Browsing by Subject "cancer"
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Item A Comparative Breast Cancer Study: Stage & Mortality in El Paso County's non-Hispanic white and Hispanic population(2003-05-01) Aravind, Raven; Russel HovermanAravind, Raven, A Comparative Breast Cancer Study: Stage & Mortality in El PasoCounty's non-Hispanic white and Hispanic population, 1990-2000. Master of Public Health (Epidemiology), May 2003, 17pp., 1 table, 3 figures, bibliography, 43 titles. This retrospective breast cancer study compares the stage of breast cancer diagnosis and mortality between Hispanic (HS) and non-Hispanic white women (NHW). The study includes 874 Hispanic women and 802 non-Hispanic white women diagnosed with breast cancer between January 1990 and December 2000 at the El Paso Cancer Treatment Center, El Paso Texas. The objectives of the study were: 1) to determine if this population of Hispanic women is being diagnosed at a later stage of breast cancer 2) to ascertain the relative survival of non-Hispanic white and Hispanic women 3) to verify if Hispanic women were being diagnosed at a younger age; and 4) to examine tumor size at diagnosis to determine if there is a need for more assertive screening measures in this population of women.Item CASE PRESENTATION AND LITERATURE REVIEW OF SQUAMOUS HISTOLOGY IN UTERINE CANCER(2013-04-12) Jaynes, JenniferPurpose: Although the most common form of endometrial cancer is pure endometrioid adenocarcinoma, there have been many instances of endometrioid adenocarcinoma with squamous differentiation. However, the incidence of pure squamous carcinoma of the endometrium is very rare. Here a case is presented of a woman with endometrial cancer that was found to contain both glandular and squamous components and was described as endometrial adenocarcinoma with extensive squamous morule formation with areas of necrosis. The objective is to compare and contrast endometrioid adenocarcinoma with squamous differentiation (EASD) and primary squamous carcinoma of the endometrium (PSCE). Methods: A current literature review of online research databases and relevant scientific journals was performed in order to compare what is known about the incidence, etiology, histopathology, diagnosis, treatment, and prognosis of PSCE with that of EASD. Results: The origin of the squamous differentiation within endometrioid adenocarcinoma arises from squamous metaplasia of glandular tissue that eventually forms adenocarcinoma. However, the origin of PSCE is postulated to arise from stem cells between glandular basement membrane and endometrial columnar epithelium. While one possible component of treatment for EASD is hormone therapy, PSCE has been shown not to express estrogen or progesterone receptors and thus is not responsive to hormone therapy. The prognosis for pure endometrioid adenocarcinoma at five years for stage I disease is 89.1%; for stage II disease is 78.8%; for stage III disease is 57.8%; and for stage IV disease is 22%. EASD has been shown to have a worse prognosis than pure endometrioid adenocarcinoma. PSCE is much less common and thus only studied out to one year. At one year, the prognosis for stage I disease is 80%; for stage III is 20%; and for stage IV is 0%. Conclusions: While EASD and PSCE share the similarity of squamous features, PSCE carries a much worse prognosis with more limited treatment options. With so few cases and so little known about PSCE, further research on this lethal carcinoma is warrantedItem Defining the Prostate Cancer Population in Texas Using Hospital Discharge Data(2004-05-01) Manuel, Christopher J.; Karan Singh; Antonio A. ReneManuel, Christopher J., Defining the prostate cancer population in Texas using hospital discharge data. Masters of Public Health (Biostatistics), May 2004, 25 pp., 6 tables, bibliography, 35 titles. The Texas Health Care Information Council (THCIC) was created by the 74th Texas Legislature in 1995. THCIC’s primary purpose is to provide data that will enable Texas consumers and health plan purchasers to make informed health care decisions. This data also serves the purpose of providing information about disease trends and hospital discharges. The purpose of this study was to describe the disease status of prostate cancer in the state of Texas. Prostate cancer is the most common non-cutaneous male malignancy and ranks as the second cause of cancer-related mortality among men in the United States. Epidemiologic data was extracted from the data set for analysis looking at disease trends based on a variety of factors such as age, race, and insurance.Item Development and Characterization of Methylene Blue Oleate Salt-Loaded Polymeric Nanoparticles as a Treatment for Glioblastoma(2016-12-01) Castañeda-Gill, Jessica M.; Jamboor K. Vishwanatha; Amalendu