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Understanding how insulin-like growth factor-I (IGF-I) signaling in mammary epithelial cells may be modified or interrupted by modifications in the cellular environment may lead to 1) methods to increase the growth and proliferation of normal mammary epithelial cells for an increase in the amount of milk produced on a per animal basis or to 2) the development of medical interventions to disrupt the growth and proliferation of cancerous mammary epithelial cells. IGF-I, a signaling protein provided by stromal cells and through the bloodstream, stimulates the proliferation of mammary epithelial cells and is crucial for mammary development. Collagen I is an extracellular matrix protein (ECM) found in skin and in other connective tissues throughout the body. The guiding question in this dissertation was how IGF-I signaling and how binding protein profile were influenced by autocrine IGF-I and by collagen I. The MAC-T cell line was chosen as the cell model utilized in these investigations because it is an immortalized bovine mammary epithelial cell line known to retain hormonal responsiveness to IGF-I. It was hypothesized that the production of IGF-I by mammary epithelial cells (autocrine secretion) would alter the response of these cells to additional IGF-I by de-sensitizing the IGF-I receptor on the cell surface. The normal mammary epithelial cell does not produce IGF-I and responds to IGF-I supplied either by stromal cells (paracrine pathway) or through the bloodstream (endocrine pathway). The IGF-I secreting bovine mammary epithelial cell line was investigated for the response of the cells to autocrine IGF-I, and the response was compared to the normal, parental cell line. To examine the effect of autocrine IGF-I on the cells, IGF-I was added both to MAC-T cells and to cells transfected to secrete IGF-I (SV40-IGF-I). The cell response of the two cell lines was compared using microphysiometry, a tool that measures IGF-IR stimulation by detecting resultant extracellular acidification. It was found that the SV40-IGF-I cell line retains IGF-I receptor sensitivity, yet, unlike the parental cell line, does not proliferate in response to IGF-I. Both cell lines exhibited increased protein synthesis in response to IGF-I as measured by amino acid uptake (AIB incorporation), but the lack of a proliferation response to additional IGF-I in the SV40-IGF-I cell line suggested that the autocrine cell line exhibited an un-coupling of IGF-IR stimulation with downstream cell proliferation. Both autocrine IGF-I and added IGF-I increased the amount of IGFBP-3 secreted by the cells into growth media. Additionally, it was hypothesized that the presence of collagen I, an important ECM protein, would alter the cell production of insulin-like binding protein-3 (IGFBP-3), a protein that modulates IGF-I interaction with the IGF-I receptor (IGF-IR). The literature reports that surface substrate can affect the phenotypic expression of cells, presumably via interaction with integrins, the cell surface receptors that connect cells to ECM proteins and that are responsible for cell adhesion and for cell migration. It was hypothesized that the MAC-T cells would interact with a collagen I surface (possibly via the a2b1 integrin) and that the stimulation of this transmembrane signaling molecule would in turn impact the IGF-I signaling pathway. Comparison studies on tissue culture plastic, collagen I BIOCOAT, and collagen I gel were performed. It was found that collagen I gel increased IGFBP-3 secretion and decreased insulin-like binding protein-2 (IGFBP-2) secretion in MAC-T cells. The collagen I BIOCOAT did not induce this response. Additional studies were performed to determine if there were differences in IGF-IR phosphorylation, exogenous IGF-I utilization, and IGFBP mRNA production by cells cultured on the three different substrates. IGF-IR phosphorylation was only evident following the addition of IGF-I to MAC-T cells on all three substrates. Measurement of residual IGF-I present in the cultured media of cells on all three substrates by radioimmunoassay did not reveal any differences in the amount of IGF-I present. Northern blot analysis revealed that the addition of IGF-I caused an increase in detected IGFBP-3 mRNA and a decrease in detected IGFBP-2 mRNA across all three surfaces. As measured by ligand blot analysis, cells cultured on all three surfaces showed an increase in IGFBP-3 protein in the media with IGF-I addition, and the collagen I gel showed more IGFBP-3 protein than the other two surfaces. However, cells cultured on collagen I gel showed a decrease in IGFBP-2 protein expression compared to cells cultured on tissue culture both with and without the addition of IGF-I. Cells cultured on tissue culture plastic and on collagen I BIOCOAT did not show a decrease in IGFBP-2 to correspond with the decreased IGFBP-2 mRNA detected in the presence of IGF-I on all three substrates. DNA assays to detect cell proliferation revealed no differences in cell DNA content in the absence of exogenous IGF-I and revealed similar increases in response to IGF-I addition on all three substrates. In conclusion, it was found that autocrine IGF-I un-couples increased IGF-IR stimulation by exogenous IGF-I from a downstream cell proliferation response. IGFBP-3 inhibits the ability of IGF-I to interact with the IGF-IR in MAC-T cells and inhibits subsequent cell proliferation. Collagen I gel increases IGFBP-3 secretion and decreases IGFBP-2 secretion by MAC-T cells. The relevance of this work is that it adds to the body of knowledge in understanding cellular function in mammary epithelial cells. It is known that the growth and the maintenance of living tissue are dependent on an intricate system of intercellular and intracellular responses which are orchestrated by the movement and secretion of proteins and other molecules. Goals of understanding mammary epithelial cell function include having the means to find ways to increase cell functionality via bioengineering and having the means to find ways to restore cells to normal function in disease processes such as cancer. / Ph. D.

