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I Sverige drabbas 1000 personer varje år av huvud- och halscancer. Rökning är den största enskilda orsaken till denna typ av cancer. Att motivera patienterna till att sluta röka är angeläget då fortsatt rökning har negativ inverkan på behandlings-resultatet samt förvärrar biverkningarna av behandlingen. Syftet med denna studie var att undersöka om patienter med huvud- och halscancer fick information om rökning och rökavvänjning inför och under strålbehandling, vad denna informa-tion innehöll samt att beskriva hur patienten upplevde informationen. Metoden var en intervjustudie som genomfördes på strålbehandlingsavdelningen, UMAS, Malmö. Åtta intervjuer genomfördes och resultatet visade att endast tre informan-ter erhållit information kring rökavvänjning från läkare och onkologisjuksköters-kor på strålbehandlingsavdelningen. Alla informanterna hade berättat för läkarna att de rökte men majoriteten upplevde inte att någon notis tagits vid denna infor-mation. En informant hade bett om hjälp för att sluta röka men avråtts av läkare vilket han upplevde som väldigt negativt. De som fått information kring rökav-vänjning upplevde detta som positivt samt kände att de blivit bekräftade. Majoriteten av informanterna hade velat delta i rökavvänjningsintervention om sådan funnits på kliniken. Det dagliga mötet mellan onkologisjuksköterskor och patienter på en strålbehandlingsavdelning innebär en möjlighet för sjuksköterskan att informera, stödja och bekräfta patienten i en rökavvänjningsintervention. / In Sweden 1000 individuals are diagnosed with head and neck cancer each year. Smoking is the major, single cause of this type of cancer. Motivating the patients to quit smoking is of great importance since smoking during treatment increases risks for treatment failure and increased side effects. The aim of this study was to investigate if patients with head and neck cancer received information about smoking and smoking cessation before and during radiation therapy, the content of the information and to describe patients' experience of the information. The method was an interview study and took place in the Department of radiation therapy, UMAS, Malmö. Eight interviews were carried out and the findings showed that only three respondents had received information of smoking cessa-tion from doctors or oncology nurses in the Department of radiation therapy. All of the respondents had informed the doctor of their smoking habit but the majority experienced that they were left without any response. One respondent had asked for smoking cessation aid but had been recommended not to quit smoking during treatment, which he had experienced as very negative. The patients who had re-ceived smoking cessation information experienced this information positive and felt both confirmed and supported. The majority of the respondents would have liked to participate in a smoking cessation intervention if such was available at the department. The daily meeting between nurses and patients in the Department of radiation therapy means an opportunity to give information, support and to con-firm the patient in a smoking cessation intervention.

Developing a head and neck cancer treatment plan for a candidate of Intensity Modulated Radiation Therapy (IMRT) requires extensive domain knowledge and subjective experience. Therefore, it takes a cancer treatment team at least 2 to 3 days to develop such a plan from scratch. Many times the team may not use a reference plan. Sometimes, to reduce the amount of time taken to generate each treatment plan, these experts recall a patient, whose plan they recently prepared, and who had similar symptoms as the candidate. Using this recalled patient's plan as the starting point, the cancer treatment team modifies it based on the differences in the symptoms of the new candidate and those of the reference patient record. The resultant plan after modification is presented as the new treatment plan for the oncologist to evaluate its suitability for treatment of the candidate. This approach is heavily dependent on the team's choice of the reference patient record. Choosing a starting treatment plan where the patient's symptoms are not the closest to the new candidate implies that more time will be spent modifying the plan than is necessary and the resultant treatment plan may not be the best achievable under the same circumstances given a better starting plan. Therefore, the team's bias in choosing the starting plan may affect the quality of treatment plan that is finally produced for the candidate. This thesis proposes a system that behaves like an un-biased radiotherapy expert - following a similar process and standards as the human experts and which searches the entire IMRT patient database and returns the record (with patient symptoms and treatment plan) for a patient whose symptoms are most similar to the