Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center: Structure, Innovations, and Initial Outcomes.

INTRODUCTION: The Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center is a triad partnership committed to increasing institutional capacity for cancer disparity research, the diversity of the cancer workforce, and community empowerment. This article provides an overview of the structure, process innovations, and initial outcomes from the first 4 years of the CaRE2 triad partnership. METHODS: CaRE2 serves diverse populations in Florida and California using a "molecule to the community and back" model. We prioritize research on the complex intersection of biological, environmental, and social determinants health, working together with scientific and health disparities communities, sharing expertise across institutions, bidirectional training, and community outreach. Partnership progress and outcomes were assessed using mixed methods and four Program Steering Committee meetings. RESULTS: Research capacity was increased through development of a Living Repository of 81 cancer model systems from minority patients for novel cancer drug development. CaRE2 funded 15 scientific projects resulting in 38 publications. Workforce diversity entailed supporting 94 cancer trainees (92 URM) and 34 ESIs (32 URM) who coauthored 313 CaRE2-related publications and received 48 grants. Community empowerment was promoted via outreaching to more than 3000 individuals, training 145 community cancer advocates (including 28 Community Scientist Advocates), and publishing 10 community reports. CaRE2 members and trainees together have published 639 articles, received 61 grants, and 57 awards. CONCLUSION: The CaRE2 partnership has achieved its initial aims. Infrastructure for translational cancer research was expanded at one partner institution, and cancer disparities research was expanded at the two cancer centers.

Prognostic Relevance of ZNF844 and Chr 19p13.2 KRAB-Zinc Finger Proteins in Clear Cell Renal Carcinoma.

BACKGROUND/AIM: Clear-cell renal cell carcinoma (ccRCC) is the most common and aggressive form of all urological cancers, with poor prognosis and high mortality. Despite growing evidence of involvement in carcinogenesis, the role of KRAB-ZFP in ccRCC has not been fully explored. KRAB Zinc finger proteins (KRAB-ZFPs) are the largest family of mammalian transcription regulators. They are differentially expressed in various tissues during cellular development and phenotypic differentiation. MATERIALS AND METHODS: In this study, the levels of transcripts of ccRCC from The Cancer Genome Atlas (TCGA) dataset were used to identify prognostic biomarkers in this disease. RESULTS: Using bioinformatics techniques, we demonstrate that approximately 60% of KRAB zinc finger proteins located on chromosome 19p13.2 are differentially expressed, with all but two being down-regulated in ccRCC. Moreover, ZNF844, a paralog of ZNF433, was the most down-regulated across all histological grades and pathological stages (p<0.001). In addition, the decrease in ZNF844 expression was associated with poor patient survival (HR=0.41; 95% CI=0.3-0.56; p<0.0001). Gene Set Enrichment Analysis of genes inversely co-expressed with ZNF844 revealed that enriched pathways were consistently related to immune and translation processes (p<0.05, FDR <0.05). Lastly, ZNF844 expression showed moderate, inverse correlation to Helper T-cell (CD4 or Th1) subtype 1 (R=-0.558, p=5.15×10-39) infiltration and with the exhausted T-cell phenotype (R=-0.37; p=4.1×10-21). CONCLUSION: Down-regulation of KRAB-ZFPs at 19p13.2 may represent a signature for ccRCC. Moreover, ZNF844 is a prognostic marker for ccRCC and may serve as a putative immune-related tumor suppressor gene.

Improving Representation of Underrepresented Minority (URM) Students in Oncology Biomedical Research Workforce: Outcome Evaluation from the ReTOOL Program.

The Research Training Opportunities for Outstanding Leaders (ReTOOL) program was implemented in 2012 to increase the representation of racial and ethnic minorities in the biomedical workforce. Specifically, the ReTOOL program aims to foster the capacity for scientific research among underserved populations as well as address the cultural appropriateness of research projects. This paper describes the impact of the ReTOOL program in enhancing the research training of underrepresented minority (URM) students. Forty URM students who completed the ReTOOL program between 2012 and 2019 were invited to participate in the program evaluation. The response rate was 73% with 29 participants. Of the 29 participants, 26 trainees self-identified as Black or African-American. A structured survey developed for the program was employed for data collection, using a Likert Scale ranging from 1 to 5, with 5 being the best. The item ratings ranged from 4.45 to 4.80. Responses to open-ended questions show that ReTOOL has been instrumental in socializing and acculturating participants into the habits of scientific thinking. The combined use of quantitative and qualitative inquiry depicts that ReTOOL has been highly successful in fostering participant enrollment in advanced health-related or professional degree programs.

