Background: Colorectal cancer is the third most common cancer and cause of related deaths worldwide. Early colorectal cancer diagnosis is vital in reducing incidence and mortality. There is a need for the development of non-invasive screening tools for enhancing the detection of the disease. Cancer specific peptides are useful cancer targeting agents that can be used to specifically improve early detection strategies. Several cancer targeting peptides have been identified. Previous work investigated the specific binding of three of these peptides (p.C, p.L and p.14) conjugated to quantum dots and were found to bind to colorectal cancer cell lines (HT-29 and Caco-2). However, their uptake, localization and biodistribution in an in vitro and in vivo colorectal cancer model have not been determined. This is essential in gaining an understanding for future diagnostic or therapeutic based applications. Primary Aim: The aim of this study was investigate the localization of three selected peptides p.C, p.L and p.14 conjugated to gold nanoparticles in an in vitro and in vivo colorectal cancer model using HRTEM. Methodology: The AuNP/peptide conjugates were characterized by HRTEM and DLS. For in vitro studies; HT-29, Caco-2 and C3A cells were exposed to the AuNP-p.C, AuNP-p.L and AuNP-p.14, collected and processed for HRTEM to assess targeting and localization. For in vivo studies; the establishment of a colorectal cancer model using the AOM/DSS model 1 and 2 was conducted. Wistar rats were assigned to 6 groups, five experimental and 1 control group. Group 1 received AOM/DSS method 1 and was treated with AuNP-p.L. Group 2 and 3 received AOM/DSS method 2 and were treated with AuNP-p.C and AuNP-p.14. Group 4 and 5 remained healthy and treated with AuNP-p.C and AuNP-p.14. Group 6 remained healthy receiving no nanoparticle treatment. After treatment, rats were sacrificed and tissue was processed for HRTEM. Tissue chosen for HRTEM analysis included: Group 1 (inflamed colon, rectum, pancreatic and kidney), Group 4 (kidney) and Group 5 (liver). Results: results obtained from nanoparticle characterization suggested that nanoparticles were conjugated to their respective peptides and were stable in dispersion. For in vitro studies, results suggested no AuNP targeting and localization in HT-29 cell lines. For in vivo studies, no colorectal cancer tumours were induced. TEM micrographs did not indicate the presence of nanoparticles in colon, rectum, pancreatic, kidney and liver tissue. However, AuNPs were found in the kidney tissue (group 4). Conclusion: Although the overall objectives were not met, this study provided insight into TEM cell preparation and optimization for future nanoparticle cell interaction research. This study also demonstrated the absence of AuNPs in healthy tissue and the presence of AuNPs in healthy kidney tissue through renal clearance, a favourable quality for diagnostic or therapeutic applications.

Submitted in fulfillment of the requirements of the Degree in Chemistry, Durban University of Technology, 2017. / High prevalence and mortality cases of prostate cancer (PCa) have increased around the world, particularly in developing countries. Several forthcoming factors have been revealed nowadays, one of them is due to the incapability of the diagnostic methods to produce reliable results, which impacts negatively on cancer-treatment. However, a sensitive diagnosis of PCa cells remains a challenge in the field of biosensors. Emerging whole-cell detection as biosensing targets has opened up avenues for successful cancer diagnostics, due to high selectivity among other cells. A switchable and flexible surface-based graphene material is one of the techniques that revolutionized smart biodevice platforms in biosensor technology. In this present study, a covalently linked poly-(N-isopropylacrylamide) (PNIPAM) to graphene oxide surface has been employed as “on/off”-switchable aptamer-based sensor for the detection of PC3 whole-cancer cell. The constructed surface has benefitted from PNIPAM, as the thermal-stimulus agent, which allows the coil-to-globule transitions by triggering temperature changes. When the system is above its lower critical solution temperature (LCST) of 32oC, PNIPAM will exist as hydrophobic -globular state providing an “on” binding region for the whole-cell, reaching the interactions on the biosurface. The “off” binding systems is only possibly when the PNIPAM turns into extended-state by lowering its temperature below LCST. The first principle studies have successfully characterized the electronic behavior with particular emphasis of PNIPAM monomer functions along with the description of the structural energetics of complex through density functional theory (DFT). Docking studies have further been performed to predict a plausible binding aptamer toward the protein-representative PCa cell. To better understand the prospect of an aptamer-based tunable biosensor, molecular dynamics (MD) highlighted the behavior of PNIPAM-grafted GO in exhibiting a globular and extended conformations at above and below LCST, permitting the biomolecules to interact with each other as well as to avoid interactions, respectively. Experimental studies have been included to validate the theoretical predictions by fabricating real-biosensor systems using electrochemical impedance technique, resulting a low-detection limit down to 14 cells/mL. Engagement between theoretical and experimental studies delivered an enhanced tunable-biosensor performance for the detection of whole cell prostate cancer. / M

