Isolation and characterization of microbiota from human pancreatic tumors and small intestine.

Pancreatic ductal adenocarcinoma has a unique tumor microbiome and the systemic depletion of bacteria or fungi using antibiotic/antifungal cocktails leads to a decrease in pancreatic tumor burden in mice. However, functional studies remain rare due to the limited availability of clinically relevant microbiota. Here, we describe in detail the isolation of bacteria and fungi from the small intestine and tumor of pancreatic cancer patients at the Rogel Cancer Center.

Pain hypersensitivity, sensorimotor impairment, and decreased muscle force in a novel rat model of radiation-induced peripheral neuropathy.

Introduction: Radiation-induced peripheral neuropathy is a rare, but serious complication often resulting in profound morbidity, life-long disability, and chronic debilitating pain. Unfortunately, this type of peripheral neuropathy is usually progressive, and almost always irreversible. To date, a standardized rat model of radiation-induced peripheral neuropathy has not been established.

Optimizing immunofluorescent staining of H vessels within an irradiated fracture callus in paraffin-embedded tissue samples.

H vessels are an essential link in angiogenic-osteogenic coupling and orchestrate the process of bone healing. H vessels are critically deficient in the setting of radiation-induced fractures, which have been reported to occur in up to 25% of patients undergoing radiotherapy. By increasing H-vessel proliferation, Deferoxamine (DFO) revitalizes the physiologic response to skeletal injury and accelerates irradiated fracture repair.

Adipose-Derived Stem Cells Enhance Graft Incorporation and Mineralization in a Murine Model of Irradiated Mandibular Nonvascularized Bone Grafting.

Background: Nonvascularized bone grafting represents a practical method of mandibular reconstruction. However, the destructive effects of radiotherapy on native bone preclude the use of nonvascularized bone grafts in head and neck cancer patients. Adipose-derived stem cells have been shown to enhance bone healing and regeneration in numerous experimental models.

Therapeutic Efficacy of Adipose-Derived Stem Cells Versus Bone Marrow Stromal Cells for Irradiated Mandibular Fracture Repair.

Background: Mesenchymal stem cells have immense potential in applications of bone healing and regeneration. However, few studies have evaluated the therapeutic efficacy of adipose-derived stem cells (ASCs) and bone marrow stromal cells (BMSCs) in irradiated bone. The purpose of this study is to compare the ability of ASCs versus BMSCs to enhance healing outcomes in a murine model of irradiated mandibular fracture repair.

Intraoperative Stromal Vascular Fraction Therapy Improves Histomorphometric and Vascular Outcomes in Irradiated Mandibular Fracture Repair.

Background: Cell-based treatments have demonstrated the capacity to enhance reconstructive outcomes in recent decades but are hindered in clinical utility by regulatory hurdles surrounding cell culture. This investigation examines the ability of a noncultured stromal vascular fraction derived from lipoaspirate to enhance bone healing during fracture repair to further the development of translatable cell therapies that may improve outcomes in irradiated reconstruction.

Methods: Isogenic male Lewis rats were divided into three groups: fracture, irradiated fracture, and irradiated fracture with stromal vascular fraction treatment.

Network Architecture of Gap Junctional Coupling among Parallel Processing Channels in the Mammalian Retina.

Gap junctions are ubiquitous throughout the nervous system, mediating critical signal transmission and integration, as well as emergent network properties. In mammalian retina, gap junctions within the Aii amacrine cell-ON cone bipolar cell (CBC) network are essential for night vision, modulation of day vision, and contribute to visual impairment in retinal degenerations, yet neither the extended network topology nor its conservation is well established. Here, we map the network contribution of gap junctions using a high-resolution connectomics dataset of an adult female rabbit retina.

Noncultured Minimally Processed Adipose-Derived Stem Cells Improve Radiated Fracture Healing.

