Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1326912 (tumorigenesis)
 57,481 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homozygosity for the severe combined immunodeficiency (scid) mutation results in a block in T- and B-lymphocyte development. An unusually high incidence of spontaneous thymic lymphoma development was observed after transfer of this mutation from the C.B-17 congenic strain background onto the diabetes-susceptible nonobese diabetic (NOD) background. Thymomagenesis in the NOD-scid/scid mouse was associated with expression of an NOD mouse-unique endogenous ecotropic murine leukemia provirus locus (Emv-30, mapped to proximal region of chromosome 11) not expressed in the standard substrain NOD/Lt thymus. All tumors exhibited insertions of ecotropic proviruses, whereas only a subset also exhibited proviral integrations of mink cell focus-forming retrovirus. Neither class of retrovirus was associated with consistent integration into genes previously associated with activation of oncogenesis. We propose that the unusual features of T-cell ontogeny characteristic of the NOD inbred strain synergize with the scid-imparted block in thymocyte development, leading to activation of the NOD-unique Emv-30 to initiate thymomagenesis.
 ...
PMID:The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated with immunodeficiency. 137 93

It was known that malignancies of plasma cell (MPC) consists of three categories, one is multiple myeloma (MM), second is plasmacytoma, third is plasma cell leukemia. One of the aim of our review is that we listed MPC cell lines reported. It became clear from the list that the success of establishment of cell lines may expected only when trials are done concerning MM cells shown extra-medullary invasion cells from patients. In contrast, IL-6 dependent cell lines may established by chance and it may not depend on cell origin. The second aim of the article is to review the usage of cell lines of MPC. We chose 7 issues; one is the correlation between the proliferation and IL-6, second is the contribution of other cytokines to MPC lines, third is how to make human MM model in SCID mouse, fourth is the chromosomal abnormalities and oncogenesis, fifth is the contribution of fibronectin and MPC lines, sixth is the issue of osteoblast activating factor (OAF), finally, we discussed the tumour aberration of MPC lines. We expect that the accumulation of these acknowledges concerning MPC cell lines would contribute to the development of plasmacytology in the future.
 ...
PMID:[Establishment and usage of human multiple myeloma cell line]. 769 92

The objective of this work was to determine whether transformation of the human breast epithelial cell line MCF-10F by the chemical carcinogens 7, 12-dimethylbenz(a)anthracene (DMBA) or benzo(a)pyrene (BP), or c-Ha-ras oncogene transfection, influence the expression of epidermal growth factor receptor (EGFR), estrogen (ER) or progesterone (PR) receptors, and the content of cathepsin-D (Cath.D). MCF-10F control cells did not express any of the phenotypes of neoplastic transformation, whereas carcinogen-treated cells and clones derived from the latter formed colonies in agar-methocel, and exhibited increased chemotaxis and chemoinvasion. Clone BP-1E was also tumorigenic in SCID mice. The BP1 cell line transfected with mutated c-Ha-ras oncogene, named BP1-Tras, became more aggressive after transfection and decreased the latency time to tumorigenesis. Radioligand binding and immunocytochemical reactions were utilized for determining the receptors and Cath.D content of control and carcinogen-treated cells and their derived clones. MCF-10F cells contained 37 fmol/mg of protein of EGFR, ER and PR were undetectable, and Cath.D content was 70 fmol/mg protein. EGFR content was significantly higher in D3-1 and BP1-E cell lines vs the control MCF-10F and the other DMBA and BP clones, correlating positively with the emergence of the transformation phenotype. Whereas EGFR levels were not significantly different in BP1-Tras cells when compared with BP1-E, the former were more tumorigenic in SCID mice, an observation suggesting an alternative pathway in these cells in the formation of tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hormone receptors and cathepsin D levels in human breast epithelial cells transformed by chemical carcinogens and c-Ha-ras transfection. 801 35

