Cancer incidence is high for aging minority and underserved populations, yet research is limited about patient-provider communications with aging racial and ethnic minority populations. Achieving high-quality cancer care is crucial to reducing health disparities for this population. However, potential shortages in professional health personnel, the cost to treat cancer, a strained health care system, and large aging populations contribute to the problem. The purpose of this qualitative study was to understand the personal experiences of aging minorities during cancer treatment decision making when communicating with their cancer care providers. Purposive sampling methods were used to recruit 10 minority women and men born between 1946 and 1964 who had experienced communicating with providers and making cancer treatment decisions. In-depth semi-structured interviews and thematic analysis of qualitative data was conducted. Important findings were barriers related to miscommunication with providers, the need for more time with the cancer doctor, and mistrust of the medical profession. Participants perceived poor interpersonal communication with providers as causing a lack of understanding regarding their cancer treatment options, which affected their decision making regarding their treatment. Barriers to communication included long wait times at public or teaching health care systems for follow up cancer care services. The findings of this study could be useful to assist health care providers in improving communication with their cancer patients, reducing cancer health disparities, and increasing the quality of cancer care for this population.

Lung cancer is a disease with a high mortality rate for the U.S. Black population. There had been considerable research done on different population demographics, necessary to achieve the Healthy People 2020 overarching goals to eliminate health disparities, gain health equity and maintain quality health. Yet, the African-born Black (AFBB) population has been understudied for nonsmall cell lung cancer (NSCLC). This study sought to determine whether within race differences in stage at diagnosis and treatment of NSCLC exists between AFBB and American-born Blacks (AMBB) populations in the United States. The study data is secondary data collected as part of the National Cancer Institute's Surveillance Epidemiologic and End Result (SEER) Program from 2004-2011. Athough no significant difference was found between AFBB (n = 119) and AMBB (n = 238) relative to NSCLC stage at diagnosis, differences in treatments were found. The proportion of AFBB patients with early stage (I and II) NSCLC who underwent surgery differed significantly from that of AMBB (p < 0.05); AFBB patients were more likely to receive surgical therapy. The proportion of AFBB patients with stages I-IV of the disease who received radiation treatment also differed significantly from that of AMBB patients (p < 0.05); the latter were more likely to receive radiation therapy. Results from logistic regression analysis indicate that AFBB patients were more likely to receive surgical treatment while AMBB patients were more likely to receive radiation treatment. This study outcome can inform other NSCLC research to provide better insights to the cause of the treatment differences within the race from differing birth places, and efficient planning, evaluation of control programs and management of the disease.

Chemotherapy persists as one of the mainstays of breast cancer treatment, particularly for triple-negative breast cancer which currently has no targeted treatment methods. While chemotherapy is beneficial for killing the malignant tumor cells, it leads to the release of damage-associated molecular patterns into the tumor microenvironment. Damage-associated molecular patterns are a contributing factor to cancer-related inflammation which can potentiate metastatic spread through several mechanisms such as the development of tumor microenvironments at metastastic sites. These damage-associated molecular patterns include nucleic acids, nucleic acid-associated lipids and vesicles, cytokines, and proteins such as high mobility group protein B1. Polyamidoamine (PAMAM) is a biodegradable, water-soluble dendrimer polymer with the ability to possess different charges and sizes depending on its terminal branches and degree of branching (i.e. generation number), respectively. Amine-terminated PAMAM-NH2 is positively charged and can bind to circulating DNA and RNA. Since most DAMP molecules are negatively charged, I hypothesized that a polycation such as PAMAM-NH2 would be an efficient nanomaterial to remove pathogenic NA DAMPs generated by chemotherapy. Building on this dendrimer, we synthesized modified cationic PAMAM-generation 3 derivatives with an aim to balance toxicity with NA-binding affinity and capacity to encapsulate chemodrugs. Our results found that these soluble and nanoparticle PAMAM materials can bind to both cell-free DNA and RNA released as a result of treating triple-negative breast cancer cells with chemotherapy drugs such as doxorubicin and paclitaxel. These PAMAM-G3 materials are termed as nucleic acid binding polymers and nucleic-acid binding polymeric nanoparticles.My thesis dissertation explores the anti-metastatic effects of nucleic-acid binding polymeric nanoparticles delivering the chemotherapy drug paclitaxel using in-vitro and in-vivo models. Two murine metastatic breast cancer models served as the basis for assessing the effects of conventional paclitaxel delivery compared to paclitaxel delivery from within PAMAM nucleic-acid binding polymeric nanoparticles with respect to primary tumor growth, extent of lung metastasis, and the systemic inflammatory response reflected in murine serum. Compared to treatment with unencapsulated paclitaxel, delivery of paclitaxel within the PAMAM nucleic-acid binding polymeric nanoparticles resulted in significantly decreased serum cell-free DNA levels, decreased inflammatory cytokines, and a lower degree of lung metastasis in the mice. The decrease in the degree of lung metastasis in mice receiving paclitaxel within the PAMAM nanoparticles was confirmed by assessing the photon flux signal of 4T1-luciferase breast cancer cells invading the murine lungs in both in-vivo and ex-vivo imaging and by using a machine learning method to quantify the degree of metastasis in H&E- stained sections of the lungs. The ability to mitigate the phenomenon of chemotherapy-induced cancer metastasis while effectively delivering the chemotherapy to the tumor microenvironment could help improve the outcomes of patients being treated with chemotherapy. This work developed a therapeutic cationic PAMAM nanocarrier-based strategy to inhibit paclitaxel-induced metastasis by scavenging cell-free nucleic acids and mitigating cell-free nucleic acid-induced inflammation.