O exercício físico intermitente tem se mostrado uma modalidade de elevado gasto calórico e, mesmo quando praticado em altas intensidades, pode ser mantido por grandes períodos de tempo. A suplementação com carboidratos tem sido utilizada e estudada como forma de manutenção do desempenho esportivo. O exercício físico intermitente e a suplementação com fontes carboidratadas produzem alterações hormonais condizentes com as alterações orgânicas provenientes da sua prática. O eixo GH/IGF-I é afetado por ambas as intervenções. Objetivou-se estabelecer um protocolo de treinamento intermitente de alta intensidade para ratos e verificar os efeitos da administração de solução de glicose a 10% sobre as concentrações sanguíneas de lactato e glicemia, além de verificar alterações séricas de GH, IGF-I, IGFBP-I e corticosterona relacionadas à prática deste tipo de exercício físico. Foram verificadas também as concentrações musculares (gastrocnêmio e sóleo) e hepáticas de glicogênio, bem como a expressão gênica do IGF-I e do IGF-Ir nestes tecidos. Para tal, quarenta (40) ratos Wistar machos foram separados em 8 grupos (n=5/grupo): TEC (Treinados, exercitados, com suplementação de carboidrato), TES (Treinados, exercitados, sem suplementação de carboidrato), TNC (Treinados, não exercitados, com suplementação de carboidrato), TNS (Treinados, não exercitados, sem suplementação de carboidrato), SEC (Sedentários, exercitados, com suplementação de carboidrato), SES (Sedentários, exercitados, sem suplementação de carboidrato), SNC (Sedentários, não exercitados, com suplementação de carboidrato), SNS (Sedentários, não exercitados, sem suplementação de carboidrato). O protocolo de exercício físico consistiu de um minuto correndo em esteira a 110% da velocidade final do teste máximo e 30 segundos a 40% desta, num total de 60 minutos, sendo o treinamento de noventa (90) dias. Como resultado foi verificado que o exercício físico agudo se mostrou uma forma de aumentar a expressão gênica de IGF-I, já o treinamento fez com que houvesse uma redução nesta expressão. O aumento da IGFBP-I ocorreu somente em ratos treinados, que apresentaram também uma maior expressão gênica de IGF-Ir no músculo gastrocnêmio quando não suplementados. Os animais não exercitados apresentaram níveis séricos de GH superiores aos exercitados. A corticosterona mostrou concentrações mais elevadas em ratos sedentários do que treinados, com ou sem exercício físico agudo. Conclui-se que o exercício físico agudo em ratos pode, em alguns hormônios estudados, produzir resultados divergentes dos esperados, já o treinamento prolongado tende a reverter as concentrações destes. / The intermittent exercise has been shown to be a kind of high caloric expenditure and, even when practiced at high levels, can be maintained for long periods of time. Supplementation with carbohydrate has been used and studied in order to maintain athletic performance. The intermittent exercise and supplementation with carbohydrate sources produce hormonal changes consistent with the organic changes from its practice. The GH/IGF-I axis is deeply affected by both interventions. The objective was to establish a protocol for high-intensity intermittent training for rats and assess the effects of administrating a glucose solution (10%) on blood concentrations of lactate and glucose in addition to investigating changes in serum GH, IGF-I, IGFBP-I and corticosterone related to the practice of this type of exercise. Also, it was analized the muscle (gastrocnemius and soleus) and hepatic concentrations of glycogen and gene expression of IGF-I and IGF-Ir in these tissues. For such, forty (40) male wistar rats were divided into eight groups (n=5/ group): TEC (trained, exercised with carbohydrate supplementation), TES (trained, exercised without carbohydrate supplementation), TNC (trained, nonexercised with carbohydrate supplementation), TNS (trained, nonexercised without carbohydrate supplementation), SEC (sedentary, exercised with carbohydrate supplementation), SES (sedentary, exercised without carbohydrate supplementation), SNC (sedentary, nonexercised with carbohydrate supplementation), SNS (sedentary nonexercised without carbohydrate supplementation). The protocol consisted of one minute on a treadmill running at 110% of maximum test speed and thirty seconds at 40% of a total 60 minutes (90 days training). As a result it was found that acute exercise proved to be a way to increase gene expression of IGF-I, since the training had led to a reduction in this expression. The increase in IGFBP-I occurred only in trained rats, which also had a higher gene expression of IGF-Ir in the gastrocnemius muscle, when not supplemented. The animals that did no exercise had higher serum GH levels than those exercised. The corticosterone showed higher concentrations in sedentary than in trained rats with or without acute exercise. We conclude that acute exercise in rats may, in some hormones, produce different results from those expected, since the prolonged training tends to reverse these concentrations.

