This  research  emphasizes  the role  of  social  media  in  customer  acquisition  retention.Furthermore, it investigates insights that have the potential to benefit tech startups inshaping  their  strategies  and  effectively  allocating  resources  to  achieve  consistentcommunication with their customer base. The field of research is particularly relevant dueto the research gap present in the literature that does not investigate how technologystartups should approach the initial acquisition and retention of the user base, consideringthe limited resources available to these newborn organizations. The research providesinsights into customers' perceptions of brands and companies on social media platforms.It offers intuitions on how to enhance customer trust through these platforms and whichare the preferred way of interaction between customers and companies both on and offsocial media.The study was performed using qualitative and quantitative primary data with the purposeof gaining a deep understanding of the research topic. However, the focus has been puton the quantitative data aiming to create objective and generalizable  results, seekingunbiased findings.The  results  of  the research  showed  how important it  is  to  have  an  effective CRM(Customer Relationship  Management) system as well as  being able to identify  theaudience, understanding, therefore, the communication method that best fit the chosentarget, with the aim of interacting with them in the expected and preferred way, beingthus one step closer on achieving customer retention and acquisition.

The purpose of this study was to determine if there was a relationship between level of funding and achievement of school systems in Tennessee based on the standards of the No Child Left Behind Act (NCLB) of 2001. This study focused on Tennessee school systems and their adequate yearly progress (AYP) status of "targeted" or "good standing" from 2007 through 2009. Federal, state, and local funding, as well as per-pupil expenditure, average teacher salary, and number of students, were used as variables. All data were gathered from the Tennessee Department of Education website. The researcher performed 6 independent samples t-tests and one chi square analysis. The study showed significant differences in the means of federal, state, and local funding levels between targeted systems and systems in good standing. Targeted systems received more federal, state, and local funding than systems in good standing from 2007 through 2009. The study showed no significant difference in mean per-pupil expenditures between targeted systems and systems in good standing. The study showed a significant difference in the mean teacher salaries. Targeted systems had higher teacher salaries than systems in good standing from 2007 through 2009. The study also showed a significant difference in the mean number of students between targeted systems and systems in good standing. Targeted systems had more students than systems in good standing. The findings indicate that targeted systems are receiving as much funding as systems in good standing. To help control for the number of students in each system, the two groups (targeted and in good standing) were compared using per-pupil federal, state and local dollars. The analysis indicated no significant difference between targeted systems and systems in good standing for federal money. The analysis did indicate a significant difference between the two groups for state and local money. However, for state money systems in good standing had the higher mean and for local money, targeted systems had the higher mean. Mean per-pupil expenditures were relatively equal between targeted systems and systems in good standing. System size, based on the number of students, showed a significant relationship with the NCLB status of a system. The mean number of students in targeted systems was more than 3 times as large as systems in good standing (17,656 to 5,284). Also, a group of systems with over 4,445 students had over 5 times the number of targeted systems than a group of systems with fewer than 2,094 students.

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Medulloblastoma (MB) is a malignant embryonal tumor of the posterior fossa belonging to the family of primitive neuro-ectodermic tumors (PNET). MB generally occurs in pediatric age, but in 14–30% of cases, it affects the adults, mostly below the age of 40, with an incidence of 0.6 per million per year, representing about 0.4–1% of tumors of the nervous system in adults. Unlike pediatric MB, robust prospective trials are scarce for the post-puberal population, due to the low incidence of MB in adolescent and young adults. Thus, current MB treatments for older patients are largely extrapolated from the pediatric experience, but the transferability and applicability of these paradigms to adults remain an open question. Adult MB is distinct from MB in children from a molecular and clinical perspective. Here, we review the management of adult MB, reporting the recent published literature focusing on the effectiveness of upfront chemotherapy, the development of targeted therapies, and the potential role of a reduced dose of radiotherapy in treating this disease.

This thesis project serves to fill experimental gaps needed to advance the goal of performing pre-clinical trials using an orthotopic rat glioblastoma model to evaluate the efficacy of high-frequency electroporation (H-FIRE) and QUAD-CTX tumor receptor-targeted cytotoxic conjugate therapies, individually and in combination, in selectively and thoroughly treating glioblastoma multiforme. In order to achieve this, an appropriate model must be developed and characterized. I have transduced F98 rat glioma cells to express red-shifted firefly luciferase, which will facilitate longitudinal tumor monitoring in vivo through bioluminescent imaging. I have characterized their response to H-FIRE relative to DI TNC1 rat astrocytes. I have demonstrated the presence of the molecular targets of QUAD in F98 cells. The in vitro characterization of this model has enabled preclinical studies of this promising glioblastoma therapy in an immunocompetent rat model, an important step before advancing ultimately to clinical human trials. / Master of Science / Treating glioblastoma multiforme (GBM), a form of cancer found in the brain, has not been very successful; patients rarely live two years following diagnosis, and there have been no major breakthrough advances in treatment to improve this outlook for decades. We have been working on two treatments which we hope to combine. The first is high-frequency electroporation (H-FIRE), which uses electrical pulses to kill GBM cells while leaving healthy cells alive and blood vessels intact. The second is QUAD-CTX, which combines a toxin with two types of protein that attach to other proteins that are more common on the surface of GBM cells than healthy cells. We have shown these to be effective at disproportionately killing human GBM cells growing in a lab setting. Before H-FIRE and QUAD-CTX may be tested on humans, we need to show them to be effective in an animal model, specifically rats. I have chosen rat glioma cells that will behave similarly to human GBM and a rat species that will not have an immune response to them. I have made these cells bioluminescent so that we may monitor the tumors as they grow and respond to our treatments. I have also shown that QUAD-CTX kills these rat glioma cells, as does H-FIRE. Because of this work, we are ready to begin testing these two treatments in rats.

