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)

The role of high-dose chemotherapy; with subsequent autologous bone marrow rescue (AutoBMR) for high risk or recurrence of advanced solid tumor was evaluated in 16 children (August 1998-March 2001). At present, 11 (69%) patients are still alive, showing no evidence of the disease, 11-31 mo after therapy (median follow-up of 17 mo). Tumor progression was reported in 5 (31%) at months 5, 6, 8, 9 and 11 (after AutoBMR rhabdosarcoma--3; Ewing's sarcoma--2). Overall and recurrence-free survival among all patients was 74 and 66%, respectively.
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PMID:[High-dose chemotherapy with autologous bone marrow transplantation in children with high-risk malignant neoformations]. 1245 56

Previous studies of tumor cell-associated procoagulants and fibrinolytic factors have strongly suggested that local thrombin and plasmin generation may be important in tumor growth and dissemination. Given that one central target of both of these serine proteases is fibrin(ogen), a logical extension of this hypothesis is that local fibrin deposition and dissolution may be key determinants of tumor progression. In this paper, the role of fibrin(ogen) and its degradation products in the growth and spontaneous metastasis of Lewis lung carcinoma was directly examined by comparative studies of control and fibrinogen-deficient mice. Fibrinogen deficiency was found to have no effect on the time required for the formation of palpable tumors, tumor angiogenesis, overall tumor architecture, or primary (s.c.) or secondary (pulmonary) tumor growth. However, fibrinogen deficiency markedly reduced the incidence of spontaneous macroscopic metastases in the lung and regional lymph nodes, a process that occurred relatively late in tumor development. Furthermore, a significant quantitative reduction in pulmonary micrometastases was observed in fibrinogen-deficient mice. Quantitative analyses of pulmonary micrometastases in primary tumor-bearing mice indicated that spontaneous showering of tumor cell emboli into the lung was robust, regardless of animal genotype. Hence, our results suggest fibrin(ogen) plays an important role in spontaneous metastasis, facilitating the stable adhesion and/or survival of metastatic emboli after tumor cell intravasation. These studies suggest that therapeutic strategies focusing on hemostatic factors may be effective in controlling solid tumor metastasis, particularly if used for the treatment of micrometastatic disease.
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PMID:Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient mice. 1246 Sep 14

Our report describes a 66-yr-old man who underwent surgical resection of the pancreas twice within a period of 3 yr for primary and recurrent intraductal papillary mucinous tumors (IPMTs). During the second operation, a minute invasive ductal carcinoma (IDC) was accidentally discovered in the resected specimen of the residual pancreas. The similarity and continuity between this IDC and recurrent IPMT were not recognized histologically. A solid tumor was found in the hepatoduodenal ligament 3 mo after the second operation. We performed a third operation, performing laparotomy and intra-operative radiotherapy, but could not extirpate the tumor. A biopsy specimen obtained from the tumor during this third operation revealed adenocarcinoma, and the patient later died because of tumor progression. We immunohistochemically analyzed the expression of HER-2/neu, Smad4, p16, p21, p53, mucin immunophenotypes and the Ki-67 labeling index in this series of pancreatic-duct neoplasias. Overexpression of HER-2/neu and loss of Smad4 were detected in the minute IDC, which was very different from the immunohistochemical features of both the primary and recurrent IPMTs. The IDC also showed a MUC1-positive/MUC2-negative phenotype. Therefore, we suggest that de novo IDC may occur in IPMT patients, especially those with multiple tumor recurrence. The present case may be helpful in understanding the pathogenesis of pancreatic duct lesions.
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PMID:Minute invasive ductal carcinoma of the residual pancreas after distal pancreatectomy for intraductal papillary-mucinous tumor. 1262 31

Molecular cytogenetic methods including fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) can be used for surgically removed solid tumors to obtain information valuable for both biomedical research and clinical oncology. FISH allows cytogenetic analysis even of cells in interphase. In addition, because CGH analysis permits comprehensive analysis of alterations in DNA copy number in a single experiment, it is possible to estimate not only the genetic pathways of carcinogenesis but also the biological characteristics, such as metastatic potential and patient prognosis at the time of diagnosing the solid tumor. The number of DNA copy number aberrations increases with tumor progression, leading to the concept of genetic staging of malignant tumors. Molecular cytogenetic analysis aids in realizing individualized, tailored medicine in cancer patients; therapeutic strategies are constructed for individual patients based on specific genetic alterations.
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PMID:Molecular cytogenetic analysis of solid tumors. 1276 95

