Crystal Structure of a Truncated Epidermal Growth Factor Receptor Extracellular Domain Bound to Transforming Growth Factor α

For mammalian cochlear hair cells, fate determination is normally completed by birth. We report here that overexpression of Math1, a mouse homolog of the Drosophila gene atonal, in postnatal rat cochlear explant cultures resulted in extra hair cells. Surprisingly, we found that the source of the ectopic hair cells was columnar epithelial cells located outside the sensory epithelium in the greater epithelial ridge, which normally give rise to inner sulcus cells. Moreover, Math1 expression also facilitated conversion of postnatal utricular supporting cells into hair cells. Thus Math1 was sufficient for the production of hair cells in the ear, and immature postnatal mammalian inner ears retained the competence to generate new hair cells.

Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears.

https://www.cell.com/molecular-cell/pdf/S1097-2765(03)00048-0.pdf

The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors.

Purpose Pertuzumab, a recombinant humanized monoclonal antibody (2C4), binds to extracellular domain II of the HER-2 receptor and blocks its ability to dimerize with other HER receptors. Pertuzumab represents a new class of targeted therapeutics known as HER dimerization inhibitors. A clinical study was conducted to investigate safety and pharmacokinetics of pertuzumab and to perform a preliminary assessment of HER dimerization inhibition as a treatment strategy. Patients and Methods Patients with incurable, locally advanced, recurrent or metastatic solid tumors that had progressed during or after standard therapy were recruited to a dose-escalation study of pertuzumab (0.5 to 15 mg/kg) given intravenously every 3 weeks. Results Twenty-one patients received pertuzumab and 19 completed at least two cycles. Pertuzumab was well tolerated. Overall, 365 adverse events were reported and 122 considered to be possibly drug related. Of these, 116 were of grade 1 to 2 intensity. The pharmacokinetics of pertuzumab w...

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2005.03.184

Phase I Clinical Study of Pertuzumab, a Novel HER Dimerization Inhibitor, in Patients With Advanced Cancer

The influence of nano-scale surface roughness on bacterial adhesion to ultrafine-grained titanium

1.Introduction. 2.Setting up a Cell Culture Lab. 3.The Physical Environment. 4.Media. 5.Standard Cell Culture Techniques. 6.Looking at Cells. 7.Contamination, How to Avoid It, Recognize It, and Get Rid of It When It's There. 8.Special Considerations for Serum Free Culture-Established Cell Lines. 9.Primary Cultures. 10.Establishing a Cell Line. 11.Special Growth Conditions. 12.Cell Culture for Commercial Settings. Glossary. Appendices: Equipment List. List of Cell Lines and Where to Get Them. Preparation of Bovine Pituitary Extract. Index.

Introduction to Cell and Tissue Culture: Theory and Technique

The high affinity activin-binding protein, follistatin, has recently been shown to block activin-stimulated activities in several in vitro systems. In the present study we sought to extend these observations and investigate the effects of follistatin on the activity of activin in stimulating the re-aggregation of Sertoli cell monolayers and proliferation of testicular germ cells, as measured by incorporation of [3H]-thymidine in vitro. Germ-Sertoli cell cocultures prepared from 21 day old rats were treated with media alone or media containing recombinant human (rh) activin A or rh activin B with or without follistatin, the low affinity activin-binding protein, alpha 2 macroglobulin, or a monoclonal antibody (mAB) known to block activin B activity. Follistatin blocked the ability of activin A to stimulate reaggregation of Sertoli cell monolayers when present at a 2-fold ratio (wt/wt) to activin. However, in these same cultures, follistatin had no effect on the ability of activin A to stimulate [3H]-thymidine incorporation. In activin B-treated cultures, both responses could be blocked by the addition of a neutralizing mAB directed against activin B. These results suggest that follistatin can modulate activin action in a cell-type specific fashion, and that this protein may play an important role in regulating the bioavailability of activin.

Follistatin modulates activin activity in a cell- and tissue-specific manner.

The human epidermal growth factor receptor (HER or ErbB) family consists of four distinct members, including the epidermal growth factor (EGF) receptor (EGFR, HER1, or ErbB1), ErbB2 (HER2 or neu), ErbB3 (HER3), and ErbB4 (HER4). Activation of these receptors plays an important role in the regulation of cell proliferation, differentiation, and survival in several different tissues. Binding of a specific ligand to one of the ErbB receptors triggers the formation of specific receptor homo- and heterodimers, with ErbB2 being the preferred signaling partner. We analyzed the levels of various ErbB receptor messenger RNAs in a series of nontransformed cell lines by real time quantitative RT-PCR. The cell lines chosen were derived from a variety of tissues, including pancreas, lung, heart, and nervous system. Further, we measured biological responses in these cell lines upon treatment with EGF, betacellulin, and two types of neuregulins, heregulin and sensory and motor neuron-derived factor. All cell lines examined expressed detectable levels of ErbB2. High levels of expression of ErbB3 were correlated with responsiveness to heregulin and sensory and motor neuron-derived factor, whereas high levels of EGFR expression were correlated with responsiveness to EGF and betacellulin. Moreover, the sensitivity of a cell line to ErbB ligands was also correlated with the levels of expression of the appropriate ErbB receptors in that cell line. These results are consistent with our hypothesis that appropriate biological responsiveness to ErbB ligands is determined by the levels of expression of specific ErbB receptor combinations within a given tissue.

Biological Response to ErbB Ligands in Nontransformed Cell Lines Correlates with a Specific Pattern of Receptor Expression

This invention discloses isolated populations of human cancer stem cells. Methods for characterizing, isolating and culturing human cancer stem cells are also disclosed. Uses for human cancer stem cells are provided.

Human cancer stem cells

Coordinating the activities of neighboring cells during development in multicellular organisms requires complex cellular interactions involving secreted, cell surface, and extracellular matrix components. Although most cloning efforts have concentrated on secreted molecules, recent work has emphasized the importance of membrane-bound molecules during development. To identify developmental genes, we raised antibodies to normal embryonic pancreatic epithelial cell surface proteins. These antibodies were characterized and used to clone the genes coding for the proteins by a panning strategy. Using this approach, we cloned the rat homologue of the mouse epithelial glycoprotein (EGP). Our immunohistochemistry data, describing the expression of EGP during rat development, as well as our in vitro data, looking at the effect of the anti-EGP antibody and the extracellular domain of EGP on embryonic pancreatic epithelial cell number and volume, strongly suggest a role for EGP during pancreatic development.

/pdf/selective-cloning-of-cell-surface-proteins-involved-in-organ-gn1ia5z7lg.pdf

Penelope E. Roberts

Papers

Introduction to Cell and Tissue Culture: Theory and Technique

Follistatin modulates activin activity in a cell- and tissue-specific manner.

Biological Response to ErbB Ligands in Nontransformed Cell Lines Correlates with a Specific Pattern of Receptor Expression

Human cancer stem cells

Selective cloning of cell surface proteins involved in organ development: epithelial glycoprotein is involved in normal epithelial differentiation.