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14 pages, 4215 KiB  
Article
Exploratory Analyses of Circulating Neoplastic-Immune Hybrid Cells as Prognostic Biomarkers in Advanced Intrahepatic Cholangiocarcinoma
by Ranish K. Patel, Michael S. Parappilly, Brett S. Walker, Robert T. Heussner, Alice Fung, Young Hwan Chang, Adel Kardosh, Charles D. Lopez, Skye C. Mayo and Melissa H. Wong
Int. J. Mol. Sci. 2024, 25(17), 9198; https://doi.org/10.3390/ijms25179198 - 24 Aug 2024
Cited by 2 | Viewed by 1877
Abstract
Existing clinical biomarkers do not reliably predict treatment response or disease progression in patients with advanced intrahepatic cholangiocarcinoma (ICC). Circulating neoplastic-immune hybrid cells (CHCs) have great promise as a blood-based biomarker for patients with advanced ICC. Peripheral blood specimens were longitudinally collected from [...] Read more.
Existing clinical biomarkers do not reliably predict treatment response or disease progression in patients with advanced intrahepatic cholangiocarcinoma (ICC). Circulating neoplastic-immune hybrid cells (CHCs) have great promise as a blood-based biomarker for patients with advanced ICC. Peripheral blood specimens were longitudinally collected from patients with advanced ICC enrolled in the HELIX-1 phase II clinical trial (NCT04251715). CHCs were identified by co-expression of pan-cytokeratin (CK) and CD45, and levels were correlated to patient clinical disease course. Unsupervised machine learning was then performed to extract their morphological features to compare them across disease courses. Five patients were included in this study, with a median of nine specimens collected per patient. A median of 13.5 CHCs per 50,000 peripheral blood mononuclear cells were identified at baseline, and levels decreased to zero following the initiation of treatment in all patients. Counts remained undetectable in three patients who demonstrated end-of-trial clinical treatment response and conversely increased in two patients with evidence of therapeutic resistance. In the post-trial surveillance period, interval counts increased prior to or at the time of clinical progression in three patients and remain undetectable in one patient with continued long-term disease stability. Using our machine learning platform, treatment-resistant CHCs exhibited upregulation of CK and downregulation of CD45 relative to treatment-responsive CHCs. CHCs represent a promising blood-based biomarker to supplement traditional radiographic and biochemical measures. Full article
(This article belongs to the Special Issue Molecular Biology of Liquid Biopsy in Cancer)
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12 pages, 3920 KiB  
Article
From Zora Neale to Missionary Mary: Womanist Aesthetics of Faith and Freedom
by Ada C. M. Thomas
Religions 2023, 14(10), 1285; https://doi.org/10.3390/rel14101285 - 12 Oct 2023
Viewed by 1516
Abstract
In this essay, I discuss the art of Missionary Mary Proctor, a contemporary folk artist from Tallahassee, Florida, in the context of the literary aesthetics of the renowned twentieth-century anthropologist and writer Zora Neale Hurston. In comparing these Southern-born African American women artists, [...] Read more.
In this essay, I discuss the art of Missionary Mary Proctor, a contemporary folk artist from Tallahassee, Florida, in the context of the literary aesthetics of the renowned twentieth-century anthropologist and writer Zora Neale Hurston. In comparing these Southern-born African American women artists, I argue that both are rooted in an aesthetic praxis deriving from their shared womanist ethics. My goal in this inquiry is to highlight the faith-based aesthetic traditions of African American women and reveal the manner in which discourses of freedom intertwine with literary and visual aesthetics and faith-based practices in African American folk art and literature. To that end, I analyze the prevalence of themes of liberation within the spiritual discourses of Southern African American women artists such as Missionary Mary Proctor and theorize the manner in which a landscape of Black female liberation is envisioned within their works. Full article
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15 pages, 273 KiB  
Article
An Ongoing Womanist Buddhist Project: Reading between the Times
by Chera Jo Watts
Literature 2022, 2(3), 154-168; https://doi.org/10.3390/literature2030013 - 3 Aug 2022
Viewed by 2832
Abstract
This article challenges the dominant Christian-centered approach to Black religious life by exploring contemporary Womanist Buddhist and Black Buddhist practice, writing, and thought alongside writings of early East Asian Buddhist nuns, noting similarities, differences, and the intersections among and between these written accounts. [...] Read more.
