Thresholds

2006 Spring.“...by recalling... memories we add to our store of dreams; we are never real historians, but always near poets, and our emotion is perhaps nothing but an expression of a poetry that was lost.” by Gaston Bachelard - Crossing a threshold, embarking on a journey, entering an unknown place. These endeavors can be internal as well as physical. Our world is becoming more and more mapped out: we can carry portable Global Positioning Systems on a voyage at sea and know what longitude and latitude we are occupying at any given moment. Radar systems used in air and ocean transportation identify obstacles. We have phones that connect us to others at the touch of a button. We are relentless in our quest to banish the possibility of being lost or alone in the world. Regardless of our efforts, however, it is still possible to experience the mystery in the unknown. In our physical environment, we can sense this vastness staring into the night sky, out to the unbroken horizon of the sea, or into a dense veil of fog. Our psyches present an even more complex landscape of the unknown. Our dreams, moments of silence, moments of loneliness offer windows into this mystery. Weaving is a way for me to express this internal landscape. As I weave I attempt to create a sort of psychic map to navigate the awe I experience when standing at the edge of infinity, whether it is on a ship's bow, completely out of sight of land, or upon waking from a dream in which another drama unfolds in the vast wilderness of the mind. I am curious about thresholds, the place where a known physical space merges with imagined places, and how these intersections can be embodied in objects. Often we are transported into a dream-like experience through memory. The wedding photograph that evokes a specific time, place, emotional state, for example, or perhaps a tactile memory triggered by a blanket from childhood. However, an object that evokes the unknown is more elusive. Seeing medieval illuminated manuscripts for the first time transported me into a dreamy imaginative state that never existed in my own memory. Despite the lack of firsthand experience, it suggests a cultural memory that is linked to a spiritual searching via the language and lush imagery within the pages of such texts. A roomful of books transports me into a place of wonder, awed by the seemingly infinite potential of human experience. I may not know the stories or the people inhabiting them, but it is the possibility they embody that intrigues me; it is as if I am about to embark on a journey to a place I've never been. This quality of possibility is captured within an ordinary object. This sense of mystery and possibility is why I weave. Tapestry is a medium in which the structure of warp and weft create a longitude and latitude for internal maps I want to use to explore these mysterious states. The process of weaving is a physical and psychic navigation of materials that evolves with the formal "terrain" of shifting colors. The hachure technique allows me to weave jagged shapes that are at once about the surface material and what could be the threshold into another reality. The idea of the voyage or journey is both subject matter and process for me. Weaving tapestries is a physical unfolding of time; I'm never quite sure where the tapestry will take me. While there are plans and formal decisions to be made, an improvisational spirit of exploration is important in the exploration of a threshold and the places just beyond

The Role of Chemokines in Melanoma Tumor Growth and Metastasis

Chemokines represent a large family of polypeptide signaling molecules that are notable for their role in chemotaxis, leukocyte homing, directional migration, and G protein coupled receptor activation. Chemo kines have recently been implicated in tumor progression and metastasis. The demonstration of chemokine expression and receptor activation in melanoma tumor cells themselves, and the tumor infiltrating leukocytes, may have important implications in terms of tumor progression and tumor cell homing to metastatic sites. In addition to their chemotactic and cell homing properties, chemokines and their receptors also play a part in other biologic functions relevant to oncogenesis, including cell proliferation, protease induction, tumor growth, and angiogenesis. Melanomas, and the cells derived from them, have been found to express a number of chemokines, including CXCL8 (interleukin-8), CXCL1–3 (MGSA-GROα–γ), CCL5 (RANTES), and CCL2 (monocyte chemotactic protein-1), which have been implicated in tumor growth and progression. Furthermore, recent studies have demonstrated organ-specific patterns of melanoma metastasis that correlate with their expression of specific chemokine receptors, including CXCR4, CCR7, and CCR10. This review will focus on the current biology of chemokines and chemokine receptors in the context of understanding their potential roles in melanoma progression and metastasis, and is not meant to be a comprehensive review of chemokine biology. Con tinued understanding and progress in the determination of the role of chemokines and their receptors in tumorigenesis and metastasis, including melanoma, may lead to novel approaches in the treatment and management of this disease