A 10-year experience with reverse shoulder arthroplasty: are we operating earlier?

INTRODUCTION: As surgeons' confidence in reverse shoulder arthroplasty (RSA) increases, they may tend to offer RSA earlier in the course of glenohumeral joint disease. This study evaluates the changes in the "tipping point" for primary RSA over a 10-year period to evaluate changes in practice. METHODS: A total of 3975 primary RSAs performed over a 10-year period were retrospectively reviewed from a multi-institutional database. Of these, 3536 primary RSAs with preoperative diagnoses of osteoarthritis with rotator cuff deficiency (1626), irreparable rotator cuff tear (396), and rotator cuff tear arthropathy (1514) were included in the analysis. Preoperative range of motion (ROM) and patient-reported outcome measures (PROMs) were used to calculate tipping points for each subgroup on a yearly basis over a 10-year period, and assessed for changes over time. RESULTS: PROMs (American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Simple Shoulder Test) and the Constant score remained similar over the 10-year study period, with all demonstrating slightly higher tipping points later in the study. ROM measures (forward elevation, abduction, and external rotation) all showed small increases over time, demonstrating better ROM before electing to undergo RSA in later years. CONCLUSIONS: With the increasing use of RSA over the last decade, the ROM tipping point for patients electing to undergo surgery has increased, whereas the PROM tipping point has remained stable. This indicates that patients undergoing RSA in the present have greater ROM preoperatively compared with 10 years ago; however, their perceived disability remains similar. Surgeons and patients continue to pursue RSA at a similar preoperative morbidity over the last 10 years.

Increasing the Representation of Minority Students in the Biomedical Workforce: the ReTOOL Program.

With the growing burden of cancer in minority populations and limited progress in eliminating cancer disparities, it has become important to develop a diverse oncology workforce in basic, clinical, and behavioral research who will address cancer disparities and increase the participation of minority populations in clinical trials. To address the lack of well-trained underrepresented minority cancer scientists in Florida, the University of Florida collaborated with Florida A&M University in 2012 to establish the Florida Prostate Cancer Research Training Opportunities for Outstanding Leaders (ReTOOL) Program. Since 2012, the ReTOOL program has expanded to (1) cover all areas of cancer disparities; (2) offer training opportunities to minority students from all historically Black colleges and universities (HBCUs) in Florida; and (3) successfully secure both intramural and extramural federal funding to continuously provide research training opportunities for minority students in Florida. Focusing primarily on training Black students, the ReTOOL model includes culturally sensitive recruitment, mentorship, didactic curriculum, networking, and hands on experience in cancer research. This paper discusses the lessons learned from administering the ReTOOL program for 5 years, which includes having the right inputs (such as majority-minority institutions partnership, funding, faculty advisors, committed mentors, culturally competent staff, and standardized program requirements) and processes (such as pipeline approach, structured applications system, didactic curriculum, research experience, and continuous mentoring) for an effective research training program. The program impact is an increase in the pool of underrepresented minority candidates with scientific and academic career progression paths focused on reducing cancer health disparities.

African Americans with pancreatic ductal adenocarcinoma exhibit gender differences in Kaiso expression.

Kaiso, a bi-modal transcription factor, regulates gene expression, and is elevated in breast, prostate, and colon cancers. Depletion of Kaiso in other cancer types leads to a reduction in markers for the epithelial-mesenchymal transition (EMT) (Jones et al., 2014), however its clinical implications in pancreatic ductal adenocarcinoma (PDCA) have not been widely explored. PDCA is rarely detected at an early stage but is characterized by rapid progression and invasiveness. We now report the significance of the subcellular localization of Kaiso in PDCAs from African Americans. Kaiso expression is higher in the cytoplasm of invasive and metastatic pancreatic cancers. In males, cytoplasmic expression of Kaiso correlates with cancer grade and lymph node positivity. In male and female patients, cytoplasmic Kaiso expression correlates with invasiveness. Also, nuclear expression of Kaiso increases with increased invasiveness and lymph node positivity. Further, analysis of the largest PDCA dataset available on ONCOMINE shows that as Kaiso increases, there is an overall increase in Zeb1, which is the inverse for E-cadherin. Hence, these findings suggest a role for Kaiso in the progression of PDCAs, involving the EMT markers, E-cadherin and Zeb1.