O exercício físico intermitente tem se mostrado uma modalidade de elevado gasto calórico e, mesmo quando praticado em altas intensidades, pode ser mantido por grandes períodos de tempo. A suplementação com carboidratos tem sido utilizada e estudada como forma de manutenção do desempenho esportivo. O exercício físico intermitente e a suplementação com fontes carboidratadas produzem alterações hormonais condizentes com as alterações orgânicas provenientes da sua prática. O eixo GH/IGF-I é afetado por ambas as intervenções. Objetivou-se estabelecer um protocolo de treinamento intermitente de alta intensidade para ratos e verificar os efeitos da administração de solução de glicose a 10% sobre as concentrações sanguíneas de lactato e glicemia, além de verificar alterações séricas de GH, IGF-I, IGFBP-I e corticosterona relacionadas à prática deste tipo de exercício físico. Foram verificadas também as concentrações musculares (gastrocnêmio e sóleo) e hepáticas de glicogênio, bem como a expressão gênica do IGF-I e do IGF-Ir nestes tecidos. Para tal, quarenta (40) ratos Wistar machos foram separados em 8 grupos (n=5/grupo): TEC (Treinados, exercitados, com suplementação de carboidrato), TES (Treinados, exercitados, sem suplementação de carboidrato), TNC (Treinados, não exercitados, com suplementação de carboidrato), TNS (Treinados, não exercitados, sem suplementação de carboidrato), SEC (Sedentários, exercitados, com suplementação de carboidrato), SES (Sedentários, exercitados, sem suplementação de carboidrato), SNC (Sedentários, não exercitados, com suplementação de carboidrato), SNS (Sedentários, não exercitados, sem suplementação de carboidrato). O protocolo de exercício físico consistiu de um minuto correndo em esteira a 110% da velocidade final do teste máximo e 30 segundos a 40% desta, num total de 60 minutos, sendo o treinamento de noventa (90) dias. Como resultado foi verificado que o exercício físico agudo se mostrou uma forma de aumentar a expressão gênica de IGF-I, já o treinamento fez com que houvesse uma redução nesta expressão. O aumento da IGFBP-I ocorreu somente em ratos treinados, que apresentaram também uma maior expressão gênica de IGF-Ir no músculo gastrocnêmio quando não suplementados. Os animais não exercitados apresentaram níveis séricos de GH superiores aos exercitados. A corticosterona mostrou concentrações mais elevadas em ratos sedentários do que treinados, com ou sem exercício físico agudo. Conclui-se que o exercício físico agudo em ratos pode, em alguns hormônios estudados, produzir resultados divergentes dos esperados, já o treinamento prolongado tende a reverter as concentrações destes. / The intermittent exercise has been shown to be a kind of high caloric expenditure and, even when practiced at high levels, can be maintained for long periods of time. Supplementation with carbohydrate has been used and studied in order to maintain athletic performance. The intermittent exercise and supplementation with carbohydrate sources produce hormonal changes consistent with the organic changes from its practice. The GH/IGF-I axis is deeply affected by both interventions. The objective was to establish a protocol for high-intensity intermittent training for rats and assess the effects of administrating a glucose solution (10%) on blood concentrations of lactate and glucose in addition to investigating changes in serum GH, IGF-I, IGFBP-I and corticosterone related to the practice of this type of exercise. Also, it was analized the muscle (gastrocnemius and soleus) and hepatic concentrations of glycogen and gene expression of IGF-I and IGF-Ir in these tissues. For such, forty (40) male wistar rats were divided into eight groups (n=5/ group): TEC (trained, exercised with carbohydrate supplementation), TES (trained, exercised without carbohydrate supplementation), TNC (trained, nonexercised with carbohydrate supplementation), TNS (trained, nonexercised without carbohydrate supplementation), SEC (sedentary, exercised with carbohydrate supplementation), SES (sedentary, exercised without carbohydrate supplementation), SNC (sedentary, nonexercised with carbohydrate supplementation), SNS (sedentary nonexercised without carbohydrate supplementation). The protocol consisted of one minute on a treadmill running at 110% of maximum test speed and thirty