P. Ranjan; Shaohua YangGlioblastoma (GBM) is the most common and aggressive primary brain tumor in older adults, resulting in an average survival of 15 months post-diagnosis and treatment. While recent research has provided essential information, GBM relapse following traditional combinatorial regimens (surgery, radiation, and chemotherapy) is common, necessitating the development of more effective, less toxic therapies. Methylene blue (MB), a dye with noted medicinal applications, has received recent consideration as a potential neurotherapeutic due to its ability to infiltrate the blood-brain barrier (BBB), improve processes within distinct brain cell compartments and types, and preferential accumulation in the brain. While MB displays these advantages, one drawback is increased administration to produce therapeutic effects, leading to excessive brain deposition and potential neurotoxicity. A common method to enhance drug delivery is via encapsulation in submicron-sized nanoparticles (NPs) composed of the biodegradable/biocompatible co-polymer, poly(lactic-co-glycolic) acid (PLGA). We have previously shown their application as potential cancer therapies, as well as preferential brain accumulation. Thus, our goal was to develop MB-loaded NPs capable of permeating the BBB in order to treat GBM, based on our hypothesis that encapsulation of MB into PLGA NPs would enhance accumulation in cancerous regions, resulting in reduced tumor size and prolonged survival. In this study, we prepared a methylene blue-oleate salt conjugate (MBOS) to enhance its stability, then formulated and characterized methylene blue oleate salt-loaded polymeric nanoparticles (MBOSNPs) via size, surface charge, drug loading (DL), and encapsulation efficiency (EE). We also analyzed their in vitro effects to establish biological, and potentially therapeutic, activity. As a result, we obtained preparations physio-chemically comparable to other at 162.4nm, with a surface charge of -31.7 and DL and EE values of 2.2% and 29.2%, respectively. Next, MB(OS)NPs were determined to produce a peak drug release at 24hrs, and induce cytotoxicity comparable to, if not better than, free drug, in two GBM cell lines. Additionally, MB(OS)NPs enhanced cellular metabolism, a capability noted in free MB. Lastly, animal studies confirmed enhanced BBB permeation by MBOSNPs compared to free MBOS, demonstrating their therapeutic potential.Item Evaluation of Reconstituted High Density Lipoprotein as an Anticancer Drug Delivery Platform(2009-12-01) Mooberry, Linda; Lacko, Andras G.Item Evaluation of the Systematic Clinical Trials Protocol Approval Process at a Matrix Cancer Center(2007-11-01) Bloomer, Tyler; Patricia Gwirtz; Rusty Reeves; Lynn BakerThe National Cancer Institute (NCI) estimates that approximately 555,550 people die of cancer each year in the United States. This is an average of a little more than 1,500 people per days and ranks cancer as the second leading cause of death behind heart disease. In 2007, an astonishing 1,444,920 new cancer cases are anticipated to be diagnosed. It is through scientific research and the necessary employment of clinical trials that advanced are made to fight this dreadful disease. A breakthrough or advancement made in the treatment of cancer begins with basic research of cells and tissues in the laboratory. Once a particular treatment or technique is developed, and proven to be successful in animal models, it can then be evaluated in people through clinical trials. Clinical trials follow a rigorous scientific process to answer specific questions relating to the new newly developed therapy or technique. A clinical trial is the only mechanism to determine the true effectiveness of a promising new therapeutic being investigated. Thus, any unnecessary delays in approving a clinical trial protocol increases the time before that trial can begin enrolling patients and therefore gain approval for new treatment options. The International Conference of Harmonization Good Clinical Practice (ICH GCP) guidance document defines a protocol as “a document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial.” The ICH GCP further goes on to describe that the protocol gives the rationale and background for a trial. The World Health Organization’s (WHO) Handbook for Good Clinical Research Practice states that “the study protocol is the core document communicating trial requirements to all parties who have responsibility to all parties who have responsibility for approval, conduct, oversight, and analysis of the research.” Thus, before any trial can begin accruing patients, its protocol, along with a study’s informed consent, must be thoroughly reviewed and approved by a network of entities to ensure that a study’s protocol outlines a trial that is safe and effective. A recent study