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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The introduction of therapeutic genes into proliferating tumor cells in vivo by direct intralesional injection of retroviral vectors can provide an effective and valuable approach for the treatment of a variety of solid tumor types. Efficient transduction of tumor cells in situ by direct injection was demonstrated using a retroviral vector containing the beta-galactosidase (beta-gal) gene. Ablation therapy in vivo was demonstrated using a retroviral vector containing the Herpes simplex virus thymidine kinase gene (HSV-TK) to deliver the TK gene into the murine colorectal tumor cell line CT26. Ablation of CT26 tumor cells in situ was achieved by directly injecting high-titer HSV-TK retroviral vector preparations into the site of tumor cell inoculation followed by intraperitoneal (i.p.) delivery of ganciclovir (GCV). This gene therapy strategy demonstrated a markedly lower rate of tumor progression, with several complete regressions, compared to animals in control groups. We also demonstrated that resistance to subsequent challenges with unmodified CT26 cells and an enhanced cellular immune response is associated with tumor regression in immunocompetent animals. Our results demonstrate the feasibility of direct in situ administration of HSV-TK retroviral vectors for the treatment of cancer and suggest that a cellular immune response may be elicited by this therapy.
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PMID:Ablation of tumor cells in vivo by direct injection of HSV-thymidine kinase retroviral vector and ganciclovir therapy. 1041 79

The role of Fas in the regulation of solid tumor growth was investigated. Murine renal carcinoma (Renca) cells were constitutively resistant to Fas-mediated killing in vitro, but exhibited increased expression of Fas and sensitivity to Fas-mediated killing after exposure to IFN-gamma and TNF. Transfected Renca cells overexpressing Fas were efficiently killed in vitro upon exposure to anti-Fas Ab (Jo2). When Fas-overexpressing Renca cells were injected into syngenic BALB/c mice, there was a consistent and significant delay in tumor progression, reduced metastasis, and prolonged survival that was not observed for Renca cells that overexpressed a truncated nonfunctional Fas receptor. The delay of in vivo tumor growth induced by Fas overexpression was not observed in IFN-gamma-/- mice, indicating that IFN-gamma is required for the delay of in vivo tumor growth. However, there was a significant increase of infiltrated T cells and in vivo apoptosis in Fas-overexpressing Renca tumors, and Fas-overexpressing Renca cells were also efficiently killed in vitro by T cells. In addition, a strong therapeutic effect was observed on Fas-overexpressing tumor cells by in vivo administration of anti-Fas Ab, confirming that overexpressed Fas provides a functional target in vivo for Fas-specific ligands. Therefore, our findings demonstrate that Fas overexpression on solid tumor cells can delay tumor growth and provides a rationale for therapeutic manipulation of Fas expression as a means of inducing tumor regression in vivo.
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PMID:IFN-gamma-dependent delay of in vivo tumor progression by Fas overexpression on murine renal cancer cells. 1060 16

During the past decade, the molecular mechanisms in the process of tumor progression, including metastasis and angiogenesis, have become better understood. Cancer metastasis consists of multiple, complex interacting steps. Each of these steps is crucial and limiting, since a failure to complete any one prevents the tumor cell from producing a metastasis. Detachment from the solid tumor by loosening the intercellular junctions and proteolysis of the extracellular matrix enables tumor cells to enter blood- and lymph vessels. The intravasation into the circulation is supported by the secretion of angiogenic factors, which induce degradation of the basal membrane in blood vessels. Adhesion to endothelial cells, extravasation from the circulation, and induction of angiogenesis are further essential steps for completing the metastatic process. Furthermore, it is well known that once a tumor cell has entered circulation, it will survive only by evasion of the immune system. The systematic identification of tumor antigens opens up new possibilities for immunotherapeutic approaches.
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PMID:[Molecular genetic principles of progression of malignant diseases]. 1087 46