seconds at 40% of a total 60 minutes (90 days training). As a result it was found that acute exercise proved to be a way to increase gene expression of IGF-I, since the training had led to a reduction in this expression. The increase in IGFBP-I occurred only in trained rats, which also had a higher gene expression of IGF-Ir in the gastrocnemius muscle, when not supplemented. The animals that did no exercise had higher serum GH levels than those exercised. The corticosterone showed higher concentrations in sedentary than in trained rats with or without acute exercise. We conclude that acute exercise in rats may, in some hormones, produce different results from those expected, since the prolonged training tends to reverse these concentrations.

O exercício físico intermitente tem se mostrado uma modalidade de elevado gasto calórico e, mesmo quando praticado em altas intensidades, pode ser mantido por grandes períodos de tempo. A suplementação com carboidratos tem sido utilizada e estudada como forma de manutenção do desempenho esportivo. O exercício físico intermitente e a suplementação com fontes carboidratadas produzem alterações hormonais condizentes com as alterações orgânicas provenientes da sua prática. O eixo GH/IGF-I é afetado por ambas as intervenções. Objetivou-se estabelecer um protocolo de treinamento intermitente de alta intensidade para ratos e verificar os efeitos da administração de solução de glicose a 10% sobre as concentrações sanguíneas de lactato e glicemia, além de verificar alterações séricas de GH, IGF-I, IGFBP-I e corticosterona relacionadas à prática deste tipo de exercício físico. Foram verificadas também as concentrações musculares (gastrocnêmio e sóleo) e hepáticas de glicogênio, bem como a expressão gênica do IGF-I e do IGF-Ir nestes tecidos. Para tal, quarenta (40) ratos Wistar machos foram separados em 8 grupos (n=5/grupo): TEC (Treinados, exercitados, com suplementação de carboidrato), TES (Treinados, exercitados, sem suplementação de carboidrato), TNC (Treinados, não exercitados, com suplementação de carboidrato), TNS (Treinados, não exercitados, sem suplementação de carboidrato), SEC (Sedentários, exercitados, com suplementação de carboidrato), SES (Sedentários, exercitados, sem suplementação de carboidrato), SNC (Sedentários, não exercitados, com suplementação de carboidrato), SNS (Sedentários, não exercitados, sem suplementação de carboidrato). O protocolo de exercício físico consistiu de um minuto correndo em esteira a 110% da velocidade final do teste máximo e 30 segundos a 40% desta, num total de 60 minutos, sendo o treinamento de noventa (90) dias. Como resultado foi verificado que o exercício físico agudo se mostrou uma forma de aumentar a expressão gênica de IGF-I, já o treinamento fez com que houvesse uma redução nesta expressão. O aumento da IGFBP-I ocorreu somente em ratos treinados, que apresentaram também uma maior expressão gênica de IGF-Ir no músculo gastrocnêmio quando não suplementados. Os animais não exercitados apresentaram níveis séricos de GH superiores aos exercitados. A corticosterona mostrou concentrações mais elevadas em ratos sedentários do que treinados, com ou sem exercício físico agudo. Conclui-se que o exercício físico agudo em ratos pode, em alguns hormônios estudados, produzir resultados divergentes dos esperados, já o treinamento prolongado tende a reverter as concentrações destes. / The intermittent exercise has been shown to be a kind of high caloric expenditure and, even when practiced at high levels, can be maintained for long periods of time. Supplementation with carbohydrate has been used and studied in order to maintain athletic performance. The intermittent exercise and supplementation with carbohydrate sources produce hormonal changes consistent with the organic changes from its practice. The GH/IGF-I axis is deeply affected by both interventions. The objective was to establish a protocol for high-intensity intermittent training for rats and assess the effects of administrating a glucose solution (10%) on blood concentrations of lactate and glucose in addition to investigating changes in serum GH, IGF-I, IGFBP-I and corticosterone related to the practice of this type of exercise. Also, it was analized the muscle (gastrocnemius and soleus) and hepatic concentrations of glycogen