Introdução: O câncer é uma doença que acomete grande parte da população mundial, sendo o segundo maior responsável pelas mortes no Brasil. A maior parte do cânceres é passível de prevenção e outra grande parte tem altos índices de cura se diagnosticados precocemente. Por isso, o papel dos profissionais de saúde é de fundamental importância para programas eficazes de rastreamento e prevenção do câncer. Objetivos: Avaliar o conhecimento e as práticas de médicos que trabalham em equipes da APS (Estratégia Saúde da Família e Unidades Básicas de Saúde Tradicionais) relacionadas à prevenção do câncer. Material e métodos: Foram realizadas entrevistas com os profissionais da atenção primária: Médicos de Família e Comunidade, Clínicos Gerais e Ginecologistas e Obstetras, vinculados a Unidades de Saúde da Família e Unidades Básicas de Saúde do município de Ribeirão Preto. Os As entrevistas foram realizadas utilizando-se um questionário semi-estruturado, subdividido em 5 partes: dados profissionais, rastreamento do câncer de mama e colo de útero, rastreamento do câncer de cólon e reto, rastreamento do câncer de pulmão e rastreamento de outros tipos de câncer. Resultados: Apesar de afirmarem conhecer as diretrizes de rastreamento de câncer dos principais órgãos nacionais de combate à doença, a análise das práticas referidas pelos entrevistados estava muito aquém daquilo preconizado por essas instituições. Conclusões: Há que se investir em estratégias de conscientização dos profissionais de saúde como um todo (e não apenas os médicos) para o correto aconselhamento de medidas de promoção de saúde relacionada ao câncer, bem como dos exames de rastreamento para o diagnóstico precoce dessas doenças. / Introduction: Cancer is a disease that affects a big part of the world\'s population, and is the second most prevalent cause of death in Brazil. The majority of cancers are preventable and another large part has high rates of cure if diagnosed in early stages. Therefore, the role of health professionals is fundamental for effective cancer prevention and screening programs. Objectives: Evaluate the practices and knowledge of physicians that work in primary health centers (Family Health Strategy Centers and traditional Health Posts) related to cancer prevention. Methodology: Interviews were made with the primary care professionals: family health practitioners, general practitioners and gynecologists and obstetricians, who work at primary health centers in Ribeirão Preto´s local health system. The Interviews were made using a semi-structured questionnaire, divided into 5 parts: professional data, cervical and breast cancer screening, colon and rectal cancer screening, lung cancer screening and screening of other types of cancer. Results: In spite of respondents declare to know the main cancer screening guidelines from the major national institutions for fighting the disease, the analysis of the referred practices of the interviewed participants were too far from what is recommend by those institutions. Conclusion: There is a need to invest in awareness strategies as a whole (and not just the the physicians) for the correct health promotion counseling related to cancer, as well as in the screening tests for early diagnosis of these diseases.