Immunohistological analysis of ABCD3 expression in Caucasian and African American prostate tumors.

In a previously published study, we showed that expression of the ABCD3 gene increased with increasing metastatic potential in a panel of prostate cancer cell lines derived from African American and Caucasian American men. Given importance of identifying biomarker(s) that can distinguish indolent versus aggressive prostate tumors, we conducted an immunohistochemical analysis of ABCD3 expression Caucasian and African American prostate tumors. ABCD3 expression in each patient population was compared with clinicopathologic characteristics, Gleason score, and age. ABCD3 expression increased with increasing Gleason score (P = 0.0094), age (P = 0.0014), and pathology grade (P = 0.0007) in Caucasian patients. Interestingly, in the AA patients, ABCD3 expression highly increased to the same degree in both low and high Gleason score tumors. Similarly, ABCD3 expression was elevated to the same degree in BPH derived from AA. Our findings demonstrate that increased ABCD3 expression correlates with Gleason Score in CA prostate tumors. However, in AA prostate tumors, ABCD3 expression was higher and was sustained in both low Gleason and high Gleason AA tumors. While the functional role of ABCD3 in prostate cancer is not completely elucidated, this gene warrants further study as a potential biomarker for aggressive prostate.

Defects in base excision repair sensitize cells to manganese in S. cerevisiae.

Manganese (Mn) is essential for normal physiologic functioning; therefore, deficiencies and excess intake of manganese can result in disease. In humans, prolonged exposure to manganese causes neurotoxicity characterized by Parkinson-like symptoms. Mn(2+) has been shown to mediate DNA damage possibly through the generation of reactive oxygen species. In a recent publication, we showed that Mn induced oxidative DNA damage and caused lesions in thymines. This study further investigates the mechanisms by which cells process Mn(2+)-mediated DNA damage using the yeast S. cerevisiae. The strains most sensitive to Mn(2+) were those defective in base excision repair, glutathione synthesis, and superoxide dismutase mutants. Mn(2+) caused a dose-dependent increase in the accumulation of mutations using the CAN1 and lys2-10A mutator assays. The spectrum of CAN1 mutants indicates that exposure to Mn results in accumulation of base substitutions and frameshift mutations. The sensitivity of cells to Mn(2+) as well as its mutagenic effect was reduced by N-acetylcysteine, glutathione, and Mg(2+). These data suggest that Mn(2+) causes oxidative DNA damage that requires base excision repair for processing and that Mn interferes with polymerase fidelity. The status of base excision repair may provide a biomarker for the sensitivity of individuals to manganese.

Advocacy resource: engaging the media and promoting your cancer program in Africa.

To address the need for a significant increase in cancer advocacy programs in Africa, the University of Florida (UF), the Prostate Net, and the African Organization for Research and Training in Cancer (AORTIC) co-hosted the first biennial International Workshop on Cancer Advocacy for African Countries (CAAC) on November 29, 2011, one-day prior to AORTIC's 8th International Cancer Conference in Cairo, Egypt. Over 70 African cancer advocates representing about 12 African countries participated in this workshop.The primary goal of the one-day workshop was to inform, educate and empower African cancer advocates to increase the promotion of their cancer programs. The first half of the workshop consisted of five formal PowerPoint presentations focused on the following topics: (a) Understanding Your Community and Assessing your Community Health Assets and Needs; (b) Developing a successful advocacy model for your cancer program; (c) Developing a Relationship with your Elected Officials to Advocate Cancer-related Policies; (d) Engaging the Media and promoting your cancer program; and (e) Developing advocacy plans for sustainability. In this article we summarize the informational content given in the PowerPoint presentation entitled "Engaging the Media and promoting your cancer program". The content given in this article is useful as a how-to guide for both the beginner and the experienced cancer advocate who wants to establish/promote a cancer awareness program.

The African cancer advocacy consortium: shaping the path for advocacy in Africa.

Although there is significant evidence of a cancer epidemic in Africa, there is limited awareness about cancer in most African countries. By partnering with international organizations and institutions such as the University of Florida and the Prostate Net, the African Organisation for Research and Training in Cancer (AORTIC) is committed to improving cancer advocacy in Africa. This paper presents some of the recent efforts on cancer advocacy in Africa, including the results of a SWOT analysis conducted for the cancer advocacy workshop and the guidelines developed by cancer advocates on best practices for cancer advocacy in Africa. One of the outcomes of these efforts is the African Cancer Advocates Consortium (ACAC) founded by cancer advocates in Africa to, "Make Cancer a Top Priority in Africa". While we have started the work to strengthen cancer advocacy in Africa, we still have a long way to go. Our goal of making cancer a priority in Africa can mainly be achieved by: (1) increasing the manpower for cancer advocacy through education and training; and (2) strengthening the network of cancer advocates across the continent.