and gene expression of IGF-I and IGF-Ir in these tissues. For such, forty (40) male wistar rats were divided into eight groups (n=5/ group): TEC (trained, exercised with carbohydrate supplementation), TES (trained, exercised without carbohydrate supplementation), TNC (trained, nonexercised with carbohydrate supplementation), TNS (trained, nonexercised without carbohydrate supplementation), SEC (sedentary, exercised with carbohydrate supplementation), SES (sedentary, exercised without carbohydrate supplementation), SNC (sedentary, nonexercised with carbohydrate supplementation), SNS (sedentary nonexercised without carbohydrate supplementation). The protocol consisted of one minute on a treadmill running at 110% of maximum test speed and thirty seconds at 40% of a total 60 minutes (90 days training). As a result it was found that acute exercise proved to be a way to increase gene expression of IGF-I, since the training had led to a reduction in this expression. The increase in IGFBP-I occurred only in trained rats, which also had a higher gene expression of IGF-Ir in the gastrocnemius muscle, when not supplemented. The animals that did no exercise had higher serum GH levels than those exercised. The corticosterone showed higher concentrations in sedentary than in trained rats with or without acute exercise. We conclude that acute exercise in rats may, in some hormones, produce different results from those expected, since the prolonged training tends to reverse these concentrations.

Background: Multiple lines of evidence implicate the insulin-like growth factor(IGF) group of proteins in human type 2 diabetes. The actions of IGF-I and IGF-IIare modulated through their interaction with IGF binding proteins. A holisticapproach to study the IGF system is preferable to analyses of individual proteininteractions as the inter-relationships between these proteins are complex. Inparticular, the associations of IGF-II and its associated binding proteins withcardiovascular risk have been inadequately studied. This study aimed to study indetail the genotype and phenotype interactions of the IGF system with longitudinalcardiovascular risk factor trends and phenotypic outcomes in type 2 diabetes.Methods: 1000 subjects of predominantly Caucasian origin from the SalfordDiabetes Cohort were studied. Measurements of IGF proteins (IGF-I, IGF-II,IGFBP-1, IGFBP-2 and IGFBP-3) were performed in 554 of these patients. 991Caucasian subjects were successfully genotyped for 76 single nucleotidepolymorphisms (SNPs) related to ten genes in the IGF system. In this project weanalysed associations of the studied SNPs with the measured IGF proteins as well aslongitudinal risk factor trends. In addition, the baseline concentrations of themeasured proteins were studied for associations with cardiovascular risk factortrends and vascular outcomes.Results: This project demonstrates for the first time that high serum IGF-IIconcentration at baseline predicts longitudinal increases in high-density lipoproteincholesterol. High baseline IGF-II was also observed to predict longitudinal weightloss. High baseline concentration of IGFBP-2 (which has a preferential associationof IGF-II over IGF-I) was associated with a number of favourable longitudinalcardiovascular risk trends like increased HDL cholesterol and decreased diastolicblood pressure. However high IGFBP-2 was also associated with deterioration inrenal function and increased all-cause and cardiovascular mortality. The IGF2 geneand the genes encoding IGFBP-2 and IGFBP-5 (proteins with IGF-II bindingaffinity) were also associated with longitudinal trends in renal function, bloodpressure and cholesterol concentration.Discussion: This study is the most detailed exploration to date of the genotype andphenotype interactions of the IGF system in a Caucasian population with type 2diabetes. Results from this study strongly hint that changes in IGF-II bioavailabilitymay influence inter-individual variations in cardiovascular risk. The precisebiological role of IGF-II merits clarification in future expression studies in renal,adipose and vascular tissues. Replication of significant results in an independentdiabetes cohort and measurement of other IGF binding proteins will be performed inthe next stage of this study.

No description available.

