Black Lung Research Articles

Treatment of a mutant KRAS lung cancer cell line with polyisoprenylated cysteinyl amide inhibitors activates the MAPK pathway, inhibits cell migration and induces apoptosis.

KRAS mutations are the most common oncogenic mutations in lung adenocarcinoma in Black Americans. Polyisoprenylated Cysteinyl amide Inhibitors (PCAIs) constitute a group of potential cancer therapy agents that we designed to specifically disrupt and suppress hyperactive G-protein signaling, such as that caused by mutated RAS proteins. Here we determine the effects of PCAIs on the viability, G-protein levels, downstream mediators, and apoptosis-related proteins on the KRAS-mutated, Black American-derived lung adenocarcinoma cell line, NCI-H23. Of the 17 PCAIs tested, compounds NSL-YHJ-2-27 and NSL-YHJ-2-46 showed the most potency with EC50 values of 2.7 and 3.3 μM, respectively. Western blotting was used to determine the effect of the PCAIs on the phosphorylation levels of MAPK pathway enzymes. After 48 h exposure to 5 μM of the PCAIs, NSL-YHJ-2-46, the MAPK proteins BRAF, MEK1/2, ERK1/2, and p90RSK were activated through phosphorylation by 90, 190, 150 and 120%, respectively. However, CRAF/RAF1 phosphorylation decreased by 40%, suggesting significant changes in the KRAS/MAPK signaling patterns. Furthermore, 5 μM of NSL-YHJ-2-27 depleted the singly polyisoprenylated monomeric G-proteins RAC 1/2/3 and CDC42 by 77 and 76%, respectively. The depletion of these key cytoskeletal proteins may account for the observed inhibition of cell migration and invasion, and spheroid invasion observed on exposure to NSL-YHJ-2-27 and NSL-YHJ-2-46. Treatment with 5 μM of NSL-YHJ-2-27 suppressed full-length inactive caspase 3 and 7 levels by 72 and 91%, respectively. An analysis of cells treated with the fluorescently labeled active caspase 3/7 irreversible inhibitor, CaspaTagTM Caspase-3/7 in situ reagent revealed a 124% increase in active caspase at 3 μM over controls. These findings clearly show the direct effects of the PCAIs on the RAS signaling pathway. Given the profound increases observed in RPS6KA1/p90RSK phosphorylation, future work will involve a determination whether the proapoptotic isoforms of RPS6KA1/p90RSK are phosphorylated due to the PCAIs treatments. These results support the potential use of the PCAIs as targeted therapies against cancers with KRAS mutations.

Geo-sustainability Challenges and Remediation Strategies: A GIS-based Assessment of Sripur Coalmine Areas, West Bengal, India

This study examines the health, risk, and safety aspects of coal mining in the Sripur area, focusing on the Bhanora West Block, Asansol, West Bengal, India as one of the 14 operational mines of Eastern Coalfields Limited in Asansol. The study addresses the increasing risks of accidents, fires, and subsidence in active, ageing, and closed mines and storage yards. The study’s incorporation of field surveys, satellite imagery, and environmental data ensures that the findings are based on a well-rounded and multi-faceted dataset. The satellite imagery data (GIS and Remote Sensing) are perceived along with available literature and environmental impact compliance reports from time to time, with particular interest in the Bhanora West coal mine, both open cast and underground. The aspect, Hill shade, LULC and stream order maps of the Damodar are generated using Q-GIS, 3.28.7. The environmental clearance data, accident data, subsidence area, and landslide data are analysed. A vast area in Sripur is observed to be under subsidence, with cracks appearing even near residential areas. The flow of the Nunia nallah is nearby, and old closed mines are not adequately backfilled, so the chance of seepage cannot be neglected though regularly attended. Pneumoconiosis (CWP), a lung disease (black lung), chronic obstructive pulmonary disease (COPD), and silicosis are common in Sripur due to dust and substandard water. Effective and riskless mining extractions using proper technologies can avoid mining hazards, such as subsidence, the influx of water in underground mines, health hazards, air/water pollution, mine fire, and intact physical landscape and observing criteria of sustainable Development Goal SDG-1 SDG-3, SDG-6, SDG 12, SDG-13, and SDG 16.