Adipose-derived stem cells mitigate deleterious effects of radiation on bone and enhance radiated fracture healing by replacing damaged cells and stimulating angiogenesis. However, adipose-derived stem cell harvest and delivery techniques must be refined to comply with the US Food and Drug Administration restrictions on implantation of cultured cells into human subjects prior to clinical translation. The purpose of this study is to demonstrate the preservation of efficacy of adipose-derived stem cells to remediate the injurious effects of radiation on fracture healing utilizing a novel harvest and delivery technique that avoids the need for cell culture.

Therapeutic Interventions to Reduce Radiation Induced Dermal Injury in a Murine Model of Tissue Expander Based Breast Reconstruction.

Background: Radiation therapy (XRT) induced dermal injury disrupts type I collagen architecture. This impairs cutaneous viscoelasticity, which may contribute to the high rate of complications in expander-based breast reconstruction with adjuvant XRT. The objective of this study was to further elucidate the mechanism of radiation-induced dermal injury and to determine if amifostine (AMF) or deferoxamine (DFO) mitigates type I collagen injury in an irradiated murine model of expander-based breast reconstruction.

Amifostine Prophylaxis in Irradiated Breast Reconstruction: A Study of Oncologic Safety In Vitro.

Background: Indications for adjuvant radiation therapy (XRT) in breast cancer have expanded. Although highly effective, XRT damages surrounding tissues and vasculature, often resulting in delayed or compromised breast reconstruction. Thus, effective yet safe methods of radiation injury prophylaxis would be desirable.

Implantable hyaluronic acid-deferoxamine conjugate prevents nonunions through stimulation of neovascularization.

Approximately 6.3 million fractures occur in the U.S.

The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety.

Background: Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine has immense potential to up-regulate angiogenesis and improve reconstructive outcomes.

Stem Cells for Bone Regeneration: Current State and Future Directions.

Mesenchymal stem cells (MSCs) are capable of differentiating into osteoblasts, chondrocytes, and adipocytes, each of which is important for musculoskeletal tissue regeneration and repair. Reconstruction and healing of bony defects remains a major clinical challenge. Even as surgical practices advance, some severe cases of bone loss do not yield optimal recovery results.

Nonvascularized Bone Graft Reconstruction of the Irradiated Murine Mandible: An Analogue of Clinical Head and Neck Cancer Treatment.

Nonvascularized bone grafts (NBGs) represent a practical method of mandibular reconstruction that is precluded in head and neck cancer patients by the destructive effects of radiotherapy. Advances in tissue-engineering may restore NBGs as a viable surgical technique, but expeditious translation demands a small-animal model that approximates clinical practice. This study establishes a murine model of irradiated mandibular reconstruction using a segmental iliac crest NBG for the investigation of imperative bone healing strategies.

Topical Deferoxamine Alleviates Skin Injury and Normalizes Atomic Force Microscopy Patterns Following Radiation in a Murine Breast Reconstruction Model.

Background: Breast cancer is most commonly managed with a combination of tumor ablation, radiation, and/or chemotherapy. Despite the oncologic benefit of these treatments, the detrimental effect of radiation on surrounding tissue challenges the attainment of ideal breast reconstruction outcomes. The purpose of this study was to determine the ability of topical deferoxamine (DFO) to reduce cutaneous ulceration and collagen disorganization following radiotherapy in a murine model of expander-based breast reconstruction.

Histologic Improvements in Irradiated Bone Through Pharmaceutical Intervention in Mandibular Distraction Osteogenesis.

Purpose: Despite the relative surgical ease and reduced donor-site morbidity of distraction osteogenesis (DO) in comparison with free tissue transfer, DO is currently precluded as a reconstructive option for head and neck cancer (HNC) patients because of the destructive effects of radiotherapy (XRT). This study investigates the ability of a novel combined therapy (CT) of radioprotective amifostine (AMF) and angiogenic deferoxamine (DFO) to mitigate XRT-induced bone injury in a murine model of DO.

Materials And Methods: Thirty male Sprague-Dawley rats were divided into 5 groups: DO (primary control), XRT (secondary control), AMF, DFO, and CT.

Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration.

Purpose: Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility.

