Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 9E3/CEF4 gene was one of the first inducible chemokine genes to be discovered. Its product, the chicken chemotactic and angiogenic factor (cCAF), is highly homologous to IL-8. It is expressed at low levels in tissues of mesenchymal origin but is highly expressed shortly after wounding and persists throughout the period of granulation tissue formation. It also is highly expressed around Rous sarcoma virus-induced tumors. The most potent natural stimulator of this gene is thrombin and in vivo cCAF is chemotactic for monocytes and lymphocytes and is angiogenic. The chemotactic properties can be potentially important in the inflammatory response and in the deterrence of tumors, whereas the angiogenic properties could be important in wound repair and tumor growth. The very rapid stimulation of 9E3 by thrombin and fast synthesis and secretion of cCAF suggest that this is a new type of stress response protein whose rapid production is designed to protect tissues rather than individual cells.
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PMID:The 9E3/CEF4 gene and its product the chicken chemotactic and angiogenic factor (cCAF): potential roles in wound healing and tumor development. 946 87

Growth of tumors induced by Rous sarcoma virus (RSV) is controlled by alleles at the major histocompatibility complex locus in chickens, indicating that immunological host defense mechanisms play a major role. We show here that the resistance phenotype of CB regressor chickens can be partially reverted by treating the animals with a monoclonal antibody that neutralizes the major serotype of chicken type I interferon, ChIFN-alpha. Injection of recombinant ChIFN-alpha into susceptible CC progressor chickens resulted in a dose-dependent inhibition of RSV-induced tumor development. This treatment was not effective, however, in CC chickens challenged with a DNA construct expressing the v-src oncogene, suggesting that the beneficial effect of type I interferon in this system resulted from its intrinsic antiviral activity and probably not from indirect immunmodulatory effects. By contrast, recombinant chicken interferon-gamma strongly inhibited tumor growth when given to CC chickens that were challenged with the v-src oncogene, indicating that the two cytokines target different steps of tumor development.
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PMID:Protective effects of type I and type II interferons toward Rous sarcoma virus-induced tumors in chickens. 1008 29

These studies were undertaken to determine the feasibility, safety, and efficacy of suicide gene therapy using adenoviral-mediated herpes simplex virus thymidine kinase (ADV/RSV-tk) and the prodrug ganciclovir (GCV) in an orthotopic murine bladder cancer model. We utilized a replication-defective adenoviral construct containing the beta-galactosidase gene as a control and the herpes simplex virus thymidine kinase gene as the therapeutic vector under the transcription control of the Rous sarcoma virus long terminal repeat promoter. Intravesically created, orthotopic bladder tumors were established in syngeneic C3H/He female mice. India ink injection and beta-galactosidase studies were performed to determine if transurethral administration, direct tumor injection, or the combination was the most efficient route of virus administration. Optimal dosing of ADV/RSV-tk was determined by direct tumor injection with increasing viral doses and treatment with GCV. Treatment efficacy, long-term survival, and toxicity were determined in separate but similar controlled experiments. Growth curve studies demonstrated reliable tumor formation by 14 days. Direct transvesical tumor injection resulted in the best distribution and intratumor gene expression as measured by X-gal staining. Dose-ranging experiments demonstrated an optimal viral dose of 5 x 10(8) plaque-forming units and a greater than twofold reduction in tumor growth for the animals treated with ADV/RSV-tk compared to controls. Efficacy studies demonstrated a greater than threefold reduction in tumor growth. No clinical or gross pathologic toxicity was detected. Long-term survival results suggested a survival benefit for the treatment animals compared to controls. We conclude that ADV/RSV-tk in combination with GCV provides effective therapy for orthotopic murine bladder cancer by significantly inhibiting tumor growth with limited toxicity to the host. These data provide further support for testing this suicide gene therapy strategy in human Phase I trials.
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PMID:In vivo adenovirus-mediated suicide gene therapy of orthotopic bladder cancer. 1098 51

Major histocompatibility (B) complex haplotypes B(Q) and B17 were examined for their effect on Rous sarcoma outcome. Pedigree matings of B(Q)B17 chickens from the second backcross generation (BC2) of Line UCD 001 (B(Q)B(Q)) mated to Line UCD 003 (B17B17) produced progeny with genotypes B(Q)B(Q), B(Q)B17, and B17B17. Six-week-old chickens were injected with subgroup A Rous sarcoma virus (RSV). The tumors were scored for size at 2, 3, 4, 6, 8, and 10 weeks postinoculation. A tumor profile index (TPI) was assigned to each bird based on the six tumor scores. Two experiments with two trials each were conducted. In Experiment 1, chickens (n = 84) were inoculated with 30 pock-forming units (pfu) RSV. There was no significant B genotype effect on tumor growth over time or TPI among the 70 chickens that developed tumors. Chickens (n = 141) were injected with 15 PFU RSV in Experiment 2. The B genotype significantly affected tumor growth pattern over time in the 79 chickens with sarcomas. The B(Q)B17 chickens had the lowest TPI, which was significantly different from B17B17 but not B(Q)B(Q). The data indicate complementation because more tumor regression occurs in the B(Q)B17 heterozygote than in either B(Q)B(Q) or B17B17 genotypes at a 15 pfu RSV dose and significantly so compared to B17B17. By contrast, the 30 pfu RSV dose utilized in the first experiment overwhelmed all genotypic combinations of the B(Q) and B17 haplotypes, suggesting that certain MHC genotypes affect the immune response under modest levels of viral challenge.
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PMID:Allelic complementation between MHC haplotypes B(Q) and B17 increases regression of Rous sarcomas. 1119 35

