Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An animal model for studying tumor dormancy was established by two-way selection of tumor-progressive and nonprogressive (tumor-dormant state) ddY mice in the same basal stock. In the tumor-progressive (prg) substrain of mice, Ehrlich ascites tumor cells (2 x 10(7)) subcutaneously inoculated into the dorsal skin formed a progressive solid tumor. In the tumor-dormant substrain (drm) of mice, the same tumor cells did not grow at all but formed a small caked nodule (1 to 3 mm in diameter) within 1 week. Some of the tumor cells persisted in the nodule at least 3 months without apparent mitotic figures. Such dormant tumor cells emerged and revealed outgrowth to overt solid tumors after they were transplanted into the dorsal skin of prg mice or into athymic mice (C57BL/6J nu/nu). To estimate the predisposition of drm mice to form tumors, the effect of certain drugs on the tumor-dormant state was examined. Estradiol, progesterone, dexamethasone, prostaglandin E2, Cyclosporin A, and collagenase all failed to promote the emergence of dormant tumor cells in drm mice.
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PMID:Tumor dormancy and the effect of selected drugs on the tumor-dormant state. 147 6

The application of flow cytometry (FCM) to solid human tumors has been hindered by the difficulty in producing high yield, viable, unaltered single cell suspensions. Carcinomas containing a high desmosomal content, such as well-differentiated squamous cell (SCC) cancers of the head and neck (H&N) region, are particularly difficult to prepare. The desire to employ FCM to study cellular DNA parameters of these tumors led to the use of a 3-methylcholanthrene induced murine SCC for the comparative testing of preparative techniques. Dissociation techniques, including mechanical, enucleation, chemical, single and combination enzymes methods, were comparatively tested. Of these, the combination enzyme treatment employing trypsin and collagenase produced the highest cell yields in the shortest time with the highest dye exclusion viability and the least expense. Several fixation systems including glutaraldehyde, paraformaldehyde, acetic acid, and ethanol were comparatively tested using percent of cell loss and quality of the DNA histograms produced as end points. Ethanol-water systems with added fetal calf serum provided minimal cell loss and high quality histograms which were stable for extended periods of time. A murine tumor, closely mimicking the histology of the human tumor of interest, may be used as a model for the determination of optimum techniques of solid tumor preparation for flow cytometric analysis.
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PMID:Solid tumor preparation for flow cytometry using a standard murine model. 244 98

The aim of this work was to determine whether treatments of rats with estradiol (E) in conditions known to decrease the proliferation rate, the mitotic index and the thymidine incorporation into the DNA of the MtTF4 tumor act at a specific point in the cell cycle. Two weeks after grafting a piece of tumor under the kidney capsule, adult male Fischer rats were treated or not treated with E. Tumors were collected between 12 h and 11 days later. Cells were dispersed by collagenase-DNAse treatment and fixed with ethanol. DNA content, cell size, cell granularity and protein content were analyzed, alone or in combination with a flow cytometer. E treatments did not apparently modify the distribution of cells according to their DNA content whereas they did increase dramatically cell size, cell granularity and cell protein content. Simultaneous analysis of DNA content and light scattering or protein content allowed us to demonstrate that there was an increase of a population of large granular and protein-rich cells regardless of the phase of the division cycle considered. These effects are time-dependent, dose-dependent and hormone-specific. This work shows both the interest of flow cytometry to describe the consequences of E treatment at any phase of the cycle of cells dispersed from a solid tumor and the limits of this method in the conditions used to specify the E target points: at the present time, it cannot be decided whether E acts at one or several points of the cell cycle for inhibiting tumor growth.
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PMID:Flow cytometry analysis of cells dispersed from the MtTF4 tumor whose growth is inhibited by estradiol treatment. 310 Mar 60

Co-culture of cancer patients' nonadherent peripheral blood lymphocytes with irradiated autologous fresh tumor cells, termed the mixed lymphocyte-tumor interaction (MLTI) test, resulted in significant stimulation of 3H-Tdr in corporation on day 6 in 19 of 37 autologous combinations. The MLTI test was performed in a microtiter wells (0.2 ml) and a variety of solid tumor cells (sarcomas and carcinomas) were used. Tumor cells were dissociated from the fresh biopsy tissue by nontrypsin enzymatic digestion (deoxyribonuclease, hyaluronidase, and collagenase) and the tumor cells enriched by depletion of macrophages using adherence procedures. Occasionally, further tumor cell purification was achieved by separation of cells on the basis of size on dis-continuous gradients. Positive MLTI resulted in stimulation as high as 20-fold over the backgrounds of PBL and tumor cells cultured alone. Mean positive MLTI was SI of 7.7. The negative MLTI were not a reflection of generalized immunosuppression, because tumor cell preparations that did not stimulate autologous PBL did stimulate allogeneic PBL. In an additional patient, PBL not responding in the autologous MLTI did respond to allogeneic tumors. MLTI using cryopreserved cells reproduced the MLTI results using fresh cells in 11 of 16 tests; the other five tests were all positive in the fresh MLTI and negative when using cryopreserved cells. Despite reports from many other groups it appears that positive MLTI were not tumor-specific. In 14 experiments we were able to simultaneously test the proliferative response to autologous tumor as well as to an autologous normal tissue (lung, liver, colon, and bowel). In eight of these experiments positive responses were obtained with tumor stimulators and in seven of these, positive proliferation was also obtained with normal tissue.
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PMID:The human mixed lymphocyte-tumor cell interaction test. I. Positive autologous lymphocyte proliferative responses can be stimulated by tumor cells as well as by cells from normal tissues. 620 46