The t(14;18) translocation is found in the majority follicular lymphomas and some high grade B-cell lymphomas. This is results in deregulation of the BCL-2 gene and appears to play a role in oncogenesis. Various numbers of cells from a cell line derived spontaneously from a patient with B-cell lymphoma bearing the t(14;18) translocation and negative for the Epstein-Barr virus (EBV) were injected by IP, IV, and SC routes into SCID mice. The mice developed lymphoma bearing the t(14;18) translocation with as few as 5 x 10(6) cells within 28 days. This was determined by histological examination. The higher the cell inoculation the more rapidly the lymphoma developed. Engraftment of the tumour cells was determined by PCR for the t(14;18) breakpoint region on peripheral blood samples and could be detected prior to development of overt lymphoma. Having established a lymphoma model the cells were treated with antisense oligonucleotides to the first open reading frame of the BCL-2 gene prior to inoculation of the SCID mice. Control treatments with sense and nonsense oligonucleotides was also performed. At 28 days the sense, nonsense and untreated cell SCID mice had developed lymphoma, however, the antisense treated group failed to develop lymphoma. The findings demonstrate the modelling of B-cell lymphoma bearing the t(14;18) translocation and the ability to modify the lymphoma process with the use of antisense oligonucleotides to the BCL-2 gene. Reduction of the BCL2 protein suppresses the oncogenic potential of these lymphoma cells confirming that it plays an essential role in the development of malignancy.
 ...
PMID:Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model. 808 13

This work was undertaken with the purpose of clarifying the factors that modulate the transformation of human breast epithelial cells. For accomplishing this goal, it was necessary to establish the adequate culture conditions for maintaining primary cultures of breast tissue for their treatment with genotoxic agents. It also was determined whether primary cultures generated from these tissues maintained the basic biological properties of the host. In this work we have been able to show that the in vivo developmental stage of the gland is important in the expression of an early transformation phenotype after treatment with chemical carcinogens in vitro; furthermore, that the culture conditions, mainly the calcium concentration in the medium, are important in the selection of that specific phenotype. Four carcinogens, 7,12-dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene (BP), methyl-N-nitro-nitrosoguanidine (MNNG), and N-methyl-N-nitrosourea (NMU) were used for treating primary human breast epithelial cell (HBEC) cultures. Ten out of 20 samples tested expressed survival efficiency in agar methocel. The immortalized human breast epithelial cell line MCF-10 was treated with the same chemical carcinogens, which induced point mutations in codons 12 and 61 and the expression of malignant phenotypes in treated cells. MCF-10 cells transfected with the mutated c-Ha-ras gene exhibited the same malignant phenotypes shown by carcinogen-treated cells, mainly tumorigenesis in SCID mice. It was concluded that both chemical carcinogens and mutated ras gene induce malignant transformation of immortalized HBEC, which suggests that the critical point in the transformation pathway is the immortalization of the cell.
 ...
PMID:A critical approach to the malignant transformation of human breast epithelial cells with chemical carcinogens. 835 40

Studies on liver metastasis of human colon cancer are limited because of a lack of suitable animal models. In this study, the usefulness of mice with severe combined immunodeficiency (SCID), which congenitally lack functional T and B lymphocytes, was evaluated in comparison with currently available nude mice. Three human colon cancer xenografts transplantable into nude mice were disaggregated enzymatically to obtain tumor cell suspensions, and implanted intrasplenically into SCID and nude mice. The incidence of splenic tumorigenesis and of liver metastases were significantly greater in SCID mice for all xenografts, in comparison with nude mice. In total, 33 of 36 SCID mice and 17 of 43 nude mice developed liver metastases. On the basis of this result, we conclude that SCID mice would be a more suitable model than nude mice for studying liver metastasis of human colon cancer.
 ...
PMID:A suitable model for experimental liver metastasis of human colon cancer xenografts using mice with severe combined immunodeficiency. 844 Dec 64

Well-characterized murine mutations are powerful analytical tools for the genetic analysis of tumorigenesis. We crossed the multiple intestinal neoplasia (Min) allele of adenomatous polyposis coli (Apc), which produces a profound pre-disposition to intestinal neoplasia, with the severe combined immunodeficiency (scid) mutation, which causes defective double-strand DNA repair and severe immunodeficiency, on the common C57BL/6J genetic background to assay for any combined effect on intestinal tumorigenesis. Several phenotypic traits were exacerbated in an apparently additive manner in the double mutant mice, including reduced immunoglobulin levels, reduced body weight and increased morbidity. However, quantitation and histological evaluation of polyp phenotype indicated that these mutations did not interact to affect either polyp frequency or progression. Thus, neither genome instability nor lack of immunosurveillance conferred by scid contributes to intestinal polyps in this model.
 ...
PMID:Frequency and histological appearance of adenomas in multiple intestinal neoplasia mice are unaffected by severe combined immunodeficiency (scid) mutation. 856 25

