Cardiac Complications of Radiation Therapy.

Radiation therapy is a critical component in managing many malignancies by improving local control and survival. The benefits of radiation may come at the expense of unintended radiation injury to the surrounding normal tissues, with the heart being one of the most affected organs in thoracic radiation treatments. As cancer survivors live longer, radiation-induced cardiotoxicity (RICT) is now increasingly recognized.

Apoptosis mechanisms induced by 15d-PMJ in HCT116 colon cancer cells: insights into CHOP10/TRB3/Akt signaling.

Agents that stimulate the endoplasmic reticulum (ER) stress pathway are being exploited pharmacologically to induce cancer cell death. Cytotoxic ER stress is typically regulated by the transcription factor, C/EBP homologous protein 10 (CHOP10). Products of CHOP10 transcription include the pro-apoptotic proteins: ER oxidoreductase 1α (ERO1α), death receptor-5 (DR5), and tribbles-related protein 3 (TRB3).

Calcium signaling induced by 15-deoxy-prostamide-J2 promotes cell death by activating PERK, IP3R, and the mitochondrial permeability transition pore.

Melanoma is the deadliest form of skin cancer in the US. Although immunotherapeutic checkpoint inhibitors and small-molecule kinase inhibitors have dramatically increased the survival of patients with melanoma, new or optimized therapeutic approaches are still needed to improve outcomes. 15-deoxy-Δ-prostamide J (15d-PMJ) is an investigational small-molecule that induces ER stress-mediated apoptosis selectively in tumor cells.

Corrigendum: Preclinical and Clinical Assessment of Cannabinoids as Anti-Cancer Agents.

[This corrects the article DOI: 10.3389/fphar.2016.

Damage-associated molecular pattern (DAMP) activation in melanoma: investigation of the immunogenic activity of 15-deoxy, Δ prostamide J.

Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity.

Prostaglandin D-ethanolamide induces skin cancer apoptosis by suppressing the activity of cellular antioxidants.

The combined incidence of melanoma and non-melanoma skin cancer (NMSC) is greater than the incidence of all other malignancies in the US. Previously, we demonstrated that the endocannabinoid, arachidonoyl-ethanolamide (AEA), was a potent inducer of apoptosis in NMSC. The metabolism of AEA to the prostaglandin, PGD-EA, was a prerequisite for AEA cytotoxicity.

Synthesis and Evaluation of the Novel Prostamide, 15-Deoxy, Δ-Prostamide J, as a Selective Antitumor Therapeutic.

15-deoxy, Δ-prostaglandin J-ethanolamide, also known as 15-deoxy, Δ-prostamide J (15d-PMJ) is a novel product of the metabolism of arachidonoyl ethanolamide (AEA) by COX-2. 15d-PMJ preferentially induced cell death and apoptosis in tumorigenic A431 keratinocytes and B16F10 melanoma cells compared with nontumorigenic HaCaT keratinocytes and Melan-A melanocytes. Activation of the ER stress execution proteins, PERK and CHOP10, was evaluated to determine whether this process was involved in 15d-PMJ cell death.

Preclinical and Clinical Assessment of Cannabinoids as Anti-Cancer Agents.

Cancer is the second leading cause of death in the United States with 1.7 million new cases estimated to be diagnosed in 2016. This disease remains a formidable clinical challenge and represents a substantial financial burden to the US health care system.

Becaplermin gel (PDGF-BB) as topical wound therapy. Plastic Surgery Educational Foundation DATA Committee.

Becaplermin gel is the first topical growth factor to demonstrate therapeutic efficacy in the healing of diabetic wounds. For diabetic patients who have poorly healing ulcers despite good perfusion and a reasonable trial of wound care, this product may be of considerable benefit. It should be tried for a 2-week time period and the results objectively assessed before continuation of therapy.

Effects of electrically charged particles in enhancement of rat wound healing.

Background: Many studies have show that various growth factors enhance wound healing in animal models. However, growth factors are expensive and complex and their wound pharmacokinetics are unknown. The clinical trials with growth factors in the treatment of chronic wounds have produced unsuccessful results.

Strategies for reducing material costs through implementation of clinical guidelines.

This paper presents a case study where the efforts to improve clinical guidelines resulted in significant savings in material costs through the standardization of the supplies and negotiation of contracts with the suppliers. It also presents an approach that is now being used to standardize material and reduce supply costs in other areas of the health system.

p53 and apoptosis alterations in keloids and keloid fibroblasts.

