Browsing by Subject "Cancer"
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Item Appropriate Delivery Of Care In American Patients With Hepatocellular Carcinoma: A Systematic Review(2013-05-01) Tan, Debra; Kristine LukensObjective: To assess and provide in-depth analysis of appropriate delivery of care in patients with hepatocellular carcinoma (HCC) based on time of diagnosis within Americans in the United States. Design: Meta-analysis of retrospective cohort studies describing receipt of appropriate treatment utilization and delivery of care for HCC. Results: Among all twenty-three included studies, a total of 7,986 of 17,286 (44.4%, 95% CI 43.7-45.1%) patients received overall treatment. Of 48,200 patients with HCC, only 10,518 (21.8%, 95% CI 21.5-22.2%) patients received curative treatment and 6,810 of 11,776 (57.8%, 95% CI 56.9-58.7%) patients who were within early stage HCC received curative treatment. Conclusion: HCC treatment is underutilized in the United States. Although the pooled treatment rate for early HCC patients receiving curative treatment is somewhat better, only about four-sevenths receive appropriate care. There are significant socio-demographic disparities with the lowest treatment rates in non-Caucasians and non-private insurance patients.Item CARDIAC FUNCTION IN CHILDHOOD CANCER SURVIVORS TREATED WITH ANTHRACYCLINES: THE ROLE OF ECHOCARDIOGRAPHIC AND ELECTROCARDIOGRAPHIC SCREENING(2014-03) Minter, Melodie M.; Bowman, W. Paul; Bashore, LisaPurpose (a): Anthracyclines have been a mainstay in cancer treatment because of their proven effectiveness in many children with acute leukemia, but have a dose limiting toxicity on cardiac function, in particular cardiomyopathy and potential arrhythmias. This cardiotoxicity is correlated with age at treatment, total cumulative dose of anthracyclines administered, and delivery of radiation therapy to the mediastinum. Current Children’s Oncology Group (COG) treatment guidelines recommend that childhood cancer survivors who received anthracyclines be monitored for long-term cardiotoxic effects using echocardiograms (ECHO) and electrocardiograms (ECG). To date there has been little research on whether following COG guidelines prevent any morbidity or mortality in these cancer survivors. Methods (b): A retrospective chart review of the anthracycline treated survivors seen in the Cook Children’s Life After Cancer Program (LACP) who received cardiac screening ECHOs and ECGs between January 1, 2011, through June 30, 2013, was performed in order to examine the clinical utility of screening ECHOs and ECGs. Results (c): Initial results from this retrospective chart review study showed that most Acute Lymphoblastic Leukemia survivors displayed no signs of cardiotoxicity on ECHOs or ECGs. Only three subjects required further cardiac evaluation from the results of their cardiac screening. Of those three, only one subject was advised to undergo interventional therapy. Conclusions (d): Preliminary results from this study suggest that these survivors who show little change in their cardiac function could benefit from less frequent screening, which would result in less time away from school and/or work and prevent extra medical cost.Item CASE STUDY: A RARE PRESENTATION OF HEPATOCELLULAR CARCINOMA(2013-04-12) Persad, LeahPurpose: The purpose of this case study is to describe a rare presentation of metastatic hepatocellular carcinoma. This patient presented for evaluation of a large mass in the posterior neck with associated pain. This unique case will provide information to the scientific and medical community about the clinical features and diagnosis of hepatocellular carcinoma in order to increase awareness of the various manifestations of this disease. Methods: The case presentation was a retrospective chart review. The materials included progress notes from physicians, laboratory data, pathology reports, and radiology reports. Results: We discuss the clinical features and diagnosis of hepatocellular carcinoma. This patient did not present with the typical clinical features of chronic liver disease but rather with a metastatic lesion in a rare location. Obtaining a final diagnosis in this case was difficult due to the unusual metastatic spread pattern that was not easily detected by standard diagnostic procedures. Conclusions: Extrahepatic metastatic hepatocellular carcinoma should be considered in the differential diagnosis of a lytic mass affecting the cervical spine in a non-cirrhotic patient.Item EXERCISE AND CANCER: A LITERATURE REVIEW(2013-04-12) Smith, JohnPurpose: A comprehensive review of the literature regarding the effects on exercise in cancer prevention and treatment, with the goal of elucidating non-pharmacological interventions for the