Browsing by Subject "Lung cancer"
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Item 4355 Impact of Demographic & Racial Differences on DNA Repair Capacity in Lung Cancer(Cambridge University Press, 2020-07-29) Duncan, Francesca Christina; Sears, Catherine; Al Narallah, Nawar; Al-Hader, Ahmad; Medicine, School of MedicineOBJECTIVES/GOALS: Lung cancer is the leading cause of cancer-related mortality in the United States for both men and women. African Americans are disproportionately affected with lung cancer, having higher incidence and mortality rates compared to Caucasian men and women. African American smokers are diagnosed with lung cancer at a lower age with lower cumulative smoking history. Differences in socioeconomic and environmental factors likely contribute to lung cancer disparities, but less is known about acquired biologic alterations that can promote initiation and progression of lung cancer, particularly in African Americans. This is of interest because there may be other biological, genetic, or environmental factors contributing to lung cancer outcomes as it relates to differences in gender and race. One potential biologic variable may be in the DNA repair capacity (DRC), which describes a cell’s ability to repair damage to DNA caused by carcinogens, oxidants, and radiation. Altered DNA repair is a hallmark of cancer, leading to mutations and malignant transformation. We hypothesize that DRC is decreased in African Americans with lung cancer compared to Caucasian Americans with lung cancer, contributing to the disparity that exists in this racial group. We will 1) perform a retrospective chart review to determine demographic differences between African Americans and Caucasians at three central Indiana hospitals and 2) determine the impact of race and lung cancer on DRC amongst African Americans and Caucasians with and without lung cancer. METHODS/STUDY POPULATION: Lung cancer patients are identified in 3 central Indiana hospitals with different payer source and patient populations using ICD codes. Collected demographics include age, gender, pack-years, lung cancer histology, treatment, and mortality. DRC is measured by host-cell reactivation (non-homologous end-joining and nucleotide excision repair pathways) by flow-cytometry. Measurement of DRC is performed on PBMCs obtained from 120 patients (male and female, African Americans and Caucasians with and without lung cancer). Correlation of DRC and lung cancer will be determined by comparing lung cancer diagnosis to quartile DRC, and adjusted for confounders (measured demographics). Correlative measures will include measures of DNA damage and genomic instability. RESULTS/ANTICIPATED RESULTS: 3450 lung cancer patients were diagnosed with lung cancer at Indiana University Hospital between 1/1/2000 – 5/31/2015. Of these, 48.2% were female and 92.7% smokers. African Americans, Caucasians and Other ethnicities represented 12%, 86% and 2%, respectively. Of smokers, 11.4% were African American. The primary payer source was Federal/Medicare. Retrospective review of lung cancer patients from two additional health systems (county and VA hospitals) will be performed as above with outcomes measured. DRC and additional correlative measures will be performed as in Methods. DISCUSSION/SIGNIFICANCE OF IMPACT: If present, altered DRC in African Americans compared to Caucasians may contribute to the disproportional impact of lung cancer on African Americans. If DRC is decreased in African Americans with lung cancer, future studies will focus on identifying potential genetic, epigenetic and environmental causes for this decrease.Item 4405 Chronic Disease in Indiana – Using a Community Health Matrix to Determine Health Factors for Indiana Counties(Cambridge University Press, 2020-07-29) Wiehe, Sarah; Zych, Aaron; Hinshaw, Karen; Alley, Ann; Claxton, Gina; Savaiano, Dennis; Pediatrics, School of MedicineOBJECTIVES/GOALS: The goal of this project was to inform four chronic disease initiatives, working together on the team Connections IN Health, and counties in Indiana on certain areas of need to assist them in collaborative planning. The chronic diseases focused on include diabetes, cardiovascular disease, stroke, asthma, lung cancer and obesity. METHODS/STUDY POPULATION: Chronic disease health outcomes and social determinants of health indicators were identified in all 92 Indiana counties. Counties were compared by composite z scores in a matrix to determine the 23 counties with the poorest health statistics for diabetes, cardiovascular