We report herein a case of cholangiocarcinoma with large cystic lesions. Computed tomography (CT) demonstrated large cysts in segment IV and the paracaval portion of the caudate lobe, and a solid tumor in the anterior segment of the right lobe of the liver which was contiguous to the cyst in the paracaval portion of the caudate lobe. The large cysts were diagnostically misleading and a liver abscess was suspected. Thus, percutaneous transhepatic drainage of the cyst was performed. The fluid in the cyst was negative bacteriologically, but malignant cells were detected. A CT scan done 2 weeks after drainage of the cyst showed progression of the solid tumor with intrahepatic metastasis and replacement of the cystic lesions by the solid tumor. Following percutaneous transhepatic portal embolization, a right hepatic trisegmentectomy with caudate lobectomy was performed. Pathological examination confirmed cholangiocellular carcinoma. These results indicate that drainage of the cystic lesion induced the tumor progression in the liver. Therefore, the possibility of cholangiocarcinoma with a large cystic lesion should be borne in mind when considering the differential diagnosis of a cystic lesion in the liver, and appropriate surgical therapy should be carefully selected.
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PMID:Rapid progression of intrahepatic cholangiocarcinoma after drainage of large cystic lesions: report of a case. 1111 Apr 7

We examined whether patients with both amyotrophic lateral sclerosis (ALS) and cancer differ from classical ALS patients, and whether motor neuron disease responds to oncological therapy. We analyzed clinical and immunological features of 14 patients (9 men, 5 women; mean age 65.3 years) with pure/definite ALS and cancer. Patients with solid tumor cancer and definite ALS were selected according to the E1 Escorial criteria; cases with ALS plus were excluded. Four patients had breast cancer, three lung adenocarcinoma, and three bowel tumor; hepatocarcinoma, kidney cancer, and mesothelioma were observed in one case each, and in one patient the primary tumor was unidentified. Patients' sera were examined for antinervous system antibodies by means of immunohistochemistry and western blot analysis. Of five patients who underwent surgical therapy, two worsened during the procedure, while the other three had no benefit. The remaining two patients did not improve after chemotherapy and radiotherapy. In none of our cases did the oncological disease progress. Death was a consequence of ALS in all eight patients who died. Median survival was 18 months and did not differ from that of 28 ALS patients matched for age, sex, and onset features (bulbar or spinal). Anti-nervous system antibodies were never detected. We conclude that our group of pure ALS patients with cancer do not significantly differ from patients with classical ALS. They usually die as a consequence of the motor neuron syndrome in the absence of cancer progression. To date we have not observed any response of ALS to antitumor therapy.
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PMID:Patients with amyotrophic lateral sclerosis and cancer do not differ clinically from patients with sporadic amyotrophic lateral sclerosis. 1112 33

It has recently been found that tumor cells express large amounts of urokinase receptor (uPAR) on their surface and that the blood soluble uPAR (suPAR) level in cancer patients is increased. However, the significance of suPAR in tumor progression is still unclear. To investigate the significance of suPAR in evaluating clinical status of solid tumor patients, an immunoradiometric assay (IRMA) based on using two monoclonal antibodies (McAbs) to different epitopes of uPAR was established to determine the serum levels of suPAR in normal individuals and solid tumor patients. The detectable range of this suPAR IRMA was 1.95-500 microg/l. The affinity constant was 4.75x10(9) l/mol. The mean rate of recovery was 101.3%, and the mean coefficients of variation for intra- and interassay were 6.40+/-2.57% (mean+/-S.D., n = 11) and 10.48+/-2.65% (n = 5), respectively. The serum suPAR levels were 2.71+/-1.12 microg/l in 62 normal individuals, 3.71+/-1.69 microg/l in 30 patients with benign tumors, and 5.82+/-2.27 microg/l in 124 patients with malignant tumors. The serum suPAR levels of these two types of tumor patients were increased in comparison with that of normal individuals (P values less than.01 and.001). The extent of their increase in malignant tumors was much greater than in benign tumors (P < .001). The serum suPAR levels of patients with malignant tumors were correlated with tumor invasion, metastasis, and surgical intervention. Our data suggest that IRMA for suPAR could be a sensitive and specific assay and that the serum suPAR level would be a valuable index for evaluating the condition and prognosis of tumor patients in clinic.
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PMID:Detection of soluble urokinase receptor by immunoradiometric assay and its application in tumor patients. 1132 11