possible prevention and treatment of this disease. Methods: A comprehensive literature search up to January 2013 to identify articles that examine the the effects of physical exercise and its use in prevention and treatment of cancer. Key words included: exercise, cancer, prevention, physical activity, treatment, and neoplasm. Searches were preformed using databases of PubMed, Cochrane library, CINAHL, and cancer lit. Results: The majority of research conducted with regards to breast, colon, prostate, and endometrial cancers has shown a reduction of 20 to 30% depending on the type and stage of cancer. Other cancers have seen inconsistent results, warranting the need for additional research in the development of an exercise prescription. Non-pharmacological treatment using exercise as an adjuvant therapy to the current standard of care has demonstrated to be beneficial. However, inconsistencies with respects to intensity, duration and type of exercise for cancer patients have fueled the debate as to the most effective exercise prescription for this disease process. Conclusions: The many epidemiological, clinical and experimental studies published have demonstrated an inverse relationship between physical activity and frequency of various types of cancer. These studies further substantiate the benefits and ultimately the need for specific directives for an exercise prescription to aide in the treatment of cancer.Item Extracellular Proliferating Cell Nuclear Antigen as a Marker and Therapeutic Target for Cancer Stem Cells.(2014-05-01) Horton, Nathan C.; Porunelloor MathewCancer is the second leading cause of death in the United States, making it a major public health issue. Due to increased efficiency in detecting and treating cancer, primary tumors account for only 10% of cancer mortalities. Today, the majority of cancer related deaths are due to metastasis and relapse after therapy, which current cancer treatments fail to prevent. Recently, cancer stem cells (CSCs) have emerged as being responsible for metastasis and relapse. CSCs are cancerous cells with stem cell characteristics including self renewal and the ability to evade chemotherapy and elimination by the immune system. A part of the innate immune system, Natural Killer (NK) cells provide the first line of defense against cancerous cells. NK cells kill cancerous cells through release of cytotoxic granules, a process regulated by activating and inhibitory receptors at the NK cell surface recognizing specific surface molecules on a tumor. Of the NK cell receptors, signaling via NKp44 is pivotal in determining the fate of tumor cells because it possesses both activating and inhibitory functions and is only expressed on activated NK cells. In this study, expression of Proliferating Cell Nuclear Antigen (PCNA), an inhibitory ligand of NKp44, is identified on the surface of a Diffuse B Cell Lymphoma, Prostate, and Breast cancer cell lines in novel association with Human Leukocyte Antigen Class I molecules. By blocking interactions between NKp44 and the PCNA/HLA I complex, NK cell mediated cytotoxicity and IFN-γ secretion is enhanced. Finally, prostate and breast cancer cells expressing PCNA at the cell surface express several molecular signatures of cancer stem cells which increase the ability of these cells to survive the metastatic process.Item EXTRACELLULAR PROLIFERATING CELL NUCLEAR ANTIGEN IS A NOVEL MARKER FOR CANCER STEM CELLS AND FACILITATES EVASION OF NK CELL EFFECTOR FUNCTION(2013-04-12) Horton, NathanPurpose: Natural Killer (NK) cells are a specialized population of lymphocytes of the innate immune system which provide vital first line defense against infections and cancer. NK cell function is strictly regulated by inhibitory and activating receptors binding corresponding ligands on the surface of target cells. NKp44, originally discovered as an activating NK cell receptor, was recently found to elicit inhibitory effects on NK cell effector function through recognition of cell surface Proliferation Cell Nuclear Antigen (PCNA), which is typically only found in the cell nucleus for DNA replication and repair. Other reports have pointed to potential associations between NKp44 and Human Leukocyte Antigen (HLA) I molecules. Methods: We have identified novel interactions between HLA I and PCNA on the surface of human tumor cells by confocal microscopy and immunoprecipitation. We have also confirmed the inhibitory nature of NKp44 recognition of PCNA in association with HLA I through a standard Chromium release assay. Results: We show PCNA on the cell surface in novel association with HLA I is a natural process which does not require provocation and occurs with endogenous PCNA. The association of HLA I and PCNA forms the inhibitory ligand for