Treatments and prognostic outcomes of combined hepatocellular-cholangiocarcinoma with distant metastasis: an analysis based on SEER data.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare liver cancer with a poor prognosis, often diagnosed at an advanced stage. The management of cHCC-CCA with distant metastasis remains challenging, and prognostic factors are not well-defined. This study aimed to investigate prognostic factors and treatment outcomes for cHCC-CCA patients with distant metastasis. Retrospective analysis was conducted using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. Patients with distant metastasis [stage M1, according to the American Joint Committee on Cancer (AJCC) 7th edition] between January 2010 and December 2020 were included. Their characteristics, clinical profiles, and prognostic information were evaluated. Cox multifactorial survival analysis and Kaplan-Meier survival curves were used for statistical analysis. A total of 130 patients were included, with 78 (60%) receiving chemotherapy. Cox multivariate survival analysis revealed worse prognosis for Black individuals compared to White individuals (P<0.05). The median overall survival was 2 months for Black patients and 5 months for White patients. Chemotherapy significantly improved patient prognosis (P<0.05), while lung metastasis emerged as an independent risk factor (P<0.05). Kaplan-Meier survival curves confirmed the impact of lung metastasis and chemotherapy on overall survival. Patients with lung metastasis had lower survival rates (P<0.05), and those receiving chemotherapy had higher survival rates (P<0.05). Subgroup analysis based on age showed lower survival rates in patients aged 75 years or older compared to those below 75 years. Chemotherapy showed significant beneficial effects on the prognosis of patients below 75 years old, but no significant difference was observed in patients aged 75 years or above. Chemotherapy improves the prognosis of cHCC-CCA patients with distant metastasis, especially for those under 75 years old. Black race and lung metastasis are poor prognostic factors.

Measuring lung diffusing capacity: an opportunity for improved medical surveillance and disability evaluation of coal miners

ObjectivesSpirometry is the primary lung function test utilised for medical surveillance and disability examination for coal mine dust lung disease. However, spirometry likely underestimates physiologic impairment. We sought to characterise...

Characteristics of Patients With Alpha-1 Antitrypsin Deficiency From Rural Appalachia: A Retrospective Single-Center Study.

Alpha-1 antitrypsin (AAT) deficiency, an autosomal co-dominant inherited condition, significantly impacts lung and liver functions, with mutations in the SERPINA1 gene, notably the Z allele, playing a pivotal role in disease susceptibility. This retrospective descriptive study from a rural Eastern Kentucky pulmonary clinic aimed to characterize patients with AAT deficiency, focusing on demographic, clinical, and laboratory parameters extracted from electronic health records (EHR) of Appalachian Regional Healthcare (ARH). Among 100 patient encounters, 56 were analyzed, revealing notable sex-based differences in smoking rates and co-existing conditions, with males showing higher rates of black lung and chronic obstructive pulmonary disease. In comparison, females exhibited higher rates of asthma, COVID-19, pneumothorax, and obstructive sleep apnea. The study emphasizes the importance of understanding genotype-phenotype correlations and demographic factors in assessing AAT deficiency, advocating for further research to refine management strategies and elucidate causal relationships.

Pathogenetic Bases of Systemic Morphological Manifestations of Coal Worker’s Pneumoconiosis: A Review

Introduction: Miners are at increased risk of developing pneumoconiosis that poses a serious threat to their health. Progressive pneumosclerosis and bronchial mucosa atrophy are typical pathological changes in this disease. At the same time, there is evidence of systemic manifestations of pneumoconiosis. In this regard, a deeper understanding of how long-term exposure to coal dust affects pathophysiological processes not only in the target organ, but also in the whole body is required. Objective: To generalize and systematize ideas about the pathogenetic foundations of systemic morphological manifestations of black lung disease. Materials and methods: To obtain information, we have carried out a search for relevant studies published in 1995–2022 in Scopus, PubMed, and RISC databases using the following keywords: pneumoconiosis, miners, morphological changes, pathogenesis, free radical oxidation, inflammation, immune response, cytokines, growth factors, and endothelial dysfunction. We selected 59 full-text publications presenting the results of completed studies on the mechanisms of development of systemic morphological changes in coal miner’s pneumoconiosis. The systematic review was made according to PRISMA guidelines and using certain PICO(S) criteria. Results: It has been shown that long-term exposure to coal dust causes activation of macrophage-related inflammation in the respiratory system, free radical oxidation, modulation of intracellular signaling pathways, and programmed cell death. Numerous studies have demonstrated the role of inflammation as the main pathogenetic factor of pneumoconiosis, which is closely related to oxidative stress and immune response. Inflammatory mediators ensure the immune response, regeneration and sclerosis of damaged tissues. In case of high cumulative doses of coal dust, these processes begin to have a destructive and tissue-damaging effect in both the lungs and other organs due to the systemic action of the above mediators. The key role of the endothelium in the development, course and outcome of inflammation is noted.