conducted at the Vanderbilt-Ingram Cancer Center (VICC) and at a VICC Affiliate Network (VICCAN) sites indicated that two particular processes took longer than all others involved in their clinical trial protocol approval process. These two particular processes were the Scientific Review Committee review process and the Contracts and Grants approval process. This was contrary to what the authors expected, in that, they believed the IRB review and approval process would take the longest. Many of the challenges reported by the authors of the study at the VICC parallel those encountered in the protocol approval process at UT Southwestern. A closer examination of these parameters is needed. The Harold C. Simmons Comprehensive Cancer Center (SCCC) at UT Southwestern Medical Center is a matrix cancer center and relies upon the interactions between other institutions and departments to conduct all phases of its cancer research. Thus, the process involved in approving a clinical trial protocol also rely upon the interactions between other institutions and departments. This is where many challenges and various institutional administrative barriers arise. Therefore, it is the goal of this practicum report to formally evaluate and document the protocol approval process at the SCCC at UT Southwestern. The report will also identify unwarranted time delays in the process and provide feasible resolutions to expediting the overall clinical trial protocol approval process without compromising patient safety or research integrity. At the cessation of this report, a further analysis may be conducted using its findings to determine whether or not these time delays in the process and provide feasible resolutions to expediting the overall clinical trial protocol approval process without compromising patient safety or research integrity. At the cessation of this report, a further analysis may be conducted using its findings to determine whether or not these time delays in approving a study protocol are consistent with approval processes encountered at other institutions and academic health center settings like the Vanderbilt-Ingram Cancer Center and the Simmons Comprehensive Cancer Center.Item Long Term Compliance and Withdrawal Rates in Gynecologic Oncology Clinical Research Studies(2003-12-01) Kersey, Jen Kelley; Robert Kaman; LaChelle Arredondo; Robin NewmanOncology is an area of study that is greatly affected by time. Patients with cancer need safe and effective treatment immediately. For some, current treatments have not worked to eliminate their disease. Their recurrent condition reinforces the need for safer and more effective treatment. This treatment must not only destroy the cancerous cells, but it must also allow for the continuation of their lives. This life can be measured by time and quality. Ideally, both would be maximized for proper treatment, yet current science has not found this model cure. For some regimens, quality of life could be maximized at the expense of quantity of life and vice versa. Both the patient and the healthcare provider should evaluate the balance of expectations. The potential of each life should be maximized for length and quality. The investigator/physician must do everything in their power to ensure that the patient’s needs are met medically. In treatment involving recurrent cancer patients, time is of the essence. Therapy, in every form, must be given immediately to extend and improve their remaining lives. If QOL assessments can predict the outcome of retention, acknowledgement of the subject’s well-being can allow for greater insight into the physical and emotional effects of the experimental treatment. The use of this information can help future generations of cancer patients by providing data that describes the therapy. The study of “Long Term Subject Compliance and Withdrawal Rates in Gynecologic Oncology Clinical Research Studies” is necessary for the evaluation of QOL assessments to subject retention, patient care practices in research and private practice may be affected through incorporation of the QOL assessment. There are many benefits that may result if significance is found in this study. The main objective of the QOL assessment is to observe the QOL of the subject in relation to the effect of the treatment on the individual. If subject retention can be predicted from the evaluation of QOL assessments, future clinical research studies, in gynecologic oncology and beyond, may modify their protocols to include the assessments. Improved subject retention will ultimately improve the accuracy of data collection. Improved accuracy will help evaluate the outcomes of treatment for cancer patients. If the QOL assessment shows a correlation to subject retention, the survey could be used as a tool, not only to assess the