NKp44, resulting in inhibition of NK effector function. Furthermore, extracellular PCNA was only found on tumor cells exhibiting a cancer stem cell phenotype. Conclusions: Thus extracellular PCNA may serve as a novel marker for cancer stem cells and provide a mechanism by which these cells evade NK cell effector functions. As a rare population of cancer cells potentially responsible for relapse after treatment, metastasis, and overall tumor growth, cancer stem cells are difficult to clinically detect in circulation and are often impervious to chemotherapy and radiation treatments. Further studies will determine the efficacy of using extracellular PCNA as a cancer stem cell marker for better detection and therapeutic targeting of these rare, yet dangerous cancer cells.Item Hematologic malignancies following external beam radiation therapy for localized prostate cancer(2010-10-01) Ojha, Rohit P.; Felini, Martha J.; Singh, Karan P.; Thertulien, RaymondOjha, Rohit P. Hematologic malignancies following external beam radiation therapy for localized prostate cancer. Doctor of Public Health (Epidemiology), December 2010, 88 pp., 6 tables, 2 illustrations, references, 96 titles. The incidence of hematologic malignancies following external beam radiation therapy (EBRT) among prostate cancer patients has received limited attention despite evidence that radiation has a role in leukemogenesis and myelomagenesis. Therefore, we investigated the effect of external beam radiation therapy on acute myeloid leukemia and myeloma incidence among prostate cancer patients. We utilized the Surveillance, Epidemiology, and End Results database to identify a cohort of men (n=168,612) with newly diagnosed prostate adenocarcinoma between January 1988 and December 2003. Cox proportional hazard regression was used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of acute myeloid leukemia and myeloma incidence following definitive therapy with EBRT alone, brachytherapy alone, or surgery alone compared to no definitive therapy. The cohort yielded 184 incident acute myeloid leukemia cases and 344 incident myeloma cases during 1,064,820 person-years of follow-up after prostate adenocarcinoma diagnosis. Patients treated with EBRT had a higher adjusted relative hazard of developing acute myeloid leukemia than patients treated with brachytherapy or surgery when each therapy group was compared to patients who were not treated with definitive therapy (EBRT: HR=2.05, 95% CI 1.29, 3.26; brachytherapy: HR=1.22, 95% CI 0.46, 3.22; surgery: HR=1.24, 95% CI 0.77, 1.98). Patients treated with EBRT, brachytherapy, or surgery did not have increased adjusted relative hazards of developing myeloma when each therapy group was compared to patients who were not treated with definitive therapy (EBRT: HR=0.97, 95% CI: 0.70, 1.35; brachytherapy: HR=0.60, 95% CI: 0.28, 1.33; surgery: HR=1.02, 95% CI: 0.75, 1.39). Our findings suggest that acute myeloid leukemia incidence is a greater concern for patients treated with EBRT than brachytherapy for localized or locally advanced prostate adenocarcinoma. However, our results indicate that neither EBRT nor brachytherapy increases the relative hazard of myeloma incidence among patients with localized or locally advanced prostate adenocarcinoma. Ultimately, our findings may contribute to the collective evidence regarding the risks and benefits of external beam radiation therapy.Item Involvement of Estrogen Receptor Beta 5 in the Progression of Glioma(2013-05-01) Li, Wenjun; Shaohua YangEmerging evidence suggests a decline of ERβ expression in various peripheral cancers and ERβ has been proposed as a cancer brake that inhibits tumor cell growth and proliferation. In the current study, we have identified ERβ5 as the predominant isoform of ERβ in human glioma and its expression was significantly increased in human glioma as compared with non-neoplastic brain tissue. Hypoxia and activation of hypoxia inducible factor (HIF) increased ERβ transcription in U87 cells, suggesting elevated ERβ expression in glioma might be induced by the hypoxic stress in the tumor. Overexpression of either ERβ1 or ERβ5 increased PTEN expression and inhibited activation of the PI3K/AKT/mTOR pathway; ERβ5 also inhibited the MAPK/ERK pathway. In U87 cells, ERβ1 and ERβ5 decreased cell proliferation and decreased cells in the S+G2/M phase. Our findings suggest hypoxia induced ERβ5 expression in glioma as a self-protective mechanism against tumor proliferation and that ERβ5 might serve as a therapeutic target for the treatment of glioma. We also reported potential association between ERβ expression and outcomes of TMZ or tamoxifen treatment for GBM, which might be of practical clinical values.Item Lymphatic Pump Treatment Enhances Pulmonary Immunity