Progressive Massive Fibrosis Identified at Federally Funded Black Lung Clinics in the US

This study of US Black Lung Clinics (established to treat coal miners) reports the prevalence of progressive massive fibrosis identified through June 2023.

Abstract B003: Inhibition of cell growth and migration by polyisoprenylated cysteinyl amide inhibitors of a mutant KRAS Black American lung cancer cell line involves MAPK pathway activation and disruption of the cytoskeleton

Abstract KRAS mutations are the most common oncogenic mutations in lung adenocarcinoma in Black Americans. Polyisoprenylated Cysteinyl Amide Inhibitors (PCAIs) constitute a group of potential cancer therapy agents that we designed to specifically disrupt and suppress hyperactive G-protein signaling, as caused by mutated RAS proteins. Here we investigate the effects of PCAIs on the viability, G-protein levels, downstream mediators, cytoskeletal structure, focal adhesion protein and apoptosis-related proteins on the KRAS-mutated, Black American-derived lung adenocarcinoma cell line, NCI-H23. Western blotting was used to determine the effect of the PCAIs on the phosphorylation levels of MAPK pathway enzymes. After 48-hour exposure to 5 μM of the PCAIs, 57 ± 3.6 to 150 ± 4.1 % increases of BRAF, MEK1/2, ERK1/2, and p90RSK phosphorylation along with a 60 ± 6.5 to 78 ± 4.0 % decrease of pRAF1 phosphorylation were observed, indicating significant changes in RAS signaling. Furthermore, 5 μM of NSL-YHJ-2-27 depleted the singly polyisoprenylated monomeric G-proteins RAC 1/2/3 and CDC42 by 77 ± 5.5 and 76 ± 2.0 %, respectively. The depletion of these key cytoskeletal proteins, and collapse of F-actin and vinculin punctates, may account for the observed inhibition of cell migration after 72-hour exposure to NSL-YHJ-2-27 and NSL-YHJ-2-46, respectively. The invasion area of 3D NCI-H23 spheroids after treatment with 10 μM of NSL-YHJ-2-27 and NSL-YHJ-2-46 decreased by 87 ± 0.1% and 92 ± 0.3 %, respectively. Treatment with 0.5 μM NSL-YHJ-2-27 and NSL-YHJ-2-46 caused cell rounding and reduction of mean cell areas by 30 ± 5.0 and 42 ± 0.6 %, respectively. Mean cell area occupied by vinculin punctates decreased by 51 ± 2.6 % and 31 ± 2.8 % after exposure to 0.5 μM NSL-YHJ-2-27 and NSL-YHJ-2-46, respectively. NSL-YHJ-2-27 (5 μM) depleted full-length inactive caspase 3 and 7 levels by 72 ± 5.8 and 91 ± 7.0 %, respectively. These findings show the direct effects of the PCAIs on the KRAS signaling pathway thereby supporting their continuous development as potential targeted therapies for cancers with RAS mutations. Citation Format: Kweku Ofosu-Asante. Inhibition of cell growth and migration by polyisoprenylated cysteinyl amide inhibitors of a mutant KRAS Black American lung cancer cell line involves MAPK pathway activation and disruption of the cytoskeleton [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B003.

