Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High- and low-metastatic cells derived from metastatic murine tumors were screened for the differential expression of proto-oncogenes which may code for cell-surface receptors to growth factors. We found that metastatic clones of 3LL carcinoma and T10 sarcoma but not non-metastatic clones of these tumors express a 6.5-kb mRNA that is recognized by a v-fms probe containing a tyrosine kinase domain. The cloning and sequence analysis of a full-length cDNA clone corresponding to the v-fms-related 6.5-kb transcript showed that this transcript is the murine homolog of platelet-derived growth factor alpha (PDGF-alpha) receptor. The cDNA contains an open reading frame that predicts a 1089 amino acid protein. Comparison with the human and rat PDGF-alpha receptor reveals an overall amino acid sequence identity of 91% and 94% respectively. Northern blot analysis shows that this gene is preferentially expressed in the high-metastatic clones and is also selectively expressed in normal mouse tissues. Immunoprecipitation using anti-PDGF-alpha receptor serum shows that 185-kDa and 170-kDa proteins were specifically precipitated from cells of the high-metastatic D122 but not from the low-metastatic A9 cells. The possibility that overexpression of PDGF-alpha receptor in high-metastatic clones may contribute to an increase in the capacity of tumor cells to generate metastases in the lung is discussed.
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PMID:Mouse platelet-derived growth factor alpha receptor: sequence, tissue-specific expression and correlation with metastatic phenotype. 132 4

The involvement of protein kinase C (PKC) in regulation of cellular properties related to tumor cell invasiveness was tested in a murine methylcholanthrene-induced fibrosarcoma tumor cell model. A metastatic clone (IE7) derived from the T10 fibrosarcoma was found to possess 30 and 90% more cytosolic and membrane-bound PKC, respectively, compared with the IC9 metastatic clone. Intravenous injection of IE7 but not IC9 cells resulted in lung tumor formation. Long-term (3 months) treatment of IE7 cells with 500 ng/ml phorbol 12,13-dibutyrate (PDB) resulted in a 4-fold reduction in total PKC activity and increase in the tumor cell metastatic ability. Short-term (2h) PDB treatment induced cytosol-to-membrane PKC translocation and decreased the IE7 cells' ability to form hematogenous metastases. Treatment of IC9 cells with PDB did not render them metastatic. To test the possible involvement of distinct PKC isoenzymes in the determination of metastatic properties, we stained the cells with appropriate anti-PKC antibodies followed by FACS analysis. IC9 and IE7 cells exhibited similar levels of fluorescent intensity when stained with either anti-PKC alpha or anti-PKC beta antibodies. The relative proportion of PKC alpha and PKC beta was not changed following short-term PDB treatment of cells, but the intensity of staining was reduced 1.5- to 2-fold following long-term PDB treatment of both cell types. The results indicate that phorbol ester-induced alterations in PKC levels and subcellular distribution affect the metastatic ability of tumor cells and suggest that tumor promoting agents that promote induction of primary tumors may also affect tumor spread by regulating hematogenous metastases formation.
Invasion Metastasis 1991
PMID:Effect of protein kinase C activating tumor promoters on metastases formation by fibrosarcoma cells. 206 Oct

We have studied an unusual, spontaneous, intradural extramedullary spinal cord tumor in 12 dogs. Animals presented with paraparesis and ataxia early in life (11/12 ranged from 6 to 38 months of age) suggesting that these tumors may be congenital. Various breeds of dogs were represented with four cases in German Shepherds and three in retrievers; there was no sex predisposition. Post-mortem examinations revealed a single intradural mass consistently located between T10 and L2, which produced extensive compression of the spinal cord. Metastasis was never observed and significant pathological changes in other organs were lacking. Microscopic examination revealed solid sheets of ovoid to fusiform cells interspersed with areas of acinar and tubular differentiation. Some areas were rarified and focal squamous metaplasia was observed. Ultrastructural features included the presence of a continuous basal lamina, junctional complexes, microvilli and occasional cilia at the apices of acinar complexes. Immunocytochemical studies did not support a neurectodermal origin. At least 13 case reports of this entity have been previously published and have been designated ependymomas, medulloepitheliomas and neuroepitheliomas. A recent case was diagnosed as a nephroblastoma and we feel that this is an interesting and provocative diagnosis. These tumors could result from remnants of renal primordium which becomes trapped between the dura and the developing spinal cord. However, firm evidence of such a histogenesis is not yet at hand.
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PMID:A novel intradural extramedullary spinal cord tumor in young dogs. 245 49