This article challenges the dominant Christian-centered approach to Black religious life by exploring contemporary Womanist Buddhist and Black Buddhist practice, writing, and thought alongside writings of early East Asian Buddhist nuns, noting similarities, differences, and the intersections among and between these written accounts. “Reading Between the Times” signals the ongoing nature of this project, and this particular paper draws heavily upon Kathryn Ann Tsai’s 1994 translation Lives of the Nuns: Biographies of Chinese Buddhist Nuns from the Fourth to Sixth Centuries along with several Womanist and/or Black Buddhist voices, such as Faith Adiele, Melanie Harris, bell hooks, Layli Maparyan, Carolyn Jones Medine, Alice Walker, reverend angel Kyodo williams, Jan Willis, and Pamela Ayo Yetunde. Rather than make definitive claims, this paper becomes curious with initial observations surrounding authorial voice, intersections of race/gender/class within a particular temporal space, “legitimacy” questions, and others—and, of course, invites more work in the future. Deploying an engaged Buddhist pedagogy to inform mindful scholarship, this paper reminds us that we have more commonalities than oppressive systems often admit or acknowledge, and it concludes with a call to action. Full article
(This article belongs to the Special Issue Spirituality, Identity and Resistance in African American Literature)
18 pages, 2844 KiB  
Article
Challenges and Opportunities for Mental Health and Psychosocial Support in the COVID-19 Response in Africa: A Mixed-Methods Study
by Alice Walker, Muhammad Abdullatif Alkasaby, Florence Baingana, William K. Bosu, Mohammed Abdulaziz, Rosie Westerveld, Adelard Kakunze, Rosemary Mwaisaka, Khalid Saeed, Namoudou Keita, Ian F. Walker and Julian Eaton
Int. J. Environ. Res. Public Health 2022, 19(15), 9313; https://doi.org/10.3390/ijerph19159313 - 29 Jul 2022
Cited by 5 | Viewed by 4834
Abstract
This research aimed to (1) assess the extent to which mental health and psycho-social support (MHPSS) was included in the national response to the COVID-19 pandemic in African countries, and (2) explore barriers and enablers to MHPSS integration into the COVID-19 response. A [...] Read more.
This research aimed to (1) assess the extent to which mental health and psycho-social support (MHPSS) was included in the national response to the COVID-19 pandemic in African countries, and (2) explore barriers and enablers to MHPSS integration into the COVID-19 response. A mixed-methods study, using an online survey and in-depth interviews, was conducted. Participants included Mental Health Focal Points at the Ministries of Health, the World Health Organization (WHO) country and regional offices, and civil society representatives. Responses were received from 28 countries out of 55 contacted. The implementation level, based on standard guidelines, of MHPSS activities was below 50% in most countries. The most implemented MHPSS activities were establishing coordination groups (57%) and developing MHPSS strategy (45%), while the least implemented activities included implementing the developed MHPSS strategy (32%) and establishing monitoring and evaluation mechanisms (21%). Key factors that hindered implementing MHPSS activities included lack of political commitment and low prioritisation of mental health during emergencies, as it was seen as a “less important” issue during the COVID-19 pandemic, when more importance was given to infection prevention and control (IPC). However, there are signs of optimism, as mental health gained some attention during COVID-19. It is imperative to build on the attention gained by integrating MHPSS in emergency preparedness and response and strengthening mental health systems in the longer term. Full article
(This article belongs to the Special Issue Mental Health Roadmap: Where We Stand and Where to Go?)
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11 pages, 245 KiB  
Article
Toward Buddhist Womanism: Tonglen Practice in The Color Purple
by Zhi Huang
Religions 2022, 13(7), 660; https://doi.org/10.3390/rel13070660 - 18 Jul 2022
Viewed by 3265
Abstract
Tonglen is a Tibetan Buddhist practice that aims at developing the practitioner’s bodhicitta. In this article, I argue that it not only finds expression in Alice Walker’s The Color Purple through the protagonist Celie, but adds more complexity to the womanist philosophy for [...] Read more.