disease, stroke, asthma, lung cancer, obesity and life expectancy. Qualitative data were used to identify local health coalitions that have the capacity and desire to work with Connections IN Health to improve these health outcomes. With input from partners, the counties were narrowed to 10 that were identified as those with the most need in the specific areas of chronic disease that the initiatives focus on. The team will begin listening sessions with two of these counties to identify strategic partnerships, funding sources, and evidence-based programs to address community-identified health priorities. RESULTS/ANTICIPATED RESULTS: The 23 counties with the poorest health outcomes related to chronic disease and factors were Blackford, Clark, Clay, Fayette, Fulton, Grant, Greene, Howard, Jay, Jennings, Knox, Lake, LaPorte, Madison, Marion, Pike, Scott, Starke, Sullivan, Vanderburgh, Vermillion, Vigo, and Washington. There was significant overlap in low z score rankings for individual health and social determinants of health measures among these 23 counties. The following 10 counties were selected for focus in the next five years based on partner input: Blackford, Clay, Grant, Jennings, Lake, Madison, Marion, Starke, Vermillion, and Washington. The Connections IN Health team has initiated listening sessions in Grant and Vermillion Counties (with data for presentation at the ACTS meeting). DISCUSSION/SIGNIFICANCE OF IMPACT: This mixed methods approach using existing data and partner input on county capacity/readiness directed Connections IN Health to counties with the most need for coalition efforts. Engagement within each county will inform next steps (e.g., capacity building, partnership development, applications for funding, implementation of evidence-based programs) and specific health focus area(s).Item Addressing unmet needs for people with cancer cachexia: recommendations from a multistakeholder workshop(Wiley, 2022-04) Garcia, Jose M.; Dunne, Richard F.; Santiago, Kristen; Martin, Lisa; Birnbaum, Morris J.; Crawford, Jeffrey; Hendifar, Andrew E.; Kochanczyk, Martin; Moravek, Cassadie; Piccinin, Doris; Picozzi, Vincent; Roeland, Eric J.; Selig, Wendy K.D.; Zimmers, Teresa A.; Surgery, School of MedicineItem Anatomic, functional and molecular imaging in lung cancer precision radiation therapy: treatment response assessment and radiation therapy personalization(2017-12) MacManus, Michael; Everitt, Sarah; Schimek-Jasch, Tanja; Li, X. Allen; Nestle, Ursula; Kong, Feng-Ming (Spring); Medicine, School of MedicineThis article reviews key imaging modalities for lung cancer patients treated with radiation therapy (RT) and considers their actual or potential contributions to critical decision-making. An international group of researchers with expertise in imaging in lung cancer patients treated with RT considered the relevant literature on modalities, including computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). These perspectives were coordinated to summarize the current status of imaging in lung cancer and flag developments with future implications. Although there are no useful randomized trials of different imaging modalities in lung cancer, multiple prospective studies indicate that management decisions are frequently impacted by the use of complementary imaging modalities, leading both to more appropriate treatments and better outcomes. This is especially true of 18F-fluoro-deoxyglucose (FDG)-PET/CT which is widely accepted to be the standard imaging modality for staging of lung cancer patients, for selection for potentially curative RT and for treatment planning. PET is also more accurate than CT for predicting survival after RT. PET imaging during RT is also correlated with survival and makes response-adapted therapies possible. PET tracers other than FDG have potential for imaging important biological process in tumors, including hypoxia and proliferation. MRI has superior accuracy in soft tissue imaging and the MRI Linac is a rapidly developing technology with great potential for online monitoring and modification of treatment. The role of imaging in RT-treated lung cancer patients is evolving rapidly and will allow increasing personalization of therapy according to the biology of both the tumor and dose limiting normal tissues.Item Anticancer effect of Moringa oleifera leaves extract against lung cancer cell line via induction of apoptosis(Elsevier, 2022-12) Bhadresha, Kinjal; Thakore, Vaidehi; Brahmbhatt, Jpan; Upadhyay, Vinal; Jain, Nayan; Rawal, Rakesh; Medicine, School of MedicineSince