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.