Les démences représentent un enjeu majeur de santé publique. Les carences organisationnelles de notre système de santé ne garantissent pas la qualité et la cohérence du parcours de soins des malades et de leurs familles. Le plan national Alzheimer 2008-2012 a introduit de nouveaux dispositifs ayant pour objectifs de mieux prendre en compte les besoins des malades et des familles et de mettre en place des offres adaptées. L’objectif général de cette thèse était d’étudier la prise en charge des démences en s'intéressant à la fois à une prise en charge pouvant être qualifiée d'optimale (le case management) et à la prise en charge effective en pratique courante. Dans une première partie, nous avons donc étudié l’efficacité du case management dans la démence et caractérisé les conditions d’optimisation de ce modèle de soins collaboratifs. Tout d’abord, nous nous sommes intéressés aux conditions d’efficacité dans un domaine où le niveau de preuve était élevé (le diabète) puis nous avons cherché à caractériser les points saillants pouvant conditionner l’efficacité du case management dans la démence. Quelques essais contrôlés randomisés de case management rapportent des résultats encourageants dans la démence sur des critères cliniques (troubles du comportement du malade, qualité de vie ou fardeau de l’aidant) ou sur l’institutionnalisation. L’efficacité est démontrée principalement auprès de patients inclus à des stades plutôt modérés. L’efficacité d’une intervention préventive dès le diagnostic est inconnue et mérite d’être testée. C’est pourquoi l’essai AIDALZ a été envisagé et est actuellement mené auprès de déments nouvellement diagnostiqués. Dans une deuxième partie, nous avons étudié la prise en charge telle qu'elle est actuellement réalisée en France. Nous avons d'abord décrit cette prise en charge et analysé les déterminants d’un recours aux soins dès le début de la maladie. Puis nous avons évalué les bénéfices de ce recours aux soins sur la survie des déments. Les différentes analyses de survie menées n’ont pas démontré de bénéfice d’un recours aux soins dès le début de la maladie chez des déments incidents des cohortes populationnelles des 3 Cités et de PAQUID. Ce travail témoigne de la difficulté de prendre en compte tous les facteurs pouvant influer sur l’accès aux soins et/ou sur la survie dans des études observationnelles. De nouvelles recherches doivent être menées pour étudier les bénéfices d’un diagnostic dès le début de la maladie sur des indicateurs variés du pronostic. Des essais d’intervention seraient nécessaires pour évaluer plus précisément l’intérêt du diagnostic et de la prise en charge dans la démence. / Dementia represents a major public health issue. The organisational carencies of our health system do not guarantee the quality of the care channels for patients and families. The national Alzheimer plan 2008-2012 has introduced new health facilities whose objectives are to better take into account patients and families needs and to implement tailored care. The main aim of this thesis was to evaluate care of demented patients, both optimal care (the case management) and usual care. In the first part we studied case management effectiveness and delineated conditions to optimize the effectiveness of this collaborative model of care. Firstly, we concentrated our attention on effectiveness conditions in diabetes and we studied case management in dementia. Some randomized controlled trials of case management reported promising impacts on clinical criteria (patient’s behavioural troubles, caregiver burden or quality of life) or patient’s institutionalization. Case management effectiveness is reported mainly for patients at moderate stages. The effectiveness of a preventive intervention early in the disease process is unknown, but it deserves further investigation; that is why, the AIDALZ trial has been planned and is currently under way. In a second part, we studied the real care of demented patients in France. We firstly described the care and analysed the determinants of an early recourse to care for incident dementia patients. Then, we evaluated the benefits of recourse to care at the onset of dementia on survival. The different survival analyses performed did not report any benefit of an early recourse to care on incident dementia patients from the PAQUID or the 3 City population-based cohorts. These findings underlie the difficulties to take into account factors interfering with recourse to care and/or survival in observational studies. Further studies should be planned to investigate the benefits of early dementia diagnosis on various prognostic indicators. Intervention trials would be necessary to conclude on the relevance of early diagnosis in dementia.