Indiana University-Purdue University Indianapolis (IUPUI) / Pancreatic ductal adenocarcinoma (PDAC), which comprises 85% of pancreatic cancers, is the 4th leading cause of cancer death in the United States with a 5-year survival rate of 8%. While human PDACs (hPDACs) are hypovascular, they also overexpress a number of angiogenic growth factors and receptors. Additionally, the use of anti-angiogenic agents in murine models of PDAC leads to reduced tumor volume, tumor spread, and microvessel density (MVD), and improved survival. Nonetheless, clinical trials using anti-angiogenic therapy have been overwhelmingly unsuccessful in hPDAC. On the other hand, pancreatic neuroendocrine tumors (PNETs) account for only 2% of pancreatic tumors, yet they are very vascular and classically angiogenic, respond to anti-angiogenic therapy, and confer a better prognosis than PDAC even in the metastatic setting. In an effort to compare and contrast the angiogenic transcriptomes of these two tumor types, we analyzed RNA-Sequencing (RNA-Seq) data from The Cancer Genome Atlas (TCGA) and found that a pro-angiogenic gene signature is present in 35% of PDACs and that it is mostly distinct from the angiogenic signature present in PNETs. The pro-angiogenic PDAC subgroup also exhibits a transcriptome that reflects active TGF-β signaling, less frequent SMAD4 inactivation than PDACs without the signature, and up-regulation of several pro-inflammatory genes, including members of JAK signaling pathways. Consequently, targeting the TGF-β receptor type-1 kinase with SB505124 and JAK1/2 with ruxolitinib blocks proliferative crosstalk between human pancreatic cancer cells (PCCs) and human endothelial cells (ECs). Additionally, treatment of the KRC (oncogenic Kras, homozygous deletion of Rb1) and KPC (oncogenic Kras, mutated Trp53) genetically engineered PDAC mouse models with ruxolitinib suppresses murine PDAC (mPDAC) progression only in the KRC model, which shows superior enrichment and differential expression of the human pro-angiogenic gene signature as compared to KPC tumors. These findings suggest that targeting both TGF-β and JAK signaling in the 35% of PDAC patients whose cancers exhibit an pro-angiogenic gene signature should be explored in a clinical trial.

Treatment outcomes of young patients with invasive breast cancer treated radically at Groote Schuur Hospital from 2013 to 2017: A single centre study Background: Breast cancer is the leading cause of cancer- related deaths globally, and the commonest cancer in women under 40 years. There is currently a lack of data relating to treatment outcomes of young women with breast cancer particularly in low-and middle-income countries. Aim: This study aims to evaluate the treatment outcomes of young patients (under 40 years) treated radically for invasive breast cancer in a low-and middle-income setting. Settings: Groote Schuur Hospital, Cape Town, South Africa Methods: A retrospective review of 101 women under 40 years, with invasive breast cancer treated radically, between 2013 and 2017 was conducted. Patient characteristics, tumour characteristics, disease stage, treatment, and follow-up were recorded. Primary objectives included evaluating overall and disease free survival, and analysing recurrence patterns and clinicopathological features. Results: The five-year overall and disease free survival for the entire cohort was 77% and 51%, respectively. Five-year overall survival by molecular subtype showed that Luminal A had the best survival, while triple negative breast cancer had the worst overall survival. Conclusion: Young women with breast cancer have poor survival outcomes despite early presentation. There is limited data regarding breast cancer treatment outcomes in patients under forty years.