The recognition that angiogenesis is a key early event in tumor progression and metastasis has led to the development of new strategies for cancer therapy. The generation of a new blood vessel network under physiological conditions is regulated by the concerted action of activators and inhibitors. Perturbation of this balance, as it occurs in solid tumor growth and metastasis, appears to be a critical point in tumorigenesis. This has led to the "angiogenic switch" hypothesis: the point at which a tumor acquires the potential to induce angiogenesis is a critical step towards malignancy. Based on experimental evidence, prevention of blood vessel development appears to be the mechanism of action of many successful chemopreventive drugs of natural or synthetic origin: a novel concept that we termed "angioprevention". The hypothesis that anti-angiogenesis is at the basis of tumor prevention also suggests that many anti-angiogenic drugs could be used for chemoprevention in higher risk populations or in early intervention. There is a growing body of experimental evidence that anti-angiogenic strategies will contribute to the future therapy of cancer, several compounds with anti-angiogenic properties are now under clinical investigation including anti-inflammatory compounds, as inflammation may play a key role in angiogenesis. We must persevere in the development of novel, powerful and safer angiogenesis inhibitors and in the use of anti-angiogenic drugs in combination with other natural or synthetic anti-cancer agents in a biological therapy strategy.
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PMID:Anti-angiogenesis and angioprevention: mechanisms, problems and perspectives. 1278 31

Recent breast cancer studies have highlighted the importance of interactions between cancer epithelium and tumor stroma. Recently, the focus of solid tumor investigations has shifted from mutations in carcinomatous epithelium to disturbances of tissue organization in cancer. The genetic basis of this microenvironment, however, remains to be clarified. To begin to resolve this problem, a total genome loss of heterozygosity (LOH) scan was done on epithelial and stromal DNA from 134 sporadic invasive breast carcinomas. In addition to detecting more frequent LOH at three loci in stroma than in epithelium, we found strong evidence that LOH frequencies were significantly elevated in specific regions of each chromosome. We detected 57 markers, which were preferentially lost either in stroma (n = 38) or epithelium (n = 19), relative to the background LOH frequencies on their respective chromosomes. This multiplicity of stromal cell LOH, and hence loss of genetic material, provides a possible mechanism for interpatient variation in host-stromal response to invading adenocarcinoma cells. This is consistent with a model in which initial, random LOH occurs equally among epithelium and stroma, but subsequent clonal selection is driven by factors, which appear to be distinctly different between malignant epithelial and surrounding stromal cells. Genetic alterations in stroma did not mimic those in epithelium, but they could play a different and parallel role in carcinogenesis and tumor progression, probably by modifying some features specific to breast cancer.
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PMID:Combined total genome loss of heterozygosity scan of breast cancer stroma and epithelium reveals multiplicity of stromal targets. 1549 39

Human neuroblastoma (NB) is the second most frequent solid tumor of childhood and represents a highly heterogeneous disease at clinical and biologic levels. Little progress has been made to improve the poor prognosis of patients with high-stage NB. Tumor progression and metastatic dissemination still represent major obstacles to the successful treatment of advanced stage disease. In order to develop and evaluate new, targeted, therapeutic strategies, fully defined and biologically relevant in vivo models of NB are strongly needed. We have developed an orthotopic model of metastatic human NB in the nude mouse, using 2 well-characterized NB cell lines. Tumor growth, vascular properties and metastatic patterns were investigated using a sensitive and newly developed in vivo echographic technology in addition to immunohistochemistry and PCR analyses. Results show that implantation of low numbers of NB cells directly into the adrenal gland of nude mice resulted in rapid and homogeneous tumor growth without tumor morbidity. Nude mice were shown to rapidly develop highly vascularized adrenal tumors that selectively metastasized to the liver and bone marrow. In addition, the newly formed mouse vessels in orthotopic but not in heterotopic tumors, were found to express the highly angiogenic alphavbeta3 integrin marker, indicating the development of a truly malignant neovasculature in orthotopic conditions only. This observation confirms the impact of the regional microenvironment on tumor biology and suggests the existence of cross-talk with the tumor cells. In conclusion, such model faithfully reproduces the growth, vascular and metastatic patterns as observed in patients. It therefore represents a powerful and biologically relevant tool to improve our understanding of the biology of NB and to develop and assess new antiangiogenic and metastasis-targeted therapies.
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PMID:In vivo echographic evidence of tumoral vascularization and microenvironment interactions in metastatic orthotopic human neuroblastoma xenografts. 1551 41