and Inhibits Solid Tumor Formation in the Lung(2009-12-01) Pedrueza, Mayela; Hodge, Lisa M.Item Mercapturic Acid Pathway: A Novel Opportunity for Targeting VHL-Mutant Renal Cell Carcinoma(2011-05-01) Dalasanur Nagaprashantina, Lokesh Prasad Gowda; Sanjay Awasthi; Laszlo ProkaiRenal cell carcinoma Renal cell carcinoma (RCC) is one of the top ten leading causes of cancer deaths in USA. The National Cancer Institute’s statistics reveal doubling of the risk of RCC in past 50 years and recent data indicates that RCC contributes to loss of 195,000 person-years of productivity per calendar year making it an important public health problem [1]. Hence, analysis of the specific signaling pathways and networks in aggressive types of RCC and characterization of the mechanisms of action of novel anti-cancer agents that selectively target the processes of oncogenic transformation and tumor progression in kidney has gained momentum in the translational research in renal oncology. RCC was first described by Konig in the year 1826. The proximal renal tubular origin of many renal tumors was confirmed by Robin and Waldeyer in 1855 and 1867, respectively [2]. The major histological sub-types of renal epithelial tumors are comprised of clear cell RCC (75%), papillary type 1 RCC (5%), papillary type 2 RCC (10%), chromophobe RCC (5%) and oncocytoma (5%) [3]. RCC occurs in both sporadic and hereditary forms. The deletions and loss of function mutations in the tumor suppressor von Hippel-Lindau (VHL) gene which is located on chromosome 3p25.3 leading to “VHL syndrome” (Online Mendelian Inheritance in Man, OMIM, catalogue number: 193300) is a major genetic risk factor for the incidence of clear cell RCC, a major sub-type of RCC [4-6]. The VHL syndrome was first described more than a 2 century ago by Treacher Collins and Eugene von Hippel following the observation of familial inheritance pattern of retinal angiomas [7,8]. Later, Arvind Lindau, a neuropathologist, described the incidence of cerebellar hemangioblastomas [9]. The VHL syndrome is also characterized by an increased predisposition to tumors of adrenal glands, inner ear, spine, and pancreatic cysts and hemangioblastomas [10-15]. Hereditary loss of VHL leads to incidence of multifocal, bilateral and highly vascular tumors in kidneys characterized by an aggressive and metastatic course of progression in younger years of life in contrast to sporadic RCC which generally affects mainly elderly population [16]. The VHL mutations have also been detected in many cases of sporadic RCC which in turn reveals the susceptibility of VHL locus to acquired mutations during life time [17]. The life-style and environmental risks for the incidence of sporadic RCC include cigarette smoking, obesity and asbestos exposure [17-20]. The significance of VHL in tumor formation and progression is due to its designated role in oxygen-sensing machinery of the cell which in turn regulates a plethora of cellular proliferative, metabolic and transcriptional processes. The cellular levels of oxygen in drosophila as well as mammals are sensed by a family of hypoxia inducible factors (HIF), proteins characterized by the presence of basic-helix-loop-helix structure and a PAS (dimerization) domain characteristic of many transcription factors. The human HIFs include HIF1-α, HIF1-β, HIF2-α, HIF2-β, HIF3- α and HIF3-β which participate in oxygen dependent re-programming of cellular transcription [21, 22]. The HIF-α subunits have N-terminal transactivation domain (NTAD) and C-terminal transactivation domain (CTAD) which are specifically regulated in oxygen dependent manner [23]. In hypoxic conditions, the transcriptional co-activators like cAMP-response-elementbinding protein (CREB)-binding protein (CBP) and p300 bind to CTAD of HIF-α. This leads to 3 activation of hypoxia inducible genes like EGFR, VEGF, PDGFβ and TGFα which in turn contribute to enhanced angiogenic and mitogenic potential to survive in hypoxic environment [24-27]. The VHL gene product, pVHL, plays a vital role in regulating the function of HIF-α when oxygen levels are normal in cells. In normoxic conditions, the HIF-α proteins are hydroxylated at asparagine residue in NTAD by factor inhibiting HIF-α (FIH) and at proline residues by HIF prolyl-hydroxylases [28,29]. The prolyl hydroxylation of HIF-α at NTAD leads to binding of pVHL-elongin-cullin2 complex to HIF-α followed by polyubiquitination and proteosomal degradation [29-33]. Thus, pVHL contributes to inhibition of HIF-α signaling. The function of pVHL extends beyond regulation of hypoxic signaling in the cells. The pVHL is required for regulation of integrins and tight junctions in epithelial cells and VHL mutant (VHL-mut) cells have increased levels of HIF2-α, α5-integrin, cyclin D1 