Tonglen is a Tibetan Buddhist practice that aims at developing the practitioner’s bodhicitta. In this article, I argue that it not only finds expression in Alice Walker’s The Color Purple through the protagonist Celie, but adds more complexity to the womanist philosophy for which Walker has been ensconced in positions of influence. More specifically, Celie follows an implied Buddhist practice of tonglen; in the process of “taking in and sending out”, her bodhicitta has been generated and cultivated. Underlying her tonglen practice is Buddhist womanism demonstrating how African American women can survive the social oppression and injustice by way of acknowledging their own terrible afflictions, empathizing with those enduring intense suffering, male and female, extending their loving kindness, comprehending the absence of intrinsic entity and the principle of dependent origination, etc. In addition, the article suggests that the fight for the survival of the oppressed is a type of Buddhist practice in Walker’s Buddhist womanism. Full article
18 pages, 753 KiB  
Review
Improving Access to Cancer Treatment Services in Australia’s Northern Territory—History and Progress
by Emma V. Taylor, Rosalie D. Thackrah and Sandra C. Thompson
Int. J. Environ. Res. Public Health 2022, 19(13), 7705; https://doi.org/10.3390/ijerph19137705 - 23 Jun 2022
Cited by 4 | Viewed by 3934
Abstract
Cancer is the leading cause of death in the Northern Territory (NT), Australia’s most sparsely populated jurisdiction with the highest proportion of Aboriginal people. Providing cancer care to the NT’s diverse population has significant challenges, particularly related to large distances, limited resources and [...] Read more.
Cancer is the leading cause of death in the Northern Territory (NT), Australia’s most sparsely populated jurisdiction with the highest proportion of Aboriginal people. Providing cancer care to the NT’s diverse population has significant challenges, particularly related to large distances, limited resources and cultural differences. This paper describes the developments to improve cancer treatment services, screening and end-of-life care in the NT over the past two decades, with a particular focus on what this means for the NT’s Indigenous peoples. This overview of NT cancer services was collated from peer-reviewed literature, government reports, cabinet papers and personal communication with health service providers. The establishment of the Alan Walker Cancer Care Centre (AWCCC), which provides radiotherapy, chemotherapy and other specialist cancer services at Royal Darwin Hospital, and recent investment in a PET Scanner have reduced patients’ need to travel interstate for cancer diagnosis and treatment. The new chemotherapy day units at Alice Springs Hospital and Katherine Hospital and the rapid expansion of tele-oncology have also reduced patient travel within the NT. Access to palliative care facilities has also improved, with end-of-life care now available in Darwin, Alice Springs and Katherine. However, future efforts in the NT should focus on increasing and improving travel assistance and support and increasing the availability of appropriate accommodation; ongoing implementation of strategies to improve recruitment and retention of health professionals working in cancer care, particularly Indigenous health professionals; and expanding the use of telehealth as a means of delivering cancer care and treatment. Full article
(This article belongs to the Special Issue Rural and Remote Health)
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20 pages, 1430 KiB  
Article
Living with Rheumatic Heart Disease at the Intersection of Biomedical and Aboriginal Worldviews
by Emma Haynes, Minitja Marawili, Makungun B. Marika, Alice Mitchell, Roz Walker, Judith M. Katzenellenbogen and Dawn Bessarab
Int. J. Environ. Res. Public Health 2022, 19(8), 4650; https://doi.org/10.3390/ijerph19084650 - 12 Apr 2022
Cited by 9 | Viewed by 4142
Abstract
Rheumatic heart disease (RHD) significantly impacts the lives of First Nations Australians. Failure to eliminate RHD is in part attributed to healthcare strategies that fail to understand the lived experience of RHD. To rectify this, a PhD study was undertaken in the Northern [...] Read more.