Abstract A087: "Trust is built in teaspoons and it's lost in buckets": Clinical trial recruitment of Black individuals with lung cancer

Abstract Black individuals with cancer are underrepresented in clinical trials, which has implications for understanding how therapies work in all patient populations. To achieve representative trial enrollment of Black persons with cancer, it is critical to understand the barriers to participation in this population. Due to stigma from perceptions around lung cancer’s association with smoking behavior, the barriers in this population may be complex compared to other cancer types. This study utilized a mixed-methods approach to decipher provider-reported barriers and facilitators to trial participation specificly among Black lung cancer patients. Providers across three institutions in the Southeastern US were interviewed using a semi-structured interview guide. Recorded and transcribed interviews and free text responses were analyzed by an independent coder using NVivo. Themes were generated using a content analysis approach. Data triangulation was achieved via anonymous surveys which were administered via REDCap. Across three institutions, 38 total, eligible, providers were recruited, having an average of 8.8 years of clinical practice. Nearly half (n=17, 44.7%) self-identified as Medical Oncologists. In the survey data barriers to clinical trial participation noted by the providers as expressed most often by black people with lung cancer were “being worried about the ’experimental nature’ of clinical trial treatments” and “not wanting to be a ’research subject’. The barrier least reported was “being worried about having to see another provider for the trial”. Provider perception of the reason that most contributes to lower trial participation of black people with lung cancer was “lack of trust in the medical system” (n = 18). Interestingly, when asked about perceptions of operational or system level barriers that contributed to lower clinical trial participation among lung cancer patients that identify as Black, providers reported “lack of appropriate trials” and “low numbers of Black patients seen”. Three overarching themes emerged from the qualitative interview data (i) Barriers to recruitment were seen at individual, institutional and structural levels. (ii) Facilitators were seen mostly at the individual provider level and were predominantly based on engendering trust between the patient and provider. (iii) Solutions were largely related to increasing awareness around clinical trials using community engagement. Providers in our study reported patient centric barriers to recruitment such as lack of trust and systems barriers such as not having appropriate trials available locally. Providers reported facilitators to increasing recruitment of Black individuals with lung cancer via community outreach and building provider/patient trust. Institutions should develop culturally appropriate outreach programs to enroll racially diverse patients to lung cancer trials and trialists should explore strategies to increase trial offering and access in key communities. Citation Format: Sarah C. Stallings, Andrew Ciupek, Kemberlee Bonnet, David G. Schlundt, William Opoku-Agyeman, Jennifer C. King, Nagla Abdel Karim, Christine M. Lovly, Melinda C. Aldrich, Soumya J. Niranjan. "Trust is built in teaspoons and it's lost in buckets": Clinical trial recruitment of Black individuals with lung cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A087.

Abstract 12571: Factors That Predict Longitudinal Transition of Symptom Cluster Profiles in Heart Failure

Background: Symptom trajectories in people with heart failure (HF) can vary over time. Few studies have explored how symptom clusters transition, essential to determine interventions. Aims: (1) Describe transitions in symptom cluster profiles in people with HF over 8 years; (2) Identify factors predicting the transitions. Methods: We conducted secondary analysis of data from the 2008, 2012, and 2016 surveys of the Health and Retirement Study (HRS), using latent transition analysis to identify cluster profiles (fatigue, dyspnea, pain, swelling, depressive symptoms, dizziness), and multinomial regression to determine the predictive factors. Results: HRS included 690 HF subjects (57% female; mean age=74.9 (SD =10.04) years). Four cluster profiles were identified: high burden, low burden, distressing, and respiratory-depressive distress. The probability staying in the same profile ranged from 0.60 to 0.89. Male sex (OR=1.39; 95% CI=0.92, 1.82), black race (OR=1.92; 95% CI=1.37, 2.73), smoking (OR=2.44; 95% CI=1.56, 3.71), having diabetes (OR=3.99; 95% CI=2.90, 6.27) and lung disease (OR=1.40; 95% CI=0.83, 1.68) were associated with an increased odds of moving from the distressing to the high burden profile. Smoking (OR=1.17; 95% CI=0.66, 1.55), having arthritis (OR=4.44; 95% CI=2.80, 6.33), lung disease (OR=1.72; 95% CI=1.17, 2.49), and diabetes (OR=3.84; 95% CI=2.87, 5.94) were associated with an increased odds of moving from the respiratory-depressive distress to the high burden profile. Black race (OR=3.58; 95% CI=2.80, 6.20), smoking (OR=1.44; 95% CI=0.91, 2.10), having arthritis (OR=1.71; 95% CI= 1.20, 2.59), lung disease (OR=1.30; 95% CI= 0.55, 1.95), and diabetes (OR=1.81; 95% CI=1.34, 2.90) were associated with an increased odds of moving from the low burden to the distressing profile. Male sex (OR=2.13; 95% CI= 1.66, 3.68), having arthritis (OR=1.51; 95% CI=1.15, 2.13) and lung disease (OR=2.28; 95% CI=1.57, 4.34) were associated with an increased odds of moving from the low burden to the respiratory-depressive distress profile. Conclusions: Although symptom cluster profiles remained stable, transitions were observed, and deterioration can occur. The identified predictive factors may enhance long-term symptom management.