candidate's symptoms. It takes in the new candidate's information (from diagnosis, scans of the tumor and interviews with the candidate), searches the database and prints out a patient record showing another patient's treatment plan as the suggested starting point for generating the new plan. The system uses Case-Based Reasoning (CBR) because it mimics the experts' approach since it makes use of previous successes and shuns reasoning that has failed in the past. This occurs by considering only treatment plans that have been implemented successfully on patients in the hospital archive. For this thesis, CBR is applied using fuzzy IF-THEN rules to search the patient database. Fuzzy logic is used because it can handle imprecise expressions commonly used in natural language to determine the appropriate weight of the patient attributes in the search process. Filtering of patient records based on parameter value ranges is also used to reduce the number of records that have to be compared. The system code developed for this thesis was prepared in Java and C Language Integrated Production System (CLIPS) using the Java Expert System Shell (JESS). This system is part of a bigger expert system that is being prepared by the Intelligent Systems Applications Center (ISAC) for Thomas Jefferson University Hospital, expected to generate a radiotherapy plan for a patient designated for IMRT treatment. Initial results from the developed prototype prove the viability of selecting similar patients using CBR. It is important to note that the overall objective of the project is to build a system that effectively aids decision support by the IMRT team when generating a new treatment plan and not to replace them. The team is expected to use the generated plan as a starting point in determining a new treatment plan. If the generated plan is sufficient, the oncologist and their team will have to check this plan (in their various capacities) against expected standards for quality control before passing it on for implementation. This will save them time in planning and allow them to focus more on the patient's needs hence a higher quality of life for the patient after treatment. / Electrical and Computer Engineering

Yes / The chemokine receptor CCR7 is expressed on lymphocytes and dendritic cells and is responsible for trafficking of these cells in and out of secondary lymphoid organs. It has recently been shown that CCR7 expression is elevated in a number of cancers, including head and neck cancers, and that its expression correlates to lymph node (LN) metastasis. However, little is known about the factors that can induce CCR7 expression in head and neck cancers. We compared the protein expression and functional responses of CCR7 under normoxia and hypoxia in head and neck cancer cell lines OSC-19, FaDu, SCC-4, A-253 and Detroit-562 cultured as monolayers, spheroids, and grown in vivo as xenografts in balb/c mice. In addition, we analysed the correlation between hypoxia marker HIF-1α and CCR7 expression in a tissue microarray comprising 80 clinical samples with various stages and grades of malignant tumour and normal tissue. Under hypoxia, the expression of CCR7 is elevated in both in vitro and in vivo models. Furthermore, in malignant tissue, a correlation is observed between hypoxia marker HIF-1α and CCR7 across all clinical stages. This correlation is also strong in early histological grade of tumours. Hypoxia plays a role in the regulation of the expression of CCR7 and it may contribute to the development of a metastatic phenotype in head and neck cancers through this axis.

We aimed to evaluate possible factors influencing the long-term survival of teeth after tumor therapy to the head and neck region with and without radiation. Between January 2019 and January 2020, patients who underwent for head and neck cancer and received dental treatment before and after at the Department of Prosthetic Dentistry of the Martin Luther University Halle- Wittenberg were enrolled in the study. Clinical examination with assessment of dental status and stimulated salivary flow rate (SFR) was performed and information about disease progression and therapy was retrieved from medical records. Of 118 patients (male: 70.3%; mean age: 63.2 12.4 years), 95 received radiotherapy (RT), and 47 were administered radio-chemotherapy (RCT). The teeth of irradiated patients exhibited a lower 5-year survival probability (74.2%) than those of nonirradiated patients (89.4%). The risk of loss (RL) after RT increased with nicotine use, presence of intraoral defects, reduced SFR, RCT and regarding mandibular teeth, and decreased with crowning following. Lower SFR increased the RL even without RT. Consideration of patient’s treatment history, individual risk profile, and clinical findings during the prosthetic planning phase could enable earlier, more targeted dental treatment after (e.g., timely crowning).