Matrix Metalloproteinases: Pro- and Anti-Angiogenic Activities

Matrix metalloproteinases (MMP) are a family of structurally related proteinases most widely recognized for their ability to degrade extracellular matrix, although recent investigations have demonstrated other biologic functions for these enzymes. MMP are typically not constitutively expressed, but are regulated by: (1) cytokines, growth factors, and cell–cell and cell–matrix interactions that control gene expression; (2) activation of their proenzyme form; and (3) the presence of MMP inhibitors [tissue inhibitors of metalloproteinases, (TIMP)]. MMP have important roles in normal processes including development, wound healing, mammary gland, and uterine involution, but are also involved in angiogenesis, tumor growth, and metastasis. Angiogenesis, characteristically defined as the establishment of new vessels from pre-existing vasculature, is required for biologic processes such as wound healing and pathologic processes such as arthritis, tumor growth, and metastasis. Blocking of MMP activity has been studied for potential therapeutic efficacy in controlling such pathologic processes. Synthetic MMP inhibitors, most notably the hydroxymates, have been engineered for this purpose and are presently in clinical trial. These inhibitors may have broad versus specific MMP inhibitory activity. As increased nonmatrix degrading capabilities of MMP are recognized, however, i.e., cytokine activation, processing of proteins to molecules of distinct biologic function, it becomes less clear whether the nonselective inhibition of MMP activity for all pathologic processes involving MMP is appropriate. This review focuses upon the contribution of MMP to the process of tumor invasion and angiogenesis, and discusses the design and use of MMP inhibitors as therapeutic agents in these processes

Label-free high-throughput photoacoustic tomography of suspected circulating melanoma tumor cells in patients in vivo

Significance: Detection and characterization of circulating tumor cells (CTCs), a key determinant of metastasis, are critical for determining risk of disease progression, understanding metastatic pathways, and facilitating early clinical intervention. Aim: We aim to demonstrate label-free imaging of suspected melanoma CTCs. Approach: We use a linear-array-based photoacoustic tomography system (LA-PAT) to detect melanoma CTCs, quantify their contrast-to-noise ratios (CNRs), and measure their flow velocities in most of the superficial veins in humans. Results: With LA-PAT, we successfully imaged suspected melanoma CTCs in patients in vivo, with a CNR >9. CTCs were detected in 3 of 16 patients with stage III or IV melanoma. Among the three CTC-positive patients, two had disease progression; among the 13 CTC-negative patients, 4 showed disease progression. Conclusions: We suggest that LA-PAT can detect suspected melanoma CTCs in patients in vivo and has potential clinical applications for disease monitoring in melanoma

In vivo functional human imaging using photoacoustic microscopy: response to ischemic and thermal stimuli

We report results of two in vivo functional human imaging experiments using photoacoustic microscopy. In Experiment 1, the hemodynamic response to an ischemic event was measured. The palm of a volunteer was imaged and a single cross-section was monitored while periodic arterial occlusions were administered using a blood pressure cuff wrapped around the upper arm and inflated to ~280 mmHg. Significant relative decreases in oxygen saturation (sO_2) and total hemoglobin (HbT) were observed during periods of ischemia. Upon release of the occlusion, significant relative increases in sO_2 and HbT due to post-occlusive reactive hyperemia were recorded. Experiment 2 explored the vascular response to a local, external thermal stimulus. Thermal hyperemia is a common physiological phenomenon and thermoregulation function in which blood flow to the skin is increased to more efficiently exchange heat with the ambient environment. The forearm of a volunteer was imaged and a single cross-section was monitored while the imaged surface was exposed to an elevated temperature of ~46°C. Due to thermal hyperemia, relative increases in sO_2 and HbT were measured as the temperature of the surface was raised. These results may contribute as clinically relevant measures of vascular functioning for detection and assessment of vascular related diseases

Treatment of pagetoid reticulosis with intensity modulated radiation therapy

Pagetoid reticulosis, also known as Woringer-Kolopp disease, is a rare variant of cutaneous T-cell lymphoma usually presenting as an isolated patch or plaque on the extremities.  Immunohistochemical staining of T-cell markers can be variable, but as the name implies the epidermotropic lymphocytes consistently display a “pagetoid” appearance.  The following case demonstrates clearance of this condition with intensity modulated radiation therapy, whereas most cases are managed with electron beam therapy if radiation therapy is implemented

Handheld photoacoustic microscopy to detect melanoma depth in vivo

We developed handheld photoacoustic microscopy (PAM) to detect melanoma and determine tumor depth in nude mice in vivo. Compared to our previous PAM system for melanoma imaging, a new light delivery mechanism is introduced to improve light penetration. We show that melanomas with 4.1 and 3.7 mm thicknesses can be successfully detected in phantom and in in vivo experiments, respectively. With its deep melanoma imaging ability and handheld design, this system can be tested for clinical melanoma diagnosis, prognosis, and surgical planning for patients at the bedside