NACP: Partnership for Native American Cancer Prevention.

Cancer trends over a two-decade period show a greater reduction in cancer mortality rates for non-Hispanic Whites than for Native Americans. The Partnership for Native American Cancer Prevention (NACP) was established to address cancer health disparities that impact Native Americans. The partners are Northern Arizona University, the University of Arizona Cancer Center, Arizona's tribal communities and the National Cancer Institute.

A "Pathology Explanation Clinic (PEC)" for Patient-Centered Laboratory Medicine Test Results.

This concept paper addresses communication issues arising between physicians and their patients. To facilitate the communication of essential diagnostic pathology information to patients, and address their questions and concerns, we propose that "Pathology Explanation Clinics" be created. The Pathology Explanation Clinics would provide a channel for direct communications between pathologists and patients.

Spatial distribution of uranium in mice kidneys detected by laser ablation inductively coupled plasma mass spectrometry.

The aim of the study is to better understand where uranium deposits in mice kidneys. The spatial distribution of uranium was examined in the kidneys of C57BL/6 mice using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Mice were exposed to varying levels of uranyl nitrate in their drinking water.

Second Flexner Century: The Democratization of Medical Knowledge: Repurposing a General Pathology Course Into Multigrade-Level "Gateway" Courses.

Starting in 1910, the "Flexner Revolution" in medical education catalyzed the transformation of the US medical education enterprise from a proprietary medical school dominated system into a university-based medical school system. In the 21st century, what we refer to as the "Second Flexner Century" shifts focus from the education of medical students to the education of the general population in the "4 health literacies." Compared with the remarkable success of the first Flexner Revolution, retrofitting medical science education into the US general population today, starting with K-12 students, is a more daunting task.

Flexner 2.0-Longitudinal Study of Student Participation in a Campus-Wide General Pathology Course for Graduate Students at The University of Arizona.

Faculty members from the Department of Pathology at The University of Arizona College of Medicine-Tucson have offered a 4-credit course on enhanced general pathology for graduate students since 1996. The course is titled, "Mechanisms of Human Disease." Between 1997 and 2016, 270 graduate students completed Mechanisms of Human Disease.

Oxygen in human health from life to death--An approach to teaching redox biology and signaling to graduate and medical students.

In the absence of oxygen human life is measured in minutes. In the presence of oxygen, normal metabolism generates reactive species (ROS) that have the potential to cause cell injury contributing to human aging and disease. Between these extremes, organisms have developed means for sensing oxygen and ROS and regulating their cellular processes in response.

Manganese (III) meso-tetrakis N-ethylpyridinium-2-yl porphyrin acts as a pro-oxidant to inhibit electron transport chain proteins, modulate bioenergetics, and enhance the response to chemotherapy in lymphoma cells.

The manganese porphyrin, manganese (III) meso-tetrakis N-ethylpyridinium-2-yl porphyrin (MnTE-2-PyP(5+)), acts as a pro-oxidant in the presence of intracellular H2O2. Mitochondria are the most prominent source of intracellular ROS and important regulators of the intrinsic apoptotic pathway. Due to the increased oxidants near and within the mitochondria, we hypothesized that the mitochondria are a target of the pro-oxidative activity of MnTE-2-PyP(5+) and that we could exploit this effect to enhance the chemotherapeutic response in lymphoma.

Mitochondria and redox homoeostasis as chemotherapeutic targets.

Characteristics of cancer cells include a more oxidized redox environment, metabolic reprogramming and apoptosis resistance. Our studies with a lymphoma model have explored connections between the cellular redox environment and cancer cell phenotypes. Alterations seen in lymphoma cells made resistant to oxidative stress include: a more oxidized redox environment despite increased expression of antioxidant enzymes, enhanced net tumour growth, metabolic changes involving the mitochondria and resistance to the mitochondrial pathway to apoptosis.

Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma.

Lymphoma cells are subject to higher levels of oxidative stress compared with their normal counterparts and may be vulnerable to manipulations of the cellular redox balance. We therefore designed a phase 2 study of imexon (Amplimexon/NSC-714597), a prooxidant molecule, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Imexon was administered at 1000 mg/m(2) IV daily for 5 days in 21-day cycles.

The copper chelator ATN-224 induces caspase-independent cell death in diffuse large B cell lymphoma.

Bcl-2 and other anti-apoptotic proteins are associated with defective caspase-dependent apoptotic pathways, resulting in chemoresistance. We have previously shown that ATN-224, a copper chelator drug, induces cell death in murine thymic lymphoma cells transfected with Bcl-2. In the current study, we tested whether ATN-224 was effective in diffuse large B cell lymphoma (DLBCL) cells, which have increased anti‑apoptotic proteins through translocation or amplification.

Genetic polymorphisms in oxidative stress-related genes are associated with outcomes following treatment for aggressive B-cell non-Hodgkin lymphoma.

Variable survival outcomes are seen following treatment for aggressive non-Hodgkin lymphoma (NHL). This study examined whether outcomes for aggressive B-cell NHL are associated with single nucleotide polymorphisms (SNPs) in oxidative stress-related genes, which can alter drug metabolism and immune responses. Genotypes for 53 SNPs in 29 genes were determined for 337 patients given anthracycline-based therapies.