HNSCC accounts for 7 percent of all new cancer occurrences. Despite currently available treatments, there continues to be a high mortality and recurrence rate in HNSCC. Well over 50 percent of all cancer patients receive chemotherapy as a standard treatment. However, only 5 percent of these cases have been shown to help with treatment of the disease. Formerly, two options were available for drug testing: in vivo animal models, and in vitro two-dimensional models. While in vivo models remain the most representative, their use is burdened by high costs, time constraints, and ethical concerns. 2D models are simple to use and cost effective, although they have been shown to produce inaccurate data regarding chemotherapeutic drug resistance due to their 2D arrangement and altered gene expression. Researchers for the past decade have been working to create 3D models that more accurately represent in vivo systems in order to evaluate chemotherapeutic efficacy and improve clinical outcomes. In line with this agenda, novel 3D head and neck cancer models were created out of electrospun synthetic polymers seeded with either HN6 or HN12 cancer cells. The models were then treated with chemotherapeutic drugs (either paclitaxel or cisplatin), and, after 72 hours, subjected to a live-dead assay in order to determine the cytotoxic effects of the drugs. 2D cultures of HN6 and HN12 were also and subject to a WST-1 assay after 72 hours. The results of the treated-scaffold assays were then compared to the results of the 2D culture assays, and, as predicted, the cancer cells in a 3D culture system proved to be more resistant to chemotherapeutic drugs. The underlying assumption for this study being that a 3D culture system based on precisely defined structural parameters would provide a practical environment to screen therapeutics for anti-cancer efficacy. To prove this, 3D scaffolds of three different fiber sizes were developed by electrospinning different concentrations of Poly(L-lactic acid) (“PLLA”) (55mg/ml, 115mg/ml, and 180mg/ml) onto a mandrel that was perforated to allow for increased porosity. The resultant small, medium, and large scaffolds were then subjected to concentrated hydrochloric acid (HCl) pretreatment in order to make them less hydrophobic. Different fiber diameters represented different ECM environments for both HN6 and HN12. It was proven that both cell types thrived best in small fibers (55mg/ml-115mg/ml) than in large fibers. It was also reaffirmed through live-dead anlaysis of cells seeded on 3D scaffolds and treated with IC90 values of cisplatin that the head and neck cancer cells were more resistant which is more representative to the 3D environment of cancer cells in vivo.

O câncer de cabeça e pescoço (CCP) apresentam incidência mundial sendo considerado um problema de saúde pública. O diagnóstico tardio dos carcinomas ainda é uma realidade presente, implicando em terapias como a radioterapia (RT). Esta terapia antineoplásica pode causar diversos efeitos colaterais tais como: mucosite, dificuldade de deglutição, alteração ou perda do paladar, xerostomia, trismo, cárie de radiação, osteorradionecrose, alterações do ligamento periodontal e infecções oportunistas. Os efeitos adversos da RT instituída para tratamento de pacientes com CCP, podem interferir significativamente na qualidade de vida desses indivíduos, causando possíveis alterações ósseas e dentais, daqueles que acometem as partes moles. Dentre elas podemos citar as mucosites, hipossialia, agenesia, cáries por radiação, trismo e osteorradionecrose (ORN). Esta última constitui uma complicação grave e de difícil tratamento. O presente estudo objetivou ponderar a relação dose-efeito da radioterapia de cabeça e pescoço, em consideração aos dentes e estruturas ósseas do complexo maxilo - mandibular, avaliando e explorando o impacto do tamanho do tumor ,sua distribuição e dosimetria no complexo maxilo mandibular de pacientes submetidos a radioterapia de CCP. A IMRT se mostrou a melhor indicação de tratamento quando comparada a RT, pois reduziu muito os efeitos encontrados nas radiografias, o que mostrou sua baixa toxicidade nos tecidos adjacentes saudáveis. A partir dos resultados obtidos observou se que a radioterapia pode provocar alterações significativas na estrutura do CMM, ademais da região própria ao tumor, e os médicos oncologistas juntamente com dentistas devem se apoiar na detecção e abordagem dessas sequelas e acompanhamento dos seus tratamentos e prevenções, sendo necessário que os profissionais de odontologia orientem e façam as devidas intervenções para proporcionar melhores condições aos pacientes em tratamento de radioterapia de cabeça e pescoço. / Head and neck neoplasms present a worldwide incidence and are considered a public health problem. The late diagnosis of carcinomas is still a reality, implicating in thera-pies such as radiotherapy. This antineoplastic therapy can cause several side effects such as: mucositis, difficulty in swallowing, alteration or loss of taste, xerostomia, tris-mus, radiation caries, osteoradionecrosis, alterations of the periodontal ligament and opportunistic infections. The adverse effects of radiotherapy instituted for the treatment of patients with cancer of the head and neck region can significantly interfere in the quality of life of these individuals, causing possible bone and dental changes in those that affect the soft parts. Among them we can mention mucositis, hyposialia, agenesis, radiation caries, trismus and osteoradionecrosis (ORN). The latter constitutes a seri-ous complication and is difficult to treat. The present study aims to evaluate the dose-effect relationship of head and neck radiotherapy, considering the teeth and bone structures of the maxillo-mandibular complex, evaluating and exploring the impact of tumor size, its distribution and dosimetry in the mandibular nipple complex of patients submitted to CCP radiotherapy. The IMRT performed a better comparison procedure when compared to what is more difficult to see on radiographs when compared to toxicity in adjacent healthy systems. From the results obtained, the effects of radio-therapy can cause changes in the structure of the CMM, besides being responsible for the tumor, and the oncologists. It is necessary that dental professionals guide and withdraw care for the treatment of head and neck radiotherapy.