Manganese-induced oxidative DNA damage in neuronal SH-SY5Y cells: attenuation of thymine base lesions by glutathione and N-acetylcysteine.

Manganese (Mn) is an essential trace element required for normal function and development. However, exposure to this metal at elevated levels may cause manganism, a progressive neurodegenerative disorder with neurological symptoms similar to idiopathic Parkinson's disease (IPD). Elevated body burdens of Mn from exposure to parental nutrition, vapors in mines and smelters and welding fumes have been associated with neurological health concerns. The underlying mechanism of Mn neurotoxicity remains unclear. Accordingly, the present study was designed to investigate the toxic effects of Mn(2+) in human neuroblastoma SH-SY5Y cells. Mn(2+) caused a concentration dependent decrease in SH-SY5Y cellular viability compared to controls. The LD50 value was 12.98 µM Mn(2+) (p<0.001 for control vs. 24h Mn treatment). Both TUNEL and annexin V/propidium iodide (PI) apoptosis assays confirmed the induction of apoptosis in the cells following exposure to Mn(2+) (2 µM, 62 µM or 125 µM). In addition, Mn(2+) induced both the formation and accumulation of DNA single strand breaks (via alkaline comet assay analysis) and oxidatively modified thymine bases (via gas chromatography/mass spectrometry analysis). Pre-incubation of the cells with characteristic antioxidants, either 1mM N-acetylcysteine (NAC) or 1mM glutathione (GSH) reduced the level of DNA strand breaks and the formation of thymine base lesions, suggesting protection against oxidative cellular damage. Our findings indicate that (1) exposure of SH-SY5Y cells to Mn promotes both the formation and accumulation of oxidative DNA damage, (2) SH-SY5Y cells with accumulated DNA damage are more likely to die via an apoptotic pathway and (3) the accumulated levels of DNA damage can be abrogated by the addition of exogenous chemical antioxidants. This is the first known report of Mn(2+)-induction and antioxidant protection of thymine lesions in this SH-SY5Y cell line and contributes new information to the potential use of antioxidants as a therapeutic strategy for protection against Mn(2+)-induced oxidative DNA damage.

Microarray genomic profile of mitochondrial and oxidant response in manganese chloride treated PC12 cells.

Environmental or occupational exposure to high levels of manganese (Mn) can lead to manganism, a symptomatic neuro-degenerative disorder similar to idiopathic Parkinson's disease. The underlying mechanism of Mn neurotoxicity remains unclear. In this study, we evaluate the primary toxicological events associated with MnCl(2) toxicity in rat PC12 cells using whole genome cDNA microarray, RT-PCR, Western blot and functional studies. The results show that a sub-lethal dose range (38-300 µM MnCl(2)) initiated slight metabolic stress evidenced by heightened glycolytic rate and induction of enolase/aldolase - gene expression. The largest shift observed in the transcriptome was MnCl(2) induction of heme-oxygenase 1 (HO-1) [7.7 fold, p<0.001], which was further corroborated by RT-PCR and Western blot studies. Concentrations in excess of 300 µM corresponded to dose dependent loss of cell viability which was associated with enhanced production of H(2)O(2) concomitant to elevation of gene expression for diverse antioxidant enzymes; biliverdin reductase, arsenite inducible RNA associated protein, dithiolethione-inducible gene-1 (DIG-1) and thioredoxin reductase 1. Moreover, Mn initiated significant reduction of gene expression of mitochondrial glutaryl-coenzyme A dehydrogenase (GCDH), an enzyme involved with glutaric acidemia, oxidative stress, lipid peroxidation and striatal degeneration observed in association with severe dystonic-dyskinetic movement disorder. Future research will be required to elucidate a defined role for HO-1 and GCDH in Mn toxicity.

Detecting gene-gene interactions in prostate disease in African American men.

