Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary germ cell neoplasms of the central nervous system (CNS) are rare tumors which generally respond to radiotherapy. Experience is limited in managing the refractory patient. We report a patient whose suprasellar dysgerminoma responded completely to 5,000 rad. Seven years later, disease recurrence was refractory to an additional 4,000 rad. Theorizing that the "blood-brain barrier" was no longer intact after extensive radiotherapy and tumor involvement of the ventricular system, the patient was treated with systemic bleomycin, cisplatin, and vinblastine. Pharmacokinetic studies revealed that the bleomycin and cisplatin entered the cerebrospinal fluid. Serial CT scans and CSF levels of beta-HCG confirmed the clinical impression of a partial remission. Subsequent tumor progression was refractory to therapy with intraventricular bleomycin. It is concluded that systemic chemotherapy may be beneficial in certain cases of CNS germ cell neoplasms.
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PMID:Treatment of a primary intracranial germ cell tumor with systemic chemotherapy. 616 45

Specimens of CSF from 76 children without neurologic disease and from 191 children with neurosurgical conditions were assayed for polyamine content. Putrescine and spermidine concentrations decreased with age. In children with intracranial tumors, polyamine concentrations in lumbar CSF were comparable with those in ventricular CSF. Putrescine level was significantly increased in children with medulloblastomas. Spermidine level was increased in children with medulloblastomas, glioblastomas, and astrocytomas. Concentrations of putrescine and spermidine were significantly increased in infants with myelomeningocele and hydrocephalus. Spermidine concentrations were significantly increased in older children with myelomeningocele, encephalocele, and hydrocephalus. Polyamines thus seem to be increased by rapid cell proliferation and by disorders affecting myelination. Since putrescine and spermidine concentrations may be of use in monitoring tumor progression, the effects of childhood growth and of hydrocephalus must be considered for children whose brain tumors are associated with hydrocephalus.
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PMID:CSF polyamines in childhood. 683 Apr 72

Following local treatment and doxorubicin-containing standard chemotherapy, 42 patients with surgical Stage II or IIIA breast cancer containing ten or more involved axillary nodes and 13 patients with Stage IIIB disease were treated with high-dose chemotherapy (TMJ) consisting of thiotepa (750 mg/m2), mitoxantrone (40 mg/m2), and carboplatin (1000 mg/m2), with autologous bone marrow (ABM) and peripheral stem cell (PSC) transplant, followed by irradiation and/or hormone therapy. Sargramostim (GM-CSF) support was given to most patients. The median time to transfusion independence was two weeks. Severe non-hematologic toxicity was uncommon, with no intensive care admission or treatment-related death. At a median follow-up of 17 months, eight patients have relapsed and five have died of tumor progression. No statement can yet be made regarding adjuvant efficacy, but this high-dose regimen is very well tolerated.
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PMID:TMJ: a well-tolerated high-dose regimen for the adjuvant chemotherapy of high risk breast cancer. 799 67

A leukemoid reaction occurs after inoculation of L1210 leukemic cells into recipient mice and the degree of granulocytosis is correlated with tumor progression. It was found that the sera of leukemic mice contained elevated levels of colony stimulating activity (CSA) when compared with normal mouse sera. Media conditioned by L1210 cells in vitro (L1210-CM) contained CSA which stimulated normal bone marrow myeloid colony growth and an auto-stimulatory activity (ASA) which stimulated L1210 cell proliferation. We studied the effects of trans-retinoic acid (RA) and 1,25 dihydroxyvitamin D3 (VD3) on the production of growth substances by L1210 cells. When L1210-CM was prepared in the presence of RA and VD3, the CSA and ASA were markedly inhibited. A combination of the two agents was more effective than either agent. Mice inoculated with 1 x 10(5) L1210 suspension culture cells treated with either agent or both combined survived significantly longer than controls. Mice inoculated with L1210 cells treated with the two agents combined survived longest. By using antibodies, preliminary analysis of growth substances generated in L1210-CM showed that it contains primarily GM-CSF and M-CSF-like activities which were distinct from ASA. Combination antibody titer assays revealed that ASA was not significantly inhibited with anti-GM-CSF and anti-M-CSF antibodies, while CSA was inhibited by between 61 and 84%. We conclude that RA and VD3 synergistically inhibit the release of growth-enhancing substances by L1210 cells which may reduce the growth advantage of leukemic cells and the resulting leukocytosis in lymphocytic leukemia.
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PMID:Modulation of growth supportive and oncogenic properties of murine leukemia cells. 802 3