A rapid and simple technique for the isolation of viable tumor cells from human and mouse solid neoplasms is described. It consists of a 5 to 10-min treatment with trypsin-collagenase-DNase mixture, followed by mechanical disaggregation of the tumor tissue and subsequently by a brief centrifugation on a discontinuous Percoll gradient. With the tumors employed, this procedure usually requires less than 1 hr and results in preparations comprising greater than 80% tumor cells with viability of 80-90%. Cell-mediated cytotoxic response was measured with: (a) unsensitized lymphocytes freshly obtained from tumor-bearing hosts; (b) lymphocytes propagated in culture with T cell growth factor; and (c) lymphocytes stimulated in cocultures with autologous or syngeneic tumor cells. The cytotoxic activity was assessed in a modified [51Cr]-release assay adapted for solid tumor cells, allowing a long incubation period (24 hr) and the use of a low number (200-1000) of highly labeled target cells (2-10 counts/min/cell).
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PMID:A rapid technique for isolation of viable tumor cells from solid tumors: use of the tumor cells for induction and measurement of cell-mediated cytotoxic responses. 698 88

A method for analyzing clonogenic cells is described. Single cells obtained from biopsies of ten malignant gliomas were treated with 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) in vitro, and tumor cell survival was compared to patient response to nitrosourea therapy. There was a direct correlation between cell sensitivity to nitrosourea and patient response to nitrosourea therapy. The limitations of in vitro and in situ methods and their interpretations are discussed. In addition, an improved method is described for disaggregating single cells from specimens of solid tumor with the use of an enzyme cocktail consisting of pronase, collagenase, and DNAse.
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PMID:Chemosensitivity testing for human brain tumors. 720 20

Arsenic trioxide (As2O3) has been implicated as a promising anticancer agent for treatment of many cancers including acute promylocytic leukemia. However, the molecular mechanisms are not yet fully defined in solid tumor cells, especially cervical cancer cells carrying human papillomavirus (HPV) genome. To analyze detailed mechanisms in vitro, we treated As2O3 to transformed HeLa cells, a well-studied cervical cancer cell line carrying HPV-18 sequence, and investigated its antiproliferative, antiviral and antimetastatic effects. As2O3 reduced survival and growth of HeLa cells in a dose- and time-dependent manner. Several indicatives of apoptosis were demonstrated by DNA fragmentation assay, DAPI nuclear staining and FACS analysis, respectively. Protein levels of p53 and cleavage of poly(ADP)-ribose polymerase were increased in a dose-dependent manner following treatment of As2O3. In parallel, semi-quantitative reverse transcription-polymerase chain reaction showed that the treatment inhibited HPV-18 E6/E7 viral gene expression in HeLa cells. Using transient transfection and CAT ELISA, we also found that AP-1 sites, located proximal to HPV-18 upstream regulatory region (URR) promoter, could be the major target sites for As2O3. Furthermore, As2O3-treated HeLa cells showed lesser capacity of invasion than those of untreated cells by in vitro invasion assay. Taken together, we proposed that antiviral effect, i.e. down-regulation of HPV E6/E7 oncogenes through targeting for AP-1 sites located in HPV URR might be associated with antiproliferative effect, i.e. induction of apoptosis as be resulted from the accumulation of p53, and that antimetastatic effect could be due to the targeted inactivation of AP-1, a transcription factor required for the expression of MMP-1 and -3. Therefore, our finding may provide a logical basis for the development of a new agent treating HPV-associated cervical neoplasia.
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PMID:Down-regulation of human papillomavirus E6/E7 oncogene by arsenic trioxide in cervical carcinoma cells. 1243 Jan 74

