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)

Feline leukemia is an infectious disease caused by a horizontally transmitted virus. Infection of animals or cultured cells with feline oncornaviruses results in the expression of a specific cell membrane antigen, feline oncornavirus-associated cell membrane antigen (FOCMA). The humoral antibody response to FOCMA is directly correlated with tumor progression. The measurement of this antibody is a useful tool for determining virus exposure. Using this procedure it was determined that cats living in leukemia "cluster" households as well as cats used as contact controls in virus injection experiments have a risk of infection of 90% or higher.
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PMID:Immune response of healthy and leukemic cats to the feline oncornavirus-associated cell membrane antigen. 16 20

Infection of normal human melanocyte and nevus cultures with an adenovirus 12-Simian Virus 40 hybrid virus (Ad12-SV40) produced transformed cells that expressed SV40-T antigen. The Ad12-SV40 cells exhibited rapid cell proliferation to high cell densities and efficient growth in soft agar, but none of 15 transformed melanocyte and nevus cultures formed tumors when injected s.c. or under the renal capsule into athymic nude mice. While the Ad12-SV40-transformed cells lost certain properties associated with the melanocytic phenotype, i.e., pigmentation, tyrosinase activity and melanosome content, the expression of melanoma-associated antigens, including nerve growth factor receptor, p97 melano-transferrin, and chondroitin sulfate proteoglycan, remained stable. The transformed melanocytes acquired the ability to express HLA-DR antigen, which is found on nevus and melanoma cells. Total ganglioside patterns in Ad12-SV40-transformed cells changed to reflect more advanced stages of tumor progression. Transformed melanocytes, like nevus and melanoma cells, showed increased GD3 content and transformed nevus cells increased GD2 which is a feature of malignant melanoma cells. Ad12-SV40-transformed human melanocytes and nevus cells are useful tools for studying tumor progression under experimental conditions.
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PMID:Transformation of normal human melanocytes and non-malignant nevus cells by adenovirus 12-SV40 hybrid virus. 255 80

Infection of epithelial cells with human papillomavirus is an important early event in the development of cervical dysplasia. However, progression to overt malignancy appears dependent upon further genetic and/or epigenetic events. We have recently developed methodologies for the simultaneous analysis of loss of heterozygosity (LOH) at multiple PCR-based microsatellite loci using semiautomated fluorescent DNA sequencing technology to determine the locations of tumor suppressor genes which are inactivated during tumor progression. While examining 30 microsatellite loci for LOH on chromosomes 3p, 4, and 11q, we detected novel tumor-specific alleles indicative of microsatellite instability (MI). The methodology allowed rapid and accurate comparison of over 3000 genotypes from 89 primary tumors and 10 cervical carcinoma-derived cell lines and showed that five tumors (5.6%) and one human papillomavirus-negative cell line, C33A, had genetic features consistent with a replication error (RER+) phenotype as defined by MI at two or more loci. In each of the RER+ tumors, LOH was also observed at one or more loci on each of the three chromosomes examined. These findings suggest that defects in DNA repair-associated genes are rarely acquired and do not supersede allelic loss during cervical carcinogenesis. In addition, the semiautomated multiplex approach has proven unequivocal in the detection and interpretation of MI and should greatly accelerate the rapidity and accuracy of analysis of such defects in tumors. Moreover, the number of loci that can be relatively easily examined in this way will also allow a detailed statistical consideration of the importance of such events.
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PMID:Analysis of replication error (RER+) phenotypes in cervical carcinoma. 864 Aug 35

Infection of the human cervix with certain papillomavirus subtypes is associated with the development of neoplastic squamous lesions that can progress to overt cervical malignancies. Recently, multistage squamous carcinogenesis has been achieved in K14-HPV16 transgenic mice, wherein expression of the human papillomavirus (HPV) type 16 early genes is targeted to basal squamous epithelial cells by regulatory elements of the human keratin-14 (K14) promoter. Immunostaining of the endothelial marker vWf revealed a parallel upregulation of angiogenesis during the early neoplastic stages in both human cervix and the epidermis of K14-HPV16 transgenic mice. Moreover, high-grade premalignant lesions and cancers in humans and transgenic mice were characterized by an additional increment in the number of new capillaries and close apposition of the microvasculature to the overlying neoplastic epithelium. Expression of the potent angiogenic factor VEGF was progressively up-regulated during carcinogenesis in both species, correlating with the increased density and altered distribution of the microvasculature. Thus, angiogenesis occurs during the premalignant stages of squamous carcinogenesis in both human cervical disease and a relevant transgenic model and may be controlled by similar molecular mechanisms in both species. These results validate the use of the transgenic model to elucidate the role of angiogenesis during HPV-associated neoplastic progression.
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PMID:Cross-species comparison of angiogenesis during the premalignant stages of squamous carcinogenesis in the human cervix and K14-HPV16 transgenic mice. 910 16