This thesis discusses the research, experimental methods, and data gathered for the investigation of a novel method for the diagnosis of melanoma skin cancer. First, a background about human skin tissue is presented. Then, a detailed description of melanoma along with current diagnosis techniques and treatment options are presented. In the experimental methods, the electrical properties of several types of tissue were analyzed, the purpose of which was to discover if a tissue type can be distinguished by its electrical properties alone. This would allow for the diagnosis of melanoma to be done by examining the electrical properties of the suspected tumor and comparing the results to known values of healthy and cancerous skin. After analyzing the data, it was concluded that tissue types can be identified by their electrical properties and it may be possible to diagnose melanoma through this method. Finally, the possibility of using a similar technology and radiofrequency tissue ablation to treat melanoma is presented.

Die thermische Magnetresonanz (ThermalMR) integriert Radiofrequenz (RF)-induzierte Erwärmung, in vivo Temperaturkartierung mittels MR-Thermometrie, anatomische und funktionelle MR-Bildgebung (MRT) und die Option für die x-Kern-MRT in einem einzigen, vielseitig einsetzbaren RF-Applikator. Der Aufbau erlaubt eine gezielte und überwachte Temperaturmodulation und kann somit als Basis für Studien dienen, welche die Klärung grundlegender Fragen bezüglich der molekularen, biochemischen, sowie physiologischen und therapeutischen Auswirkungen der Temperatur in Organismen ermöglichen. In dieser Arbeit wurde ein kostengünstiges, automatisiertes Open-Source-3D-Mehrzweck-Messsystem mit Submillimeter-Genauigkeit implementiert und validiert, um technische Entwicklungen in der thermischen MR wie Antennendesign, Signalgeneratoren, und simulationsbasierte Methoden zu prüfen. Um den Anforderungen eines modernen ThermalMR-Systems gerecht zu werden, wird ein neuer auf einem Phasenregelkreis basierender RF-Signalgenerator für Hyperthermie entwickelt und über dessen Entwurf, Implementierung, Validierung und Anwendung berichtet. Der Signalgenerator ist in der Lage, 32 unabhängige RF-Signale mit präziser Einstellung der Parameter dieser Signale zu erzeugen. Das in dieser Arbeit entwickelte Mehrkanal-RF-Überwachungsmodul ermöglicht das Detektieren von Abweichungen bezogen auf die gewählten Einstellungen und ermöglicht eine Korrektur der RF-Signale in einem Regelkreis. Darüber hinaus ermöglicht das Überwachungsmodul das Erkennen von Bewegungen und ermöglicht zusätzliche Sicherheit in einem realen Behandlungssetup. In dieser Arbeit wurden Forschung und Entwicklung in Informatik, Physik und Biowissenschaften synergetisch miteinander verbunden. Die in dieser Arbeit entwickelte Infrastruktur bildet eine technologische Basis für zukünftige ThermalMR-Anwendungen. / Thermal magnetic resonance (ThermalMR) integrates radio frequency (RF)-induced heating, in vivo temperature mapping using MR thermometry, anatomic and functional MR imaging (MRI), and the option for x-nuclei MRI in a single, multi-purpose RF applicator. This permits supervised targeted temperature modulation, thus enables pioneering studies to clarify fundamental questions pertaining to the molecular, biochemical, broader physiological and therapeutic effects of temperature in organisms. In this work, a cost-effective, automated open source 3D multipurpose measurement system with submillimeter fidelity was implemented and validated to facilitate technical developments in ThermalMR such as RF antenna design and algorithm verification. The design, implementation, validation, and application of the first phase-locked loop based RF signal generator in hyperthermia that is capable of generating 32 channels of independent RF signals with fine-tuning resolutions of the signals’ parameters meet the demanding requirements of a state-of-the-art RF heating system. The multi-channel RF supervision module developed in this work outperforms state-of-the-art counterparts. The detection of head motion in a hyperthermia setting was demonstrated for the first time with the RF supervision module. This work synergistically connects research and development in computer science, physics, and life science. The infrastructure developed in this work forms a technological basis for future ThermalMR applications.