and lower p27 levels along with loss of epithelial morphology [34]. The introduction of pVHL into VHL-mut RCC leads to cell cycle arrest, epithelial differentiation and suppression of tumor forming ability [35, 36]. Thus, pVHL plays a vital role in regulating multiple signaling processes of importance in oncogenic transformation, survival of tumors in hypoxic conditions along with a role in maintaining epithelial phenotype.Item NOVEL USE OF PROLIFERATING CELL NUCLEAR ANTIGEN AS A BIOMARKER OF METASTATIC CANCER(2014-03) Horton, Nathan; Mathew, Porunelloor A.Novel biomarkers to identify metastatic tumor cells are needed to better identify these cells and to appropriately choose therapeutic measures. Cancer stem cells are believed to be responsible for metastasis and relapse after therapy. We have identified novel expression of Proliferating Cell Nuclear Antigen on the cell surface of tumors and characterized these cells as potential cancer stem cells. This research may facilitate the generation of novel immune based cancer therapies to specifically identify and target metastatic tumor cells. Purpose (a): Primary tumors account for 10% of cancer related deaths. Thus, identifying novel biomarkers on tumor cells which resist treatment or potentially become metastatic is vital. Proliferating Cell Nuclear Antigen (PCNA) has traditionally been used as a biomarker to identify and grade tumor biopsies based on PCNA's involvement in DNA replication. Typically located intracellularly, we have recently identified PCNA at the cell surface. When recognized by the Natural Killer (NK) cell receptor, NKp44, PCNA inhibits NK cell effector functions, allowing tumor cells to escape immunosurveillance. We have characterized tumor cells expressing cell surface PCNA to evaluate the use of cell surface PCNA as a potential marker of cancer stem cells, believed to be responsible for relapse and metastasis. Methods (b): We analyzed extracellular PCNA expressing tumor cells for expression of vimentin by confocal microscopy and expression of CD44 and CD24 by flow cytometry, which mark cancer stem cells. We also analyzed these cells for expression of genes which can induce formation of cancer stem cells or maintain stem cell characteristics by real time PCR. Finally, since stem cells are often quiescent, we analyzed cell cycle progression of these cells using propidium iodide and flow cytometry analysis. Results (c): Expression of vimentin is exclusive to cells expressing extracellular PCNA. These cells also express intermediate levels of CD44, which marks metastatic cells in vivo, and differentially express genetic markers of cancer stem cells. Populations of tumor cells expressing PCNA at the cell surface were enriched for cells in the G2/M phase of the cell cycle. Conclusions (d): Extracellular PCNA may be a marker for metastatic cancer stem cells based on intermediate expression of CD44, concomitant expression of vimentin, and expression of genetic markers. Alternatively, extracellular PCNA marks cells in the G2/M phase. Further studies in mouse models will be needed to confirm extracellular PCNA as a marker for cancer stem cells.Item Optimization of Reconstituted High Density Lipoprotein nanoparticles as a Delivery System for Neuroblastoma(2013-12-01) Hinze, Cheryl L.; Lacko, Andras G.Despite many advances in cancer therapy over the last few decades, cancer remains one of the most common causes of death in not only the United States, but around the world. Two of the major problems cancer patients face today are the horrific side effects associated with chemotherapy, and the development of drug resistance. Both of these become even bigger problems when they are applied to children. Neuroblastoma is one of the most common forms of pediatric cancer. High risk Neuroblastoma patients are commonly faced with intensive multi-modal therapies in attempt to overcome a very aggressive disease. Due to the intensive therapy required, side effects can often linger even after remission is achieved in these patients, and multi-drug resistance is common due to the high levels of Doxorubicin administered. New solutions are needed in order to overcome both of these problems in Neuroblastoma as well as other types of cancer. In this thesis, we studied the effects of different formulation and preparation techniques for the reconstituted high density lipoprotein nanoparticle model for anti-cancer agent delivery. During these studies we found that naturally derived mixes of phosphatidylcholine, and lower levels of apolipoprotein A-1 increase the encapsulation efficiency of the rHDL nanoparticles. We also determined that the addition of lyophilization during preparation before cholate dialysis, forms a more homogeneous preparation. After the optimization