Numerous studies have demonstrated the importance of urokinase plasminogen activator (uPA) and its receptor, uPAR, in the processes of tumor progression and metastasis. Thus, the uPA/uPAR interaction may represent an important target for inhibiting metastatic disease. The baculovirus expression system was used to produce high levels of a secreted uPA-Immunoglobulin G fusion protein (uPA-IgG) which could then be used for displacing uPA from the surface of tumor cells. The recombinant uPA-IgG fusion protein was placed under the control of either the viral polyhedrin promoter or a copy of the viral basic protein promoter. Recombinant viruses were then used to infect Sf9 and BTI-Tn-5B1-4 cells. Infection of both cell types resulted in the production of secreted uPA-IgG. The molecular mass of the secreted protein as determined by SDS-PAGE was approximately 40 kDa. The highest level of secreted uPA-IgG, 444 microg/ml, was found in the culture medium of BTI-Tn-5B1-4 cells 72 h post-infection with the basic protein promoter-uPA-IgG virus. In the case of Sf9 cells, the highest level of secreted protein was 195 microg/ml. The amount of cell-associated uPA-IgG in infected BTI-Tn-5B1-4 cells was significantly less than that of infected Sf9 cells, reflecting the superior secretory capability of the BTI-Tn-5B1-4 cells. The uPA-IgG was readily purified using a combination of zinc chelate and sephacryl S-100 column chromatography. Routinely, greater than 100 mg of greater than 95% pure protein could be obtained per liter of culture medium collected at 72 h post-infection of BTI-Tn-5B1-4 cells with the basic protein promoter virus. BIAcore analysis and competition binding assays using LOX human malignant melanoma cells expressing uPAR indicated that the purified recombinant protein possessed similar ligand binding characteristics to that of human uPA.
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PMID:Production of a urokinase plasminogen activator-IgG fusion protein (uPA-IgG) in the baculovirus expression system. 918 59

Sixty patients with poor-prognosis malignant lymphoma associated with acquired immunodeficiency syndrome (AIDS) were treated with a standard chemotherapy regimen: cyclophosphamide 600 mg/m2 i.v., day 1; vincristine 1.4 mg/m2 i.v., day 1; epirubicin 70 mg/m2 i.v., day 1; and bleomycin 10 mg/m2 i.v., on day 14. Granulocyte colony-stimulating factor, 5 microg/kg/day, was administered subcutaneously on days 4-14 to ameliorate severe myelosuppression. All patients were in an advanced stage of AIDS with <200 absolute CD4+ cells/mm3 and the presence of adverse prognostic factors related to lymphoma, such as high or high-intermediate clinical risk, multiple extranodal involvement, presence of bulky disease, and high levels of beta 2 microglobulin. Complete response (CR) was achieved by 33 patients (54%); no partial response was observed, and 27 cases were considered failures. All 27 died secondary to tumor progression without any response to salvage chemotherapy. Twenty patients in CR died of opportunistic infections related to AIDS. Actuarial 5-year survival shows that time to treatment failure for the 13 patients who remain in CR is 3.1 years. However, disease-free survival was 14.5 months. Overall survival for the entire group was 13.6 months. Side effects secondary to chemotherapy were frequent and severe, but no death related to treatment was observed. Infection-related granulocytopenia was observed in 27 cycles (8%). This study indicates that standard chemotherapy could be useful in patients with AIDS-associated lymphoma because CR rate, duration of remission, and survival were similar to those with other intensive, but more toxic, regimens. Until a new and better therapy for AIDS is found, treatment of patients with AIDS-related lymphoma will be regarded as palliative, and less toxic regimens will be considered. The use of a standard regimen appears to be an adequate therapeutic approach in this group of patients.
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PMID:Treatment of acquired immunodeficiency syndrome-related lymphoma with a standard chemotherapy regimen. 1003 62

Major advances in cancer therapy result from development of multidrug chemotherapy regimens. Besides death from tumor progression, infections are currently one of the major causes of mortality and morbidity. Because of the risk of complications and mortality, the treatment for febrile neutropenia is admission to hospital and administration of broad-spectrum antibiotics. Response rates of initial antimicrobial treatment vary considerably (40-92%). Due to the heterogeneity of populations in randomized studies, comparison of efficacy and identification of risk factors is limited. This is the main reason why the European Society of Biomodulation and Chemotherapy (ESBiC) is conducting a surveillance study that concentrates more on the evaluation of risk factors than on the therapeutic outcome of prospective randomized antimicrobial regimens: European Surveillance of Infections in Cancer Patients (ESIC). The present contribution is to determine which cancer patients are at low risk for fever, and can benefit from first-line treatment with treatment options such as monotherapy as well as on an outpatient basis.
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PMID:European Surveillance of Infections in Cancer Patients--ESIC. 1039 5