Metastatic cancer was treated with interleukin 2 and lymphokine-activated killer cells with the addition of the cyclooxygenase inhibitor ibuprofen in an attempt to reduce side effects in 13 patients (eight male and five female). Twenty-six patients treated with only interleukin 2 and lymphokine-activated killer cells formed the control group. After interleukin 2 administration, a significantly increased number of lymphokine-activated killer cells were transfused in ibuprofen-treated patients. Cytotoxic effects were not significantly different in the treated and untreated groups. With regard to cell phenotype, both groups of patients manifested significant activation of the immune system as measured by T10 and OK1a. Symptom scores were dramatically reduced in patients treated with ibuprofen. Temperature above 37 degrees C were rare. Ibuprofen did not significantly alter rate of response in this immunotherapy trial (38% vs 42%). Ibuprofen is now routinely used in all of our current immunotherapy trials.
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PMID:Ibuprofen causes reduced toxic effects of interleukin 2 administration in patients with metastatic cancer. 278 76

A case with recurrent pigmented intraspinal tumour with malignant progression is presented. The primary tumour grew around the nerve roots T9 and T10, was attached to dura and infiltrated the vertebral bone tissue. On light microscopy it was comprised of monomorphic cells with large amount of cytoplasmic pigment and many large pigmented globoid bodies. Mitoses were not observed. On electron microscopy, in addition to cytoplasmic melanosomes of regular size, macromelanosomes were numerous. The tumour cells were surrounded partially by basement membrane like material. On these bases a histological diagnosis of benign pigmented tumour of neural crest origin was suggested (a possible pigmented meningioma or pigmented schwannoma). The patient got a recurrence one year after the primary operation. Biopsy from the re-operation showed histologically the same type of tumour with more pleomorphic cells. Subsequently, the tumour grew progressively and metastases were observed in the lungs and in the skin. The patient died two years after the primary operation. The malignant progression of the tumour and other reports on similar tumours was most consistent with a diagnosis of malignant pigmented schwannoma and this was confirmed later on with immunohistochemical staining showing positive staining for basement membrane components, collagen type IV and laminin as well as a positive staining for S-100 protein. The present findings show that despite benign histological features these tumours can behave very aggressively and stress the need of more information on this type of tumour.
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PMID:Intraspinal pigmented schwannoma with malignant progression. 322 5

Clones of the T10 sarcoma, originated in a (H-2b X H-2k)F1 mouse, differ in their metastatic competence, correlated with differences in the expression of antigens of the two parental haplotypes. In fact, the metastatic phenotype is determined by the H-2Dk antigen. Whether the different major histocompatibility complex gene products control the metastatic phenotype via their different immunogenic properties was tested. The involvement of the immune system in controlling the development of metastases was inferred from experiments in which nonmetastatic T10 cloned cells were found to produce both experimental and spontaneous metastases in syngeneic immune-suppressed mice. After the testing of T-cell-mediated immune responses, metastatic T10 cloned cells, which expressed the H-2Db and H-2Dk antigens, were nonimmunogenic in their syngeneic hosts, whereas nonmetastatic T10 cloned cells, which expressed predominantly the H-2Db antigens, evoked a strong T-cell response. H-2Db and H-2Dk antigens expressed on T10 cells appeared to differ in their immunogenicity. This was further supported by the observation that whereas a good antibody response was elicited by H-2Db antigens expressed on T10 cells, only a low anti-H-2Dk antibody was produced. The different T10 cloned cells were not susceptible to natural killer (NK) activity in an in vitro assay, yet in vivo studies suggested the participation of NK activity in controlling T10 metastasis. In animals with depressed NK activity, metastases were generated even by nonmetastatic clones, whereas in animals in which NK activity was elevated, even metastatic clones failed to generate metastases. Both T-cell-mediated immune responses, probably restricted by the H-2D products and NK reactivity, appeared to participate in controlling the development of metastases by T10 cells.
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PMID:Metastatic capacity of cloned T10 sarcoma cells that differ in H-2 expression: inverse relationship to their immunogenic potency. 389 52