Protecting the Unsung Heroes

Black lung: the scourge that used to send coal miners into an early grave. We thought modern technology had largely defeated it. But black lung is back. How can that be? And how can we protect these hard-working people who are still essential to our economies?

Coal Production Trends and Black Lung Disease Incidence Rate in Indonesia during 2013-2021

Coal Production Trends and Black Lung Disease Incidence Rate in Indonesia during 2013-2021

Reducing roadblocks to employee health care through benefit design implications and unintended consequences of utilization management in cancer treatment

PurposeHR leaders and corporate benefits managers must balance organizational costs with decisions about which new tools and treatments will be covered by their employee health insurance plans. Getting it right can mean the difference between life and death for cancer patients. Most HR leaders, however, are not experts in cancer treatment and do not know how to make sure their plan benefits do not create roadblocks to treatment.Design/methodology/approachA total of 295 people who were diagnosed with cancer from 2019 to 2022 participated in the 2023 CancerCare Biomarker Survey, which was conducted in January 2023.FindingsCancerCare’s 2023 survey of cancer patients found that biomarker testing helped doctors tailor therapy for nearly all the patients (93%) whose cancers were tested over the past three years. Two in 10 cancer patients (20%) avoided unnecessary chemotherapy and/or radiation and one in 10 (10%) became eligible for a clinical trial because of biomarker testing.Research limitations/implicationsBiomarker testing is a necessary tool in the advancing world of precision cancer treatment. Despite the significant and demonstrable benefits to surveyed patients, three out of 10 respondents (29%) who received biomarker testing did not have the test covered by their insurance. Some survey respondents reported that biomarker test coverage was originally denied and they had to fight to get it covered. Others had to find ways to pay out-of-pocket or seek financial assistance to cover the cost of the testing.Practical implicationsUnfortunately, health insurance plans often limit cancer patients’ access to recommended biomarker testing, impose burdensome prior authorization (PA) protocols or require unaffordable cost-sharing, which can prevent or delay cancer patients’ access to optimal treatments. PA, a significant source of roadblocks to timely testing and treatment, was required by a quarter (25%) of the cancer patients surveyed.Originality/valueBiomarker testing is increasingly a health care equity issue and there are significant gaps in the rate of biomarker testing between black and white lung and colorectal cancer patients, which can lead to disparities in clinical trial participation and hinder access to the most effective treatments. A key way to address these barriers is to broaden insurance coverage of biomarker testing, as recommended by medical experts.