This study evaluated the synergistic effect of Allium sativum (AS) with suicide gene therapy for transitional cell carcinoma (TCC) of the bladder. Subcutaneous TCCs were established in syngeneic C3H/He mice with 1 x 10(5) MBT-2 cells. AS liquid extract was injected at the site of tumor transplantation on Day 1 for three weeks (Experiment I) and into the established tumors weekly for five weeks (Experiment II) in combination with or without gene therapy using a replication-defective adenoviral vector containing a herpes simplex virus thymidine kinase (HSV-TK) gene under the transcriptional control of Rous sarcoma virus (RSV) promoter (Ad-RSV-TK, 5 x 10(8) plaque-forming units) plus ganciclovir (20 mg/kg/day i.p.). AS demonstrated a statistically significant reduction in incidence of TCC (cumulative dose 25 mg of AS). Combination AS-suicide gene therapy significantly inhibited the tumor growth compared with the controls, which was evidenced by apoptosis on histomorphological and immunohistochemical studies. These results suggest that AS had a definite antitumor effect in inhibiting tumorigenesis and growth of TCC in a murine model. AS treatment combined with suicide gene therapy had significant additive antitumor effects on TCC and may provide a novel and effective treatment modality for TCC of the bladder.
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PMID:Allium sativum potentiates suicide gene therapy for murine transitional cell carcinoma. 1134 Oct 51

This study was designed to examine the alloantigen system L effects on Rous sarcomas in three B complex genotypes. The parental stock was 50% Modified Wisconsin Line 3 x White Leghorn Line NIU 4 and 50% inbred Line 6.15-5. Pedigree matings of two B(2)B(5) L(1)L(2) sires to five B(2)B(5) L(1)L(2) dams per sire produced experimental chicks segregating for B and L genotypes. Chicks were inoculated with 20 pock-forming units (pfu) of Rous sarcoma virus (RSV) at 6 weeks of age. Tumors were scored six times over 10 weeks postinoculation after which the tumor scores were used to assign a tumor profile index (TPI) to each chicken. Tumor growth over time and TPI were evaluated by repeated-measures analysis of variance and analysis of variance, respectively. Six trials were conducted with a total of 151 chickens. The major histocompatibility (B) complex affected the responses as the B(2)B(2) and B(2)B(5) genotypes had significantly lower tumor growth over time and TPI than the B(5)B(5) genotype. Separate analyses revealed no significant L system effect in B(2)B(2) or B(2)B(5) backgrounds. However, L genotype significantly affected (P < 0.05) both tumor growth over time and TPI in B(5)B(5) chickens. B(5)B(5) L(1)L(2) birds had TPI significantly lower than B(5)B(5) L(1)L(1) chickens but not B(5)B(5) L(2)L(2). Mortality was lower in the B(5)B(5) L(1)L(2) birds than in B(5)B(5) L(2)L(2) chickens. The L system, or one closely linked, affects the growth and ultimate outcome of Rous sarcomas. The response may depend upon the genetic background as well as MHC type.
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PMID:Alloantigen system L affects the outcome of rous sarcomas. 1185 13

A gene-directed enzyme pro-drug therapy (GDEPT) based on purine nucleoside phosphorylase (PNP), that converts the prodrug, fludarabine to 2-fluoroadenine, has been described, but studies are limited compared with other GDEPTs. We investigated the in vitro and in vivo efficacies of PNP-GDEPT for treating androgen-independent (AI) prostate cancer. The PNP gene controlled by Rous sarcoma virus (RSV) constitutive promoter was delivered using a recombinant ovine adenovirus vector (OAdV220) that uses a different receptor from human adenovirus type 5. In vitro, OAdV220 provided increased transgene expression over a comparable human Ad5 vector in infected AI, murine RM1 prostate cancer cells. Subsequent in vivo testing was therefore confined to OAdV220. Transduction of RM1 cells with OAdV220 before implantation in immunocompetent mice dramatically inhibited subcutaneous (s.c.) tumor growth when fludarabine phosphate was administered systemically and increased mouse survival in a dose-dependent manner. In tumor-bearing C57BL/6 mice, a single intratumoral injection of OAdV220 produced detectable PNP activity for at least 6 days and with prodrug, retarded the growth of aggressive RM1 s.c. tumors by 35% at day 14. There was a consistent trend to reduction of pre-established intraprostatic RM1 tumors. A similar regimen induced significant therapeutic efficacy in human PC3 xenografts. Thus, ovine adenovirus-mediated GDEPT using the PNP system was effective in vivo against AI prostate cancers, the aggressive murine RM1, and the human PC3 lines. Methods that improve viral dissemination and stimulate the immune system in vivo may further improve efficacy.
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PMID:Gene therapy for prostate cancer delivered by ovine adenovirus and mediated by purine nucleoside phosphorylase and fludarabine in mouse models. 1204 Apr 57