Rheumatic heart disease (RHD) significantly impacts the lives of First Nations Australians. Failure to eliminate RHD is in part attributed to healthcare strategies that fail to understand the lived experience of RHD. To rectify this, a PhD study was undertaken in the Northern Territory (NT) of Australia, combining Aboriginal ways of knowing, being and doing with interviews (24 participants from clinical and community settings) and participant observation to privilege Aboriginal voices, including the interpretations and experiences of Aboriginal co-researchers (described in the adjunct article). During analysis, Aboriginal co-researchers identified three interwoven themes: maintaining good feelings; creating clear understanding (from good information); and choosing a good djalkiri (path). These affirm a worldview that prioritises relationships, positive emotions and the wellbeing of family/community. The findings demonstrate the inter-connectedness of knowledge, choice and behaviour that become increasingly complex in stressful and traumatic health, socioeconomic, political, historical and cultural contexts. Not previously heard in the RHD domain, the findings reveal fundamental differences between Aboriginal and biomedical worldviews contributing to the failure of current approaches to communicating health messages. Mitigating this, Aboriginal co-researchers provided targeted recommendations for culturally responsive health encounters, including: communicating to create positive emotions; building trust; and providing family and community data and health messages (rather than individualistic). Full article
(This article belongs to the Special Issue Health Inequalities in Socially Disadvantaged Communities)
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18 pages, 725 KiB  
Article
“Weaving a Mat That We Can All Sit On”: Qualitative Research Approaches for Productive Dialogue in the Intercultural Space
by Emma Haynes, Minitja Marawili, Alice Mitchell, Roz Walker, Judith Katzenellenbogen and Dawn Bessarab
Int. J. Environ. Res. Public Health 2022, 19(6), 3654; https://doi.org/10.3390/ijerph19063654 - 19 Mar 2022
Cited by 17 | Viewed by 4814
Abstract
Research remains a site of struggle for First Nations peoples globally. Biomedical research often reinforces existing power structures, perpetuating ongoing colonisation by dominating research priorities, resource allocation, policies, and services. Addressing systemic health inequities requires decolonising methodologies to facilitate new understandings and approaches. [...] Read more.
Research remains a site of struggle for First Nations peoples globally. Biomedical research often reinforces existing power structures, perpetuating ongoing colonisation by dominating research priorities, resource allocation, policies, and services. Addressing systemic health inequities requires decolonising methodologies to facilitate new understandings and approaches. These methodologies promote a creative tension and productive intercultural dialogue between First Nations and Western epistemologies. Concurrently, the potential of critical theory, social science, and community participatory action research approaches to effectively prioritise First Nations peoples’ lived experience within the biomedical worldview is increasingly recognised. This article describes learnings regarding research methods that enable a better understanding of the lived experience of rheumatic heart disease—an intractable, potent marker of health inequity for First Nations Australians, requiring long-term engagement in the troubled intersection between Indigenist and biomedical worldviews. Working with Yolŋu (Aboriginal) co-researchers from remote Northern Territory (Australia), the concept of ganma (turbulent co-mingling of salt and fresh water) was foundational for understanding and applying relationality (gurrutu), deep listening (nhina, nhäma ga ŋäma), and the use of metaphors—approaches that strengthen productive dialogue, described by Yolŋu co-researchers as weaving a ‘mat we can all sit on’. The research results are reported in a subsequent article. Full article
(This article belongs to the Special Issue Health Inequalities in Socially Disadvantaged Communities)
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14 pages, 260 KiB  
Article
Maternal Supplementation with Dietary Betaine during Gestation to Improve Twin Lamb Survival
by Billie-Jaye Brougham, Alice C. Weaver, Alyce M.F. Swinbourne, Bobbie E. Lewis Baida, Jennifer M. Kelly, Simon K. Walker, David O. Kleemann and William H.E.J. van Wettere
Animals 2020, 10(10), 1749; https://doi.org/10.3390/ani10101749 - 26 Sep 2020
Cited by 17 | Viewed by 3376
Abstract
Betaine increases the synthesis of creatine, an energy-rich amino acid that increases adenosine triphosphate (ATP) and has neuroprotective properties which may improve post-natal lamb survival. This study determined whether maternal betaine supplementation during gestation would improve body weight, thermoregulation, time to stand and [...] Read more.