Tumor growth and metastasis depend on angiogenesis; therefore, efforts are made to develop specific angiogenic inhibitors. Halofuginone (HF) is a potent inhibitor of collagen type alpha1(I). In solid tumor models, HF has a potent antitumor and antiangiogenic effect in vivo, but its effect on brain tumors has not yet been evaluated. By employing magnetic resonance imaging (MRI), we monitored the effect of HF on tumor progression and vascularization by utilizing an implanted malignant fibrous histiocytoma metastatic rat brain tumor model. Here we demonstrate that treatment with HF effectively and dose-dependently reduced tumor growth and angiogenesis. On day 13, HF-treated tumors were fivefold smaller than control (P < .001). Treatment with HF significantly prolonged survival of treated animals (142%; P = .001). In HF-treated rats, tumor vascularization was inhibited by 30% on day 13 and by 37% on day 19 (P < .05). Additionally, HF treatment inhibited vessel maturation (P = .03). Finally, in HF-treated rats, we noticed the appearance of a few clusters of satellite tumors, which were distinct from the primary tumor and usually contained vessel cores. This phenomenon was relatively moderate when compared to previous reports of other antiangiogenic agents used to treat brain tumors. We therefore conclude that HF is effective for treatment of metastatic brain tumors.
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PMID:Halofuginone inhibits angiogenesis and growth in implanted metastatic rat brain tumor model--an MRI study. 1554 56

Angiogenesis and inflammation play critical roles in tumor growth. Using an in vivo tumor model, we report that thalidomide (100 mg kg(-1)day(-1)) or clotrimazole (120 mg kg(-1) day(-1)), inhibit blood vessel formation (determined by hemoglobin content), leukocyte recruitment [myeloperoxidase (MPO) activity; N-acetylglucosa-minidase (NAG) activity], and vascular endothelial growth factor production. Inhibition of angiogenesis ranged from 35% to 65%. Clotrimazole was the most potent antiangiogenic compound and the agent capable of inhibiting tumor growth. Thalidomide was able to reduce the inflammatory reaction (MPO and NAG activities) by 50% to 70%, but was unable to delay tumor development. These results suggest that for this type of solid tumor the degree of neovascularization, rather than inhibition of inflammatory cell recruitment, is a determinant factor in tumor development. As the contribution of angiogenesis and inflammation to cancer progression vary markedly among different tumor types, it may be relevant to consider these factors in cancer therapy using antiangiogenesis/antiinflammatory approaches.
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PMID:Differential effects of antiangiogenic compounds in neovascularization, leukocyte recruitment, VEGF production, and tumor growth in mice. 1558 Oct 54

Central nervous system (CNS) cancers are the second most frequent malignancy (and the most common solid tumor) in childhood. In recent years, significant advances in surgery, radiotherapy, and chemotherapy have improved survival in children with these tumors. However, a significant proportion of patients with CNS tumors suffer progressive disease despite such treatment. Advances in the understanding of the nature of the blood-brain/tumor barrier, chemotherapy resistance, tumor biology, and the role of angiogenesis in tumor progression and metastases have led to the advent of newer therapeutic strategies that circumvent these obstacles or target specific receptors that control signal transduction and/or angiogenesis in tumor cells. Ongoing clinical trials will determine whether these novel treatment modalities will improve outcomes for children with brain tumors.
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PMID:Recent advances in the treatment of pediatric brain tumors. 1564 97


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