Human melanomas may express both in vivo and in vitro functional IL-Rs and may be expected to directly respond to injected IL2. This may generate biological situations which may be favourable for the patient, but also for tumor progression. Here, we analyse the latter hypothesis. MELP is a melanoma cell line derived from a patient whose metastasis increased in size during IL2/IFN alpha biotherapy [correction of biotheraphy]. These cells have been characterized in vitro for their phenotype and for their sensitivity to IL2. In vitro MELP cells express an IL2-R alpha(+) beta(+) gamma(-) phenotype and IL2 treatment induces the acquisition of new functional characteristics represented (i) by the increased surface expression of two markers of metastatic evolution (ICAM-1 and CD44); (ii) by the stable induction of the IL2-R gamma with the appearance of functional IL2-R beta complex, which are also recognized by GM-CSF; (iii) by the inhibition of transcription of a regulatory cytokine such as IL6; (iv) by a differential effect of IL6 on CD44 surface expression in MELP cells treated or not with IL2 (MILG cells); (v) by the acquisition of faster growth rates and appearance of piling up and multilayer cellular organization; (vi) by the development of rapidly growing tumors in nude mice. IL2 induces in MELP cells a tumor progression process that could mimic the metastatic evolution observed in vivo during biotherapy. Therefore, MELP phenotype may help to define a subset of patients in which IL2 therapy may trigger unfavourable evolution.
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PMID:IL2 triggers a tumor progression process in a melanoma cell line MELP derived from a patient whose metastasis increased in size during IL2/INFalpha biotherapy. 864 92

Upon stimulation with LPS, peritoneal-elicited macrophages (PEM) from mammary tumor-bearing mice display a diminished ability to produce nitric oxide (NO) and lyse tumor targets. In contrast, when these cells are stimulated with LPS in combination with IFN-gamma, they perform these functions at normal levels. Kinetic studies revealed that these defects became more pronounced with tumor progression and were accompanied by similar changes in inducible nitric oxide synthase (iNOS) mRNA levels. Since this tumor is known to produce PGE2, granulocyte-macrophage CSF (GM-CSF), and phosphatidyl serine, we evaluated the effects of these products on NO production and cytolytic activity. Pretreatment of normal PEM with PGE2 or recombinant GM-CSF had negligible effects on NO production and cytolytic capacity. In contrast, phosphatidyl serine caused a concentration-dependent inhibition of these functions in response to LPS, which could be partially overcome by the addition of IFN-gamma. Moreover, iNOS mRNA levels paralleled these changes and were analogous to the alterations observed in the tumor-bearers' PEM. iNOS mRNA stability was not reduced in these cells; however, the rate of transcription was diminished relative to normal levels, suggesting that the defects causing these alterations are occurring at or before the level of iNOS transcription. These data implicate tumor-derived phosphatidyl serine in the alterations observed in tumor-bearers' macrophages and suggest that reduced iNOS transcription is responsible for the diminished capacity of these macrophages to produce NO and lyse tumor targets.
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PMID:Phosphatidyl serine is involved in the reduced rate of transcription of the inducible nitric oxide synthase gene in macrophages from tumor-bearing mice. 902 20

Using a human melanoma/Scid xenograft model with the C8161, M24-met, LD-1 and other human melanoma lines to investigate spontaneous metastasis, we made the observation of marked splenomegaly (up to five times normal weight and size) in only those xenografts exhibiting high degrees of spontaneous metastasis. Evaluation of this revealed the cause to be massive myelopoiesis due to ectopic granulocyte/ colony-stimulating factor (G-CSF) production by the melanoma cells. Because of these observations linking G-CSF expression with metastasis of human melanoma, we decided to investigate the mechanism of this ectopic production. No gross amplification or rearrangement of the G-CSF gene could be detected as the basis for the increased transcriptional activity in any of these lines. Human-human somatic cell hybridization studies carried out between the metastatic C8161 and several different nonmetastatic non-G-CSF-expressing lines revealed, in addition to metastatic dominance, 3- to 10-fold enhancement of G-CSF transcription and expression in the fusions compared with C8161 itself. The suggestion of a trans-dominant mechanism was further supported by transfection studies with a human G-CSF promoter-CAT-reporter construct, which revealed 3- to 5-fold increased reporter activity in only those melanoma lines and hybrids expressing G-CSF. Furthermore, no obvious autocrine or paracrine effects of this ectopic G-CSF expression on the melanoma lines' growth or metastasis were apparent, as all of the G-CSF-expressing lines lacked the G-CSF receptor and injections of purified recombinant G-CSF exerted no stimulatory effects on their tumorigenicity, latency, growth, or metastasis in Scid mice. Thus, we advance the hypothesis that G-CSF expression is serving as a marker of a more generalized trans-dominant pathway linked to tumor progression and metastasis. This hypothesis has direct relevance to many human cancers where ectopic hormone or growth factor production occurs with no obvious autocrine or paracrine benefit to the tumor.
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PMID:Ectopic G-CSF expression in human melanoma lines marks a trans-dominant pathway of tumor progression. 906 Aug 33