Radioprotection With Amifostine Enhances Bone Strength and Regeneration and Bony Union in a Rat Model of Mandibular Distraction Osteogenesis.

Background: Using distraction osteogenesis (DO) to regenerate robust endogenous bone could greatly enhance postoncologic reconstruction of head and neck cancer. However, radiation (XRT) corrosive effects still preclude DO's immense potential. We posit that adjunctive pretreatment with the radioprotectant amifostine (AMF) can optimize wound healing and allow for successful DO with quantifiable enhancements in bony union and strength despite previous surgical bed irradiation.

Significant Differences in the Bone of an Isogenic Inbred Versus Nonisogenic Outbred Murine Mandible: A Study in Rigor and Reproducibility.

Inattention to differences between animal strains is a potential cause of irreproducibility of basic science investigations. Accordingly, the authors' laboratory sought to ensure that cross-comparisons of results generated from studies of mandibular physiology utilizing the Sprague Dawley and Lewis rat strains are valid. The authors specifically investigated baseline histomorphometrics, bone mineral density, and biomechanical strength of the unaltered endogenous mandibles of the inbred, isogenic Lewis rat, and the outbred, nonisogenic Sprague Dawley rat to determine if they are indeed equal.

Role of parathyroid hormone in regeneration of irradiated bone in a murine model of mandibular distraction osteogenesis.

Background: The purpose of this study was to measure the histologic and histomorphometric effects of parathyroid hormone (PTH) treatment on irradiated bone undergoing distraction osteogenesis (DO).

Methods: Thirty-four rats were divided into 3 groups. The control group underwent DO and the radiation control group underwent radiotherapy (RT) before DO.

Rod-cone crossover connectome of mammalian bipolar cells.

The basis of cross-suppression between rod and cone channels has long been an enigma. Using rabbit retinal connectome RC1, we show that all cone bipolar cell (BC) classes inhibit rod BCs via amacrine cell (AC) motifs (C1-6); that all cone BC classes are themselves inhibited by AC motifs (R1-5, R25) driven by rod BCs. A sparse symmetric AC motif (CR) is presynaptic and postsynaptic to both rod and cone BCs.

A Comparison of Vascularity, Bone Mineral Density Distribution, and Histomorphometrics in an Isogenic Versus an Outbred Murine Model of Mandibular Distraction Osteogenesis.

Purpose: The vascularity, bone mineral density distribution, and histomorphometric data between the inbred, isogenic Lewis rat and the outbred, nonisogenic Sprague Dawley rat within mandibular distraction osteogenesis (MDO) were evaluated to allow future researchers to compare the results generated from these 2 animals. We hypothesized that little difference would be found between the 2 strains within these metrics.

Materials And Methods: We implemented a comparative study between the Lewis and Sprague Dawley rat strains within MDO.

Amifostine Treatment Mitigates the Damaging Effects of Radiation on Distraction Osteogenesis in the Murine Mandible.

According to the American Society of Clinical Oncology, in 2012, more than 53,000 new cases of head and neck cancers (HNCs) were reported in the United States alone and nearly 12,000 deaths occurred relating to HNC. Although radiotherapy (XRT) has increased survival, the adverse effects can be unrelenting and their management is rarely remedial. Current treatment dictates surgical mandibular reconstruction using free tissue transfer.

Bone marrow stem cells assuage radiation-induced damage in a murine model of distraction osteogenesis: A histomorphometric evaluation.

The purpose of this study is to determine if intraoperatively placed bone marrow stem cells (BMSCs) will permit successful osteocyte and mature bone regeneration in an isogenic murine model of distraction osteogenesis (DO) following radiation therapy (XRT). Lewis rats were split into three groups, DO only (Control), XRT followed by DO (xDO) and XRT followed by DO with intraoperatively placed BMSCs (xDO-BMSC). Coronal sections from the distraction site were obtained, stained and analyzed via statistical analysis with analysis of variance (ANOVA) and subsequent Tukey or Games-Howell post-hoc tests.