BACKGROUND: The most common male malignancy in the United States is prostate cancer; however its rate of occurrence varies significantly among ethnic groups. In a previous cDNA microarray study on CaP tumors from African American (AA) and Caucasian (CA) patients, we identified 97 candidate genes that exhibited opposite gene expression polarity with respect to race groups; genes up-regulated in AA were simultaneously down-regulated in CA. PURPOSE: The purpose of this study was to narrow the 97 member gene list, to a smaller number of genes in order to focus studies on a limited number of genes/SNPs that might explain prostate cancer disparity in African Americans. METHODS: We performed genotype-phenotype, SNP and expression transcript levels correlations using HapMap Yoruba population with 85 of our 97 prostate candidate genes using SCAN database. RESULTS: Findings revealed an association of SNPs surrounding ABCD3 gene with basal gene expression of RanGAP1 is important in prostate tumors in AA. Hence, to confirm our results in clinical biospecimen, we monitored expression of ABCD3 in a novel panel of African American and Caucasian prostate cancer paired cell lines. The LNCaP, C4-2B showed 2-fold increase; MDA-2PC-2B cell line, derived from AA, showed highest fold-change, 10-fold. The EGFR over expressing DU-145 WT cell line exhibited a 4-fold increase in expression relative to non transfected DU-145 prostate cell lines. Furthermore, Ingenuity Network analysis implicated our AA prostate candidate genes are involved in three network hubs, ERK, MapK and NFkB pathways. CONCLUSIONS: Taken together, these findings are intriguing because other members of the ABC gene family, namely, ABCC3, ABCD1, and ABCD2 have been shown to confer chemoresistance in certain cancer types. Equally important, is the fact that activation of the MapK/ERK pathway via EGFR stimulation is vital for increased transcription of numerous cancer related genes. It is especially noteworthy that overexpression of EGFR has been widely observed in AA prostate tumors. Collectively our findings lead us to think that a novel signaling cascade, through which increased aggressiveness and chemoresistance is achieved, may explain prostate cancer health disparity in AA males and the nature of aggressive CaP tumors in general.

Prostate cancer health and cultural beliefs of black men: The Florida Prostate Cancer Disparity Project.

BACKGROUND: Since behavioral factors are significant determinants of population health, addressing prostate cancer (CaP)-related health beliefs and cultural beliefs are key weapons to fight this deadly disease. This study investigated the health beliefs and cultural beliefs of black men relative to CaP, and the key socio-demographic correlates of these beliefs. METHODS: The study design was a cross-sectional survey of 2,864 Florida black men, age 40 to 70, on their perceived susceptibility, perceived severity, attitude, outcomes beliefs, perceived behavioral control, CaP fatalism, religiosity, temporal orientation, and acculturation relative to CaP screening and prevention. RESULTS: The men reported favorable attitude and positive outcome beliefs, but moderate perceived behavioral control, CaP susceptibility and CaP severity. They also had low level of acculturation, did not hold fatalistic beliefs about CaP, had high religious coping skills and had high future time perspective. Several demographic variables were found to be associated with health beliefs and cultural beliefs. DISCUSSION: Our study provides rich data with regard to the health and cultural beliefs that might serve to inform the development of CaP control initiative for US-born and foreign-born black men.

Microarray comparison of prostate tumor gene expression in African-American and Caucasian American males: a pilot project study.

African American Men are 65% more likely to develop prostate cancer and are twice as likely to die of prostate cancer, than are Caucasian American Males. The explanation for this glaring health disparity is still unknown; although a number of different plausible factors have been offered including genetic susceptibility and gene-environment interactions. We favor the hypothesis that altered gene expression plays a major role in the disparity observed in prostate cancer incidence and mortality between African American and Caucasian American Males. To discover genes or gene expression pattern(s) unique to African American or to Caucasian American Males that explain the observed prostate cancer health disparity in African American males, we conducted a micro array pilot project study that used prostate tumors with a Gleason score of 6. We compared gene expression profiling in tumors from African-American Males to prostate tumors in Caucasian American Males. A comparison of case-matched ratios revealed at least 67 statistically significant genes that met filtering criteria of at least +/- 4.0 fold change and p < 0.0001. Gene ontology terms prevalent in African American prostate tumor/normal ratios relative to Caucasian American prostate tumor/normal ratios included interleukins, progesterone signaling, Chromatin-mediated maintenance and myeloid dendritic cell proliferation. Functional in vitro assays are underway to determine roles that selected genes in these onotologies play in contributing to prostate cancer development and health disparity.