The goal of cancer chemotherapy is to develop effective, safe, and well-tolerated medications. The over-expression of certain receptors on cancer cell membrane provides a basis for active targeting by not only specific interaction between drug delivery system and cells, but also facilitated cellular uptake via receptor-mediated endocytosis. In this study, LDV oligomers up to six LDV repeating units were synthesized via solid phase peptide synthesis method, and evaluated as drug carrier as well as targeting moiety to deliver doxorubicin (Dox) to human malignant melanoma cells (A375), which over-express integrin α 4 β 1 . Cells expressing different levels of integrin α 4 β 1 or modulated using integrin α 4 -specific siRNA knock-down technique were verified by western blot and PCR. Magnetic beads with tripeptides LDV, VDL, or LNV on the surface were used in the binding specificity studies. Results verified that LDV was the minimally required ligand sequence for the specific binding to integrin α 4 β 1 , of which the interaction depends on the amount of integrin and can be utilized for the design of targeted drug delivery. The studies on A375 cells uptake of FITC-labeled LDV oligomers examined the effects of EDTA, temperature, endocytosis inhibitor, and competitive ligand. Cellular uptake mechanism was revealed to be temperature-dependent, receptor-mediated endocytosis, involving the specific interaction between LDV and integrin α 4 β 1 . The internalization extent of LDV monomer was the highest and was also inhibited to the most by the addition of free LDV when compared to other LDV oligomers. Cytotoxicity profiles of Dox-conjugated LDV oligomers were obtained on wild-type A375, integrin α4 knock-down A375, and normal human epithelial keratinocytes (NHEK) using SRB assay. A significant decrease (3∼6 folds) in the cytotoxicity of oligo(LDV)-Dox on A375 cells were observed when the integrin α4 expression was knocked down by ∼50%. Cytotoxicity further decreased on NHEK, which has the lowest integrin α4 expression among three cell lines. In contrast to oligo(LDV)-Dox, free Dox was not able to differentiate between cancerous and normal cells. This result demonstrated the potential of oligo(LDV) as targeting ligand. However, increase of repeating LDV unit did not lead to any apparent trend in cytotoxicity capacity. To facilitate the intracellular Dox release, hydrazone bond (HYD) was introduced between LDV and Dox. In vitro Dox release profiles in pH 6.0, 7.4, and rat plasma proved the pH-sensitivity of LDV-HYD-Dox. Cytotoxicity studies showed an increased cytotoxic effect of LDV-HYD-Dox when compared with LDV-Dox on wild-type A375 (2.5 times), knock-down A375 (1.5 times); while no significant difference in cytotoxicity on NHEK was observed. In vivo animal study supported the in vitro findings on LDV-HYD-Dox, which showed a significant inhibition of tumor growth and longest mice life span when compared to free Dox, poly(L,D,V)-Dox, and LDV-Dox, with averagely only ¼ of the tumor size and almost twice the life span of that from the free Dox group. In conclusion, based on the concept of specific interaction between LDV and integrin α 4 β 1 , oligo(LDV)-Dox targeted drug delivery system was developed and proved to be effective in the delivery of Dox to melanoma cells.

In breast cancer, the genetic profiling of circulating cell-free DNA (cfDNA) from blood plasma was shown to have good potential for clinical use. In contrast, only a few studies were performed investigating urinary cfDNA. In this pilot study, we analyzed plasma-derived and matching urinary cfDNA samples obtained from 15 presurgical triple-negative breast cancer patients. We used a targeted next-generation sequencing approach to identify and compare genetic alterations in both body fluids. The cfDNA concentration was higher in urine compared to plasma, but there was no significant correlation between matched samples. Bioinformatical analysis revealed a total of 3339 somatic breast-cancer-related variants (VAF ≥ 3%), whereof 1222 vs. 2117 variants were found in plasma-derived vs. urinary cfDNA, respectively. Further, 431 shared variants were found in both body fluids. Throughout the cohort, the recovery rate of plasma-derived mutations in matching urinary cfDNA was 47% and even 63% for pathogenic variants only. The most frequently occurring pathogenic and likely pathogenic mutated genes were NF1, CHEK2, KMT2C and PTEN in both body fluids. Notably, a pathogenic CHEK2 (T519M) variant was found in all 30 samples. Taken together, our results indicated that body fluids appear to be valuable sources bearing complementary information regarding the genetic tumor profile.