O carcinoma epidermoide de cabeça e pescoço (HNSCC) é uma das neoplasias mais frequentes e geralmente está associado a inflamação crônica e níveis sistêmicos de citoquinas. Seus principais fatores de risco são a exposição ao tabaco e álcool. Publicações recentes sugerem que a infecção por papiloma vírus HPV está relacionada com a tumorigênese de cabeça e pescoço e pode alterar o perfil e o desfecho deste tumor. A transição epitelial-mesenquimática (EMT) é um processo importante durante a tumorigênese pelo qual células epiteliais obtêm um fenótipo migratório e invasivo. Os efeitos da infecção por HPV e de citocinas inflamatórias neste processo ainda não são bem compreendidos em HNSCC. O presente estudo teve como objetivo transfectar células normais e neoplásicas com os genes E6/E7 de HPV16 e investigar os mecanismos pelos quais a EMT é ativada por citocinas inflamatórias e por infecção por HPV. Taxas de proliferação, viabilidade, migração e invasão celular induzidas por IL-6, TNF-a e TGF-beta foram avaliadas em linhagens celulares derivadas de queratinócitos normais e de carcinoma de língua (HaCat e SCC25, respectivamente) transfectadas com os genes E6/E7 de HPV16 e a expressão dos marcadores relacionados a EMT foram analisados por PCR em tempo real nas linhagens SCC25, HaCat e FaDu (carcinoma de faringe). Os resultados sugerem que o HPV modificou a morfologia das linhagens normal e tumoral. Na linhagem HaCat, o ambiente inflamatório estimulou modificações importantes para o desenvolvimento de condições patológicas. A inserção dos genes E6/E7 de HPV16 diminuiu a proliferação e a viabilidade na linhagem HaCat e o ambiente inflamatório não modificou a resposta iniciada pelo HPV. Na linhagem SCC25 a inserção de HPV em associação com inflamação reduziu a progressão da EMT, ao contrário do que foi observado na linhagem FaDu. A relação de HPV com inflamação levando a progressão de EMT é controversa e dependente do sítio anatômico em tumores de cabeça e pescoço / Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent neoplasias and is often associated with chronic inflammation and systemic cytokine levels. Its main risk factors are tobacco and alcohol exposition. Recent publications suggest that the infection by human papillomavirus (HPV), especially high-risk types, is related to head and neck tumorigenesis and may alter the tumor profile and outcome. Epithelial-mesenchymal transition (EMT) is an important process during tumorigenesis by which epithelial cells gain a migratory and invasive phenotype. The effects of HPV infection and inflammatory cytokines on this process are still not well understood in HNSCC. The present study aimed to transfect normal and neoplastic cells with E6/E7 genes of HPV type 16, and to investigate the mechanisms by which EMT is activated by inflammatory cytokines and by HPV infection. Proliferation, viability, migration and cell invasion rates induced by IL-6, TNF-a and TGF-beta cytokines will be also evaluated in cell lines derived from normal keratinocyte and tongue carcinoma (HaCat and SCC25, respectively) transfected with HPV16 E6/E7 genes and the expression of the EMT-related markers were analyzed by real-time PCR in the SCC25, HaCat and FaDu (pharyngeal carcinoma). The results suggest that HPV modified the morphology of normal and tumor cell lines. In the HaCat cell line, the inflammatory environment stimulated important modifications for the development of pathological conditions. Insertion of HPV16 E6/E7 genes decreased proliferation and viability in the HaCat and the inflammatory environment did not modify the HPV-initiated response. In the SCC25 cell line the insertion of HPV in association with inflammation reduced the progression of EMT, unlike was observed in FaDu. The relationship of HPV with inflammation leading to progression of EMT is controversial and depends on anatomical site in head and neck carcinoma

O câncer é considerado uma doença genética, extremamente complexa, que resulta de alterações concomitantes em genes geralmente relacionados à proliferação, diferenciação e morte celular. Os tumores de cabeça e pescoço englobam ampla variedade de neoplasias malignas que tem origem na mucosa do segmento aerodigestório superior, sendo responsável por cerca de 5% de todos os novos tumores diagnosticados. A Odontologia desempenha hoje um papel importante nas diferentes fases terapêuticas contra o câncer, seja na fase que antecede a cirurgia, em que uma avaliação prévia poderá reduzir de forma efetiva complicações oriundas de processos infecciosos ou inflamatórios crônicos, de origem bucal, que podem exacerbar após o tratamento cirúrgico, seja na prevenção das sequelas bucais que