Functional results and survival have been improved in osteosarcoma during the last ten years, thanks to better conservative surgical techniques and more efficient drugs to prevent metastases. Of the several possible programmes of chemotherapy, the authors considered that the T10 programme of Rosen is the most reliable, this author claiming a survival rate of 90 p. 100 with an average follow-up of twenty months. This programme was adopted by the authors in the Paediatric Department of the Gustave Roussy Institute (Villejuif). Thirty one patients were treated and assessed after an average follow-up of 19 months. The results were favourable, only three patients presenting with metastases. One died. Amongst the thirty surviving patients, twenty-three were treated by local resection and eight by amputation.
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PMID:[Chemotherapy of osteogenic sarcoma]. 391 12

Experiments were made to investigate the effect of four anesthetic drugs that are commonly used in surgical practice on the postoperative growth of mouse tumors in syngeneic recipients. These experiments revealed that some of the anesthetics when applied for surgical excision of the local tumor, strongly accelerated postoperative progression of spontaneous lung metastases produced by the 3LL Lewis lung carcinoma and by the B16 melanoma. Some of the drugs caused the appearance of metastases in organs, such as the liver, in which spontaneous metastases are not usually produced by these tumors. A T10 sarcoma clone that does not produce detectable metastases in immune intact mice even following intravenous injection, did produce metastases when injected into animals treated with pentothal sodium.
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PMID:Anesthetic drugs accelerate the progression of postoperative metastases of mouse tumors. 727 67

All pediatric osteosarcomas treated in our hospital between 1985 and 1995 were reviewed. There were 26 patients, 15 males and 11 females, aged 20 or less at diagnosis. All had limb primaries. Nineteen patients had localized disease and seven presented with metastases. Intensive multiagent chemotherapy was given both pre- and postoperatively. Most patients were treated with the Rosen T10 regimen or its modifications. Only one patient had limb salvage surgery; all others had amputation. With a median follow-up of 74 months, the 5-year disease-free survival among patients with localized disease was 65.2%. Being female and having a high 6-hour postinfusion methotrexate level with a median level greater than 700 mumol/L were good prognostic factors. Three of the seven patients with metastatic disease were alive at 21, 26, and 140 months after diagnosis. All of them had lung secondaries. Survival rates achieved in our center were comparable to those reported in literature. However, our amputation rate was high and further development in expertise for limb salvage treatment is a goal.
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PMID:Multidisciplinary management of osteosarcoma: experience in Hong Kong. 961 20

Between 1989 and 1996, 21 skeletally immature patients were treated for osteosarcoma of the extremity. Their average age was 12.6 years (range 9-16 years). We classified the location and extent of the lesion in bone on magnetic resonance imaging (MRI) with reference to the growth plate and joint margin into five subtypes. This classification served as a guide for the level of resection and the type of reconstruction required for a limb salvage procedure. All patients received neoadjuvant chemotherapy using a modified T10 protocol before the definitive operation. These patients were followed up for periods ranging from 11-86 months, with a mean of 35. 5 months. Patients were assessed for (1) local tumour recurrence, (2) metastatic disease, (3) allograft complications and (4) extremity function and joint stability. Excellent function was retained in 2, good in 13 and fair function in 6 patients. The MRI classification proved useful for the resection and provides an insight into the possible functional outcomes.
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PMID:Classifying the location of osteosarcoma with reference to the epiphyseal plate helps determine the optimal skeletal resection in limb salvage procedures. 1044 33


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