With a great need for new and better cancer treatments, microwaves and gold nanoparticles (GNPs) are increasingly being suggested to be used in radiotherapy. In thisreport, the authors present an investigation of how human tissue,both malignant and healthy, behaves under microwave radiation.Specifically, the focus has been on gradual transitions between healthy and GNP-treated cancerous tissue inside a waveguide.Here, the electromagnetic material property of concern is therelative permittivity. The permittivities of human tissues andGNPs have been modelled using well known analytical models.Furthermore, numerical simulations have been performed usingCOMSOL Multiphysics and the results have been compared to analytical equations suggested to describe the energy absorption in the material. The study shows that the analytical equations are in agreement with the numerical simulations for lower propagating electromagnetic (EM) modes. Some possible electromagnetic resonance has been seen within the GNP treated cancer tissue. Furthermore, the extensive analytical models and numerical software tools created will be of importance for future research of the feasibility of this cancer treatment method. / Med ett stort behov av nya, bättre cancer-behandlingar föreslås mikrovågsstrålning och guldnanopartiklar (GNPs) att användas i strålterapi. I denna rapport presenterar författarna en undersökning av hur mänsklig vävnad beter sig under mikrovågsstrålning. Specifikt har fokus varit på gradvisa övergångar mellan frisk och GNP fylld cancervävnad i en vågledare. Här är den elektromagnetiska egenskapen av intresse den relativa permittiviteten. Permittiviteterna av mänsklig vävnad och GNPs har modellerats med välkända analytiska modeller. Vidare har numeriska simuleringar utförts i COMSOL Multiphysics och resultaten av dessa har jämförts med de analytiska ekvationerna som sägs beskriva absorbtion av energi inuti materialet. Undersökningen visar att de analytiska ekvationerna stämmer överens med de numeriska simuleringarna för lägre propagerande elektromagnetiska (EM) moder. Möjlig elektromagnetisk resonans har setts inom den GNP fyllda cancervävnaden. De omfattande analytiska modellerna och numeriska mjukvaruverktygen som tagits fram kommer vara viktiga för framtida forskning på denna cancerbehandling. / Kandidatexjobb i elektroteknik 2022, KTH, Stockholm

Cancer is a disease characterized by complexity and unpredictability. Consequently, its treatment is difficult and all too often unsuccessful. Almost all cancers are treated with some combination of the traditional anti-cancer armamentarium: surgery, chemotherapy, and radiotherapy. Recently, however, gene therapy has emerged as a promising addition to this existing repertoire. Its application as a single agent, or in combination with other anti-cancer treatments is proving successful in both pre-clinical and clinical settings. In this work I have investigated the combination of a conventional chemotherapy drug, cisplatin, with a type of cancer gene therapy known as cytosine deaminase + 5-fluorocytosine suicide gene therapy. Suicide gene therapy is the intracellular conversion of non-toxic prodrug to its active form by a metabolic enzyme of non-mammalian origin. There are many established enzyme/prodrug combinations, but here the bacterial enzyme cytosine dearninase (CDA) was used to convert inert 5-fluorocytosine (5FC) to highly toxic 5-fluorouracil (5FU). Of the various vector systems for therapeutic gene delivery, adenoviral (Ad) vectors have proven particularly suitable for application to cancer. This work used a first generation adenovirus type 5 vector expressing the enzyme cytosine deaminase (AdCDA) cloned from E. coli. The combination of AdCDA/5FC with cisplatin was chosen because the combination of 5FU and cisplatin, both of which are used extensively in cancer treatment, has proven effective clinically and demonstrates synergy in vitro. This combination was evaluated in murine mammary carcinoma MTIA2 cells, human colorectal carcinoma HT29 cells, HT29pl4 cells, the photofrin resistant sub-line of HT29 cells, and murine melanoma Bl6/FIO cells. The classical clonogenic assay was used to evaluate this combination treatment since it provides an accurate indication of the effectiveness a cancer treatment will have in vivo. AdCDA infected MTIA2, HT29, and HT29pl4 cell lines exhibited a dose response to increasing concentrations of SFC that was significantly different from control vector infected cells. Similarly, uninfected cells demonstrated a dose response to increasing concentrations of cisplatin. The effect of the combination on clonogenic survival, administered in the sequence of a 48 h exposure to SFC followed by 1 h exposure to cisplatin, was greater than additive compared to the effect of the two treatments alone. F10 cells exhibited a dose response to increasing concentrations of cisplatin. However, it could not be shown reproducibly that AdCDA infected FlO cells exhibited a dose response to SFC that differed significantly from control vector infected cells. Work with the FlO cells was inconclusive regarding the combination treatment, but it rendered information regarding the sensitivity of these cells to what is hypothesized to be an unidentified component present in some preparations of 5FC. Evaluation of this treatment in vivo, using both murine and human tumor cell lines, will further define the potential of AdCDA/5FC + cisplatin as a clinically relevant cancer treatment. / Thesis / Master of Science (MSc)