The copper chelator ATN-224 induces peroxynitrite-dependent cell death in hematological malignancies.

Chemoresistance due to oxidative stress resistance or upregulation of Bcl-2 contributes to poor outcome in the treatment of hematological malignancies. In this study, we utilize the copper-chelator drug ATN-224 (choline tetrathiomolybdate) to induce cell death in oxidative stress-resistant cells and cells overexpressing Bcl-2 by modulating the cellular redox environment and causing mitochondrial dysfunction. ATN-224 treatment decreases superoxide dismutase 1 (SOD1) activity, increases intracellular oxidants, and induces peroxynitrite-dependent cell death.

Mitochondrial adaptations to oxidative stress confer resistance to apoptosis in lymphoma cells.

Acquired resistance to drugs commonly used for lymphoma treatment poses a significant barrier to improving lymphoma patient survival. Previous work with a lymphoma tissue culture model indicates that selection for resistance to oxidative stress confers resistance to chemotherapy-induced apoptosis. This suggests that adaptation to chronic oxidative stress can contribute to chemoresistance seen in lymphoma patients.

Mitochondria are the primary source of the H(2)O(2) signal for glucocorticoid-induced apoptosis of lymphoma cells.

Glucocorticoids are a class of steroid hormones commonly used for the treatment of hematological malignancies due to their ability to induce apoptosis in lymphoid cells. An understanding of the critical steps in glucocorticoid-induced apoptosis is required to identify sources of drug resistance. Previously, we found that an increase in hydrogen peroxide is a necessary signal for glucocorticoid-induced apoptosis.

Factors determining sensitivity and resistance of tumor cells to arsenic trioxide.

Previously, arsenic trioxide showed impressive regression rates of acute promyelocytic leukemia. Here, we investigated molecular determinants of sensitivity and resistance of cell lines of different tumor types towards arsenic trioxide. Arsenic trioxide was the most cytotoxic compound among 8 arsenicals investigated in the NCI cell line panel.

Lymphoma cells with increased anti-oxidant defenses acquire chemoresistance.

Chronic inflammation increases lymphoma risk. Chronic inflammation exposes cells to increased reactive oxygen species (ROS). Constant exposure to ROS selects for oxidative stress-resistant cells with upregulated anti-oxidant defense enzymes.

Manganese porphyrin, MnTE-2-PyP5+, Acts as a pro-oxidant to potentiate glucocorticoid-induced apoptosis in lymphoma cells.

Using current chemotherapy protocols, over 55% of lymphoma patients fail treatment. Novel agents are needed to improve lymphoma survival. The manganese porphyrin, MnTE-2-PyP(5+), augments glucocorticoid-induced apoptosis in WEHI7.

Hydrogen peroxide signaling is required for glucocorticoid-induced apoptosis in lymphoma cells.

Glucocorticoid-induced apoptosis is exploited clinically for the treatment of hematologic malignancies. Determining the required molecular events for glucocorticoid-induced apoptosis will identify resistance mechanisms and suggest strategies for overcoming resistance. In this study, we found that glucocorticoid treatment of WEHI7.

Increased cytochrome c correlates with poor survival in aggressive lymphoma.

Mitochondria are central to a variety of cellular processes, from metabolism to cell death. In this study, we demonstrated that an increase in the critical mitochondrial protein, cytochrome c, correlated with drug resistance in a cell culture model of aggressive lymphoma. Increased cytochrome c expression was also correlated with decreased survival in the aggressive diffuse large B-cell and mantle cell lymphomas, but not in the indolent follicular lymphoma.

Modulation of cell surface protein free thiols: a potential novel mechanism of action of the sesquiterpene lactone parthenolide.

Background: There has been much interest in targeting intracellular redox pathways as a therapeutic approach for cancer. Given recent data to suggest that the redox status of extracellular protein thiol groups (i.e.

Increased manganese superoxide dismutase expression or treatment with manganese porphyrin potentiates dexamethasone-induced apoptosis in lymphoma cells.

Glucocorticoid-induced apoptosis is exploited for the treatment of hematologic malignancies. Innate and acquired resistance limits treatment efficacy; however, resistance mechanisms are not well understood. Previously, using WEHI7.

Modulation of human glutathione s-transferases by polyphenon e intervention.

Purpose: Green tea consumption has been associated with decreased risk of certain types of cancers in humans. Induction of detoxification enzymes has been suggested as one of the biochemical mechanisms responsible for the cancer-preventive effect of green tea. We conducted this clinical study to determine the effect of repeated green tea polyphenol administration on a major group of detoxification enzymes, glutathione S-transferases (GST).

Glucose 6-phosphate dehydrogenase overexpression models glucose deprivation and sensitizes lymphoma cells to apoptosis.

Glucocorticoids are one component of combined treatment regimens for many types of lymphoma due to their ability to induce apoptosis in lymphoid cells. In WEHI7.2 murine thymic lymphoma cells, altering catalase and glutathione peroxidase activity by transfection or the use of chemical agents modulates the ability of glucocorticoids to induce apoptosis.