Introdução: O câncer é uma doença que acomete grande parte da população mundial, sendo o segundo maior responsável pelas mortes no Brasil. A maior parte do cânceres é passível de prevenção e outra grande parte tem altos índices de cura se diagnosticados precocemente. Por isso, o papel dos profissionais de saúde é de fundamental importância para programas eficazes de rastreamento e prevenção do câncer. Objetivos: Avaliar o conhecimento e as práticas de médicos que trabalham em equipes da APS (Estratégia Saúde da Família e Unidades Básicas de Saúde Tradicionais) relacionadas à prevenção do câncer. Material e métodos: Foram realizadas entrevistas com os profissionais da atenção primária: Médicos de Família e Comunidade, Clínicos Gerais e Ginecologistas e Obstetras, vinculados a Unidades de Saúde da Família e Unidades Básicas de Saúde do município de Ribeirão Preto. Os As entrevistas foram realizadas utilizando-se um questionário semi-estruturado, subdividido em 5 partes: dados profissionais, rastreamento do câncer de mama e colo de útero, rastreamento do câncer de cólon e reto, rastreamento do câncer de pulmão e rastreamento de outros tipos de câncer. Resultados: Apesar de afirmarem conhecer as diretrizes de rastreamento de câncer dos principais órgãos nacionais de combate à doença, a análise das práticas referidas pelos entrevistados estava muito aquém daquilo preconizado por essas instituições. Conclusões: Há que se investir em estratégias de conscientização dos profissionais de saúde como um todo (e não apenas os médicos) para o correto aconselhamento de medidas de promoção de saúde relacionada ao câncer, bem como dos exames de rastreamento para o diagnóstico precoce dessas doenças. / Introduction: Cancer is a disease that affects a big part of the world\'s population, and is the second most prevalent cause of death in Brazil. The majority of cancers are preventable and another large part has high rates of cure if diagnosed in early stages. Therefore, the role of health professionals is fundamental for effective cancer prevention and screening programs. Objectives: Evaluate the practices and knowledge of physicians that work in primary health centers (Family Health Strategy Centers and traditional Health Posts) related to cancer prevention. Methodology: Interviews were made with the primary care professionals: family health practitioners, general practitioners and gynecologists and obstetricians, who work at primary health centers in Ribeirão Preto´s local health system. The Interviews were made using a semi-structured questionnaire, divided into 5 parts: professional data, cervical and breast cancer screening, colon and rectal cancer screening, lung cancer screening and screening of other types of cancer. Results: In spite of respondents declare to know the main cancer screening guidelines from the major national institutions for fighting the disease, the analysis of the referred practices of the interviewed participants were too far from what is recommend by those institutions. Conclusion: There is a need to invest in awareness strategies as a whole (and not just the the physicians) for the correct health promotion counseling related to cancer, as well as in the screening tests for early diagnosis of these diseases.

Cutaneous malignancies represent a quarter of all new cancer diagnoses in the UK. The key to reducing the tumours’ associated mortality and morbidity is early diagnosis and treatment. Prompt diagnosis remains predominately a clinical skill, but relatively little investigation of the cognitive psychology underpinning expertise in this domain has been undertaken. This thesis aims to improve understanding of these processes and investigate how lesional diagnostic expertise might be enhanced. A large database of diagnostically tagged images was captured specifically for this project. A series of separate studies were undertaken to give insight into how lesional diagnosis occurs and how it can be improved. The studies highlighted that non-analytical pattern recognition (NAPR) is likely to predominate in distinguishing malignant and non-malignant skin lesions and that the widely-promoted rules advocating analytical pattern recognition (APR) are not effective for discriminating melanoma from benign pigmented lesions. The keystone to promoting the development of NAPR and thus diagnostic expertise would seem to be increasing a novice’s personal library of examples with relevant feedback. Studies demonstrated that current undergraduate exposure was variable but universally sparse, so simulation by way of diagnostically tagged images was developed which showed accuracy could be improved by increased exposure. This improvement occurred in both a content specific and dose responsive manner. These studies also highlighted that the learning curves for skin lesions are not uniform. Further studies demonstrated that the choice of images had implications on the development of diagnostic expertise; suggesting it was important that these images represent clinical practice rather than “classic” examples traditionally advocated for teaching purposes. In addition, studies highlighted the potential benefit of the 3D models developed during this project. Building on the idea that a personal catalogue of relevant referent images was crucial to enhanced diagnostic accuracy, prototype software was developed to exteriorise the experts’ library of examples; in the tests described novices utilising the software delivered superior accuracy than medical students on the completion of their undergraduate teaching. In summation, the work described shows that by utilising dermato-informatic approaches lesional diagnostic competence can be improved significantly.