Bröstcancer är den vanligaste cancerformen som drabbar kvinnor och allt fler överlever sin bröstcancerbehandling tack vare välutvecklade behandlingsstrategier som kirurgi, strål- och läkemedelsbehandling. Kvinnorna går från att vara i beroendeställning till sjukvården till att åter bli självständiga efter en omtumlande period av behandling. Dessa omställningar kan medföra nya erfarenheter för kvinnorna som i sin tur kan komma att påverka deras livsvärld och den vardag de sedan återgår till. Sjuksköterskan har i denna process ett lika stort ansvar att främja hälsa och lindra lidande såväl under som efter behandlingsperioden. För att kunna göra detta behöver sjuksköterskan se kvinnorna och dess livsvärld som levda kroppar. Detta för att förstå vilka långsiktiga utmaningar kvinnorna kan komma att möta efter att ha avslutat sin behandlingsresa och för att fortsätta kunna stödja de till en långsiktig och hållbar hälsa. Därav är syftet för denna allmänna litteraturöversikt att belysa kvinnors upplevelse av livsvärlden efter avslutad bröstcancerbehandling. För att kunna besvara syftet har 10 artiklar med kvalitativ ansats valts ut efter kvalitetsgranskning och analys. Sökningar har gjorts i databaserna CINAHL och PubMed. Resultatet presenteras under tre huvudteman: “Upplevelser av den levda kroppen”, “Emotionella och sociala aspekter” och “Personlig utveckling”. Majoriteten av kvinnorna upplevde en förändring av den fysiska kroppen och de flesta uttryckte att den största utmaningen var den emotionella påfrestningen och att fortsätta livet efteråt. Det beskrivs av många kvinnor att det finns en oro kring framtiden. Däremot beskriver många kvinnor att de känt en personlig utveckling och en stor tacksamhet till att få möjligheten att fortsätta leva. / Breast cancer is the most common form of cancer that affects women, and more and more are surviving their breast cancer treatment thanks to well-developed treatment strategies such as surgery, radiation and drug therapy. The women transition from a position of dependency on healthcare to regaining independence after a shattering period of treatment. These changes can lead to new experiences for the women, which in turn can affect their world of life and the everyday life they then return to. In this process, the nurse has an equal responsibility to promote health and alleviate suffering both during and after the treatment period. To be able to do this, the nurse needs to see the women and their life world as living bodies. This is to understand what long-term challenges the women may face after completing their treatment journey and to continue to be able to support them to long-term and sustainable health. Hence, the purpose of this general literature review is to shed light on women's experience of the life world after completion of breast cancer treatment. In order to answer the purpose, 10 articles with a qualitative approach have been selected after quality review and analysis. Searches have been made in the databases CINAHL and PubMed. The results are presented under three main themes: "Experiences of the lived body", "Emotional and social aspects" and "Personal development". The majority of women experienced a change in the physical body and most expressed that the biggest challenge was the emotional strain and moving on with life afterwards. It is described by many women that there is a concern about the future. On the other hand, many women describe that they felt a personal development and great gratitude for having the opportunity to continue living.