Administration of active TG2 to two different in vitro angiogenesis assays resulted in the accumulation of a complex extracellular matrix (ECM) leading to the suppression of endothelial tube formation without causing cell death. Matrix accumulation was accompanied by a decreased rate of ECM turnover, with increased resistance to matrix metalloproteinase-1. Intratumor injection of TG2 into mice bearing CT26 colon carcinoma tumors demonstrated a reduction in tumor growth, and in some cases tumor regression. In TG2 knockout mice, tumor progression was increased and survival rate reduced compared to wild-type mice. In wild-type mice, an increased presence of TG2 was detectable in the host tissue around the tumor. Analysis of CT26 tumors injected with TG2 revealed fibrotic-like tissue containing increased collagen, TG2-mediated crosslink and reduced organized vasculature. TG2-mediated modulation of cell behavior via changes in the ECM may provide a new approach to solid tumor therapy.
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PMID:Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth. 1629 9

We have previously reported that a disintegrin inhibits solid tumor growth and metastasis in mouse model [I.C. Kang, Y.D. Lee, D.S. Kim, A novel disintegrin salmosin inhibits tumor angiogenesis, Cancer Res. 59 (1999) 3754-3760; S.I. Kim, K.S. Kim, H.S. Kim, D.S. Kim, Y. Jang, K.H. Chung, Y.S. Park, Inhibitory effect of the salmosin gene transferred by cationic liposomes on the progression of B16BL6 tumors, Cancer Res. 63 (2003) 6458-462]. In this study, we have investigated the modulatory effect of a disintegrin, saxatilin, on the balance between MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in human ovarian cancer cell line MDAH 2774. Functional mechanism of the disintegrin-mediated transcriptional regulation of MMP-9 and TIMP-1 was examined in the ovarian cancer cell line. Saxatilin strongly induced TIMP-1 expression in dose- and time-dependent manners, while the disintegrin suppressed MMP-9 expression. Further analyses clearly indicated that interaction of the disintegrin and integrin alphavbeta3 results in the TIMP-1 promoter activation via c-fos to suppress TNF-alpha-induced cancer cell invasion. These results demonstrate that integrin alphavbeta3-mediated transcriptional regulation of MMP-9 and TIMP-1 is critical for suppressing the ovarian cancer cell invasion.
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PMID:Integrin alphavbeta3-mediated transcriptional regulation of TIMP-1 in a human ovarian cancer cell line. 1885 76

In recent years, evidence has emerged supporting the hypothesis that cancer is a stem cell disease. The cancer stem cell field was led by the discovery of leukemia stem cells (Tan, B.T., Park, C.Y., Ailles, L.E., and Weissman, I.L. (2006) The cancer stem cell hypothesis: a work in progress. Laboratory Investigation. 86, 1203-1207), and within the past few years cancer stem cells have been isolated from a number of solid tumor including those of breast and brain cancer among others (Al-Hajj M., Wicha M.S., Benito-Hernandez A., Morrison, S.J., and Clarke, M.F. (2003) Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 100, 3983-3988; Singh, S.K., Clarke, I.D., Terasaki, M., Bonn, V.E., Hawkins, C., Squire, J., and Dirks, P.B. (2003) Identification of a Cancer Stem Cell in Human Brain Tumors. Cancer Research. 63, 5821-5828). Cancer stem cells exhibit far different properties than established cells lines such as relative quiescence, multidrug resistance, and multipotency (Clarke, M.F., Dick, J.E., Dirks, P.B., Eaves, C.J., Jamieson, C.H.M., Jones, D.L., Visvader, J., Weissman, I.L., and Wahl, G.M. (2006) Cancer Stem Cells-Perspectives on Current Status and Future Directions: AACR Workshop on Cancer Stem Cells. Cancer Research. 66, 9339-9344). In addition, our laboratory has demonstrated that breast cancer stem cells exhibit a strong metastatic phenotype when passaged in mice. Since stem cells exhibit these somewhat unique properties, it will be important for endocrinologists to evaluate hormonal action in these precursor cells for a more thorough understanding of cancer biology and development of more effective treatment modalities. A relatively easy and low cost method was developed to isolate breast cancer stem cells from primary needle biopsies taken from patients diagnosed with primary invasive ductal carcinoma during the routine care of patients with consent and IRB approval. Fresh needle biopsies (2-3 biopsies at 2 cm in length) were enzymatically dissociated in a collagenase (300 U/ml)/hyaluronidase (100 U/ml) solution followed by sequential filtration. Single cell suspensions were cultured on ultra low attachment plastic flasks in defined medium and formed non-adherent tumorspheres. The tumorspheres exhibited surface marker expression of CD44(+)/CD24(low/-)/ESA(+), previously defined as a "breast cancer stem cell" phenotype by Al Hajj et al. (Al-Hajj M., Wicha M.S., Benito-Hernandez A., Morrison, S.J., and Clarke, M.F. (2003) Prospective identification of tumorigenic breast cancer cells.
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PMID:Breast tumor-initiating cells isolated from patient core biopsies for study of hormone action. 1976 16


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