of the particle formulation and preparation, we tested the efficacy of two model anti-cancer agents in different cancer cells. First we showed the ability of the rHDL-siRNA nanoparticles to knockdown the SR-B1 protein is greater than the knockdown of a commercial transfection kit. Finally we prove that the rHDL also improves the cytotoxic efficacy of a novel treatment for Neuroblastoma involving Imatinib Mesylate and Saquinavir. In conclusion, the results of this thesis show a more detailed knowledge of the rHDL nanoparticle formulation as well as how it can be applied as an effective delivery system for both siRNA and chemotherapeutic agents. This data should help push our formulations closer to clinical applications, and toward helping reduce the toxic side effects of many chemotherapeutic agents, as well as reducing the incidence of drug resistance.Item Reactions to Race and Cancer Screening Utilization.(2006-05-01) Arabadi, Adib; Roberto CardarelliAsrabadi, Adib., Reactions to Race and Cancer Screening Utilization. Master of Science (Biomedical Sciences), May, 2006, 43 pp., 4 tables, bibliography. As cancer rates continue to rise, the importance of patient compliance with appropriate screening methods also increases. This study explored a realm of preventive services where few studies have gone to date. The study sample was selected from the 2004 Behavioral Risk Factor Surveillance System (BRFSS) which included 37,985 participants. The associations of reactions to race and possible confounders with cancer screening utilizations for breast, cervical, and colorectal cancers were examined. Bivariate analyses as well as univariate and multivariate logistic regression analyses were conducted to explore these associations. The results demonstrated that negative reaction to race were not associated with cancer screening utilization. However, other associations between independent variables and utilization of mammogram, Pap smear, and colonoscopy/sigmoidoscopy screening were discovered. Further in-depth exploration of reactions to race in relation to cancer screening is warrantedItem REMOVING BARRIERS TO BREAST CANCER SCREENING AMONG ETHNIC MINORITIES IN TEXAS(2014-03) Oyewole, Olusegun; Linnear, Kim; Cardarelli, Kathryn; Martin, Marcus; Petties, Karin; Williams, Angela; Lafayette, Camille; Martinez, Erika; Harris, PhyllisPurpose (a): This project seeks to reduce breast cancer mortality among ethnic minorities in Dallas County, Texas through an integrated breast cancer prevention program that includes outreach and education, delivery of screening services, follow-up navigation and screening behavior maintenance. While perceived susceptibility, perceived severity, perceived benefits and cues to action are important predictors of health-seeking behaviors, removal of perceived barriers has been found to be the most important factor in moving people from inactivity to action. This research seeks to answer the question: Does this program significantly reduce the perceived barriers to mammography screening among the participants? Methods (b): Participants had a pre-survey assessing their knowledge, attitude and behavior about breast cancer determinants and prevention as well as their perceived severity of breast cancer, perceived susceptibility to it, perceived benefit of regular screening and perceived barriers to regular screening. This was followed by up to 8 weeks of education and a post-survey. McNemar’s tests were done to compare the pre- and post-surveys on questions relating to perceived barriers to screening and mammogram use. Results (c): A significant reduction in perceived barrier to breast cancer screening was found among study participants. There was also a significant improvement in mammogram use among them during the intervention. Conclusions (d): The integrated breast cancer prevention program leads to a significant reduction in perceived barriers to screening with consequent improvement in mammogram use in study participants.Item Smoking cessation and survival among people diagnosed with non-metastatic cancer(BioMed Central Ltd., 2020-08-05) Barnett, Tracey E.; Lu, Yan; Gehr, Aaron W.; Ghabach, Bassam; Ojha, Rohit P.BACKGROUND: We aimed to estimate the effects of smoking cessation on survival among people diagnosed with cancer. METHODS: We used data from a Comprehensive Community Cancer Program that is part of a large urban safety-net hospital system. Eligible patients were diagnosed with primary invasive solid tumors between 2013 and 2015, and were current smokers at time of diagnosis. Our exposure of interest was initiation of smoking cessation within 6 months of cancer diagnosis. We estimated inverse probability weighted restricted mean survival time (RMST) differences and risk ratio (RR) for all cause 3-year mortality. RESULTS: Our study population comprised 369 patients, of whom 42% were aged < 55 years, 59% were male, 44% were racial/ethnic minorities, and 59% were uninsured. The 3-year RMST was 1.8 (95% CL: - 1.5, 5.1) months longer for individuals who initiated smoking cessation within 6 months of cancer diagnosis. The point estimate for risk of 3-year mortality was lower for initiation of smoking cessation within 6 months of diagnosis compared with no initiation within 6 months (RR = 0.72, 95% CL: 0.37, 1.4). CONCLUSIONS: Our point estimates suggest longer 3-year survival, but the results are compatible with 1.5 month shorter or 5.1 longer 3-year overall survival after smoking cessation within 6 months of cancer diagnosis. Future studies with larger sample sizes that test the comparative effectiveness of different smoking cessation strategies are needed for more detailed evidence to inform decision-making about the effect of smoking cessation on survival among cancer patients. IMPLICATIONS FOR CANCER SURVIVORS: The benefits of smoking cessation after cancer diagnosis may include longer survival, but the magnitude of benefit is unclear.Item Spectral Properties of Doxorubicin Doped rHDL Nanoparticles(2018-05) Shah, Sunil A.; Gryczynski, Zygmunt; Lacko, Andras G.; Borejdo, Julian; Krishnamoorthy, Raghu R.; Fudala, RafalDoxorubicin, also known as Adriamycin, is an anthracycline antibiotic which first gained clinical prominence in the early 1970's as an effective antitumor agent. It is still used today to treat a spectrum of cancers like lymphoma, bladder, stomach, lung, breast, ovarian, and several others. Due to its production of free radicals to attack tumor cells, Doxorubicin interferes with mitochondrial phosphorylation and also induces cardiotoxicity. Thus, efficient and biocompatible delivery methods are needed for targeted drug delivery to overcome systemic toxicity. To maintain a high level of growth, tumor cells overexpress Scavenger receptors type B-1 (SR-B1). This cellular characteristic can be used to target and selectively deliver doxorubicin to tumor cells by packing it in reconstituted high density lipoprotein (rHDL) nanoparticles, which bind selectively to SR-B1 receptors. Nanoparticles as target-specific drug delivery agents are increasingly used in cancer therapy to enhance bioavailability and to reduce off target toxicity of anti-cancer agents. Several different formulations of rHDL nanoparticles to incorporate doxorubicin were synthesized. Doxorubicin's intrinsic fluorescence was used to photophysically characterize the properties of loaded rHDL nanoparticles including absorption, emission, excitation, steady-state and time resolved anisotropy measurements, and quenching to study drug shielding by nanoparticles. Overall the fluorescence properties of the rHDL: doxorubicin complex may reveal valuable novel characteristics of this drug delivery vehicle that may be particularly applicable when used in systemic (intravenous) therapy.Item SR-B1 RHDL DIRECTED NANOPARTICLES AS A DRUG DELIVERY SYSTEM AGAINST TRIPLE NEGATIVE BREAST CANCER(2013-04-12) Johnson, RebeccaPurpose: Triple Negative Breast Cancer (TNBC), is a heterogeneous group of tumors with diverse histology, molecular uniqueness and response to treatment. As a result of ineffective treatments, TNBC tumors often progress to metastatic lesions in the brain and lung. Brain metastases of invasive breast cancer are associated with 1 and 2 year survival rate of 20% and < 2% respectively. Current anti-HER2 or hormone positive targeted breast cancer treatments do not benefit TNBC patients; consequently, these patients rely primarily on chemotherapy. Alternative targeted therapies are urgently needed to improve survival for TNBC patients. This study is focused on developing a new approach for filling the current void in effective treatment for TNBC patients. Methods: Cells were seeded and treated with free drug and drug loaded rHDl particle for 24 hours. Cell Viability was determined using the cell viability assay CCK8. 96 well plates were read at 450nm Results: Using the CCK8 cell viability assay preliminary data reveals the potential of Temsirolimus loaded rHDL nanoparticles to reduce the effective concentration at lower doses vs. the free drug in the MDA-MB-231 cell line. Conclusions: rHDL particles are small non-immunogenic nanoparticles that have the potential to decrease the side effects that accompany high concentrations of chemotherapeutic drugs. This study proposes the using the mTOR inhibitor Temsirolimus encapsulated into the rHDL nanoparticle as an effective treatment against TNBC vs the free drug.Item Synergy 2008: Annual Research Report(2008-01-01)Item Synergy 2010: Annual Research Report(2010-01-01)