The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors

<p><b>Abstract</b></p> <p>Background</p> <p>Poor distribution of some anticancer drugs in solid tumors may limit their anti-tumor activity.</p> <p>Methods</p> <p>Here we used immunohistochemistry to quantify the distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab in relation to blood vessels and to regions of hypoxia in human tumor xenografts. The antibodies were injected into mice implanted with human epidermoid carcinoma A431 or human breast carcinoma MDA-MB-231 transfected with <it>ERBB2 </it>(231-H2N) that express high levels of ErbB1 and ErbB2 respectively, or wild-type MDA-MB-231, which expresses intermediate levels of ErbB1 and low levels of ErbB2.</p> <p>Results</p> <p>The distribution of cetuximab in A431 xenografts and trastuzumab in 231-H2N xenografts was time and dose dependent. At early intervals after injection of 1 mg cetuximab into A431 xenografts, the concentration of cetuximab decreased with increasing distance from blood vessels, but became more uniformly distributed at later times; there remained however limited distribution and binding in hypoxic regions of tumors. Injection of lower doses of cetuximab led to heterogeneous distributions. Similar results were observed with trastuzumab in 231-H2N xenografts. In MDA-MB-231 xenografts, which express lower levels of ErbB1, homogeneity of distribution of cetuximab was achieved more rapidly.</p> <p>Conclusions</p> <p>Cetuximab and trastuzumab distribute slowly, but at higher doses achieve a relatively uniform distribution after about 24 hours, most likely due to their long half-lives in the circulation. There remains poor distribution within hypoxic regions of tumors.</p

Application of bone growth factors—the potential of different carrier systems

Aim The aim of the present review was to characterize the potential of different biomaterials as carriers for bone growth factors. Introduction Beyond mechanical and structural characteristics, one of the features that account for a potential carrier is the possibility to couple growth factor molecules to it. As simple adsorption of the growth factor to the carrier surface by soak loading produces a burst release of growth factors with rapid decrease of biological activity, the ability to accomplish controlled release of functional growth factor molecules is one of the crucial characteristics for an appropriate carrier material. Conclusion The variety of carrier materials requires different strategies to either couple growth factors to the material surface or to incorporate them into the carrier matrix. The present review outlines current technical approaches and discusses future trends in the use of carrier materials for bone growth factors

Influence of postpartum onset on the course of mood disorders

BACKGROUND: To ascertain the impact of postpartum onset (PPO) on the subsequent time course of mood disorders. METHODS: This retrospective study compared per year rates of excited (manic or mixed) and depressive episodes between fifty-five women with bipolar (N = 22) or major depressive (N = 33) disorders with first episode occurring postpartum (within four weeks after childbirth according to DSM-IV definition) and 218 non-postpartum onset (NPPO) controls. Such patients had a traceable illness course consisting of one or more episodes alternating with complete symptom remission and no additional diagnoses of axis I disorders, mental retardation or brain organic diseases. A number of variables reported to influence the course of mood disorders were controlled for as possible confounding factors RESULTS: Bipolar women with postpartum onset disorder had fewer excited episodes (p = 0.005) and fewer episodes of both polarities (p = 0.005) compared to non-postpartum onset subjects. No differences emerged in the rates of depressive episodes. All patients who met criteria for rapid cycling bipolar disorder (7 out of 123) were in the NPPO group. Among major depressives, PPO patients experienced fewer episodes (p = 0.016). With respect to clinical and treatment features, PPO-MDD subjects had less personality disorder comorbidity (p = 0.023) and were less likely to be on maintenance treatment compared to NPPO comparison subjects (p = 0.002) CONCLUSION: Such preliminary findings suggest that PPO mood disorders may be characterized by a less recurrent time course. Future research in this field should elucidate the role of comorbid personality disorders and treatment. Moreover it should clarify whether PPO disorders are also associated with a more positive outcome in terms of social functioning and quality of life

Muscle precursor cells in the developing limbs of two isopods (Crustacea, Peracarida): an immunohistochemical study using a novel monoclonal antibody against myosin heavy chain

In the hot debate on arthropod relationships, Crustaceans and the morphology of their appendages play a pivotal role. To gain new insights into how arthropod appendages evolved, developmental biologists recently have begun to examine the expression and function of Drosophila appendage genes in Crustaceans. However, cellular aspects of Crustacean limb development such as myogenesis are poorly understood in Crustaceans so that the interpretative context in which to analyse gene functions is still fragmentary. The goal of the present project was to analyse muscle development in Crustacean appendages, and to that end, monoclonal antibodies against arthropod muscle proteins were generated. One of these antibodies recognises certain isoforms of myosin heavy chain and strongly binds to muscle precursor cells in malacostracan Crustacea. We used this antibody to study myogenesis in two isopods, Porcellio scaber and Idotea balthica (Crustacea, Malacostraca, Peracarida), by immunohistochemistry. In these animals, muscles in the limbs originate from single muscle precursor cells, which subsequently grow to form multinucleated muscle precursors. The pattern of primordial muscles in the thoracic limbs was mapped, and results compared to muscle development in other Crustaceans and in insects