L’infection par le VIH est caractérisée en l’absence d’intervention par une évolution progressive vers un état d’immunodépression favorisant la survenue d’affections opportunistes et entrainant le décès. La connaissance de l’évolution spontanée de l’infection par le VIH repose sur les données observationnelles issues des cohortes. La meilleure façon d’aborder l’histoire naturelle de cette infection est de l’étudier à partir de la date de séroconversion, ce qui ne peut se faire que dans les cohortes dites incidentes. Ces cohortes incidentes font appel à des structures parfois lourdes et des procédures rigoureuses que l’on peut plus aisément mettre en place dans les pays à ressources élevées. Les cohortes de personnes à date estimée de séroconversion permettent d’identifier les facteurs de risque de la transmission, d’étudier l’évolution de l’infection, d’étudier l’évolution de ses marqueurs et ses déterminants en minimisant le biais de sélection inhérent aux études prévalentes. L’évolution naturelle concerne la période qui s’écoule entre la date d’infection et le décès pour les patients qui n’ont pas bénéficié de prescription du traitement antirétroviral. Cette période s’arrête à la date de prescription des antirétroviraux pour ceux qui en bénéficient.La cohorte ANRS 1220 Primo-CI de personnes à date estimée de séroconversion pour le VIH-1 a été mise en place en juin 1997 sur le site de l'ANRS d'Abidjan en Côte d'Ivoire, au Centre national de transfusion sanguine (CNTS), avec la coordination de l'INSERM U330/593/897-ISPED de Bordeaux. C’est l’une des rares cohortes de séroconverteurs pour le VIH-1 dans le contexte des pays à faibles ressources et l’unique en Afrique de l’ouest. Dans cette cohorte de patients dépistés parmi les donneurs de sang effectuant plus de deux dons de sang par an, les données cliniques et biologiques ont été recueillies régulièrement pour tous les patients, tous les six mois depuis leur inclusion dans la cohorte.Les principaux apports de la cohorte Primo-CI dans la lutte contre le VIH en Côte d’Ivoire, ont consisté à recueillir des informations sur les facteurs de risque d’infection par le VIH pour aider à améliorer la sélection des donneurs de sang. La cohorte Primo-CI a permis d’améliorer également les capacités de la structure de prise en charge qui a servi de centre de recrutement et de prise en charge des patients de la cohorte. Cette cohorte a contribué à la mise en place d’un cadre d’échanges réguliers entre les médecins chargés de la sélection des dons de sang et l’équipe de la cohorte Primo-CI.Nos données ont fourni des estimations de la probabilité d'atteindre les critères d'initiation des antirétroviraux depuis le premier contact dans une population de séroconverteurs récents pour le VIH en Afrique de l’ouest et de la probabilité de survenue des événements morbides au cours du temps.L'ADN intracellulaire du VIH-1 était la variable la plus fortement associée à la progression de la maladie, indépendamment des autres variables explicatives. Il était suivi des lymphocytes CD4 avec une association plus faible. La charge virale plasmatique VIH-1 était faiblement associée à la progression de la maladie et ce après la prise en compte de l'ADN.La cohorte ANRS 1220 Primo-CI a participé à plusieurs travaux de collaborations portant sur les seuils d’éligibilité aux antirétroviraux, la comparaison de la baisse des lymphocytes CD4 avec des patients européens, la morbidité et la mortalité liées au SIDA et le rôle prédictif de l'ADN intracellulaire du VIH-1. Elle a également contribué à la réalisation de travaux scientifiques en virologie et immunologie qui ne portent pas sur l’objectif principal de ce travail. / In the absence of any intervention, HIV infection is characterized by a gradual evolution towards a state of immunosuppression favoring the occurrence of opportunistic infections and causing death. The natural history of HIV infection is usually documented based on data from observational cohorts. But the best way to address the natural history of this infection is to observe subjects from the date of their seroconversion (within an “incident” cohort). However these incident cohorts often involve heavy structures and complex procedures that are more easily set-up in high-resources countries.Cohorts of individuals with estimated date of seroconversion can identify risk factors for HIV transmission, study the evolution of the infection, and study the evolution of its markers and determinants by minimizing the selection bias inherent in prevalent studies. The natural history of HIV is defined by the period between the date