A controlled internal electric field perpendicular to the skin-fat interface is selective in heating up fat and, consequently, has the ability to induce lethal thermal damage to subcutaneous adipose tissues while sparing overlying and underlying tissues. In vitro adipocyte cells are heat sensitive to thermal exposures of 50 and 45 degrees C on the order of minutes, 1 and 3 minutes, respectively. In vivo, 15 minutes thermal exposures to 43-45 degrees C result in a delayed adipocyte cellular death response-in this study, 9 days. The novel RF device presented herein effectively delivers therapeutic thermal exposures to subcutaneous adipose tissues while protecting epidermal and dermal layers.

Ascites refers to the abnormal accumulation of fluid in the peritoneum resulting from an underlying pathology, such as metastatic cancer. Among all cancers, advanced-stage epithelial ovarian cancer is most frequently associated with the production of malignant ascites and is the leading cause of death from gynecologic malignancies. Despite decades of evidence showing that the accumulation of peritoneal fluid portends the poorest outcomes for cancer patients, the role of malignant ascites in promoting metastasis and therapy resistance remains poorly understood. This review summarizes the current understanding of malignant ascites, with a focus on ovarian cancer. The first section provides an overview of heterogeneity in ovarian cancer and the pathophysiology of malignant ascites. Next, analytical methods used to characterize the cellular and acellular components of malignant ascites, as well the role of these components in modulating cell biology, are discussed. The review then provides a perspective on the pressures and forces that tumors are subjected to in the presence of malignant ascites and the impact of physical stress on therapy resistance. Treatment options for malignant ascites, including surgical, pharmacological and photochemical interventions are then discussed to highlight challenges and opportunities at the interface of drug discovery, device development and physical sciences in oncology.

MCS-MTWLP may be a promising approach to improve therapeutic outcome for patients with cutaneous vascular lesions featuring large blood vessels.

A key reason for the persistently grim statistics associated with metastatic ovarian cancer is resistance to conventional agents, including platinum-based chemotherapies. A major source of treatment failure is the high degree of genetic and molecular heterogeneity, which results from significant underlying genomic instability, as well as stromal and physical cues in the microenvironment. Ovarian cancer commonly disseminates via transcoelomic routes to distant sites, which is associated with the frequent production of malignant ascites, as well as the poorest prognosis. In addition to providing a cell and protein-rich environment for cancer growth and progression, ascitic fluid also confers physical stress on tumors. An understudied area in ovarian cancer research is the impact of fluid shear stress on treatment failure. Here, we investigate the effect of fluid shear stress on response to platinum-based chemotherapy and the modulation of molecular pathways associated with aggressive disease in a perfusion model for adherent 3D ovarian cancer nodules. Resistance to carboplatin is observed under flow with a concomitant increase in the expression and activation of the epidermal growth factor receptor (EGFR) as well as downstream signaling members mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) and extracellular signal-regulated kinase (ERK). The uptake of platinum by the 3D ovarian cancer nodules was significantly higher in flow cultures compared to static cultures. A downregulation of phospho-focal adhesion kinase (p-FAK), vinculin, and phospho-paxillin was observed following carboplatin treatment in both flow and static cultures. Interestingly, low-dose anti-EGFR photoimmunotherapy (PIT), a targeted photochemical modality, was found to be equally effective in ovarian tumors grown under flow and static conditions. These findings highlight the need to further develop PIT-based combinations that target the EGFR, and sensitize ovarian cancers to chemotherapy in the context of flow-induced shear stress. Keywords: ovarian cancer; epidermal growth factor receptor (EGFR); mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK); extracellular signal-regulated kinase (ERK); chemoresistance; fluid shear stress; ascites; perfusion model; photoimmunotherapy (PIT); photodynamic therapy (PDT); carboplatin J. Clin. Med. 2020, 9, 924 3 of 27 anatomical structures [4,[27][28][29][30]]. An area that remains understudied is the effect of fluid shear stress on response to chemotherapy and the modulation of molecular pathways associated with aggressive disease [11,16,17,31]. J. Clin. Med. 2020, 9, x FOR PEER REVIEW 3 of 27 Figure 1. (A) A schematic of ovarian cancer metastases involving tumor cells or clusters (yellow) shedding from a primary site and disseminating along ascitic currents of peritoneal fluid (green arrows) in the abdominal cavity. Ovarian cancer typically disseminates in four common abdominopelvic sites: (1) cul-de-sac (an extension of the peritoneal cavity between the r...