New diagnostic methods and novel therapeutic agents spawn additional and heterogeneous information, leading to an increasingly complex decision-making process for optimal treatment of cancer. A great amount of information is collected in organ-specific multidisciplinary tumor boards (MDTBs). By considering the patient’s tumor properties, molecular pathological test results, and comorbidities, the MDTB has to consent an evidence-based treatment decision. Immunotherapies are increasingly important in today’s cancer treatment, resulting in detailed information that influences the decision-making process. Clinical decision support systems can facilitate a better understanding via processing of multiple datasets of oncological cases and molecular genetic information, potentially fostering transparency and comprehensibility of available information, eventually leading to an optimum treatment decision for the individual patient. We constructed a digital patient model based on Bayesian networks to combine the relevant patient-specific and molecular data with depended probabilities derived from pertinent studies and clinical guidelines to calculate treatment decisions in head and neck squamous cell carcinoma (HNSCC). In a validation analysis, the model can provide guidance within the growing subject of immunotherapy in HNSCC and, based on its ability to calculate reliable probabilities, facilitates estimation of suitable therapy options. We compared actual treatment decisions of 25 patients with the calculated recommendations of our model and found significant concordance (Cohen’s κ = 0.505, p = 0.009) and 84% accuracy.

γδ T cells are unique players in shaping immune responses, lying at the intersection between innate and adaptive immunity. Unlike conventional αβ T cells, γδ T cells largely populate non-lymphoid peripheral tissues, demonstrating tissue specificity, and they respond to ligands in an MHC-independent manner. γδ T cells display rapid activation and effector functions, with a capacity for cytotoxic anti-tumour responses and production of inflammatory cytokines such as IFN-γ or IL-17. Their rapid cytotoxic nature makes them attractive cells for use in anti-cancer immunotherapies. However, upon transformation, γδ T cells can give rise to highly aggressive lymphomas. These rare malignancies often display poor patient survival, and no curative therapies exist. In this review, we discuss the diverse roles of γδ T cells in immune surveillance and response, with a particular focus on cancer immunity. We summarise the intriguing dichotomy between pro- and anti-tumour functions of γδ T cells in solid and haematological cancers, highlighting the key subsets involved. Finally, we discuss potential drivers of γδ T-cell transformation, summarising the main γδ T-cell lymphoma/leukaemia entities, their clinical features, recent advances in mapping their molecular and genomic landscapes, current treatment strategies and potential future targeting options.

Castration-resistant prostate cancer (CRPC) remains an aggressive incurable disease in men mainly due to treatment resistance. Current treatments do not effectively eradicate cancer stem cells (CSCs), which play a pivotal role in tumour maintenance, progression and drug resistance. Aldehyde dehydrogenases (ALDHs) have been used in some tumour types as CSC markers. Their high expression and high functional activity found in CSCs is also associated with drug resistance. Emerging evidence suggests deregulation of certain ALDH isoforms have implications in cancer. The role of ALDHs in prostate cancer as potential biomarkers and therapeutic targets has not been fully explored yet. Accordingly, this study investigated the expression, regulation and function of selected ALDH isoforms in prostate cancer. This study showed that ALDH1A3, ALDH1B1, ALDH2 and ALDH7A1 are highly expressed in primary prostate cancer cells (n=9) compared to benign (n=9) prostate cells. The expression of ALDH1A3 was high in the stem cells (SCs) (n=3) as well as the more differentiated counterparts (n=16). Treatment of both benign and malignant primary prostate cancer cells with all-trans retinoic acid (atRA) also resulted in increased expression of ALDH1A3 and ALDH3A1, supporting a feedback loop between atRA and ALDHs. Furthermore, SerBob, Bob and LNCaP cells were sensitive to treatment with epigenetic drugs and led to significantly higher expression of ALDH1A2, ALDH3A1 and ALDH7A1 respectively. Importantly, siRNA suppression of ALDH1A3 and ALDH7A1 led to reduced SC properties of primary prostate cultures including reduced cell viability, migration and colony formation, and increased differentiation of transit amplifying (TA) cells to committed basal (CB) cells. Novel ALDH-affinic probes showed reduced cell viability of primary prostate epithelial cultures as a single agent and also when used in combination with docetaxel. The results indicate the potential of using ALDH-affinic compounds as single agents for therapeutic intervention or in combination with docetaxel to sensitise resistant cells to this anticancer drug. The data in this thesis provides novel findings, which supports ALDH1A2, -1A3 and -7A1 as potential biomarkers and/or therapeutic targets for drug intervention. Although, a study analysing a larger number of samples is necessary to fully understand ALDH isoform expression in CSC, TA and CB cells it is envisaged that an ALDH-targeted therapy have potential in future treatment strategies for prostate cancer. / Prostate Cancer UK