Over the last several years, injectable drugs have been a growing area for the treatment of various therapeutic conditions and they are projected to comprise an even larger proportion among the drugs that will be available in the years to come. The injectable drugs are administered by various routes such as intramuscular (IM), intravenous (IV), subcutaneous (SC) and others, however, the majority of these drugs are administered subcutaneously. Even though subcutaneous delivery has been utilized for a number of years, very little is known about the processes governing the absorption of macromolecules from the interstitial space; and the resulting impact of these processes on the bioavailability (BA) and pharmacokinetic (PK) profiles. Also, there is no established In vitro - In vivo correlation (IVIVC) for subcutaneously administered immediate release (IR) peptide based drugs in a biorelevant manner. The contribution of IVIVC in drug development of orally administered drugs is very well known. For oral drugs, the in vivo process of drug absorption is often rate limited by the rate at which drug dissolves in the gastrointestinal tract. This can be simulated by measuring the rate of dissolution in an in vitro apparatus, which can be correlated with the in vivo absorption rate to produce an IVIVC. This research program involved efforts to develop biorelevant IVIVC methods and model for subcutaneously administered peptide based drugs. The in vivo component of this Program involves the use of clinical data from a bioequivalence (BE) study of Iplex™ [(IGF-I (Insulin like growth factor-I)/IGFBP-3 (Insulin like growth factor binding protein-3)], administered subcutaneously, that was conducted at the Center for Drug Studies (CDS), VCU School of Pharmacy in the year 2005 (Barr et. al., 2005). The PK parameters for Increlex™ (IGF-I) are calculated from the clinical data obtained from another study (Rabkin et. al., 1996). Literature research and molecular modeling research formed the basis of our hypotheses that unbound and bound IGF-I are absorbed from the blood capillaries and lymphatic capillaries respectively and that simulation of these physiologic variables is possible with the use of the modified Hanson Microette® device. The Hanson Microette® device is a vertical diffusion cell system that has been modified to simulate the pores in the capillaries with the use of a synthetic membrane. The flow and composition of circulatory fluid was simulated by the use of modified Hanks balanced salts solution (HBSS). A validated RP-HPLC (reversed-phase high performance liquid chromatography) method has been used for the analysis of IGF-1/IGFBP-3 in the in vitro samples. The in vitro permeation/release results gave the in vitro component to conduct IVIVC analysis. The General Electric (GE) healthcare sourced polycarbonate nucleopore track etched membranes were the only set of membranes that resulted in significant permeation in the in vitro experiments. IVIVC results demonstrated high inter and intra-membrane variability for the membranes (available from today’s technology) that were used to simulate the in vivo membrane characteristics. Currently, there are no validated biorelevant IVIVC methods for SC formulations. The methods described here are the basis for future in vitro method development that will be of significant value for (a) predicting the in vivo performance of SC formulations based on the in vitro data, and (b) provide a reproducible in vitro method as the basis of developing an IVIVC for other subcutaneously administered drugs. This will provide an important tool for both development and regulation of this growing class of drugs.

IGFBP-3 expressing rekombinant vaccinia viruses used for tumor therapy Insulin-like growth factor-binding protein-3 (IGFBP-3) is a major regulator of endocrine effects of IGF and is capable to suppress the growth of variety of cancer. Several studies have shown that IGFBP-3 can induce the apoptosis of cancer cells via IGF-dependent and IGF-independent mechanisms. In our study, we have constructed recombinant vaccinia viruses (VACV) expressing IGFBP-3 under the control of the early H5 and synthetic early/late (E/L) promoter to investigate the potential effect on cancer growth in our cervical cancer model. We have shown that the expression of IGFBP-3 alone had no effect on tumor growth. On the other hand, the co-expression of IGFBP-3 enhanced the anti-cancer effect of immunization with the fusion protein SigE7LAMP, which gave rise to the anti-cancer immunity directed against HPV16 induced tumors. We have shown that the double-recombinant P13-SigE7LAMP-H5-IGFBP-3 can enhance the protective immune responses against MK16/ABC induced tumors. Furthermore, we have show that both double-recombinant viruses P13-SigE7LAMP-H5- IGFBP-3 and P13-SigE7LAMP-E/L-IGFBP-3 can increase the anti-cancer effect of SigE7LAMP expression in the therapy of TC-1 induced tumors. Key words: IGFBP-3, IGF, VACV, HPV16, E7 oncoprotein,...

No description available.