patient’s well being, but also to predict withdrawal. This project could identify “at-risk” factors of the subject population. Subjects who are at-risk for withdrawal should be followed closely. Excluding subjects that meet the clinical protocol would be unethical. To protect the validity of the study and ensure ethical measures are taken, those subjects that have factors associated with drop-out should be enrolled in the study and monitored closely. The survey may give insight to the types of ancillary or palliative care that may be needed during the patient’s fight with cancer. This research hopes to identify that quality of life assessments are an integral dimension of the research practice. The care of the patient rests in the hands of the physicians providing treatment. They are responsible for the needs and best interest of the patients. Wide discrepancies between the rating of specific outcomes of treatment by the patient and physician have been noted in current literature. This study may help show that the patient driven quality of life assessment is an important aspect of patient care, and should be integrated as a common tool for the care of gynecologic oncology patients. The use of this tool outside of the research setting should also be explored. Future studies in quality of life, beyond that of gynecologic oncology, may be investigated. This study hopes to initiate further research for the quality of life assessment because the QOL assessment gives data regarding well-being from the patient’s perspective. Future studies should also research the confounding factors that may influence subject withdrawal. These additional collaborative factors may contribute to compliance or those “at-risk” for drop out. By maximizing subject retention and protecting subject safety, healthcare research can provide results that reflect the true investigational question.Item North Texas Health & Science - 2011, Issue 2(University of North Texas Health Science Center at Fort Worth, 2011-01-01)Item Novel Method to Obtain Contact Angles of Tumor Biopsies(American Chemical Society, 2023-08-07) Rincon, Julio; Kastellorizios, MichailCharacterizing the strength of a solid-liquid interface can be done by depositing a single drop of liquid on a planar solid surface and measuring the angle of the formed semicircle, called the contact angle. The contact angle of pure water is indicative of a surface's hydrophobicity and is a useful metric in biomedical applications such as tissue scaffolding and drug/tissue interactions. However, the roughness and inhomogeneity of most biological surfaces make obtaining accurate contact angles of such materials challenging. Here, we developed an instrument and methodology to obtain contact angles of tissue sections. Breast cancer tumor and nearby healthy tissue sections were used as the model biological surface. The custom instrument was built on existing equipment by improving drop dispensing accuracy in the nanoliter range, an XYZ stage, additional side view cameras, and microscope-based sample visualization. The method takes into account the inherent surface inhomogeneity and topology of tissue and the required method of illumination for contact angle acquisition. As such, the system uses an inverted microscope with a high sensitivity camera, an XYZ stage for accurate droplet placement on tissue, and multiple cameras to obtain contact angles around the entire perimeter of the drop. We tested the system with breast cancer biopsies and adjacent normal tissue from 75 patients and report here a trend of tumor exhibiting higher water contact angles, and thus higher hydrophobicity, compared to their respective normal adjacent tissue. The system described here can be used to characterize any type of biological tissue, which can be sectioned, with any liquid including water or solutions with dissolved or suspended therapeutic molecules and particles.Item ONCOLOGY RESOURCES IN TARRANT COUNTY(2013-04-12) Bernard, ElizabethPurpose: Many strides have been made in the field of cancer prevention and cure, resulting in an increase in cancer patient longevity and survivorship in the population. This increased demand for cancer services has left many individuals in search for local support. While most research has led to improvements in the life span of cancer patients, there has been little exploration of the quality and availability of local support measures for the expansive number of cancer survivors. The purpose of this investigation is to expose some of the options available in the North Texas community for families and patients in need of cancer resources. Methods: The Blue Book Directory of Community Resources lists organizations and institutes detailing cancer care management and financial backing for the Tarrant County and Fort Worth