Neuropilin (Nrp) overexpression is correlated with increased invasion and metastasis in many epithelial carcinomas including breast cancer. The exact molecular mechanism of how Nrp promotes cancer cell tumourigenicity is unknown. Nrp is a coreceptor for VEGF, hepatocyte growth factor (HGF), and also shown to activate TGF-beta on tumour cells. We hypothesize that binding of Nrp potentiates growth factor (GF) signalling and results in GF-dependent aggressive phenotype in breast cancer. In the current study, Nrp was shown to potentiate HGF signalling in vitro in MCF-7 cells by increasing phosphorylation of the MET receptor. However MDA-MB-231 cell line failed to show any differences after Nrp knockdown, due to constitutively activated MET. Nrp is also shown to increase the number and size of cancer stem cell (CSC) enriched mammospheres through NF-kB pathway activation. These results suggest a novel function of Nrp in CSCs and identify it as a potential target for effective cancer therapy.

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Augmented Soft Tissue Mobilization, a massage therapy which uses a solid instrument rather than human fingers to treat musculoskeletal injuries, has been successful in treating tendinitis. Davidson et al. studied the functional and morphological affects of ASTM on collagenase induced Achilles tendinitis in Sprague-Dawley rats. Morphological observations showed a significant increase in the number and activation of fibroblasts in the ASTM treated Groups. The authors suggested that the physical force of ASTM may promote tendon healing via increased fibroblast recruitment. An important, but unexplained, question is how ASTM would affect the fibroblasts of native, noncollagenase injured, tendons. Studies have shown that mechanical forces can alter cellular functions. The purpose of this study was to examine the morphological changes in native Sprague-Dawley rat Achilles tendons after ASTM therapy using different application pressures.Three animal Groups were randomly established: A) control Group with no ASTM; B) light ASTM with 1 Newton of pressure; and C) heavy ASTM with 3 Newtons of pressure. Upon completion of the therapy, the Achilles tendons of each Group were examined with light and electron microscopy techniques to assess fibroblast number, tendon morphology, and the presence of type I and type III collagen. Fibroblast counts from each Group were compared using a two-way ANOVA, multiple regression, and curvilinear regression analysis. Morphological differences were shown between the three Groups, especially between the non force Group and the two force Groups. The ASTM Group treated with one Newton demonstrated the greatest mean fibroblast count (165.1+/-55.8&160.7+/-49.8). Electron microscopy revealed the presence of activated fibroblasts in the tendons of the two force Groups, ASTM Groups. Polarizing microscopy showed a dramatic increase in the amount of Type III collagen in the two force Groups compared to the non force Group.Ball State UniversityMuncie, IN 47306

A brief introduction to cancer biology and treatment is presented with a focus on current clinical advances in the delivery of chemotherapy and antiangiogenic therapies. Mathematical oncology is then surveyed with summaries of various models of tumor growth, tumor angiogenesis and other relevant biological entities such as angiogenic growth factors. Both strictly time-dependent ordinary differential equation (ODE)-based and spatial partial differential equation (PDE)-based models are considered. These biological models are first developed into an ODE model where various treatment options can be compared including different combinations of drugs and dosage schedules. This model gives way to a PDE model that includes the spatially heterogeneous blood vessel distribution found in tumors, as well as angiogenic growth factor imbalances. This model is similarly analyzed and implications are summarized. Finally, including the effects of interstitial fluid pressure into an angiogenic activity model is performed. This model displays the importance of factor convection on the angiogenic behaviour of tumours.

A brief introduction to cancer biology and treatment is presented with a focus on current clinical advances in the delivery of chemotherapy and antiangiogenic therapies. Mathematical oncology is then surveyed with summaries of various models of tumor growth, tumor angiogenesis and other relevant biological entities such as angiogenic growth factors. Both strictly time-dependent ordinary differential equation (ODE)-based and spatial partial differential equation (PDE)-based models are considered. These biological models are first developed into an ODE model where various treatment options can be compared including different combinations of drugs and dosage schedules. This model gives way to a PDE model that includes the spatially heterogeneous blood vessel distribution found in tumors, as well as angiogenic growth factor imbalances. This model is similarly analyzed and implications are summarized. Finally, including the effects of interstitial fluid pressure into an angiogenic activity model is performed. This model displays the importance of factor convection on the angiogenic behaviour of tumours.

Modifications of biomaterial surface properties are employed to increase osteoblast differentiation and bone formation. Microtextured metallic surfaces promote osteoblast differentiation and high surface energy- achieved by controlling surface hydrocarbon contamination- increases osteoblast differentiation and peri-implant bone formation. Recombinant human bone morphogenic protein 2 (BMP2) is approved to induce bone formation in a number of applications. It is used clinically in combination with biomaterials to improve peri-implant bone formation and osseointegration. The amount of BMP2 that is required is large and inflammatory (swelling/seroma) and bone-related (ectopic bone/bone resorption) complications have been reported after BMP2 treatment. The aim of this study was to examine potential deleterious effects of BMP2 on the inflammatory environment and apoptosis of osteoblasts. Surface roughness and energy decreased pro-inflammatory interleukins and increased anti-inflammatory interleukins. In contrast, BMP2 abolished the surface effect, increasing pro-inflammatory interleukin (IL) 6, IL8, and IL17 in a surface roughness-dependent fashion and decreasing anti-inflammatory IL10 on rough surfaces. 5Z-7-Oxozeaenol and Dorsomorphin, but not H-8, blocked the effect of BMP2 on IL1A expression. There was an increase in expression of IL6 when treated with BMP2 for the control and H-8 groups, but both 5Z-7-Oxozeaenol and Dorsomorphin blocked the effect. Both 5Z-7-Oxozeaenol and H-8 blocked the effect of BMP2 on IL10 expression. BMP2 treatment had little effect on apoptosis in human mesenchymal stem cells (MSCs). Exogenous BMP2 had no effect on TUNEL. Caspase-3 activity was increased only at 200ng/ml BMP2. BAX/BCL2 decreased in MSCs treated with 50 and 100ng/ml BMP2. In contrast, BMP2 increased caspase-3 activity and TUNEL at all doses in normal human osteoblasts (NHOst). BAX/BCL2 increased in NHOst treated with BMP2 in a dose-dependent manner. Cells treated with 200 ng/ml BMP2 had an 8-fold increase in BAX/BCL2 expression in comparison with untreated cells. Similarly, BMP2 increased DNA fragmentation in NHOst cells. The BMP2-induced increase in DNA fragmentation was eliminated by 5-Z7-Oxozeaenol and Dorsomorphin. The results suggest that while surface features modulate an initial controlled inflammatory response, the addition of BMP2 induces a pro-inflammatory response. The effect of BMP2 on apoptosis depends on cell maturation state, inducing apoptosis in committed osteoblasts. BMP2 together with microtextured orthopaedic and dental implants may increase inflammation and possibly delay bone formation. Dose, location, and delivery strategies are important considerations in BMP2 as a therapeutic and must be optimized to minimize complications.

Thesis (M.S.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed Jan. 29, 2010). Includes bibliographical references (p. 55-60).

Thesis (M. Phil.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 140-156). Also available online.

Thesis (Ph. D.)-- State University of New York at Binghamton, Department of Biological Sciences, 2009.

Thesis (Ph.D.)--University of Tennessee Health Science Center, 2009. / Title from title page screen (viewed on February 4, 2010). Research advisor: John M. Cunningham, M.D. Document formatted into pages (xiv, 115 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 89-103).