Betaine increases the synthesis of creatine, an energy-rich amino acid that increases adenosine triphosphate (ATP) and has neuroprotective properties which may improve post-natal lamb survival. This study determined whether maternal betaine supplementation during gestation would improve body weight, thermoregulation, time to stand and suck, colostrum intake and survival to weaning of twin lambs. Twin-bearing Merino ewes received dietary betaine at either 0 g/day (Control, CTL), 2 g/day from ram introduction to parturition (Early betaine, EB) or 4 g/day from Day 80 of gestation to parturition (Late betaine, LB). Ewes were housed individually during parturition and measures were collected at 4, 24 and 72 h and Day 7 post-partum, and at marking (53.2 ± 0.2 days of age) and weaning (99.3 ± 0.2 days of age). The EB treatment resulted in heavier lambs at weaning compared with CTL and LB lambs (p < 0.05). Time to stand and suck from birth was longer in EB lambs (p < 0.05), whereas, the interval from birth to first suck was shorter for LB lambs (p < 0.05). Lamb survival rate was the highest for LB lambs at 72 h and Day 7 (p < 0.05), and lowest for EB lambs on Day 7 (p < 0.05). These data indicated that betaine supplementation at 4 g/day during the second half of pregnancy improved twin lamb survival to Day 7 and shortened the interval from birth to first suck; whereas feeding ewes 2 g/day of betaine for the duration of pregnancy increased twin lamb body weight at weaning, but increased both the time to attain behavioural milestones and mortalities before Day 7. Full article
(This article belongs to the Special Issue Maternal Nutrition on Fetal and Newborns Health)
12 pages, 271 KiB  
Essay
Their American Dream
by Danné E. Davis
Genealogy 2020, 4(2), 45; https://doi.org/10.3390/genealogy4020045 - 7 Apr 2020
Cited by 1 | Viewed by 5884
Abstract
Centuries before W.E.B. DuBois named the colorline—i.e., racism—as the problem of the 20th century, skin color stratification was a persistent phenomenon. In 1983 Black feminist, scholar, and Pulitzer Prize winning author Alice Walker termed “colorism” as “prejudicial or preferential treatment of same-race people [...] Read more.
Centuries before W.E.B. DuBois named the colorline—i.e., racism—as the problem of the 20th century, skin color stratification was a persistent phenomenon. In 1983 Black feminist, scholar, and Pulitzer Prize winning author Alice Walker termed “colorism” as “prejudicial or preferential treatment of same-race people based solely on their [skin] color”. Using the tools of genealogy, I conducted a critical family history of my parents, Lem and Mae’s, pursuit of their American Dream. Such exploration digs deep to decipher the nexuses of a family’s evolution. Dr. Maya Angelou routinely shared stories about her past to impart the importance of embracing one’s history. For my parents, the American Dream meant opportunity, which included home ownership. Their American Dream began as African Americans in the United States’ Jim Crow south. Lem was a light-skinned man; Mae a dark-complexion woman. They met, married, and bought a small home in segregated Columbia, South Carolina. Bearing the cloak of oppression, my parents joined millions of southern Blacks in the Great Migration relocating to northern cities—my parents landed in Boston, Massachusetts. Throughout their journey, Lem and Mae reached back to their ancestors, and drew from within themselves to improve their circumstances. Full article
(This article belongs to the Special Issue Genealogy and Critical Family History)
32 pages, 1084 KiB  
Article
Re-Framing Hottentot: Liberating Black Female Sexuality from the Mammy/Hottentot Bind
by Shaweta Nanda
Humanities 2019, 8(4), 161; https://doi.org/10.3390/h8040161 - 14 Oct 2019
Cited by 7 | Viewed by 29256
Abstract
Taking up Michele Wallace’s call to interrogate popular cultural forms and unravel their relationship with the political discourse of the time, this paper begins by examining the popular discourse about Black female sexuality in the USA. White, cis-hetero-patriarchal cultural and visual imagination still [...] Read more.