Purpose: In the contemporary management of early-stage lung cancer with RadiationTherapy (RT), there is increased imaging utilization for the diagnosis and treatment and follow-up after completion of treatment. We evaluated whether this increased radiation exposure to patients with early-stage lung cancer that receive stereotactic body radiotherapy (SBRT) significantly increases the risk of radiation-induced carcinogenesis (RIC). Methods: Following IRB approval, one hundred and ninety-six consecutively treated lung cancer patients treated with SBRT were selected for analysis. Information collected included demographics and all ionizing imaging scans one year before SBRT treatment and one year following treatment. These included chest X-rays (CXR), computerized tomography scan (CT scan), positron emission tomography scan (PET-CT scan), bone scan, ventilation-perfusion scan (VQ scan), cone-beam CT scans. In addition to the lung cancer patients, comparative data on ten prostate and breast cancer patients each was collected to get an estimate of the radiation-induced risk (RIC) in other common malignancies. For each patient, the total effective dose (mSv) was calculated by the sum of all effective doses for all scans (1 year before SBRT to 1-year post-SBRT). After calculating the total effective dose, the summed dose was used to calculate the RIC using the RadRat tool. For the study, we decided that a 1% increase in the baseline risk of radiation-induced lung cancer will be considered a significant increase. Results: Among lung cancer patients, there were 87 males (44.4%) and 109 females (55.6%). The median number of Pre-SBRT CXRs (PA/lateral) was 2 (Range: 1-22), the median number of pre-SBRT CT scans was 2 (Range: 1-6), the median number of pre-SBRT PET-CT scans was 1 (Range: 1-4), the median number of Bone Scans or VQ scans pre-SBRT was 1. The median effective exposure dose from all scans was 72mSv (Range: 24-140.36mSv). The median excess lifetime risk (ELR) of developing lung cancer (a chance in 100,000) with a 90% uncertainty range was 57.15. The Excess Future risk (EFR), the risk from 2019 to the end of the expected lifetime of developing cancer (a chance in 100,000), showed a median of EFR mean of 73.75 (Range: 8.45- 416). The total future risk (TFR, a sum of baseline and excess risk) of developing cancer, from 2019 to end of an expected lifetime was 2732.5 (Range: 808-8290), the median of TFR upper bound was 2785.5 (Range: 856-8400) and median of TFR lower bound was 2679.5 (Range: 761- 8183). At 6 months, survival was 94.7% (144/152), at 1 year, 79% (94/119), at 3 years 32.5% (27/83). At five years, with survival data on 77 patients available, 9 (11.6%) were alive. Regarding the comparison of RIC from imaging before RT for patients with prostate cancer, the median total effective radiation dose from all pre-SBRT and post-SBRT scans was 20mSv (Range: 20-30mSv), and the median of mean ELR for development of RIC prostate cancer was 4.24 (per 100,000). Regarding early-stage breast cancer, the median total effective radiation dose from all pre-RT and post-RT scans was 16.56mSv (Range: 10.52-31.48mSv), and the median of mean ELR for development of RIC was 35.95 (per 100,000). Conclusion: The median excess cancer lifetime radiation-induced cancer risk for the lung cancer cohort was 0.05%, which is significantly less than the 1% risk that was determined to be clinically significant as per our study objective. The survival in this cohort of patients was poor. Enhanced imaging to enhance staging accuracy, safety during SBRT treatment, and adequate follow-up outweigh the RIC risk.