populace. Results: The M.D. Anderson Center offers diagnosis, treatment, and management for patients that are low-income or uninsured. The American Cancer Society of North Texas provides cancer patients, families, and the public with support groups, rehabilitation clinics, and prevention education services. Breast Health Education supplies mammograms and breast health instruction to qualified members. The Moncrief Cancer institute offers cancer prevention methods and social health opportunities. Lastly, Cancer Care Services promotes emotional and financial support for patients and relatives. Conclusions: These organizations offer support, management, education, and treatment for cancer patients and their loved ones. There are obstacles with eligibility and access to each individual resource due to different qualifications including prognosis, age, and financial status. Improvements could be made to increase awareness about these organizations through advertisements and social media.Item PREPARATION OF A CISPLATIN PRODRUG FOR USE AGAINST NON-SMALL CELL LUNG CANCER(2014-03) Redfearn, Warren; Shi, Yi; Koneru, Bhuvaneswari; Di Pasqua, AnthonyBackground: Lung cancer is the leading cause of cancer-related death in the United States, and non-small cell lung cancer (NSCLC) the most common type. NSCLC is extremely difficult to treat, resulting in a poor prognosis for patients. Platinum (Pt) anti-cancer agents, such as cisplatin, remain a mainstay in the clinic; however, these Pt complexes act nonspecifically, and thus result in serious side-effects. Development and delivery of a Pt complex with an improved therapeutic index would be highly advantageous to the fight against NSCLC. We prepared trans, cis, cis-bis(heptanoato)amine(cyclohexylamine)dichloridoplatinum(IV), referred to here as PtC, and studied its DNA binding and toxicity toward normal lung and NSCLC cells. Methods: A lipophilic Pt(IV) complex, PtC, was synthesized and characterized, and its binding to DNA and toxicity toward various cancer and normal cell lines determined. Results: We confirmed that the synthesized Pt complex binds to DNA in a manner similar to that of cisplatin, which suggests that it is cisplatin prodrug; however, probably due to its lipophilic nature and improved stability, PtC is much more toxic toward NSCLC cell lines than is cisplatin, and has a much improved therapeutic index. Conclusions: PtC shows promise as a therapeutic agent against NSCLC, and, furthermore, its lipophilic nature allows for us to incorporate it into mesoporous silica nanoparticles for fine-controlled release and the targeting of tumors.Item Prescription Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Incidence of Depression Among Older Cancer Survivors With Osteoarthritis: A Machine Learning Analysis(Sage Publications, 2023-04-27) Shaikh, Nazneen F.; Shen, Chan; LeMasters, Traci; Dwibedi, Nilanjana; Ladani, Amit; Sambamoorthi, UshaOBJECTIVES: This study examined prescription NSAIDs as one of the leading predictors of incident depression and assessed the direction of the association among older cancer survivors with osteoarthritis. METHODS: This study used a retrospective cohort (N = 14, 992) of older adults with incident cancer (breast, prostate, colorectal cancers, or non-Hodgkin's lymphoma) and osteoarthritis. We used the longitudinal data from the linked Surveillance, Epidemiology, and End Results -Medicare data for the study period from 2006 through 2016, with a 12-month baseline and 12-month follow-up period. Cumulative NSAIDs days was assessed during the baseline period and incident depression was assessed during the follow-up period. An eXtreme Gradient Boosting (XGBoost) model was built with 10-fold repeated stratified cross-validation and hyperparameter tuning using the training dataset. The final model selected from the training data demonstrated high performance (Accuracy: 0.82, Recall: 0.75, Precision: 0.75) when applied to the test data. SHapley Additive exPlanations (SHAP) was used to interpret the output from the XGBoost model. RESULTS: Over 50% of the study cohort had at least one prescption of NSAIDs. Nearly 13% of the cohort were diagnosed with incident depression, with the rates ranging between 7.4% for prostate cancer and 17.0% for colorectal cancer. The highest incident depression rate of 25% was observed at 90 and 120 cumulative NSAIDs days thresholds. Cumulative NSAIDs days was the sixth leading predictor of incident depression among older adults with OA and cancer. Age, education, care fragmentation, polypharmacy, and zip code level poverty were the top 5 predictors of incident depression. CONCLUSION: Overall, 1 in 8 older adults with cancer and OA were diagnosed with incident depression. Cumulative NSAIDs days was the sixth leading predictor with an overall positive association with incident depression. However, the association was complex and varied by the cumulative NSAIDs days.Item Production of Extracellular Matrix-Degrading Proteases by a Rat B Cell Line.CRL-1631(2002-05-01) Badeaux, Kathleen S.; R. GoldfarbBadeaux, K. Production of Extracellular Matrix-Degrading Proteases by a Rat B Cell Line.CRL-1631. Master of Science (Microbiology and Immunology), May 2002. 