tissue at all spheroid sizes while only the implantation of 750 microns spheroids resulted in significantly increased collagenase type IV activity. The growth of C6 astrocytoma cells in monolayer and spheroid culture in vitro and in vivo is associated with distinct alterations in intracellular and extracellular activity of the proteolytic enzymes assessed. Increased extracellular release of these enzymes may play important roles in tumor-associated angiogenesis, tumor invasiveness, tumor induced hemorrhage and tumor-associated edema.
 ...
PMID:General protease and collagenase (IV) activity in C6 astrocytoma cells, C6 spheroids and implanted C6 spheroids. 165 4

The mRNAs encoding 2 metalloproteinases, stromelysin 2 and collagenase I, have been detected by in situ hybridization in 26 carcinomas of the head and neck. 23 tumors of 26 expressed these mRNAs. Collagenase mRNAs were present in individual invasive cancer cells and in tumor cells at the periphery of poorly differentiated clusters (4 cases). Numerous stromal cells, principally fibroblasts were labeled (18 cases). Stromelysin mRNAs have been localized in tumor cells frequently arranged along disrupted basement membranes (8 cases). Many stromal cells in close contact to cancer cells also expressed the stromelysin mRNAs (17 cases). Normal residual cells were never labeled. These observations plead for the role of stromelysin produced by both stromal and tumor cells in the breakdown of basement membranes and the involvement of both collagenase and stromelysin in stromal invasion in carcinomas of the head and neck in vivo.
 ...
PMID:Detection of mRNAs encoding collagenase I and stromelysin 2 in carcinomas of the head and neck by in situ hybridization. 165 73

Three cancer cell lines, IMC-2, IMC-3 and IMC-4, were established from a single tumor of a patient with maxillary cancer. We examined responses to epidermal growth factor (EGF) of these 3 cell lines with regard to cell growth and tumor invasion. The growth rate of IMC-2 in nude mice was markedly faster than that of the IMC-3 and IMC-4 cell lines. Assay for invasion through fibrin gels showed significantly enhanced invasive capacity of IMC-2 cells in response to EGF, but no change for IMC-3 and IMC-4 cells. We examined response to EGF of IMC-2 cells with regard to expression of a growth-related oncogene (c-fos), proteinases and their inhibitors. Expression of c-fos was transiently increased in IMC-2 cells at rates comparable to those seen in the 2 other lines in the presence of EGF. There was no apparent effect of EGF on the expression of urokinase-type plasminogen activator and 72-kDa type-IV collagenase in IMC-2 cells. In contrast, EGF specifically enhanced the expression of plasminogen activator inhibitor-I (PAI-I) and tissue inhibitor of metalloproteinases-I (TIMP-I) in IMC-2 cells. Our data suggest that proteinase inhibitors or other related factors may play an important role in tumor growth and invasion in response to EGF.
 ...
PMID:The response to epidermal growth factor of human maxillary tumor cells in terms of tumor growth, invasion and expression of proteinase inhibitors. 165 98

When cultured on plastic and treated with transforming growth factor alpha (TGF alpha), human keratinocytes exhibit an increase in proliferation at the colony periphery, apparently as a consequence of enhanced cell migration (Barrandon and Green, 1987). To investigate the effects of TGF alpha on a differentiating stratified squamous epithelium and to begin to examine the molecular basis mediating this influence, we cultured human epidermal cells on a gelled lattice of collagen and fibroblasts, floating on the air-liquid interface. Under these conditions, raft cultures differentiate and exhibit morphological and biochemical features of human skin in vivo (Asselineau et al., 1986; Kopan et al., 1987). When 3-wk-old raft cultures were treated with TGF alpha, basal cells showed a marked increase in cell proliferation. At elevated concentrations of TGF alpha, the organization of cells within the artificial tissue changed and islands of basal cells entered the collagen matrix. Biochemical analysis of the response revealed that type I collagenase and gelatinase were induced by keratinocytes within 12 h after TGF alpha treatment. In contrast, invasion of basal cells into the collagen matrix was not significant until 48-72 h post-treatment, suggesting that collagenase and gelatinase production may be a prerequisite to this phenomenon. These results have important implications for the possible role of TGF alpha in squamous cell carcinoma and tumor invasion.
 ...
PMID:Transforming growth factor alpha induces collagen degradation and cell migration in differentiating human epidermal raft cultures. 166 88