ancient times, Moringa oleifera has been a common vegetable in many nations. It has a large number of phenolic compounds with a diverse range of biological activity. It has anticancer properties that can be exploited to create novel medications for the treatment of various malignancies. The current study was conducted to evaluate the in vitro anticancer activities of M. oleifera leaves extracts. The M. oleifera leaves extracts significantly inhibited cell proliferation in the human cancer cell line A549 in a dose-dependent manner. Morphological studies indicated that the extract of moringa leaves stimulated apoptosis as demonstrated by cell shrinkage, blebbing, chromatin condensation, and nuclear fragmentation. Quantitative RT-PCR analyses of Bax and Bcl-2 showed abnormal expression profiles of these genes under various treatment conditions. This study demonstrates that M. oleifera leaves may have the ability to suppress the growth of cancer cells while also enhancing human health and developing new food ingredients. The phytochemicals from M. oleifera leaves can be employed as the primary medications to cure cancer, according to in vitro studies.Item Anticancer effect of Moringa oleifera leaves extract against lung cancer cell line via induction of apoptosis(Elsevier, 2022) Bhadresha, Kinjal; Thakore, Vaidehi; Brahmbhatt, Jpan; Upadhyay, Vinal; Jain, Nayan; Rawal, Rakesh; Medicine, School of MedicineSince ancient times, Moringa oleifera has been a common vegetable in many nations. It has a large number of phenolic compounds with a diverse range of biological activity. It has anticancer properties that can be exploited to create novel medications for the treatment of various malignancies. The current study was conducted to evaluate the in vitro anticancer activities of M. oleifera leaves extracts. The M. oleifera leaves extracts significantly inhibited cell proliferation in the human cancer cell line A549 in a dose-dependent manner. Morphological studies indicated that the extract of moringa leaves stimulated apoptosis as demonstrated by cell shrinkage, blebbing, chromatin condensation, and nuclear fragmentation. Quantitative RT-PCR analyses of Bax and Bcl-2 showed abnormal expression profiles of these genes under various treatment conditions. This study demonstrates that M. oleifera leaves may have the ability to suppress the growth of cancer cells while also enhancing human health and developing new food ingredients. The phytochemicals from M. oleifera leaves can be employed as the primary medications to cure cancer, according to in vitro studies.Item Augmenting antibody response to EGF-depleting immunotherapy: Findings from a phase I trial of CIMAvax-EGF in combination with nivolumab in advanced stage NSCLC(Frontiers Media, 2022-08-03) Evans, Rachel; Lee, Kelvin; Wallace, Paul K.; Reid, Mary; Muhitch, Jason; Dozier, Askia; Mesa, Circe; Luaces, Patricia L.; Santos-Morales, Orestes; Groman, Adrienne; Cedeno, Carlos; Cinquino, Aileen; Fisher, Daniel T.; Puzanov, Igor; Opyrchal, Mateusz; Fountzilas, Christos; Dai, Tong; Ernstoff, Marc; Attwood, Kristopher; Hutson, Alan; Johnson, Candace; Mazorra, Zaima; Saavedra, Danay; Leon, Kalet; Lage, Agustin; Crombet, Tania; Dy, Grace K.; Medicine, School of MedicineBackground: CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy which has shown survival benefit as a switch maintenance treatment after platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). The primary objective of this trial is to establish the safety and recommended phase II dose (RP2D) of CIMAvax-EGF in combination with nivolumab as second-line therapy for NSCLC. Methods: Patients with immune checkpoint inhibitor-naive metastatic NSCLC were enrolled using a "3+3" dose-escalation design. Toxicities were graded according to CTCAE V4.03. Thirteen patients (one unevaluable), the majority with PD-L1 0%, were enrolled into two dose levels of CIMAvax-EGF. Findings: The combination was determined to be safe and tolerable. The recommended phase 2 dose of CIMAvax-EGF was 2.4 mg. Humoral response to CIMAvax-EGF was achieved earlier and in a greater number of patients with the combination compared to historical control. Four out of 12 evaluable patients had an objective response.Item Barriers to mental health service use and preferences for addressing emotional concerns among lung cancer patients(Wiley, 2014-07) Mosher, Catherine E.; Winger, Joseph G.; Hanna, Nasser; Jalal, Shadia I.; Fakiris, Achilles J.; Einhorn, Lawrence H.; Birdas, Thomas J.; Kesler, Kenneth A.; Champion, Victoria L.; Psychology, School