Keloids are the result of a dysregulated wound-healing process and are characterized by formation of excess scar tissue that proliferates beyond the boundaries of the inciting wound. In this study, we investigated the expression of key proteins involved in regulating apoptosis in keloids. Twenty archival paraffin-embedded keloid samples were randomly selected for an immunoperoxidase assay with antibodies against fas, p53, bcl-2, and bcl-x proteins using the target antigen-retrieval technique.

The multidisciplinary in-hospital wound care team: two models.

The cost of community- and hospital-acquired pressure ulcers is particularly high in terms of both patient morbidity and economics. Multidisciplinary wound care teams were developed independently at two different hospitals to deal with the needs of patients with pressure ulcers and to control costs. Although the goals of the teams at both institutions were similar, the strategies for achieving the goals were different because they were adapted to the needs of the particular institution.

Analysis of p53 gene mutations in keloids using polymerase chain reaction-based single-strand conformational polymorphism and DNA sequencing.

Background: Keloids are the result of a dysregulated wound healing process. They are characterized by the formation of excess scar tissue that proliferates beyond the boundaries of the original wound. Somatic mutations of p53 have been implicated as causal events in up to 50% of all human malignancies.

Understanding dressings.

Currently our understanding of chronic wound pathophysiology is deficient in knowing what specifically is lacking during arrested wound healing. Autologous or allogenic keratinocytes have been used successfully to treat chronic wounds, as have composites containing diverse substances such as allogenic dermis, polyglycolic acid, or collagen mesh combined with keratinocytes or fibroblasts (Table 6). In spite of great technological advances and increased understanding, there is much work to be done.

Hydrogels and hydrocolloids: an objective product comparison.

It is difficult for providers to make selections from the vast array of currently available wound care products. There has been a paucity of objective data generated by a non-biased source comparing one product to another. In order for our Wound Care Team to recommend products for system-wide formulary purchase and patient use, we needed to develop a process for product comparison.

Acute and chronic animal models for excessive dermal scarring: quantitative studies.

Excessive scarring in the form of keloids and hypertrophic scars continues to be a clinical problem for some patients. The lack of an animal model for such scarring has been an obstacle to studying the cellular and molecular biology of these entities. Previous observations made by the authors that some surgical scars in the rabbit ear remain raised for months after wounding prompted us to investigate whether the rabbit ear might provide a model by which to study excessive dermal scarring.

Alpha 1-antitrypsin is degraded and non-functional in chronic wounds but intact and functional in acute wounds: the inhibitor protects fibronectin from degradation by chronic wound fluid enzymes.

Fluid obtained from chronic and acute wounds were examined for the presence of fibronectin, alpha 1-antitrypsin, and proteinases capable of degrading both proteins. Immunoblot analysis of fluids from ten chronic wounds revealed that fibronectin and alpha 1-antitrypsin were degraded in nine of ten samples. In contrast, both fibronectin and alpha 1-antitrypsin were intact in acute wound fluids.

Tissue inhibitor of metalloproteinases-1 is decreased and activated gelatinases are increased in chronic wounds.

The balance between matrix deposition and tissue turnover is fundamental in wound healing. It is likely that the balance between proteolytic enzymes and their inhibitors contributes to this balance. Matrix metalloproteinases are clearly important in tissue turnover, but their roles in wound healing are poorly understood.

Excessive scarring as a consequence of healing.

Synthesis and degradation of collagen is an essential component of wound healing. In most persons, this deposition of collagen results in the formation of a fine line scar which restores much of the tensile strength to the injured tissue and is cosmetically acceptable. However, in certain individuals, the result of wound healing is the excessive accumulation of collagen, resulting in a hypertrophic scar or keloid.

Effects of oxygen on wound responses to growth factors: Kaposi's FGF, but not basic FGF stimulates repair in ischemic wounds.

Kaposi's fibroblast growth factor (K-FGF, FGF-4) is a newer member of FGF family with uncharacterized wound healing properties. Basic fibroblast growth factor (bFGF, FGF-2) has been well studied and accelerates repair in normal and impaired wound healing models. K-FGF and bFGF are known to have similar biological effects in tissue culture, and both stimulate fibroblast and endothelial cell proliferation.

The use of omental transposition in the treatment of recurrent sarcoma of the back.

We report 2 patients with paraspinous sarcoma treated with omental transposition tunneled through a defect in the lumbar fascia that resurfaced in the soft tissues of the lower back. Traditional reconstruction with skin flaps was unsatisfactory because of prior irradiation to the area. In 1 patient the omentum obliterated a cavity connecting the dura to the skin to prevent cerebrospinal fluid leak.