Taking up Michele Wallace’s call to interrogate popular cultural forms and unravel their relationship with the political discourse of the time, this paper begins by examining the popular discourse about Black female sexuality in the USA. White, cis-hetero-patriarchal cultural and visual imagination still represents Black women either as asexual and maternal mammies or as the deviant ‘Other’ that is as Venus Hottentots or ‘hypersexual’ Jezebels. Maternal and sexual scripts were first naturalized by popular and scientific discourse(s), and then covertly deployed by the dominant white hetero-patriarchal set up to mask the exploitation of Black women, and constrict the opportunities of growth that were available to them even after the emancipation. This paper analyzes how Black women writers like Elizabeth Alexander and Alice Walker, and visual artists such as Renee Cox develop an oppositional gaze, to use hooks’s phrase, and ‘re-frame’ the Venus Hottentot from their radical and subversive points of view. Building on theoretical insights of Gina Dent, Cornel West, and Audre Lorde, this paper engages with the oft-neglected relationship between pleasure, desire, identity, and Black female sexuality. Thus, Black female sexuality that has been expunged and/or termed ‘deviant’ actually becomes a source of empowerment for Black women. Full article
(This article belongs to the Special Issue Unsilencing Black Sexuality in the African Diaspora)
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10 pages, 172 KiB  
Article
Black Lesbians to the Rescue! A Brief Correction with Implications for Womanist Christian Theology and Womanist Buddhology
by Pamela Ayo Yetunde
Religions 2017, 8(9), 175; https://doi.org/10.3390/rel8090175 - 1 Sep 2017
Cited by 3 | Viewed by 8905
Abstract
Foundational Black Womanist Christian Theology has suffered from the focus on Alice Walker’s 1983 four-part womanist definition at the exclusion of her 1979 short story, Coming Apart. The focus on the 1983 definition and the exclusion of Coming Apart has left an [...] Read more.
Foundational Black Womanist Christian Theology has suffered from the focus on Alice Walker’s 1983 four-part womanist definition at the exclusion of her 1979 short story, Coming Apart. The focus on the 1983 definition and the exclusion of Coming Apart has left an invisbilizing effect on the centrality of reliance on African-American lesbian literature and wisdom in womanist Christian methodology. The invisibilization can be corrected, in part, through interpolating Coming Apart with the 1983 definition, utilizing a Black Buddhist lesbian Womanist hermeneutic, and additional Womanist engagement in Womanist Consultations. This correction has implications for Christian theologies that may be heterosexist, homophobic, and patriarchal, Biblical interpretation, preaching, and epistemological processes. Full article
(This article belongs to the Special Issue Race and Religion: New Approaches to African American Religions)
20 pages, 367 KiB  
Article
Infertility and Its Treatments in Association with Autism Spectrum Disorders: A Review and Results from the CHARGE Study
by Kristen Lyall, Alice Baker, Irva Hertz-Picciotto and Cheryl K. Walker
Int. J. Environ. Res. Public Health 2013, 10(8), 3715-3734; https://doi.org/10.3390/ijerph10083715 - 19 Aug 2013
Cited by 20 | Viewed by 9484
Abstract
Previous findings on relationships between infertility, infertility therapies, and autism spectrum disorders (ASD) have been inconsistent. The goals of this study are first, to briefly review this evidence and second, to examine infertility and its treatments in association with having a child with [...] Read more.
Previous findings on relationships between infertility, infertility therapies, and autism spectrum disorders (ASD) have been inconsistent. The goals of this study are first, to briefly review this evidence and second, to examine infertility and its treatments in association with having a child with ASD in newly analyzed data. In review, we identified 14 studies published as of May 2013 investigating infertility and/or its treatments and ASD. Overall, prior results showed little support for a strong association, though some increases in risk with specific treatments were found; many limitations were noted. In new analyses of the CHildhood Autism Risk from Genetics and the Environment (CHARGE) population-based study, cases with autism spectrum disorder (ASD, n = 513) and controls confirmed to have typical development (n = 388) were compared with regard to frequencies of infertility diagnoses and treatments overall and by type. Infertility diagnoses and treatments were also grouped to explore potential underlying pathways. Logistic regression was used to obtain crude and adjusted odds ratios overall and, in secondary analyses, stratified by maternal age (≥35 years) and diagnostic subgroups. No differences in infertility, infertility treatments, or hypothesized underlying pathways were found between cases and controls in crude or adjusted analyses. Numbers were small for rarer therapies and in subgroup analyses; thus the potential for modest associations in specific subsets cannot be ruled out. However, converging evidence from this and other studies suggests that assisted reproductive technology is not a strong independent risk factor for ASD. Recommendations for future studies of this topic are provided. Full article
(This article belongs to the Special Issue The Environment Risk of Autism)
15 pages, 187 KiB  
Article
The Effects of Arsenic Trioxide on DNA Synthesis and Genotoxicity in Human Colon Cancer Cells
by Jacqueline J. Stevens, Barbara Graham, Alice M. Walker, Paul B. Tchounwou and Christian Rogers
Int. J. Environ. Res. Public Health 2010, 7(5), 2018-2032; https://doi.org/10.3390/ijerph7052018 - 28 Apr 2010
Cited by 46 | Viewed by 12811
Abstract
Colon cancer is the third leading cause of cancer-related deaths worldwide. Recent studies in our laboratory have demonstrated that arsenic trioxide is cytotoxic in human colon cancer (HT-29), lung (A549) and breast (MCF-7) carcinoma cells. The purpose of the present study is to [...] Read more.
