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Inhibitors for growth hormone and related hormones, and methods of use thereof

A growth hormone, hormone technology, applied in the field of hormones

Inactive Publication Date: 2012-10-03
AUCKLAND UNISERVICES LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, hGH also exhibits many IGF-1-independent effects during growth

Method used

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  • Inhibitors for growth hormone and related hormones, and methods of use thereof
  • Inhibitors for growth hormone and related hormones, and methods of use thereof
  • Inhibitors for growth hormone and related hormones, and methods of use thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0239] Preparation of antibodies will be performed according to standard methods in the art. For example, the preparation method of polyclonal antibodies described by Bean (Eric S. Bean (2001) Polyclonal Antibodies. In: Basic Methods in Antibody Production and Characterization antibodies. Howard, G, and Bethel D. (ed.), CRC Press, 5:21-50, 2000). According to the method of Stewart (Sandy J. Stewart (2001) Monoclonal Antibody Production. In: Basic Methods in Antibody Production and Characterization antibodies. Howard, G. and Bethel D. (ed.), CRC Press, 6: 51-68, 2000) , or according to Monoclonal Antibody Preparation Technology and Application, Lawrence B Schook eds, Marcel Dekker Inc, New York, 1987, monoclonal antibodies and corresponding hybridomas can be prepared. Hybridomas can be subcloned, grown and maintained using standard methods in the art. For example, it can be grown and maintained in an in vivo medium, such as DMEM or RPMI-1640. Alternatively, in vivo culture c...

Embodiment 1

[0329] Example 1: Materials and methods

[0330] Cell lines and cell transfection

[0331] Human endometrial cancer cell lines, RL95-2 and AN3, were provided by American TypeCulture Collection (ATCC). Eagle's medium and Ham's F12 medium (1:1) adjusted by Dulbecco's, and 10mM HEPES and 2.0g / L sodium bicarbonate, 10% fetal bovine serum, 100IU / ml penicillin, 100μg / ml streptomycin, 2mM L - Glutamine and 0.005 mg / ml insulin were used to culture RL95-2 cells. With minimal essential medium (Eagle) containing 2mM L-glutamine, and containing 1.5g / L sodium bicarbonate, 10% fetal bovine serum, 100IU / ml penicillin, 100μg / ml streptomycin, 0.1 non-essential amino acids and AN3 cells were cultured in Earle's BBS with 1.0 mM sodium pyruvate. The two kinds of cells were cultured in a 37°C, 5% CO2 incubator.

[0332] BamHI derived from pMT-hGH vector (Palmiter RD, Norstedt G, Gelinas RE, Hammer RE, Brinster RL (1983). Metallothionein-human GH fusion genes stimulate growth of mice. Science...

Embodiment 2

[0367] Example 2: Results

[0368] Overexpression of hGH in endometrial cells increases the total number of cells

[0369] The aforementioned autocrine of hGH shows that it can affect cell function and increase carcinogenicity in breast cancer cell models (Kaulsay KK, Zhu T, Bennett W, Lee KO, Lobie PE (2001). The effects of autocrine human growth hormone (hGH ) on human mammary carcinoma cell behavior aremediated via the hGH receptor. Endocrinology 142: 767-77, Mukhina S, Mertani HC, Guo K, Lee KO, Gluckman PD, Lobie PE (2004). Phenotypic conversion of human mammary carcinoma cells by manautocrine growth hormone.Proc Natl Acad Sci USA101:15166-71, Zhu T, Starling-Emerald B, Zhang X, Lee KO, Gluckman PD, Mertani HC et al(2005).Oncogenic transformation of human mammalian epithelial cells by autocrine human growthhormone.Cancer Res 65:317-24). To determine whether autocrine hGH affects cell function in an endometrial tumor model, RL95-2 cells were stably transfected with an ...

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PUM

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Abstract

The present invention encompasses novel inhibitors for growth hormone and related hormones, including prolactin, and placental lactogen, and other hormones. The invention specifically encompasses antibodies, antibody fragments, and modifications thereof, as well as polynucleotides, such antisense polynucleotides, interfering RNAs, and small interfering RNAs, and uses thereof, for inhibition of one or more of such hormones. In particular aspects, the invention encompasses methods of producing such inhibitors, compositions comprising one or more of these inhibitors, and methods of inhibiting a cell, e.g., inhibiting cell proliferation, cell survival, or cell motility, especially for a cancer cell, using one or more of the inhibitors. The invention also encompasses methods of diagnosis and monitoring, and methods of treatment, especially for cancer, using one or more of the disclosed compositions or inhibitors.

Description

[0001] related application [0002] This non-provisional application has priority over U.S.S.N. 60 / 940939, filed May 30, 2007, which is hereby incorporated by reference in its entirety. technical field [0003] The present invention relates to novel inhibitors of growth hormone and related hormones, particularly prolactin, and other hormones described herein. The present invention particularly relates to antibodies, antibody fragments, and modifications thereof, and polyoligonucleotides, such as antisense polyoligonucleotides, interfering RNAs, and small interfering RNAs, and the use of these inhibitors to inhibit growth hormone and / or or related hormone methods. In particular aspects, the invention relates to methods of making these inhibitors, compositions comprising one or more of these inhibitors, and methods of using one or more of these inhibitors to inhibit cells, particularly tumor cells, e.g., to inhibit cell proliferation , cell survival, or cell motility. The inv...

Claims

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Application Information

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IPC IPC(8): A61K31/713A61K39/395C07K16/18C07K16/26C12N15/11G01N33/50C12N15/113
CPCC12N2310/14C07K2317/11C07K2316/95C07K16/26C12N15/1136G01N33/57407A61K31/713C07K2317/23A61P15/08A61P35/00C07K2317/73C07K2317/75
Inventor P·罗比
Owner AUCKLAND UNISERVICES LTD
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