30 pp., 9 illustrations, 1 table, 16 bibliography titles. Previously B lymphocytes have been reported to accumulate at the site of tumor development and to play a role in immune surveillance against metastatic tumors. Investigating this mechanism, we studied B lymphocyte production of extracellular matrix-degrading proteinases: matrix metalloproteinases (MMPs) and components of the urokinase plasminogen activator (uP A) system. Our studies include RT-PCR of CRL-1631 eDNA revealing mRNA for MMP-2, MMP-9, TIMP-1, TIMP-2 and uPAR. MMP-2 and MMP-9 activity was verified by gelatin zymography. TIMP-1, TIMP-2 and uPAR protein expression was confirmed by Western blot analyses. I also report, for the first time, MT -1 MMP gene and protein expression in B cells by RT-PCR and Western blot, respectively. CRL-1631 invasion through Matrigel model basement membrane was significantly inhibited by BB-94, confirming MMP involvement in this cell line's invasiveness. Therefore, B cells use multiple proteases in the degradation of the extracellular matrix, ECM, and this may be one factor responsible for their accumulation at the site of established tumors.Item Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer(MDPI, 2020-07-01) Buller, Casey W.; Mathew, Porunelloor A.; Mathew, Stephen O.Natural killer (NK) cells play a pivotal role in the immune system, especially in the recognition and clearance of cancer cells and infected cells. Their effector function is controlled by a delicate balance between the activating and inhibitory signals. We have identified 2B4 (CD244, SLAMF4) and CS1 (CD319, SLAMF7) as NK cell receptors regulating NK cell cytotoxicity. Lectin-like transcript 1 (LLT1), a member of the C-type lectin-like domain family 2 (CLEC2D), induced IFN-g production but did not directly regulate cytolytic activity. Interestingly, LLT1 expressed on other cells acts as a ligand for an NK cell inhibitory receptor NKRP1A (CD161) and inhibits NK cytolytic function. Extensive research has been done on novel therapies that target these receptors to increase the effector function of NK cells. The 2B4 receptor is involved in the rejection of melanoma cells in mice. Empliciti, an FDA-approved monoclonal antibody, explicitly targets the CS1 receptor and enhances the NK cell cytotoxicity against multiple myeloma cells. Our studies revealed that LLT1 is expressed on prostate cancer and triple-negative breast cancer cells and allows them to evade NK-cell-mediated killing. In this review, we describe NK cell receptors 2B4, CS1, and LLT1 and their potential in targeting cancer cells for NK-cell-mediated immunotherapy. New cancer immunotherapies like chimeric antigen receptor T (CAR-T) and NK (CAR-NK) cells are showing great promise in the treatment of cancer, and CAR cells specific to these receptors would be an attractive therapeutic option.Item Signaling in Natural Killer Cells: NK Cell Activation by LLT1 Receptor(2008-05-01) Bambard, Nowland D.; Jerry Simecka; Richard Easom; Harlan JonesBambard, Nowland D., Signaling in Natural Killer Cells: NK Cell Activation by LLT1 Receptor. Doctor of Philosophy (Microbiology and Immunology), May 2008, 162 pp., 1 table, 30 illustrations, bibliography, 179 titles. Natural Killer (NK) cells are large granular lymphocytes of the innate immune system that constitute the first line of defense against viral pathogens and cancer. Unlink cells of the adaptive immune response, NK cells do not recognize specific antigens expressed on MHC receptors, rather they recognize tumorgenic and virally infected cells through a complex balance of activating and inhibiting receptors expressed on the surface of human NK cells. LLT1 is expressed on numerous immune cells and subsequent functional analysis indicates that LLT1 plays an activating role on NK cells by way of stimulating interferon-gamma (IFN-G) secretion. LLT1 has also been shown to have a role on non-immune cells, inhibiting the formation and function of osteoclasts. Additionally, the natural ligand of LLT1 has been identified as NKR-P1A (CD161), an NK cell inhibitory receptor known to play an important role in immune regulation. We hypothesize that LLT1 employs multiple signaling pathways to accomplish its activating functions on human NK cells, and may be associated with one of four known transmembrane accessory proteins associated with NK cell activating receptors. We activated LLT1 on NK92 cells