Infection with specific genotypes of human papillomavirus (HPV) has been strongly implicated in cervical carcinogenesis. However, HPV infection alone is insufficient for malignant transformation of the cervical epithelium. An alteration of microsatellite repeats is the result of slippage owing to strand misalignment during DNA replication and is referred to as microsatellite instability (MSI). These defects in DNA repair pathways have been related to human carcinogenesis; however, the role of MSI in the tumorigenesis of cervical cancer remains unclear. The clinical and pathological features of cervical cancers which are MSI-positive have also not been fully characterized. This study investigated the prevalence of MSI in cervical cancer and its relationship to clinico-pathological characteristics and HPV infection. Polymerase chain reaction-based microsatellite assay combined with tissue microdissection was used to examine for MSI in 50 cervical squamous cell carcinomas in Hong Kong women. In addition, the immunohistochemical staining was performed to determine the expression of major DNA mismatch repair genes, hMSH2 and hMLH1. Six cases (12%) displayed a low frequency of MSI (MSL-L) showing MSI at one locus only in 5 loci examined. Seven cases (14%) showed a high frequency of MSI (MSI-H) having MSI at 2 or more loci. Grouping MSI-L and MSI-H cases together as MSI-positive, statistical analysis of HPV infection, tumor grade, clinical stage and clinical status failed to disclose differences between MSI-positive and MSI-negative cases (p > 0.05). However, MSI-H correlated with advanced stage of disease (p < 0.05). Individuals with MSI-H tumors appeared to have reduced overall survival compared to individuals with MSI-L and MSI-negative tumors, but the difference was not statistically significant (p = 0.059). An absence of either MSH2 or MLH1 expression was observed in 2 MSI-L and 4 MSI-H cases, respectively. The results suggest that MSI is present in a subgroup of cervical squamous cell carcinomas, and defects resulting in MSI may be related to tumor progression and possibly poor prognosis in cervical cancer.
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PMID:Microsatellite instability, expression of hMSH2 and hMLH1 and HPV infection in cervical cancer and their clinico-pathological association. 1158 36

Expression of increased levels of matrix metalloproteinase-9 (MMP-9) has been implicated in tumor progression and angiogenesis. Much of our knowledge of the controls of MMP-9 levels has focused on transcription. Here we show that MMP-9 levels are also controlled by translational efficiency in murine prostate carcinoma cells. The murine prostate carcinoma cells 148-1,LMD and 148-1,PA were derived from a single mouse that had been implanted with urogenital sinus transformed by ras and myc. 148-1,PA secretes little MMP-9 yet has equivalent amounts of MMP-9 mRNA as the cell line 148-1,LMD that secretes substantially more. Infection with a retroviral vector for murine MMP-9 led to more expression of MMP-9 in both cases, but the differential remained. Human MMP-9 is equally expressed in both cells after infection with a vector for human MMP-9 indicating that the effect is species-specific. Pulse chase analysis revealed that MMP-9 was synthesized more rapidly in the 148-1,LMD cells than in the 148-1,PA cells. Markedly more MMP-9 mRNA was associated with polysomes in the cell line synthesizing more MMP-9. These results indicate regulation of MMP-9 synthesis at the level of translational efficiency.
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PMID:Regulation of matrix metalloproteinase-9 (MMP-9) by translational efficiency in murine prostate carcinoma cells. 1191 73

Infection with human papillomavirus (HPV) of specific high-risk type triggers a series of events in target cells, which will eventually lead to development of genital neoplasia. The integration of high-risk HPV DNA into the cell genome has been regarded as a crucial event in tumor progression. With respect to different HPV types, the knowledge of HPV integrated loci is still limited. We have now determined the genomic variation and chromosomal location of HPV 33 DNA in the cell line UT-DEC-1, established from a vaginal mild dysplasia lesion. The viral sequence of the cell line was determined, and a variant of the prototype HPV 33 strain was identified, showing nucleotide substitutions resulting in amino acid changes in the E2, L2 and E4 open reading frames. In late passage UT-DEC-1 cells, a deletion of more than half of the 3' part of E1 and major parts of the E2 and E4 genes provided evidence for integration. The flanking sequences of the integration site were completely homologous to published sequences from chromosomal band 5p14, and remained unchanged in all subclones established from late passage cells. There were no chromosomal deletions or gross rearrangements at the integration site, and only a single heterozygotic copy of HPV 33 was detected. The karyotype of late passage cells showed only minor changes compared with early passage cells. During passaging of the cell line, there were progressive changes towards a malignant phenotype, and in parallel to this, the cells carrying episomal HPV 33 of the early passages was completely superseded by cells containing the integrated virus. Thus, our results show that this single copy heterozygote integration of HPV 33 into chromosome band 5p14 appears to be associated with emergence of cells escaping senescence, and with growth advantage compared with cells carrying episomal virus.
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PMID:Single copy heterozygote integration of HPV 33 in chromosomal band 5p14 is found in an epithelial cell clone with selective growth advantage. 1208 29


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