Retinoids such as retinoic acid (RA) are potent anti-arthritic and anti-neoplastic agents. We investigated the mechanism by which RA inhibits induction of collagenase gene transcription by inflammatory mediators, tumor promoters, and proto-oncogenes. We found that the RA receptors (RARs) are potent inhibitors of AP-1 activity generated either by cJun homodimers or cJun/cFos heterodimers. In addition, both cJun and cFos can inhibit RAR activity. In vitro experiments suggested that this inhibition is due to an interaction between RAR and AP-1 proteins that results in mutual loss of DNA-binding activity. The RARs need not bind to the AP-1 site, neither does AP-1 bind to RA response elements. An understanding of this antagonism between the RAR and AP-1 might help to elucidate the anti-neoplastic and anti-arthritic effects of RA as well as its effects on cell differentiation and proliferation.
 ...
PMID:Antagonism between retinoic acid receptors and AP-1: implications for tumor promotion and inflammation. 166 79

Although the incidence of, and deaths due to, malignant melanoma are rising at a rapid rate, few experimental models mimic the highly metastatic properties associated with the pathogenesis of the human disease, making study of the disease difficult. Thus, new human models are required to understand melanoma biology, especially its metastatic properties. Here we describe C8161, a highly invasive and spontaneously metastatic human melanoma cell line, which grows progressively in the subcutis of athymic nude mice with an average doubling time of approximately 6 days. By the time the tumor reaches a diameter of 1 cm, amelanotic metastases in lymph nodes, skin, peritoneal wall, spleen and lungs have formed. By comparing C8161 to variants from other well-characterized human malignant melanomas (A375 and MeWo) with differing metastatic traits, properties presumed to be involved in metastatic propensity were examined. C8161 showed a 2- to 14-fold higher ability to invade reconstituted basement membrane barriers in the MICS and correspondingly high type-IV collagenase mRNA levels and collagenolytic activity, as compared with other melanoma cell lines. Likewise, differential adhesion to immobilized RBM or HUVEC monolayers was observed, but did not correlate to rank orders of malignant properties. Recently, a correlation between surface expression of ICAM-1 and secondary tumor formation by human melanomas has been described in several laboratories. Basal levels of ICAM-1 on C8161, A375 and MeWo human melanomas were compared, but no correlation with metastatic potential was noted. Proto-oncogene expression in C8161 cells was compared with A375P and A375M variants using Northern blot analysis. c-myc expression was 6-fold greater than both A375 variants; c-fos expression was 3.4-fold less than A375P and 1.7-fold less than A375M; c-jun in C8161 cells was 2.5-fold and 2.1-fold greater than expression in A375P and A375M, respectively. Because C8161 is so highly malignant, amenable to experimental manipulation, and its behavior in nude mice mimics the clinical course of malignant melanoma, this cell line will prove valuable for studying properties associated with human melanoma tumor progression.
 ...
PMID:Characterization of a highly invasive and spontaneously metastatic human malignant melanoma cell line. 167 Oct 30

To assess the usefulness of immunocytochemical analysis of bone marrow in patients with neuroblastoma, marrow smears from 33 staging procedures in 12 patients were examined using an indirect immunoalkaline phosphatase technique with monoclonal antibodies raised against human neural tissue. Marrow aspirate and trephine collagenase digest specimens from individual sites were each tested with the monoclonal antibody UJ13A and with a pool of three related antibodies. The results were compared with morphological assessment of conventionally stained aspirates and trephine specimens taken at the same time. Immunostaining suggested the presence of tumour in seven of 18 staging procedures in which conventional techniques had shown infiltration. Tumour infiltration was also suggested in four of 10 staging procedures with suspicious trephine specimens, but in none of three with relatively innocent histological and cytological features. Immunological investigation provides no additional information about the presence of infiltration if conventional microscopy has shown definite tumour. When histological appearances are suspicious, immunostaining of stored aspirate smears or collagenase digest specimens may provide evidence of infiltration. There are insufficient data to comment on the value of immunostaining when conventional techniques reveal "normal" marrow, but the impression gained from this study is that immunostaining has a limited role in the detection of metastatic neuroblastoma, which yet remains to be defined.
 ...
PMID:Immunocytochemical examination of bone marrow in disseminated neuroblastoma. 169 Feb 23

