The HER-2/neu oncogene is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene has been shown to be amplified in human breast cancer cell lines. In the current study, alterations of the gene in 189 primary human breast cancers were investigated. HER-2/neu was found to be amplified from 2- to greater than 20-fold in 30% of the tumors. Correlation of gene amplification with several disease parameters was evaluated. Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer. It retained its significance even when adjustments were made for other known prognostic factors. Moreover, HER-2/neu amplification had greater prognostic value than most currently used prognostic factors, including hormonal-receptor status, in lymph node-positive disease. These data indicate that this gene may play a role in the biologic behavior and/or pathogenesis of human breast cancer.

https://science.sciencemag.org/content/sci/235/4785/177.full.pdf

Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene

Background The HER2 gene, which encodes the growth factor receptor HER2, is amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers, increasing the aggressiveness of the tumor. Methods We evaluated the efficacy and safety of trastuzumab, a recombinant monoclonal antibody against HER2, in women with metastatic breast cancer that overexpressed HER2. We randomly assigned 234 patients to receive standard chemotherapy alone and 235 patients to receive standard chemotherapy plus trastuzumab. Patients who had not previously received adjuvant (postoperative) therapy with an anthracycline were treated with doxorubicin (or epirubicin in the case of 36 women) and cyclophosphamide with (143 women) or without trastuzumab (138 women). Patients who had previously received adjuvant anthracycline were treated with paclitaxel alone (96 women) or paclitaxel with trastuzumab (92 women). Results The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression (median, 7.4 ...

Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2

Mutations of the gene Lps selectively impede lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant to endotoxin yet highly susceptible to Gram-negative infection. The codominant Lpsd allele of C3H/HeJ mice was shown to correspond to a missense mutation in the third exon of the Toll-like receptor-4 gene (Tlr4), predicted to replace proline with histidine at position 712 of the polypeptide chain. C57BL/10ScCr mice are homozygous for a null mutation of Tlr4. Thus, the mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane. Destructive mutations of Tlr4 predispose to the development of Gram-negative sepsis, leaving most aspects of immune function intact.

http://science.sciencemag.org/content/sci/282/5396/2085.full.pdf

Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene

Defective LPS signaling in C3 H/HeJ and C57 BL/10 ScCr mice: Mutations in Tlr4 Gene

Carcinoma of the breast and ovary account for one-third of all cancers occurring in women and together are responsible for approximately one-quarter of cancer-related deaths in females. The HER-2/neu proto-oncogene is amplified in 25 to 30 percent of human primary breast cancers and this alteration is associated with disease behavior. In this report, several similarities were found in the biology of HER-2/neu in breast and ovarian cancer, including a similar incidence of amplification, a direct correlation between amplification and over-expression, evidence of tumors in which overexpression occurs without amplification, and the association between gene alteration and clinical outcome. A comprehensive study of the gene and its products (RNA and protein) was simultaneously performed on a large number of both tumor types. This analysis identified several potential shortcomings of the various methods used to evaluate HER-2/neu in these diseases (Southern, Northern, and Western blots, and immunohistochemistry) and provided information regarding considerations that should be addressed when studying a gene or gene product in human tissue. The data presented further support the concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers.

https://science.sciencemag.org/content/sci/244/4905/707.full.pdf

Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.

Recombinant DNA techniques developed in recent years enable the efficient isolation and characterization of DNA sequences that code for specific genes. Isolated DNA fragments represent unique tools that permit the investigation of a diverse array of questions, such as determination of the size and coding potential of a specific messenger RNA (mRNA), elucidation of the structure and chromosomal location of a particular gene, determination of the relatedness of genes between different species, identification of sites of biosynthesis, regulation of gene expression, and , perhaps most important, identification of genetic alterations that may be responsible for genetic disease. Laboratory manipulation of gene sequences, employing chemical DNA synthesis and enzymatic methods, enables interspecies transfer of genetic information and even production of rare proteins of medical importance in organisms such as Escherichia coli, Saccharomyces cerevisiae, or mammalian cells in the culture. We employed recombinant DNA techniques for the isolation and characterization of mouse and human DNA sequences that code for the biosynthetic precursor of the β-subunit of nerve growth factor (βNGF). Our strategy was to first clone a complementary DNA (cDNA) of mouse βNGF mRNA and subsequently use this cDNA as a tool to isolate the human gene that codes for the human βNGF protein, which has not yet been characterized.

Isolation and Characterization of DNA Sequences Coding for Mouse and Human β-Nerve Growth Factor

Antikörper gegen CD22, Immunkonjugate sowie ihre Verwendungen

La presente invention concerne des anticorps anti-CD22 et leurs immuno-conjugues, ainsi que des procedes d'utilisation desdits anticorps anti-CD22 et de leurs immuno-conjugues.

Alane M. Gray

Papers

Isolation and Characterization of DNA Sequences Coding for Mouse and Human β-Nerve Growth Factor

Antikörper gegen CD22, Immunkonjugate sowie ihre Verwendungen

Anticorps et immuno-conjugués, et leurs utilisations

Anti-CD22 Antikörper, Immunkonjugate sowie ihre Verwendungen

Antikörper und immunkonjugate sowie ihre verwendungen