Macrophage colony-stimulating factor (M-CSF) is a hematopoietin whose actions are essential for growth and survival of macrophages, placental development, ramification of microglia and tumor progression. The expression of the receptor for macrophage colony-stimulating factor (c-fms) is regulated by two distinct promoters: distal and proximal. The distal promoter is active in trophoblasts during embryogenesis and the proximal promoter directs expression to the cells of myeloid lineage. Here we report the generation of transgenic mice expressing beta-galactosidase under the control of the human proximal c-fms promoter and demonstrate the promoter activity in astrocytes, cells of neurological origin that partially take over the role of the macrophages in the central nervous system. Enzymatic activity of beta-galactosidase was detected in homogenated spleen, bone marrow and brain and in the cell extracts from peritoneal macrophages of transgenic mice. Immunohistochemical staining of brain showed the presence of beta-galactosidase in astrocytes. We hypothesize that M-CSF released by astrocytes, upon stimulation by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) or interleukin-1 (IL-1), regulates the expression of its own receptor.
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PMID:The promoter of macrophage colony-stimulating factor receptor is active in astrocytes. 914 89

We compared the cytogenetic pattern of 20 different primary tumor cell cultures (PTCC) of renal cell carcinoma (RCC) to their cytokine secretion and oncogene expression. High secretion of IL-6 (gene locus on chromosome 7p21-p14) was correlated with the gain of an additional chromosome 7. Structural changes involving chromosome 5q22, the site of the GM-CSF gene, were matched with the high secretion of GM-CSF in PTCC. No such association was found for beta 2-microglobulin, TGF-beta 1, TNF-alpha, IL-8, and oncogenes, such as c-fos, c-myc, and pan-ras. Our approach may be useful in simultaneously analyzing several factors contributing to tumor progression and may contribute to understanding the multistep development of RCC.
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PMID:Comparison of cytogenetics, cytokine secretion, and oncogene expression in primary cultures of renal carcinoma cells. 926 Jun 6

Progression of cervical cancer is associated with excessive circulating levels of cytokines, which are known to be modulators of tumor angiogenesis. The concentrations of cytokines and growth factors were assayed using enzyme-linked immunosorbant assays in the serum of 61 women in various stages of cancer [stage 0 (n = 6), stage I (n = 15), stage II (n = 15), stage III (n = 15), and stage IV (n = 10)] and of 20 healthy control subjects. Our results indicated that b-FGF and TNF-beta levels were significantly elevated in stage I, and serum levels of TGF-beta and IL-7 were elevated in stages II-IV of invasive carcinoma. Our experimental subjects had significantly increased serum levels of IL-6, GM-CSF, and angiogenin in stages I-IV of cervical cancer, and TNF-alpha serum levels were elevated in all stages of invasive carcinoma. The serum levels of IL-8 and IL-10 were elevated only in stages II-III, and the levels of IL-2 were elevated in stages III-IV. The serum levels of IL-1 alpha and IL-1 beta remained unaltered in all stages of cancer progression. Progression of cervical cancer is associated with increased serum levels of angiogenin, IL-2, IL-6, IL-7, IL-8, IL-10, b-FGF TNF-alpha, TGF-beta, TNF-beta, and GM-CSF during different stages, all of which have the potential to be angiogenic amplifiers.
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PMID:Circulating serum levels of cytokines and angiogenic factors in patients with cervical cancer. 954 28


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