with target cells expressing its natural ligand CD161 and analyzing IFN-G production in the presence of pharmacological inhibitors specific for various signaling mechanisms. These results indicate that LLT1 employs Src-PTK, p38 and ERK signaling pathways, but not PKC, P13K or calcineurin. These results were followed up with phosphorylation analysis, which confirmed that the ERK signaling pathway is associated with LLT1 IFN-G production. Finally, by analyzing IFN-G mRNA we found that LLT1 activation is not associated with any detectable change in IFN-G mRNA levels, suggesting that LLT1 stimulates NK IFN-G production by modulating post transcriptional or translational events. Identification of the signaling pathways associated with LLT1 is of great medical significance as this may provide us with novel insights into activating NK cells to counter infection and cancer.Item Understanding cancer genetic risk assessment motivations in a remote tailored risk communication and navigation intervention randomized controlled trial(Informa UK Limited, trading as Taylor & Francis Group, 2022-12-16) Le Compte, Circe G.; Lu, Shou-En; Ani, Julianne; McDougall, Jean; Walters, Scott T.; Toppmeyer, Deborah; Boyce, Tawny W.; Stroup, Antoinette; Paddock, Lisa; Grumet, Sherry; Lin, Yong; Heidt, Emily; Kinney, Anita Y.BACKGROUND: National guidelines recommend cancer genetic risk assessment (CGRA) (i.e. genetic counseling prior to genetic testing) for women at increased risk for hereditary breast and ovarian cancer (HBOC). Less than one-half of eligible women obtain CGRA, leaving thousands of women and their family members without access to potentially life-saving cancer prevention interventions. PURPOSE: The Genetic Risk Assessment for Cancer Education and Empowerment Project (GRACE) addressed this translational gap, testing the efficacy of a tailored counseling and navigation (TCN) intervention vs. a targeted print brochure vs. usual care on CGRA intentions. Selected behavioral variables were theorized to mediate CGRA intentions. METHODS: Breast and ovarian cancer survivors meeting criteria for guideline-based CGRA were recruited from three state cancer registries (N = 654), completed a baseline survey, and were randomized. TCN and targeted print arms received the brochure; TCN also participated in a tailored, telephone-based decision coaching and navigation session grounded in the Extended Parallel Process Model and Ottawa Decision Support Framework. Participants completed a one-month assessment. Logistic regression was used to compare the rate of CGRA intentions. CGRA intentions and theorized mediator scores (continuous level variables) were calculated using mixed model analysis. RESULTS: CGRA intentions increased for TCN (53.2%) vs. targeted print (26.7%) (OR = 3.129; 95% CI: 2.028, 4.827, p < .0001) and TCN vs. usual care (23.1%) (OR = 3.778, CI: 2.422, 5.894, p < .0001). Perceived risk (p = 0.023) and self-efficacy (p = 0.035) mediated CGRA intentions in TCN. CONCLUSIONS: Improvements in CGRA intentions and theorized mediators support the use of a tailored communication intervention among women at increased HBOC risk. (Clinicaltrials.gov: NCT03326713.)Trial registration: ClinicalTrials.gov identifier: NCT03326713.Item Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal(MDPI, 2023-01-22) Kumar, Suneel; Mathew, Stephen O.; Aharwal, Ravindra P.; Tulli, Hardeep S.; Mohan, Chakrabhavi D.; Sethi, Gautam; Ahn, Kwang-Seok; Webber, Kassidy; Sandhu, Sardul S.; Bishayee, AnupamCancer represents the second most deadly disease and one of the most important public health concerns worldwide. Surgery, chemotherapy, radiation therapy, and immune therapy are the major types of treatment strategies that have been implemented in cancer treatment. Unfortunately, these treatment options suffer from major limitations, such as drug-resistance and adverse effects, which may eventually result in disease recurrence. Many phytochemicals have been investigated for their antitumor efficacy in preclinical models and clinical studies to discover newer therapeutic agents with fewer adverse effects. Withaferin A, a natural bioactive molecule isolated from the Indian medicinal plant Withania somnifera (L.) Dunal, has been reported to impart anticancer activities against various cancer cell lines and preclinical cancer models by modulating the expression and activity of different oncogenic proteins. In this article, we have comprehensively discussed the biosynthesis of withaferin A as well as its antineoplastic activities and mode-of-action in in vitro and in vivo settings. We have also reviewed the effect of withaferin A on the expression of miRNAs, its combinational effect with other cytotoxic agents, withaferin A-based formulations, safety and toxicity profiles, and its clinical potential.