Background and ObjectiveMolecules native to tissue that fluoresce upon light excitation can serve as reporters of cellular activity and protein structure. In skin, the fluorescence ascribed to tryptophan is a marker of cellular proliferation, whereas the fluorescence ascribed to cross‐links of collagen is a structural marker. In this work, we introduce and demonstrate a simple but robust optical method to image the functional process of epithelialization and the exposed dermal collagen in wound healing of human skin in an organ culture model.Materials and MethodsNon‐closing non‐grafted, partial closing non‐grafted, and grafted wounds were created in ex vivo human skin and kept in culture. A wide‐field UV fluorescence excitation imaging system was used to visualize epithelialization of the exposed dermis and quantitate wound area, closure, and gap. Histology (H&E staining) was also used to evaluate epithelialization.ResultsThe endogenous fluorescence excitation of cross‐links of collagen at 335 nm clearly shows the dermis missing epithelium, while the endogenous fluorescence excitation of tryptophan at 295 nm shows keratinocytes in higher proliferating state. The size of the non‐closing wound was 11.4 ± 1.8 mm and remained constant during the observation period, while the partial‐close wound reached 65.5 ± 4.9% closure by day 16. Evaluations of wound gaps using fluorescence excitation images and histology images are in agreement.ConclusionsWe have established a fluorescence imaging method for studying epithelialization processes, evaluating keratinocyte proliferation, and quantitating closure during wound healing of skin in an organ culture model: the dermal fluorescence of pepsin‐digestible collagen cross‐links can be used to quantitate wound size, closure extents, and gaps; and, the epidermal fluorescence ascribed to tryptophan can be used to monitor and quantitate functional states of epithelialization. UV fluorescence excitation imaging has the potential to become a valuable tool for research, diagnostic and educational purposes on evaluating the healing of wounds. Lasers Surg. Med. 48:678–685, 2016. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Sprayable formulations of AgNPs were prepared by exchanging citrate capping agents with LL37-SH peptides. The AgNP@LL37 material was then combined with type I collagen to form a stable film once sprayed. The AgNP@LL37 spray prevented Pseudomonas aeruginosa (P. aeruginosa) proliferation and eradicated a P. aeruginosa biofilm, while being non-toxic for human skin fibroblasts embedded within 3D artificial skin constructs. Finally, no silver infiltration was observed after spraying on a full-thickness skin wound in a mouse model.

Endogenous molecules that exhibit fluorescence hold the potential to serve as reporters of tissue structure, activity and physiology. Fluorescence excitation spectroscopy is one means to measure and express tissue's innate fluorescence. This review focuses on the application of endogenous fluorescence ultraviolet excitation spectroscopy to dermatology.

Cryogen spray cooling (CSC) is a heat extraction process that protects the epidermis from thermal damage during dermatologic laser surgery. The objective of the present work is to investigate radial and temporal variations in the heat transferred through the surface of a skin phantom during CSC. A fastresponse thermal sensor is used to measure surface temperatures every 1 mm across a 16 mm diameter of the sprayed surface of the phantom. An analytical expression based on Fourier's law and Duhamel's theorem is used to compute surface heat fluxes from temperature measurements. Results show that radial and temporal variations of the boundary conditions have a strong influence on the homogeneity of heat extraction from the skin phantom. However, there is a subregion of uniform cooling whose size is time dependent. It is also observed that the surface heat flux undergoes a marked dynamic variation, with a maximum heat flux occurring at the centre of the sprayed surface early in the spurt followed by a quick decrease. The study shows that radial and temporal variations of boundary conditions must be taken into account and ideally controlled to guarantee uniform protection during CSC of human skin.