of ScienceOBJECTIVE: This study examined barriers to mental health service use and preferences for addressing emotional concerns among lung cancer patients (N=165) at two medical centers in the Midwestern United States. METHODS: Lung cancer patients completed an assessment of anxiety and depressive symptoms, mental health service use, barriers to using these services, and preferences for addressing emotional concerns. RESULTS: Only 45% of distressed patients received mental health care since their lung cancer diagnosis. The most prevalent patient-reported barriers to mental health service use among non-users of these services (n=110) included the desire to independently manage emotional concerns (58%) and inadequate knowledge of services (19%). In addition, 57% of distressed patients who did not access mental health services did not perceive the need for help. Seventy-five percent of respondents (123/164) preferred to talk to a primary care physician if they were to have an emotional concern. Preferences for counseling, psychiatric medication, peer support, spiritual care, or independently managing emotional concerns also were endorsed by many patients (range=40-50%). Older age was associated with a lower likelihood of preferring to see a counselor. CONCLUSIONS: Findings suggest that many distressed lung cancer patients underuse mental health services and do not perceive the need for such services. Efforts to increase appropriate use of services should address patients' desire for autonomy and lack of awareness of services.Item Blood-based biomarkers for precision medicine in lung cancer: precision radiation therapy(2017-12) De Ruysscher, Dirk; Jin, Jianyue; Lautenschlaeger, Tim; She, Jin-Xiong; Liao, Zhongxing; Kong, Feng-Ming (Spring); Medicine, School of MedicineBoth tumors and patients are complex and models that determine survival and toxicity of radiotherapy or any other treatment ideally must take into account this variability as well as its dynamic state. The genetic features of the tumor and the host, and increasingly also the epi-genetic and proteomic characteristics, are being unraveled. Multiple techniques, including histological examination, blood sampling, measurement of circulating tumor cells (CTCs), and functional and molecular imaging, can be used for this purpose. However, the effects of radiation on the tumor and on organs at risk (OARs) are also influenced by the applied dose and volume of irradiated tissues. Combining all these biological, clinical, imaging, and dosimetric parameters in a validated prognostic or predictive model poses a major challenge. Here we aimed to provide an objective review of the potential of blood markers to guide high precision radiation therapy. A combined biological-mathematical approach opens new doors beyond prognostication of patients, as it allows truly precise oncological treatment. Indeed, the core for individualized and precision medicine is not only selection of patients, but even more the optimization of the therapeutic window on an individual basis. A holistic model will allow for determination of an individual dose-response relationship for each organ at risk for each tumor in each individual patient for the complete oncological treatment package. This includes, but is not limited to, radiotherapy alone. Individualized dose-response curves will allow for consideration of different doses of radiation and combinations with other drugs to plan for both optimal toxicity and complete response. Insights into the interactions between a multitude of parameters will lead to the discovery of new pathways and networks that will fuel new biological research on target discovery.Item A case of squamous cell lung cancer presented as a cystic lesion and recurrent pneumothoraces(Elsevier, 2021-03-09) Aldaghlawi, Fadi; Von Holzen, Urs; Li, Liang; Hadid, Walid; Medicine, School of MedicineWe report a rare case of a 70-year-old male with recurrent pneumothoraces within one year treated with intermittent insertion of chest tube on each occasion. Diagnostic testing was notable for a cystic lesion in the left lung that was initially interpreted as bulla on chest x-ray and chest computed tomographic scan. Due to thickening and nodularity changes of the thin wall of the cystic lesion, the patient underwent left upper lobectomy. Pathology showed poorly differentiated squamous cell carcinoma of the cystic lesion wall. This case emphasizes the importance of monitoring pulmonary cystic lesions especially in patients with a history of smoking and emphysema.