Metabolic response of lung cancer cells to radiation in a paper-based 3D cell culture system.

This work demonstrates the application of a 3D culture system-Cells-in-Gels-in-Paper (CiGiP)-in evaluating the metabolic response of lung cancer cells to ionizing radiation. The 3D tissue-like construct-prepared by stacking multiple sheets of paper containing cell-embedded hydrogels-generates a gradient of oxygen and nutrients that decreases monotonically in the stack. Separating the layers of the stack after exposure enabled analysis of the cellular response to radiation as a function of oxygen and nutrient availability; this availability is dictated by the distance between the cells and the source of oxygenated medium.

Identification of Dormancy-Associated MicroRNAs for the Design of Osteosarcoma-Targeted Dendritic Polyglycerol Nanopolyplexes.

The presence of dormant, microscopic cancerous lesions poses a major obstacle for the treatment of metastatic and recurrent cancers. While it is well-established that microRNAs play a major role in tumorigenesis, their involvement in tumor dormancy has yet to be fully elucidated. We established and comprehensively characterized pairs of dormant and fast-growing human osteosarcoma models.

Host-derived pericytes and Sca-1+ cells predominate in the MART-1- stroma fraction of experimentally induced melanoma.

Identification of cell types in tumor-associated stroma that are involved in the development of melanoma is hampered by their heterogeneity. The authors used flow cytometry and immunohistochemistry to demonstrate that anti-MART-1 antibodies can discriminate between melanoma and stroma cells. They investigated the cellular composition of the MART-1-, non-hematopoietic melanoma-associated stroma, finding it consisted mainly of Sca-1+ and CD146+ cells.

Tumor-stromal cell interactions and opportunities for therapeutic intervention.

Tumor tissue is composed of both cancer cells and stromal cells recruited from normal tissue. These cells include fibroblastic cells, endothelial cells, and cells of hematopoietic origin. The host-derived stromal cells play a critical role in all aspects of cancer biology including transformation, progression, tumor growth, and drug resistance.

Bone marrow is a reservoir for proangiogenic myelomonocytic cells but not endothelial cells in spontaneous tumors.

The hypothesis that bone marrow-derived, circulating endothelial cells incorporate into tumor blood vessels is unresolved. We have measured the numbers of bone marrow-derived versus resident endothelial cells in spontaneous prostate cancers during different stages of tumor progression and in age-matched normal prostates. Bone marrow-derived endothelial cells were rare in dysplasia and in well differentiated cancers representing between 0 and 0.

Targeting angiogenesis-dependent calcified neoplasms using combined polymer therapeutics.

Background: There is an immense clinical need for novel therapeutics for the treatment of angiogenesis-dependent calcified neoplasms such as osteosarcomas and bone metastases. We developed a new therapeutic strategy to target bone metastases and calcified neoplasms using combined polymer-bound angiogenesis inhibitors. Using an advanced "living polymerization" technique, the reversible addition-fragmentation chain transfer (RAFT), we conjugated the aminobisphosphonate alendronate (ALN), and the potent anti-angiogenic agent TNP-470 with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer through a Glycine-Glycine-Proline-Norleucine linker, cleaved by cathepsin K, a cysteine protease overexpressed at resorption sites in bone tissues.

Tumor dormancy of primary and secondary cancers.

Tumor dormancy is a phenomenon whereby cancer cells persist below the threshold of diagnostic detection for months to decades. This condition may arise due to either cell cycle arrest or a dynamic equilibrium state in which cell proliferation is in balance with cells undergoing apoptosis. Tumor dormancy is usually a reference to occult cancer cells that persist for an extended period of time after treatment, but primary cancers can also exhibit extended growth plateaus below the limits of detection.

Endothelial progenitor cells contribute to accelerated liver regeneration.

Two classes of circulating endothelial cells (CECs) have been identified and are distinguished by the expression of the stem cell markers CD117 or CD133 together with endothelial-specific antigens. Stem cell marker-positive CECs originate from bone marrow and have been designated as circulating endothelial progenitors (CEPs). We have demonstrated that exogenous vascular endothelial growth factor (VEGF) effectively mobilizes CEP cells.

Chronic suppression of angiogenesis following radiation exposure is independent of hematopoietic reconstitution.

Radiation can potentially suppress neovascularization by inhibiting the incorporation of hematopoietic precursors as well as damaging mature endothelial cells. The purpose of these studies was to quantify the effect of radiation on angiogenesis and to examine the relationship between bone marrow reconstitution and neovascularization. Immune competent, severe combined immunodeficient, RAG1-deficient, and green fluorescence protein transgenic mice in the C57 genetic background, as well as the highly angiogenic 129S1/SvlmJ strain of mice, underwent whole-body or localized exposure to radiation.

Analysis of tumor-associated stromal cells using SCID GFP transgenic mice: contribution of local and bone marrow-derived host cells.

The green fluorescence protein (GFP) from the UBI-GFP/BL6 transgenic line was bred into C57BL/6J-scid and C.B-17-scid mice for investigating host-tumor cell interactions. These mice express high levels of GFP under the control of the ubiquitin promoter in virtually all cells examined.

X-linked dominant growth suppression of transplanted tumors in C57BL/6J-scid mice.

Tumor susceptibility, angiogenesis, and immune response differ between mouse strains. We, therefore, examined the growth rates of tumor xenografts in three genetically isolated strains of severe combined immunodeficient mice (C.B-17, C57BL/6J, and C3H).

Enhancement of intravascular sclerotherapy by tissue engineering: short-term results.

Background/purpose: Treatment of vascular malformations with sclerotherapy is often complicated by reexpansion secondary to endothelial recanalization. This study examined the use of an autologous fibroblast construct to enhance intraluminal scar formation after sclerotherapy.

Methods: New Zealand rabbits (n = 15) underwent ethanol sclerotherapy of a segment of the facial vein.

Diaphragmatic reconstruction with autologous tendon engineered from mesenchymal amniocytes.

Purpose: This study examined the effects of amniocyte-based engineered tendons on partial diaphragmatic replacement.

Methods: Ovine mesenchymal amniocytes were labeled with green fluorescent protein (GFP), expanded, and seeded into a collagen hydrogel. Composite grafts (20 to 25 cm2) based on acellular dermis (group I), or acellular small intestinal submucosa (group II) received either a cell-seeded or an acellular hydrogel within their layers.

Control of T lymphocyte morphology by the GTPase Rho.

Background: Rho family GTPase regulation of the actin cytoskeleton governs a variety of cell responses. In this report, we have analyzed the role of the GTPase Rho in maintenance of the T lymphocyte actin cytoskeleton.

Results: Inactivation of the GTPase Rho in the human T lymphocytic cell line HPB-ALL does not inhibit constitutively high adhesion to the integrin beta1 substrate fibronectin.

Persistence of microscopic human cancers in mice: alterations in the angiogenic balance accompanies loss of tumor dormancy.

Some human tumor lines do not form visible tumors when inoculated into immunosuppressed mice. The fate of these human tumor lines was followed by transfecting them with green fluorescence protein before inoculating them into mice. Although the tumor lines failed to grow progressively, they formed small dormant microscopic foci maintained at constant mass by balanced proliferation and apoptosis.