28 research outputs found
Mammary tumors that become independent of the type I insulin-like growth factor receptor express elevated levels of platelet-derived growth factor receptors
<p>Abstract</p> <p>Background</p> <p>Targeted therapies are becoming an essential part of breast cancer treatment and agents targeting the type I insulin-like growth factor receptor (IGF-IR) are currently being investigated in clinical trials. One of the limitations of targeted therapies is the development of resistant variants and these variants typically present with unique gene expression patterns and characteristics compared to the original tumor.</p> <p>Results</p> <p>MTB-IGFIR transgenic mice, with inducible overexpression of the IGF-IR were used to model mammary tumors that develop resistance to IGF-IR targeting agents. IGF-IR independent mammary tumors, previously shown to possess characteristics associated with EMT, were found to express elevated levels of PDGFRα and PDGFRβ. Furthermore, these receptors were shown to be inversely expressed with the IGF-IR in this model. Using cell lines derived from IGF-IR-independent mammary tumors (from MTB-IGFIR mice), it was demonstrated that PDGFRα and to a lesser extent PDGFRβ was important for cell migration and invasion as RNAi knockdown of PDGFRα alone or PDGFRα and PDGFRβ in combination, significantly decreased tumor cell migration in Boyden chamber assays and suppressed cell migration in scratch wound assays. Somewhat surprisingly, concomitant knockdown of PDGFRα and PDGFRβ resulted in a modest increase in cell proliferation and a decrease in apoptosis.</p> <p>Conclusion</p> <p>During IGF-IR independence, PDGFRs are upregulated and function to enhance tumor cell motility. These results demonstrate a novel interaction between the IGF-IR and PDGFRs and highlight an important, therapeutically relevant pathway, for tumor cell migration and invasion.</p
Small Interfering RNA Targeted to IGF-IR Delays Tumor Growth and Induces Proinflammatory Cytokines in a Mouse Breast Cancer Model
Insulin-like growth factor I (IGF-I) and its type I receptor (IGF-IR) play significant roles in tumorigenesis and in immune response. Here, we wanted to know whether an RNA interference approach targeted to IGF-IR could be used for specific antitumor immunostimulation in a breast cancer model. For that, we evaluated short interfering RNA (siRNAs) for inhibition of in vivo tumor growth and immunological stimulation in immunocompetent mice. We designed 2′-O-methyl-modified siRNAs to inhibit expression of IGF-IR in two murine breast cancer cell lines (EMT6, C4HD). Cell transfection of IGF-IR siRNAs decreased proliferation, diminished phosphorylation of downstream signaling pathway proteins, AKT and ERK, and caused a G0/G1 cell cycle block. The IGF-IR silencing also induced secretion of two proinflammatory cytokines, TNF- α and IFN-γ. When we transfected C4HD cells with siRNAs targeting IGF-IR, mammary tumor growth was strongly delayed in syngenic mice. Histology of developing tumors in mice grafted with IGF-IR siRNA treated C4HD cells revealed a low mitotic index, and infiltration of lymphocytes and polymorphonuclear neutrophils, suggesting activation of an antitumor immune response. When we used C4HD cells treated with siRNA as an immunogen, we observed an increase in delayed-type hypersensitivity and the presence of cytotoxic splenocytes against wild-type C4HD cells, indicative of evolving immune response. Our findings show that silencing IGF-IR using synthetic siRNA bearing 2′-O-methyl nucleotides may offer a new clinical approach for treatment of mammary tumors expressing IGF-IR. Interestingly, our work also suggests that crosstalk between IGF-I axis and antitumor immune response can mobilize proinflammatory cytokines
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Response of Bermudagrass to Rotations of Selective Grass Herbicides
The 1985 and 1986 Cotton Reports have the same publication and P-Series numbers.Several herbicides are now available or are being tested to control grass weeds in cotton and other crops. Most labels suggest repeat applications of the same herbicide applied in a single season. Cotton growers may apply two different grass herbicides in the same season because of herbicide cost, availability, or effectiveness. Three tests in 1985 compared the effectiveness of grass herbicides applied in rotation with other grass herbicides
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Application of Herbicides in Cotton Through Gravity Flow Furrow Irrigation
The 1985 and 1986 Cotton Reports have the same publication and P-Series numbers.The objective of this experiment was to evaluate the potential of applying herbicides in the irrigation water during a furrow irrigation as an alternate method of herbicide application in cotton. Further research is needed to study this method of applying herbicides. If a program could be designed for the Arizona cotton grower, it would help reduce production costs. However before this method can be recommended the environmental impact of such a treatment must be investigated to prevent jeopardizing currently labelled herbicides in cotton
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Preplant and Pre-harrow Cyanazine (Bladex) Trials
Research was conducted at Maricopa, AZ in 1986 and 1987 to measure cotton and weed control response to preplant applications of cyanazine (Bladex) and prometryn (Caparol). Cyanazine was applied in combination with pendimethalin and trifluralin as either preplant incorporated or preharrow treatments. Neither cyanazine or prometryn significantly reduced cotton stands or yields
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Controlling Purple and Yellow Nutsedge with Postemergence Applications of EPTC
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Factors Affecting the Response of Cotton to Preplant Applications of EPTC (Eptam) and Butylate (Sutan +)
Research was conducted at Maricopa, AZ with EPTC (S -ethyl dipropyl carbamothioate) and butylate (S-ethyl bis(2-methylpropyl)carbamothioate) in 1986 to identify factors that influence the activity of these two thiocarbamates on cotton (Gossypium hirsutum). Butylate and eptc were applied alone and in combination with other cotton herbicides as either a preplant incorporated or preharrow treatment. The greatest injury to cotton and poorest weed control resulted when butylate or EPTC was applied alone on flat ground and incorporated to a depth of 2 inches or 4 to 6 inches. Adequate weed control and minimal injury to cotton was observed when these two thiocarbamates were applied pre-harrow
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