Fibronectin (FN) is an extracellular matrix (ECM) protein involved in tumor growth and metastasis. Five human FN cDNA segments encoding for FN fragments, all starting with the II1 repeat and ending with different C-terminal extensions, have been stably expressed in chick embryo fibroblasts (CEF). These FN cDNAs induce the formation of an organized ECM in CEF as long as they retain a sequence coding for a 13-amino acid stretch (FN13), with collagen binding activity, localized between type II2 and I7 repeats. An FN13 synthetic peptide induces in control CEF the assembly of an FN-ECM comparable with that observed in CEF-expressing FN fragments. The activity of FN13 is specific for its amino acid sequence, although the cysteine present in the 6th position can be substituted with a polar serine without affecting the induction of a fibrillar FN-ECM. A less fibrillar matrix is induced by FN13-modified peptides in which the cysteine is methylated or substituted by a non-polar alanine. FN13 induces the assembly of an FN-ECM also in Rous sarcoma virus-transformed CEF lacking the ECM and in hepatoma (SK-Hep1) and fibrosarcoma (HT-1080) human cell lines. FN13 also promotes the adhesion of CEF and Rous sarcoma virus-CEF at levels comparable with those obtained with purified intact FN. Finally, FN13 inhibits the migratory and invasive properties of tumorigenic cells, whereas intact FN favors their migration. All FN13-modified peptides show similar effects, although with reduced efficiency. None of these activities is supported by a scrambled peptide. These data suggest a possible role of FN13 in tumor growth and metastasis inhibition and its possible use as anti-tumorigenic agent.
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PMID:Matrix assembly induction and cell migration and invasion inhibition by a 13-amino acid fibronectin peptide. 1258 55

The chicken major histocompatibility (B) complex (MHC) affects disease outcome significantly. One of the best characterized systems of MHC control is the response to the oncogenic retrovirus, Rous sarcoma virus (RSV). Genetic selection altered the tumor growth pattern, either regressively or progressively, with the data suggesting control by one or a few loci. Particular MHC genotypes determine RSV tumor regression or progression indicating the crucial B complex role in Rous sarcoma outcome. Analysis of inbred lines, their crosses, congenic lines, and noninbred populations has revealed the anti-RSV response of many B complex haplotypes. Tumor growth disparity among lines identical at the MHC but differing in their background genes suggested a non-MHC gene contribution to tumor fate. Genetic complementation in tumor growth has also been demonstrated for MHC and non-MHC genes. RSV tumor expansion reflects both tumor cell proliferation and viral replication generating new tumor cells. In addition, the B complex controls tumor growth induced by a subviral DNA construct encoding only the RSV v-src oncogene. Immunity to subsequent tumors and metastasis also exhibit MHC control. Genotypes that regressed either RSV or v-src DNA primary tumors had enhanced protection against subsequent homologous challenge. Regressor B genotypes had lower tumor metastasis compared with progressor types. Together, the data indicate that B complex control of RSV tumor fate is strongly defined by the response to a v-src-determined function. Differential RSV tumor outcomes among various B genotypes may include immune recognition of a tumor-specific antigen or immune system influences on viral replication.
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PMID:Major histocompatibility (B) complex control of responses against Rous sarcomas. 1510 61

The formation of a provisional extracellular matrix represents an important step during tumor growth and angiogenesis. Proteins that participate in this process become activated and undergo conformational changes that expose biologically active cryptic sites. Activated matrix proteins express epitopes not found on their native counterparts. We hypothesized that these epitopes may have a restricted tissue distribution, rendering them suitable targets for therapeutic human monoclonal antibodies (huMabs). In this study, we exploited phage antibody display technology and subtractive phage selection to generate human monoclonal antibody fragments that discriminate between the activated and native conformation of the extracellular matrix protein vitronectin. One of the selected antibody fragments, scFv VN18, was used to construct a fully human IgG/kappa monoclonal antibody with an affinity of 9.3 nM. In immunohistochemical analysis, scFv and huMab VN18 recognized activated vitronectin in tumor tissues, whereas hardly any activated vitronectin was detectable in normal tissues. Iodine 123-radiolabeled huMabVN18 was shown to target to Rous sarcoma virus-induced tumors in chickens, an animal model in which the epitope for huMab VN18 is exposed during tumor development. Our results establish activated vitronectin as a potential target for tumor therapy in humans.
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PMID:Activated vitronectin as a target for anticancer therapy with human antibodies. 1519 94


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