The current issue of Visceral Medicine focuses on colorectal cancer. Despite intense screening efforts, colorectal cancer still belongs to the most frequent cancers in both males and females in the EU. Particularly in rectal cancer there have been major developments in the surgical techniques over the last years that have led to a substantial reduction in local disease recurrence.

This dissertation examines sociodemographic determinants and preventive health behaviors among women 40-64 years of age who participated in the Virginia Department of Health’s Every Woman’s Life breast cancer screening program. Utilizing secondary data, this research sought to explore patterns of breast cancer incidence, mammography screening utilization and sources of health information among low-income women. The Virginia Department of Health provided a large sample size (N=34,942) on which to perform binary logistic regression analyses. Sociodemographic determinants and preventive health behaviors were analyzed as potential influencing factors in the diagnosis of breast cancer, the stage at the time of diagnosis and source of health information. Additionally, frequencies across all variables were explored and compared to state and national statistics, where appropriate. In this study, cancer and preventive health disparities reported in the literature persist within this sample of low income women. The binary regression analyses demonstrated that there are marginally worse outcomes for each level of decreasing income. Those with the most “wealth” were less likely to be diagnosed with invasive breast cancer and were more likely to obtain health information from a health provider. Additionally, it was determined that those without a prior mammogram were more likely to be diagnosed with breast cancer and the cancer was more likely to be invasive. The aims of the Every Woman’s Life program align with Affordable Care Act (2010) to strengthen health care and eliminate cancer disparities. Highlighting program characteristics and presenting these analyses allows policymakers, program officials and practitioners an opportunity to tailor health promotion activities while considering all tiers of influence.

Indiana University-Purdue University Indianapolis (IUPUI) / In this study we compared the distribution of HPV types in cervical cancer specimens from women living in either Indiana or Botswana. Paraffin-embedded blocks of formalin-fixed cervical cancer specimens were identified from women living in Indiana (n=51) or Botswana (n=171)

Indiana University-Purdue University Indianapolis (IUPUI) / Human papillomavirus (HPV) infection results in serious health issues including cervical, anal, vulvar, penile and oropharyngeal cancers. There are three vaccines against HPV but vaccination rates in the United States remain low. One barrier to uptake is a concern that individuals who are vaccinated may increase their risky sexual behaviors or decrease their use of cervical cancer screenings, an adjustment in perceived level of risk for HPV that can be studied using risk compensation theory. Methods Three distinct studies examined risk compensation after HPV vaccination. A systematic review examined literature from January 1, 2008-June 30, 2015, using three databases. A qualitative study using semi-structured interviews of 22 healthcare providers that assessed their beliefs regarding sexual disinhibition and cervical cancer screening following vaccination. A cross-sectional survey that assessed cervical cancer screening practices, awareness and comfort with recommendations, and knowledge regarding the purpose of a Papanicolaou (Pap) test. Results Twenty articles were included in the systematic review. None of the studies of sexual behaviors and/or biological outcomes found evidence of riskier behaviors after HPV vaccination. Instead, the studies found vaccinated individuals were less likely to report risky sexual behaviors, sexually transmitted infections (STIs), and pregnancy. Qualitative interviews found no healthcare providers believed the HPV vaccine would result in increased risky sexual behavior or decreased cervical cancer screening, and these concerns would not influence their vaccination recommendations. The survey included 291 women 21-35 years old; 62% were non-Hispanic black, 84% had a Pap test in the last three years, and 33% had at least one HPV vaccine. Logistic regression showed that vaccinated women did not have greater odds of having a Pap test in the past three years (OR=1.32; 95% CI=0.66-2.65; p=0.427). However, this odds ratio was significant when controlling for age and race (AOR=3.06; 95% CI=1.37-6.83; p=0.006). Conclusion These studies found no evidence of increased risky sexual behaviors or decreased cervical cancer screening rates after HPV vaccination. Furthermore, vaccinated women showed less evidence of risk compensation. These results should alleviate concerns about administering the HPV vaccination among parents and providers.