ocorrem durante e após o tratamento por radioterapia, como a osteorradionecrose dos tecidos da região irradiada. Esse estudo teve como objetivo avaliar, bilateralmente, por meio da eletromiografia (EMG), o padrão de comportamento (morfológico e funcional) da atividade dos músculos masseter e temporal nas condições clínicas de Repouso, Protrusão, Lateralidades direita e esquerda, Máxima Intercuspidação Habitual (MIH) e Mastigação com Parafilme M®. Avaliou também a espessura muscular por meio da ultrassonografia no Repouso e na Máxima Intercuspidação Habitual (MIH) e a força de mordida molar máxima direita e esquerda de dez indivíduos dentados totais, portadores de câncer de cabeça e pescoço, após tratamento de radioterapia no \"Hospital do Câncer de Barretos (Fundação Pio XII)\" e compará-los com um Grupo controle, pareados sujeito a sujeito, por peso, idade e gênero. As médias eletromiográficas evidenciaram que no Repouso, Protrusão e na Lateralidade esquerda ocorreram diferenças estatisticamente significantes. Na avaliação com o ultrassom, a espessura muscular foi maior para os indivíduos com câncer no repouso e na MIH com resultados estatisticamente significante somente para o temporal direito durante a MIH. Foi possível verificar durante a realização dos exames eletromiográficos que o comportamento de ativação das fibras musculares era desordenado nos indivíduos com câncer quando comparados com o Grupo controle. Os indivíduos tratados de câncer de cabeça e pescoço avaliados no presente estudo revelaram atividade eletromiográfica aumentada quando comparada com o Grupo de indivíduos controle para todas as situações clínicas. Este resultado é um forte indício de hiperatividade muscular. Pode-se concluir que o tratamento aplicado em indivíduos com câncer de cabeça e pescoço gerou um aumento na atividade eletromiográfica e na espessura dos músculos da mastigação e da força de mordida quando comparados com indivíduos controles. Estes resultados são indicativos de disfunção muscular e de contração desorganizada e ineficiente das fibras musculares do sistema estomatognático. / Cancer is considered a genetic disease, extremely complex, resulting in concomitant changes in genes generally related to proliferation, differentiation and cell death. Tumors of the head and neck are a wide variety of malignancies that originate in the lining of the upper aerodigestive segment, accounting for about 5% of all new tumors diagnosed. Dentistry plays an important role in the different phases therapies against cancer, in the stage prior to surgery, in which a prior assessment can effectively reduce complications arising from chronic inflammatory or infectious processes of oral origin, which may exacerbate after surgical treatment, or prevention of the sequelae that occur during buccal and after treatment by radiotherapy as osteoradionecrosis of tissue irradiated area. This study aimed to evaluate by electromyography (EMG), the activity behavior (morphological and functional) of the masseter and temporal muscles in clinical conditions of rest, protrusion, right and left lateral, maximum intercuspal habitual (MIH) and chew with Parafilm M®. Also assessed muscle`s thickness by ultrasound in rest and maximal intercuspal habitual (MIH) and maximal molar bite force, both sides, in ten dentate patients after cancer of the head and neck radiotherapy treatment ended in the \"Hospital de Cancer de Barretos (Fundação Pio XII)\" and compare them with a control group matched for each subject, by weight, age and gender. The EMG average showed that in the rest, protrusion and left laterality clinical conditions the differences were statistically significant. In the evaluation with ultrasound, muscle thickness was greater for individuals with cancer at rest and MIH, with statistically significant only for the right temporal muscle during the MIH. It was verified during the examinations that the behavior of electromyographic activation of muscle fibers was disordered in individuals with cancer when compared with the control group. Individuals treated for head and neck cancer in the current study revealed electromyographic activity increased when compared with the group of control subjects for all clinical situations. This result is a strong indication of muscle hyperactivity. It can be concluded that the treatment applied to individuals with cancer of the head and neck caused an increase in the thickness, electromyographic activity of masticatory muscles and maximal molar bite force compared with control subjects. These results are indicative of muscle dysfunction and disorganized and ineffective contraction of the muscle fibers of the stomatognathic system.