Abstract 48: Increasing the racial diversity of lung adenocarcinoma cell lines

Abstract Lung cancer is a prominent source of cancer health disparities. Black males tend to smoke less, but have a 37% higher chance of developing lung cancer. The three most common histological subtypes of lung cancer are lung adenocarcinoma (LUAD), squamous cell lung cancer (LUSQ), and small cell lung cancer (SCLC). To study lung cancer development, progression, and treatment, numerous tools are needed, including lung cancer cell lines. We undertook a literature and web-based investigation of lung cancer cell line availability from different racial/ethnic groups. We identified 188 cell lines from White individuals, 374 cell lines from Asian subjects, but only 26 cell lines from Blacks and none from Hispanic patients. We conclude that Black and Hispanic lung cancer cell lines are strongly underrepresented. Here we focus on LUAD cell lines since LUAD is the most common histological subtype in all racial/ethnic groups. While 67 White LUAD cell lines have been established, we only identified 5 Black LUAD lines. To remedy this lack of Black LUAD cell lines, we are collecting LUAD samples from Black patients to establish new cell lines (with full consent). In addition, we aim to increase the representation of Black cell lines by creating isogenic cell line variants of existing cell lines, like NCI-H23. NCI-H23 was derived from a Black male patient and carries a KRASG12C heterozygous mutation. We are using CRISPR/CAS9-based genome editing to introduce amino acid substitutions, including KRASG12V and KRASG12A. Our gene editing DNA includes a silent restriction site to help identify edited clones. A fluorescently labeled structured tracrRNA is included during the genomic editing process, allowing the electroporated cells to undergo fluorescence-activated cell sorting. We use the polymerase chain reaction to amplify the relevant genomic region, followed by restriction digestion to identify potential clones and sequencing to confirm successful editing. Several clones are currently under evaluation. Once new hetero- and homozygous KRAS mutants have been identified, we will test the efficacy of polyisoprenylated cysteinyl amide inhibitors (PCAIs). PCAIs have been shown to disrupt the RAS-mediated signaling pathway in racially/ethnically diverse cell lines (manuscript submitted). By generating newly-established and isogenic Black LUAD cell lines, we intend to ensure that potential therapeutics are tested on cell lines with the appropriate racial/ethnic genetic background. In the future, we hope to establish similar cell lines from Hispanic LUAD subjects. Citation Format: Christopher Leon, Matthew A. Gladstone, Chunli Yan, Diana I. Romero, Yong Huang, Nazarius S. Lamango, Ite A. Offringa. Increasing the racial diversity of lung adenocarcinoma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 48.

The Health of Coal Miners’ Wives: A Historical Analysis

Abstract Existing coal mining health literature has not adequately addressed the health of women and girls who reside (and perform reproductive labor) within the households of male coal miners exposed to coal dust and other coal toxins. This study compares archival data on the health at the time of death for coal miners’ wives and non-coal miners’ wives to determine if there are statistical differences between these groups of women. Findings indicate that there is a statistical difference between these groups of women in age at death, with wives of miners dying 7 years earlier, on average. It also indicates that women providing reproductive labor within a mining household are at a higher risk of particular health conditions—some that have been acknowledged in the existing literature and some that have not. These findings are especially important given the deadly resurgence of black lung in Appalachia.

Increased odds of mortality from non-malignant respiratory disease and lung cancer are highest among US coal miners born after 1939

ObjectivesCoal miners suffer increased mortality from non-malignant respiratory diseases (NMRD), including pneumoconioses and chronic obstructive pulmonary disease, compared with the US population. We characterised mortality trends from NMRD, lung cancer...

Abstract C022: Treatment of a Black American lung cancer cell line harboring KRAS mutations with polyisoprenylated cysteinyl amide inhibitors reveals effects on the MAP kinase signaling pathway, cell migration and apoptosis

Abstract KRAS mutations are the most common oncogenic mutations in lung adenocarcinoma in Black Americans. Polyisoprenylated cysteinyl amide inhibitors (PCAIs) constitute a group of cancer therapy agents designed to specifically disrupt and suppress hyperactive G protein signaling, such as that triggered by RAS mutations. Here we determine the effects of PCAIs on the viability, G-proteins levels, downstream mediators, and apoptosis-related proteins on the KRAS-mutant, Black American-derived lung adenocarcinoma cell line, NCI-H23. Of the 17 PCAIs tested, compounds NSL-YHJ-2-27 and NSL-YHJ-2-46 showed the most potency with EC50 values of 2.7 and 3.3 µM, respectively. To determine the effect of the PCAIs on the levels of Mitogen-Activated Pathway Kinase (MAPK)-related enzymes, western blot analysis was performed. After 48 hours exposure to 5 μM of the compounds, 57 to 150% increases of BRAF, ERK1/2, MEK1/2, and p90RSK phosphorylation along with a 60 to 78% decrease of pCRAF were observed, indicating significant disruptions in RAS signaling. Furthermore, 5 μM of NSL-YHJ-2-27 depleted the singly polyisoprenylated monomeric G-proteins RAC 1/2/3 and CDC42 by 77 and 76%, respectively. The depletion of these key cytoskeletal proteins may account for the observed 52 and 42% reduction in cell migration after 24 h exposure to NSL-YHJ-2-27 and NSL-YHJ-2-46, respectively. Western blot analysis was used to determine the effect PCAIs on caspase activation necessary for the initiation of apoptosis. After treatment with 5 μM of NSL-YHJ-2-27, full-length inactive caspase 3 and 7 levels dropped by 72 and 60%, while cleaved active caspase 3 and 7 levels increased by 274 and 130%, respectively. Treatment with 5 μM of NSL-YHJ-2-46 depleted full-length caspase 7 by 53% and increased cleaved active caspase 3 levels by 83%. These findings clearly show the direct effects of the PCAIs on the RAS signaling pathway, perhaps through the activation of proapoptotic isoforms of p90RSK. These results support the potential use of the PCAIs to serve as targeted therapies in cancers harboring RAS mutations. Citation Format: Matthew D. Gregory, Pablo E. Puente, Nadine L. Belony, Jassy Mary S. Lazarte, Nada Tawfeeq, Yong Huang, Ite A. Offringa, Nazarius S. Lamango. Treatment of a Black American lung cancer cell line harboring KRAS mutations with polyisoprenylated cysteinyl amide inhibitors reveals effects on the MAP kinase signaling pathway, cell migration and apoptosis [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C022.