Various approaches to isolation of tumor cells are analyzed on the basis of examination of 46 human pulmonary tumors of different histologic types. Mechanical treatment alone resulted in the death of the majority of tumor cells. Short trypsin treatment (for 10-15 min in several stages) proved to be the most suitable for disaggregation of small-cell carcinoma, adenocarcinoma, and carcinoid samples. A specific approach has been developed for isolation of cells from squamous-cell carcinoma, consisting in tumor treatment with 0.25 percent trypsin at 4 degrees C for 16-18 h, followed by DNAase, collagenase, and trypsin treatment, and then again trypsin treatment at 37 degrees C for 10-15 min. The suggested approaches permit a harvest of at least 6 x 10(6) tumor cells from 1 g of tissue, with more than 70 percent of these cells viable.
 ...
PMID:[Preparation of tumor cells from human lung cancer tissue for the purpose of cloning]. 170 81

We have investigated the effect of the immunomodulator ubenimex (hereafter referred to as bestatin) on the enzymatic degradation of the extracellular matrix by human renal cell carcinoma SN12M cells during the invasive process. The invasion of SN12M cells into reconstituted basement membrane (Matrigel) was inhibited by the presence of bestatin in a concentration-dependent manner. However, bestatin did not have any effect on tumor cell adhesion and migration to the extracellular matrices which may be involved in tumor cell invasion. Bestatin inhibited the degradation of type IV collagen by tumor cells, but not by tumor-conditioned medium (TCM), in a concentration-dependent manner. We also found that bestatin inhibited hydrolysing activities towards substrates of aminopeptidases in SN12M cells. Since bestatin was found to inhibit aminopeptidase activity, the inhibition of tumor invasion by bestatin is likely to be associated with its action as an enzyme inhibitor. Bestatin only slightly inhibited tumor cell plasmin activity, which can lead to the conversion of the latent collagenase to the active form, but this slight effect was not significant. The zymography of TCM from SN12M cells showed that the treatment of tumor cells with bestatin resulted in the disappearance of the 68 kDa type IV collagenase-enzyme level (active form) and slight reduction of the 72 kDa type IV collagenase-enzyme level (latent form). These results indicated that bestatin may inhibit tumor cell invasion through a mechanism involving its inhibitory action on aminopeptidases in tumor cells, suggesting that the aminopeptidase may partly be associated with the conversion of a latent form of type IV procollagenase to an active form or the secretion of the collagenases from tumor cells.
 ...
PMID:Inhibition of tumor invasion and extracellular matrix degradation by ubenimex (bestatin). 173 47

The ability to metastasize requires that tumor cells be able to degrade matrix. Nontoxic compounds that inhibit matrix digestion might be useful as anti-metastatic agents. We have investigated whether phenytoin, a drug commonly used in clinical practice that inhibits the production of collagenase by some cells, inhibits metastases in a standard animal model of metastasis: In vitro, phenytoin inhibited the proliferative response of B16 F10 melanoma cells to serum-containing media (75% inhibition at 25 micrograms/ml) but had no effect on their ability to degrade a type I collagen gel (1-100 micrograms/ml). Treatment of these cells with phenytoin prior to inoculation in vivo did not inhibit tumor growth, implantation in a surgical wound, or incidence of spontaneous metastases from a primary tumor growing in the foot. Pretreatment of mice with phenytoin (15, 40, and 75 mg/kg/day) diminished pulmonary metastases following tail vein injection in a minimal but dose dependent fashion; mean number of pulmonary colonies 4.6 +/- 3.1 (75/mg/kg/day) vs. 10.2 +/- 9.9 (control). However, tumor growth, implantation, and spontaneous metastases were not inhibited by pretreating the mice with the same doses of phenytoin. It is concluded that phenytoin has an insignificant inhibitory effect on tumor growth and metastasis.
 ...
PMID:Search for anti-metastatic therapy: effects of phenytoin on B16 melanoma metastasis. 173 31


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