Colon cancer is the third leading cause of cancer-related deaths worldwide. Recent studies in our laboratory have demonstrated that arsenic trioxide is cytotoxic in human colon cancer (HT-29), lung (A549) and breast (MCF-7) carcinoma cells. The purpose of the present study is to investigate the effects of arsenic trioxide on DNA synthesis and the possible genotoxic effects on human colon cancer cells. HT-29 cells were cultured according to standard protocol, followed by exposure to various doses (0, 2, 4, 6, 8, 10, and 12 μg/mL) of arsenic trioxide for 24 h. The proliferative response (DNA synthesis) to arsenic trioxide was assessed by [3H]thymidine incorporation. The genotoxic effects of arsenic-induced DNA damage in a human colon cancer cell line was evaluated by the alkaline single cell gel electrophoresis. Results indicated that arsenic trioxide affected DNA synthesis in HT-29 cells in a biphasic manner; showing a slight but not significant increase in cell proliferation at lower levels of exposure (2, 4 and 6 µg/mL) followed by a significant inhibition of cell proliferation at higher doses (i.e., 8 and 10 µg/mL). The study also confirmed that arsenic trioxide exposure caused genotoxicity as revealed by the significant increase in DNA damage, comet tail-lengths, and tail moment when compared to non-exposed cells. Results of the [3H]thymidine incorporation assay and comet assay revealed that exposure to arsenic trioxide affected DNA synthesis and exhibited genotoxic effects in human colon cancer cells. Full article
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12 pages, 210 KiB  
Article
Arsenic Trioxide Modulates DNA Synthesis and Apoptosis in Lung Carcinoma Cells
by Alice M. Walker, Jacqueline J. Stevens, Kenneth Ndebele and Paul B. Tchounwou
Int. J. Environ. Res. Public Health 2010, 7(5), 1996-2007; https://doi.org/10.3390/ijerph7051996 - 28 Apr 2010
Cited by 43 | Viewed by 10601
Abstract
Arsenic trioxide, the trade name Trisenox, is a drug used to treat acute promyleocytic leukemia (APL). Studies have demonstrated that arsenic trioxide slows cancer cells growth. Although arsenic influences numerous signal-transduction pathways, cell-cycle progression, and/or apoptosis, its apoptotic mechanisms are complex and not [...] Read more.
Arsenic trioxide, the trade name Trisenox, is a drug used to treat acute promyleocytic leukemia (APL). Studies have demonstrated that arsenic trioxide slows cancer cells growth. Although arsenic influences numerous signal-transduction pathways, cell-cycle progression, and/or apoptosis, its apoptotic mechanisms are complex and not entirely delineated. The primary objective of this research was to evaluate the effects of arsenic trioxide on DNA synthesis and to determine whether arsenic-induced apoptosis is mediated via caspase activation, p38 mitogen–activated protein kinase (MAPK), and cell cycle arrest. To achieve this goal, lung cancer cells (A549) were exposed to various concentrations (0, 2, 4, 6, 8, and 10 µg/mL) of arsenic trioxide for 48 h. The effect of arsenic trioxide on DNA synthesis was determined by the [3H]thymidine incorporation assay. Apoptosis was determined by the caspase-3 fluorescein isothiocyanate (FITC) assay, p38 MAP kinase activity was determined by an immunoblot assay, and cell-cycle analysis was evaluated by the propidium iodide assay. The [3H]thymidine-incorporation assay revealed a dose-related cytotoxic response at high levels of exposure. Furthermore, arsenic trioxide modulated caspase 3 activity and induced p38 MAP kinase activation in A549 cells. However, cell-cycle studies showed no statistically significant differences in DNA content at subG1 check point between control and arsenic trioxide treated cells. Full article
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