The transcription factor E2F is regulated during the cell cycle through interactions with the product of the retinoblastoma susceptibility gene and related proteins. It is thought that E2F-mediated gene regulation at the G1/S boundary and during S phase may be one of the rate-limiting steps in cell proliferation. It was reported that in vivo overexpression of E2F-1 in fibroblasts induces S phase entry and leads to apoptosis. This observation suggests that E2F plays a role in both cell cycle regulation and apoptosis. To further understand the role of E2F in cell cycle progression, cell death, and tumor development, we have blocked endogenous E2F activity in HBL-100 cells, derived from nonmalignant human breast epithelium, using dominant-negative mutants under the control of a tetracycline-dependent expression system. We have shown here that induction of dominant-negative mutants led to strong downregulation of transiently transfected E2F-dependent chloramphenicol acetyl transferase reporter constructs and of endogenous c-myc, which has been described as a target gene of the transcription factor E2F/DP. In addition, we have shown that blocking of E2F could efficiently protect from apoptosis induced by serum starvation within a period of 10 d, whereas control cells started to die after 24 h. Surprisingly, blocking of E2F did not alter the rate of proliferation or of DNA synthesis of these cells; this finding indicates that cell-cycle progression could be driven in an E2F-independent manner. In addition, we have been able to show that blocking of endogenous E2F in HBL-100 cells led to rapid induction of tumor growth in severe combined immunodeficiency mice. No tumor growth could be observed in mice that received mock-transfected clones or tetracycline to block expression of the E2F mutant constructs in vivo. Thus, it appears that E2F has a potential tumor-suppressive function under certain circumstances. Furthermore, we provide evidence that dysregulation of apoptosis may be an important step in tumorigenesis.
 ...
PMID:Blocking the transcription factor E2F/DP by dominant-negative mutants in a normal breast epithelial cell line efficiently inhibits apoptosis and induces tumor growth in SCID mice. 864 62

The salient feature of solid tumor growth is the strict dependence on local angiogenesis. We have previously demonstrated that IL-8 is an angiogenic factor present in freshly isolated specimens of human non-small cell lung cancer (NSCLC). Using a model of human NSCLC tumorigenesis in SCID mice, we now report that IL-8 acts as a promoter of human NSCLC tumor growth through its angiogenic properties. Passive immunization with neutralizing antibodies to IL-8 resulted in more than 40% reduction in tumor size and was associated with a decline in tumor-associated vascular density and angiogenic activity. IL-8 did not act as an autocrine growth factor for NSCLC proliferation. The reduction in primary tumor size in response to neutralizing antibodies to IL-8 was also accompanied by a trend toward a decrease in spontaneous metastasis to the lung. These data support the notion that IL-8 plays a significant role in mediating angiogenic activity during tumorigenesis of human NSCLC, thereby offering a potential target for immunotherapy against solid tumors.
 ...
PMID:Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice. 867 90

The success of solid tumor growth and metastasis is dependent upon angiogenesis. Neovascularization within the tumor is regulated, in part, by a dual and opposing system of angiogenic and angiostatic factors. We now report that IP-10, a recently described angiostatic factor, as a potent angiostatic factor that regulates non-small cell lung cancer (NSCLC)-derived angiogenesis, tumor growth, and spontaneous metastasis. We initially found significantly elevated levels of IP-10 in freshly isolated human NSCLC samples of squamous cell carcinoma (SCCA). In contrast, levels of IP-10 were equivalent in either normal lung tissue or adenocarcinoma specimens. The neoplastic cells in specimens of SCCA were the predominant cells that appeared to express IP-10 by immunolocalization. Neutralization of IP-10 in SCCA tumor specimens resulted in enhanced tumor-derived angiogenic activity. Using a model of human NSCLC tumorigenesis in SCID mice, we found that NSCLC tumor growth was inversely correlated with levels of plasma or tumor-associated IP-10. IP-10 in vitro functioned as neither an autocrine growth factor nor as an inhibitor of proliferation of the NSCLC cell lines. Reconstitution of intratumor IP-10 for a period of 8 wk resulted in a significant inhibition of tumor growth, tumor-associated angiogenic activity and neovascularization, and spontaneous lung metastases, whereas, neutralization of IP-10 for 10 wk augmented tumor growth. These findings support the notion that tumor-derived IP-10 is an important endogenous angiostatic factor in NSCLC.
 ...
PMID:Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. 906 58


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