Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer.

Purpose: Preclinical studies in ErbB2-positive cell lines demonstrated a synergistic interaction between lapatinib and trastuzumab, suggesting that dual blockade is more effective than a single agent alone. EGF104900 compared the activity of lapatinib alone or in combination with trastuzumab in patients with ErbB2-positive, trastuzumab-refractory metastatic breast cancer (MBC).

Patients And Methods: Patients with ErbB2-positive MBC who experienced progression on prior trastuzumab-containing regimens were randomly assigned to receive either lapatinib alone or in combination with trastuzumab.

A switch in Notch gene expression parallels stem cell to endothelial transition in infantile hemangioma.

Background: Infantile hemangioma (IH) is the most common benign tumor of infancy, yet its pathogenesis is poorly understood. Notch family members are known to play a role in vascular development during embryogenesis and postnatal tumor angiogenesis, yet the role of Notch signaling in the pathogenesis of IH has not been investigated. This study aims to survey Notch expression in IH.

Clinical Recommendations of DEGRO and AGO on Preferred Standard Palliative Radiotherapy of Bone and Cerebral Metastases, Metastatic Spinal Cord Compression, and Leptomeningeal Carcinomatosis in Breast Cancer.

Background: To provide guidance for clinical practice on preferred standard palliative radiotherapy (RT) of different sites of metastasis for breast cancer patients based on current published evidence complemented by expert opinion.

Methods: The breast cancer expert panel of the German Society for Radiation Oncology (DEGRO) and members of the Working Party of Gynecologic Oncology (AGO) Breast Committee formulated recommendations based on the panel's interpretation of the level of evidence referring to the criteria of evidence-based medicine added to the AGO grades of recommendation.

Results: For different types and sites of metastasis, distinct therapeutic goals (alleviation of symptoms, pain relief, local tumor control, prevention or improvement of neurological deficits, stabilization of the spine or other bones) require complex approaches considering individual factors (i.

Fast diffraction computation schema for multilayer crossed gratings containing layers with 1D periodicity.

The diffraction computation of crossed gratings is very slow compared with that of line-space gratings of the same size when using a modal method such as rigorous coupled wave analysis (RCWA) or the Chandezon coordinate transformation method. It is well known that the main bottleneck in terms of computation speed is the solution of an eigenproblem for each RCWA slice or interface in the case of the C-method. Even if the crossed grating contains layers that are periodic only in one direction, usually the full 2D problem has to be solved for this layer in order to connect it to the full system solution.

Differential functions of genes regulated by VEGF-NFATc1 signaling pathway in the migration of pulmonary valve endothelial cells.

We have reported that vascular endothelial growth factor (VEGF)-A induces the proliferation of human pulmonary valve endothelial cells (HPVECs) through nuclear factor in activated T cells (NFAT)c1 activation. Here we show that VEGF-A increases the migration of HPVECs through NFATc1 activation, suggesting that VEGF-A/NFATc1 regulates the migration of HPVECs. To learn how this pathway may be involved in post-natal valvular repair, HPVECs were treated with VEGF-A, with or without cyclosporine A to selectively block VEGF-NFATc1 signaling.

APC promoter hypermethylation is an early event in endometrial tumorigenesis.

The aim of the current study was to investigate the role of promoter methylation of adenomatous polyposis coli (APC) and epithelial cadherin (E-cadherin) genes in endometrial tumorigenesis. The methylation status of both genes was investigated in 43 cases of normal endometrium, 21 simple hyperplasia, 17 atypical hyperplasia, and 86 endometrial carcinoma (EC). Additionally, the methylation pattern of both genes was analyzed in 24 primary ECs and their corresponding metastases.

The role of intra-cerebrospinal fluid treatment and prophylaxis in patients with solid tumors.

Metastasis to the central nervous system (CNS), including neoplastic meningitis (NM), is a devastating complication of systemic cancer. With the improved survival of cancer patients, the incidence of CNS metastasis is rising, especially among those with breast or lung carcinoma. New therapies that effectively treat these primary tumors outside of the CNS have underscored the significance of CNS metastases; they have become a significant clinical issue and a therapeutic challenge.

Intravital molecular imaging of small-diameter tissue-engineered vascular grafts in mice: a feasibility study.

Objectives: Creating functional small-diameter tissue-engineered blood vessels has not been successful to date. Moreover, the processes underlying the in vivo remodeling of these grafts and the fate of cells seeded onto scaffolds remain unclear. Here we addressed these unmet scientific needs by using intravital molecular imaging to monitor the development of tissue-engineered vascular grafts (TEVG) implanted in mouse carotid artery.

Endothelial progenitor cells as a sole source for ex vivo seeding of tissue-engineered heart valves.

Purposes: We investigated whether circulating endothelial progenitor cells (EPCs) can be used as a cell source for the creation of a tissue-engineered heart valve (TEHV).

Methods: Trileaflet valved conduits were fabricated using nonwoven polyglycolic acid/poly-4-hydroxybutyrate polymer. Ovine peripheral blood EPCs were dynamically seeded onto a valved conduit and incubated for 7, 14, and 21 days.

Chemical interrogation of FOXO3a nuclear translocation identifies potent and selective inhibitors of phosphoinositide 3-kinases.

Activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is one the most frequent genetic events in human cancer. A cell-based imaging assay that monitored the translocation of the Akt effector protein, Forkhead box O (FOXO), from the cytoplasm to the nucleus was employed to screen a collection of 33,992 small molecules. The positive compounds were used to screen kinases known to be involved in FOXO translocation.

Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells.

Fatty acid binding protein 4 (FABP4) plays an important role in maintaining glucose and lipid homeostasis. FABP4 has been primarily regarded as an adipocyte- and macrophage-specific protein, but recent studies suggest that it may be more widely expressed. We found strong FABP4 expression in the endothelial cells (ECs) of capillaries and small veins in several mouse and human tissues, including the heart and kidney.

A multilocus phylogeny of the Metarhizium anisopliae lineage.

Metarhizium anisopliae, the type species of the anamorph entomopathogenic genus Metarhizium, is currently composed of four varieties, including the type variety, and had been demonstrated to be closely related to M. taii, M. pingshaense and M.

Active adaptation of the tethered mitral valve: insights into a compensatory mechanism for functional mitral regurgitation.

Background: In patients with left ventricular infarction or dilatation, leaflet tethering by displaced papillary muscles frequently induces mitral regurgitation, which doubles mortality. Little is known about the biological potential of the mitral valve (MV) to compensate for ventricular remodeling. We tested the hypothesis that MV leaflet surface area increases over time with mechanical stretch created by papillary muscle displacement through cell activation, not passive stretching.

Patellofemoral interactions in walking, stair ascent, and stair descent using a virtual patella model.

Restoration of normal patella kinematics is an important clinical outcome of total knee arthroplasty. Failure of the patella within total knee systems has been documented and, upon occurrence, often necessitates revision surgery. It is thus important to understand patella mechanics following implantation, subject to load states that are typically realized during walking and other gaits.

Vasculogenesis in infantile hemangioma.

Infantile hemangioma is a vascular tumor that occurs in 5-10% of infants of European descent. A defining feature of infantile hemangioma is the dramatic growth and development into a disorganized mass of blood vessels. Subsequently, a slow spontaneous involution begins around 1 year of age and continues for 4-6 years.

Quantifying nonlinear anisotropic elastic material properties of biological tissue by use of membrane inflation.

Determination of material parameters for soft tissue frequently involves regression of material parameters for nonlinear, anisotropic constitutive models against experimental data from heterogeneous tests. Here, parameter estimation based on membrane inflation is considered. A four parameter nonlinear, anisotropic hyperelastic strain energy function was used to model the material, in which the parameters are cast in terms of key response features.

Progenitor cells in infantile hemangioma.

Infantile hemangioma is a vascular tumor that occurs in 5% to 10% of infants of European descent. A hallmark of infantile hemangioma is its life cycle, which is divided into 3 stages. The proliferating phase spans in the first year of postnatal life and is characterized by cellular masses without a defined vascular architecture and nascent blood vessels with red blood cells evident within the lumenal space.

[Rare neuroendocrine carcinoma of the gall bladder. Coincidental occurrence of an endometrioid ovarian adenocarcinoma].

History And Clinical Findings: The histological investigation of a surgical specimen (after cholecystectomy) from a 73-year-old woman revealed a poorly differentiated carcinoma with glandular structures and a lymph node metastasis.

Investigations: Comparative immunochemistry, done to exclude metastatic growth of the previously demonstrated endometrioid ovarian carcinoma, was (1) negative for CK7 and CA125, positive for CK20, chromogranin A and synaptophysin (gall bladder and lymph node metastasis); (2) positive for CK7 and CA125, negative for CK20, chromogranin A and synaptophysin (ovary).

Diagnosis: The tumor lesion within the gall bladder and lymph node was classified as a neuroendocrine carcinoma, not a metastasis of the ovarian carcinoma.

Chapter 13. An in vivo experimental model for postnatal vasculogenesis.

Rapid and complete vascularization of ischemic tissues and thick engineered tissues is likely to require vasculogenesis. Therefore, the search for clinically relevant sources of vasculogenic cells and the subsequent development of experimental models of vasculogenesis is of utmost importance. Here, we describe a methodology adapted from the Matrigel plug assay to deliver human blood-derived endothelial progenitor cells (EPCs) and mature smooth muscle cells (SMCs) subcutaneously into immunodeficient mice.

Methotrexate monotherapy for high-risk gestational trophoblastic neoplasia after therapy with etoposide, methotrexate, and dactinomycin: a case report.

We present a case of high-risk metastatic gestational trophoblastic neoplasia treated successfully with methotrexate monotherapy after severe toxicity from the combination chemotherapy: etoposide, dactinomycin, methotrexate, vincristine, and cyclophosphamide.

Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma.

Infantile hemangiomas are localized and rapidly growing regions of disorganized angiogenesis. We show that expression of vascular endothelial growth factor receptor-1 (VEGFR1) in hemangioma endothelial cells (hemECs) and hemangioma tissue is markedly reduced compared to controls. Low VEGFR1 expression in hemECs results in VEGF-dependent activation of VEGFR2 and downstream signaling pathways.

P16 alterations increase the metastatic potential of endometrial carcinoma.

Objective: The aim of this study was to investigate the role of p16 in tumorigenesis of endometrial carcinoma (EC).

Methods: Expression of p16 protein was analyzed using immunohistochemistry. The methylation status of p16 promoter region was determined by methylation-specific PCR.