Treatment of acne with spironolactone: a retrospective review of 395 adult patients at Mayo Clinic, 2007-2017.

BACKGROUND: Few large studies have assessed spironolactone treatment of adult female acne. OBJECTIVES: To explore the role of spironolactone in the treatment of adult female acne. METHODS: We performed a retrospective case series assessing the efficacy of spironolactone treatment of a cohort of women evaluated at Mayo Clinic in Rochester, Minnesota, from 2007 through 2017. RESULTS: In total, 395 patients (median age, 32 years) received a median spironolactone dose of 100 mg daily. Approximately two-thirds of patients (66.1%) had a complete response; 85.1% had a complete response or a partial response greater than 50%. Median times to initial response and maximum response were 3 and 5 months. Efficacy was observed across all severity subtypes of acne, including those with papulopustular and nodulocystic acne. Patients received long-term treatment with spironolactone (median duration, 13 months) and had few adverse effects. CONCLUSIONS: Spironolactone is a safe and effective treatment of acne for women.

Tissue invasion and metastasis: Molecular, biological and clinical perspectives.

Cancer is a key health issue across the world, causing substantial patient morbidity and mortality. Patient prognosis is tightly linked with metastatic dissemination of the disease to distant sites, with metastatic diseases accounting for a vast percentage of cancer patient mortality. While advances in this area have been made, the process of cancer metastasis and the factors governing cancer spread and establishment at secondary locations is still poorly understood. The current article summarizes recent progress in this area of research, both in the understanding of the underlying biological processes and in the therapeutic strategies for the management of metastasis. This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), ß-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-ß), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei, Albatrellus confluens, Cordyceps militaris, Ganoderma lucidum, Poria cocos and Silybum marianum, together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer. Together, these strategies could represent new, inexpensive, low toxicity strategies to aid in the management of cancer metastasis as well as having holistic effects against other cancer hallmarks.

The intersection between DNA damage response and cell death pathways.

Apoptosis is a finely regulated process that serves to determine the fate of cells in response to various stresses. One such stress is DNA damage, which not only can signal repair processes but is also intimately involved in regulating cell fate. In this review we examine the relationship between the DNA damage/repair response in cell survival and apoptosis following insults to the DNA. Elucidating these pathways and the crosstalk between them is of great importance, as they eventually contribute to the etiology of human disease such as cancer and may play key roles in determining therapeutic response. This article is part of a Special Issue entitled "Apoptosis: Four Decades Later".

The interplay between inflammation and oxidative stress in carcinogenesis.

Emerging data suggest that primary dysfunction in the tumor microenvironment is crucial for carcinogenesis. These recent findings make a compelling case for targeting the milieu for cancer chemoprevention as well as therapy. The stroma is an integral part of its physiology, and functionally, one cannot totally dissociate the tumor surrounding from the tumor cells. A thorough understanding of the tumor and stroma will aid us in developing new treatment targets. In this review, we shed light at the key aspects of the carcinogenic process and how oxidative stress and inflammation contribute to this process. We dissect the connection between metastasis and oxidative stress and focus on the key players in the tumor microenvironment that leads to inflammation, oxidative stress and DNA damage. Moreover, we consider the role of inflammation in disease, specifically cancer and metastasis. Finally, we discuss the potential applications in prognosis and cancer treatment.

Biomarkers to assess the targeting of DNA repair pathways to augment tumor response to therapy.

Hyper-activation of DNA repair pathways can enable tumor cells to survive DNA damage. Therefore, targeting specific DNA repair pathways might prove efficacious for cancer therapy. The advent of personalized therapy necessitates novel biomarkers to assess tumor response to therapy. Biological indicators are vital in the field of cancer research and treatment. The focus of this review is on the DNA repair machinery as an emerging target for enhancement of therapy. Additionally, DNA damage and repair biomarkers for prognosis in different types of cancer will be discussed. The application of biomarkers to assess tumor response to therapy based on targeting DNA repair pathways can potentially improve patient quality of life and aid in treatment design.

Targeting DNA damage and repair: embracing the pharmacological era for successful cancer therapy.

DNA is under constant assault from genotoxic agents which creates different kinds of DNA damage. The precise replication of the genome and the continuous surveillance of its integrity are critical for survival and the avoidance of carcinogenesis. Cells have evolved an arsenal of repair pathways and cell cycle checkpoints to detect and repair DNA damage. When repair fails, typically cell cycle progression is halted and apoptosis is initiated. Here, we review the different sources and types of DNA damage including DNA replication stress and oxidative stress, the repair pathways that cells utilize to repair damaged DNA, and discuss their biological significance, especially with reference to cancer induction and cancer therapy. We also describe the main methodologies currently used for the detection of DNA damage with their strengths and limitations. We conclude with an outline as to how this information can be used to identify novel pharmacological targets for DNA repair pathways or enhancers of DNA damage to develop improved treatment strategies that will benefit cancer patients.

Nanotechnology in cancer therapy: targeting the inhibition of key DNA repair pathways.

Cancer therapy has been changing over the decades as we move away from the administration of broad spectrum cytotoxic drugs and towards the use of therapy targeted for each tumor type. After the induction of DNA damage through chemotherapeutic agents, tumor cells can survive due to their proficient DNA repair pathways, some of which are dysregulated in cancer. Latest improvements in nanotechnology and drug discovery has led to the discovery of some very unique, highly specific and innovative drugs as inhibitors of various DNA repair pathways like base excision repair and double strand break repair. In this review we look at the efficacy and potency of these small chemical molecules to target the processing of DNA damage induced by standard therapeutic agents. Emphasis is given to those drugs currently under clinical trials. We also discuss the future directions of using this nanotechnology to increase the therapeutic ratio in cancer treatment.