Prostate cancer disparities in Black men of African descent: a comparative literature review of prostate cancer burden among Black men in the United States, Caribbean, United Kingdom, and West Africa.

BACKGROUND: African American men have the highest prostate cancer morbidity and mortality rates than any other racial or ethnic group in the US. Although the overall incidence of and mortality from prostate cancer has been declining in White men since 1991, the decline in African American men lags behind White men. Of particular concern is the growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry in the Caribbean Islands, United Kingdom and West Africa. This higher incidence of prostate cancer observed in populations of African descent may be attributed to the fact that these populations share ancestral genetic factors. To better understand the burden of prostate cancer among men of West African Ancestry, we conducted a review of the literature on prostate cancer incidence, prevalence, and mortality in the countries connected by the Transatlantic Slave Trade. RESULTS: Several published studies indicate high prostate cancer burden in Nigeria and Ghana. There was no published literature for the countries Benin, Gambia and Senegal that met our review criteria. Prostate cancer morbidity and/or mortality data from the Caribbean Islands and the United Kingdom also provided comparable or worse prostate cancer burden to that of US Blacks. CONCLUSION: The growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry follows the path of the Transatlantic Slave Trade. To better understand and address the global prostate cancer disparities seen in Black men of West African ancestry, future studies should explore the genetic and environmental risk factors for prostate cancer among this group.

Prostate cancer cognitive-behavioral factors in a West African population.

BACKGROUND: Similar to African American men, several published studies indicate high incidence of prostate cancer among Nigerian men. However, there is no published study on personal factors that influence prostate cancer detection in this population. We explored prostate cognitive-behavioral factors among indigenous Nigerian men and Nigerian immigrants residing in the US. METHODS: A cross-sectional survey methodology was employed to collect data from Nigerian men residing in Abeokuta (Nigeria) and Houston (US). Study participants were men between 35 and 79 years. RESULTS: The demographic characteristics of both study groups were similar. Based on two-sample comparison results, indigenous Nigerian men demonstrated significant differences from US Nigerian men on several prostate cancer personal cognitive-behavioral factors, including perceived susceptibility to prostate cancer, attitude towards prostate cancer screening and prostate cancer knowledge. CONCLUSION: Emigration of Nigerian men from Nigeria to the US has a significant impact on prostate cancer knowledge and beliefs.

African-Caribbean cancer consortium for the study of viral, genetic and environmental cancer risk factors.

This is a short summary of a meeting of the "African-Caribbean Cancer Consortium", jointly organized by the University of Pittsburgh, Department of Epidemiology and the University of Pittsburgh Cancer Institute, held in Montego Bay, Jamaica as a satellite meeting at the Caribbean Health Research Council, 52nd Annual Council and Scientific meeting on May 4, 2007.

Inhibitory effects of cigarette smoke on glial inducible nitric oxide synthase and lack of protective properties against oxidative neurotoxins in vitro.

Epidemiological studies consistently report an inverse correlation between cigarette smoking and associated risk for Parkinson's disease (PD). The degeneration of dopaminergic neurons may involve the toxic metabolic products of glial cell monoamine oxidase (MAO) and inducible nitric oxide synthase (iNOS). This study evaluates the direct protective effects of cigarette smoke (CS) against potential neurotoxic products of MAO, such as 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA) and hydrogen peroxide (H2O2) in brain neuroblastoma. Moreover, the effects of CS were also evaluated on endotoxin/cytokine activated glioma iNOS protein expression and MAO enzyme activity. Cigarette smoke condensates (CSCs) were acquired from Marlboro 20 Class A and Kentucky 2R4F reference research (2R4F) cigarettes. The CSCs did not protect against 6-OHDA or H2O2 toxicity in neuroblastoma, and exhibited a very mild protective effect [approximately 10%] against MPP+. Neither CSC demonstrated antioxidant capability, but conversely contained high concentration of NO2-. Paradoxically, in glioma cells, iNOS protein expression and endogenous enzymatic NO2- production were significantly blocked by both CSCs. Both CSCs also inhibited glioma MAO-A and MAO-B [1.4.3.4]. Kinetic analysis indicated that 2R4F-CSC displayed competitive inhibition and the Marlboro-CSC exerted potent competitive and non-competitive inhibition. In conclusion, these data suggest that cigarette smoke does not appear to directly protect against the toxicity of the selected neurotoxins. In contrast, CS exerts pronounced effects on glia, whereby its presence can simultaneously attenuate cytokine induction of iNOS and MAO.