Although a considerable amount of effort has been placed on discovering the etiologies of cancer, the majority of the basic cancer research existing today has focused on understanding the molecular mechanism of tumor formation and metastasis. Metastatic spread of tumors continues to be a major obstacle to successful treatment of malignant tumors. Approximately 30% of those patients diagnosed with a solid tumor have a clinically detectable metastasis and for the remaining 70%, metastases are continually being formed throughout the life of the tumor. Even after the tumor is excised, the threat of death is attributable to the metastasis that may occur through the remaining tumor cells. In addition, treating the metastasis often proves futile since metastasis often vary in size, composition, and anatomical location. New treatments blocking the formation of metastasis will provide greater chances of survival for cancer patients. One family of enzymes that has been shown over the years to play a role in tumor progression is the matrix metalloproteinase (MMP) family. The main function of MMPs, also known as matrixins, is degradation of the extracellular matrix physiologic function involving MMPs include wound healing, bone resorption and mammary involution. MMPs, however, also contribute to pathological conditions including rheumatoid arthritis, coronary artery disease, and cancer. Tumor cells are believed to utilize the matrix degrading capability of these enzymes to spread to distant sites. In addition, MMPs also are thought to promote the growth of these tumor cells once they have metastasized. This review will discuss the role of MMPs and their inhibitors in tumor invasion, angiogenesis and metastasis with special emphasis on the gelatinases, MMP-2 and MMP-9.
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PMID:The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. 1134 15

The formation of new microvasculature by capillary sprouting, or angiogenesis, is a prerequisite for solid tumor growth. The genetic alterations required to activate the angiogenic program in tumor angiogenesis are still only vaguely known, but dominantly acting oncoproteins may have a much greater impact than previously realized. Here we have studied the consequences of oncogenic transformation on tumor angiogenesis in a mouse mammary carcinoma model. We provide evidence that the expression of vascular endothelial growth factor (VEGF) and of the VEGF receptor-2 (Flk-1), a signaling system centrally involved in tumor angiogenesis, occurs efficiently in tumors formed by Ras-transformed mammary epithelial cells and that both TGF-beta1 and hypoxia are potent inducers of VEGF expression in these cells. VEGF induction in the tumor periphery is mainly triggered by TGF-beta1, whereas VEGF expression in perinecrotic areas is regulated by both hypoxia and TGF-beta1. As the Ras-transformed tumor cells convert into migrating, fibroblastoid cells that start to produce TGF-beta during tumor progression, the TGF-beta effect on VEGF expression becomes propagated throughout the tumor tissue. Thus, in progressed tumors, areas of TGF-beta1 activation and hypoxia may overlap and hence cooperate to induce VEGF expression and angiogenesis. Nevertheless, the overexpression of VEGF in non-Ras-transformed mouse mammary epithelial cells was not sufficient to promote vascularization in vivo. Based on these findings, we conclude that amongst the multiple mutations that render a normal cell tumorigenic, oncogenic Ras is a major player that in conjunction with the tumor's micro-environment sets the stage for tumor cell invasion and angiogenesis.
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PMID:Transforming growth factor-beta and Ras regulate the VEGF/VEGF-receptor system during tumor angiogenesis. 1177 56

Hypoxia, a common consequence of solid tumor growth in breast cancer and other cancers, serves to propagate a cascade of molecular pathways which include angiogenesis, glycolysis, and alterations in microenvironmental pH. Hypoxia-inducible factors, heterodimeric DNA binding complexes composed of two subunits, provide critical regulation of this response. This review presents a synopsis of the genes induced by hypoxia in the context of breast cancer and discusses how upregulation of HIF-1 activity, and the homologous factor HIF-2, are not only fundamental for the adaptation to hypoxia but also may be critical for tumor progression.
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PMID:Hypoxia-induced pathways in breast cancer. 1224 95

Improved understanding of tumor biology has led to the identification of numerous growth factors that are involved in malignant transformation and tumor progression. Many of these factors induce cellular responses through receptors with intrinsic tyrosine kinase (TK) activity. Therefore, inhibiting receptor TK activity is a way to effectively block the tumorigenic effects that arise from these pathways. The HER family of TK receptors is overexpressed or dysregulated in many types of human cancer. As a result these receptors were identified as targets for cancer therapy. Several agents have been developed that reversibly, or irreversibly, inhibit one, two or all of the HER receptors. Tarceva and Iressa are HER1-TK inhibitors that are advanced in development. Clinical data show that these agents as monotherapy have antitumor activity in patients with various types of solid tumor and are well tolerated; encouraging data are also produced when Tarceva or Iressa are combined with chemotherapeutic agents. Other dual or pan-HER, reversible or irreversible, TK inhibitors are being investigated in phase I trials. Early data show that they are generally well tolerated and have provided evidence of antitumor activity. HER-TK inhibitors are exciting agents that are likely to have a substantial impact on the way we treat patients with cancer.
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PMID:HER-targeted tyrosine-kinase inhibitors. 1242 50


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