The Activism of Dance Performance in Appalachia: Utilizing the Arts to Address Social and Environmental Crisis and Injustice in the Mountains

Abstract For well over a century, the human and more-than-human of Central Appalachia have endured oppression and exploitation, primarily due to natural resource extraction. In spring 2008, the author led a dark touri to a mountaintop removal coalmining site in Southern West Virginia for colleagues, which included Dance Professor Deborah McLaughlin. As a result, the two collaborated on three evening-length dance/theater works highlighting social and environmental crises and injustices in the region. The performances incorporated contemporary dance, poetry, the spoken word, and the visual arts, as well as contemporary and traditional music. The first, Eating Appalachia: Selling Out to the Hungry Ghost, focused on mountaintop removal coalmining and its environmental and cultural destruction. With Sounds of Stories Dancing, the duo paid homage to millions of mountain residents forced to leave the region to find stable employment, despite longing to remain. In the final piece, The Shadow Waltz, they honored the lives of coalminers with black lung disease, as well as their families. This essay discusses the challenges of creating art that critiques socially constructed messages portrayed as given truths, as well as the educational and social successes of daring to dance truth to power.

Digging Our Own Graves: Coal Mining &amp; the Struggle over Black Lung Disease, by BarbaraEllen Smith. Haymarket Books, 2020, pp. 318 pages. ISBN: 978‐1‐64259‐275‐7, US $23.95

Digging Our Own Graves: Coal Mining &amp; the Struggle over Black Lung Disease, by BarbaraEllen Smith. Haymarket Books, 2020, pp. 318 pages. ISBN: 978‐1‐64259‐275‐7, US $23.95

Characteristics of Mycoplasma hyopneumoniae Strain ES-2 Isolated From Chinese Native Black Pig Lungs.

Mycoplasma hyopneumoniae is the primary pathogen of swine enzootic pneumonia and causes great economic losses to the swine industry worldwide. In China, M. hyopneumoniae seriously hinders the healthy development of the native black pigs. To prevent and treat porcine respiratory disease caused by M. hyopneumoniae, the characteristics of M. hyopneumoniae strain ES-2 isolated from Chinese native black pig lungs with gross lesions at post-mortem were studied for the first time in this study. Strain ES-2 cell was round or oval cells and most sensitive to kanamycin. The diameters of most strain ES-2 cells ranged from 0.4 to 1.0 μm with maximum viability of 1010 CCU/ml. Experimental challenge of animals with strain ES-2 showed respiratory disease could be reproduced, with pneumonic lung lesions evident. Comparative genomics analysis identified that 2 genes are specific to pathogenic M. hyopneumoniae strains, which may be predicted to be a molecular marker. These findings suggest that the study on the characteristics of M. hyopneumoniae strain ES-2 will guide the rapid and accurate drug use in the clinic, and develop a theoretical foundation for accurately diagnosing and treating the infection caused by pathogenic M. hyopneumoniae.