of infection and either the date of death for patients who were not prescribed antiretroviral therapy or the date of antiretroviral therapy prescription for others.The ANRS 1220 Primo-CI Cohort of people with a known date of HIV-1 seroconversion was launched in June 1997 in the site of the ANRS Abidjan in Côte d'Ivoire, National Blood Transfusion Centre (CNTS), with the coordination of U330/593/897-ISPED INSERM Bordeaux. This is one of the few adult cohorts of HIV-1 seroconverters in the context of low-resource countries and the only one in West Africa. Within this cohort of patients recruited among blood donors performing more than two blood donations per year, the clinical and laboratory data were collected routinely every six months from their inclusion.One of the main contributions of the Primo-CI cohort in the fight against HIV in Côte d’Ivoire was the collection of information on the risk factors for HIV infection. It helped to improve the selection of blood donors. It also helped to improve the capacity of the health structure where the cohort patients were recruited and followed-up.This cohort has contributed to establish a system for regular exchanges between physicians responsible for the selection of blood donations and the team of the Primo-CI cohort. Our data have provided estimates of the probability of reaching the criteria for initiating antiretroviral drugs from the first contact and the probability of occurrence of morbid events over time, in a population of recent HIV seroconverters in West Africa.The HIV-1 intracellular DNA was the variable most strongly associated with disease progression, independently of other variables. It was followed by lower CD4. Plasma viral load HIV-1 was poorly associated with disease progression after taking into account the HIV-1 intracellular DNA.Finally, the ANRS 1220 Primo-CI cohort participated in several collaborative studies regarding the threshold of eligibility for antiretroviral drugs, the comparison of the decrease in CD4 lymphocytes with European patients, morbidity and mortality related to AIDS and the predictive role of HIV-1 intracellular DNA. It also contributed to scientific studies in virology and immunology that do not concern the main objective of this work.

The purpose of this study was to define a lower standard cuff occlusion time to induce reactive hyperemia in assessing endothelial dysfunction. In this study, strong evidence was found by a novel technique that used oscillometric methods, which supported that 3 minute reactive hyperemia was sufficient to elicit a significant difference in arterial compliance from baseline. Twenty healthy Cal Poly students were assessed, (n=12 female, n=8 male) aged 22 years old with a standard deviation of 2.04 years. Arterial compliance was estimated by measuring the peak-to-peak oscillations for baseline, 3 minute reactive hyperemia, and 5 minute reactive hyperemia tests, with the result being statistical evidence of an increase in arterial compliance after 3 minutes of cuff occlusion compared to baseline. The peak-to-peak mean for the 3 minute reactive hyperemia test was significantly greater than the baseline peak-to-peak mean with p-values less than 0.0001. These results support that 3 minute reactive hyperemia is sufficient to assess endothelial dysfunction using oscillometry techniques. Endothelial dysfunction is the most significant predictor of a major adverse cardiovascular event, so this test can be used as an early detection tool for cardiovascular disease and allow patients to find treatment before irreversible damage is done to the body. Implementing this test into routine doctor checkups has the potential to have a significant effect on cardiovascular disease, which is the leading cause of death globally. The currently accepted clinical benchmark performed in hospitals uses high-frequency ultrasound with a standard cuff occlusion time of 5 minutes. Although noninvasive, 5 minutes of cuff occlusion causes slight discomfort to the patient and is not desirable. This test was improved and shortened by using a system based on the oscillometric method of blood pressure measurement. By reducing the duration of the test from 5 minute reactive hyperemia to 3 minute reactive hyperemia, this will make the procedure practical for an increased number of patients, providing a noninvasive option to regularly check for early symptoms of cardiovascular disease.

Ovarian cancer (OVCA) is the most lethal gynecological cancer with a 5-year survival rate less than 50%. Despite new therapeutic strategies, such as targeted therapies and immune checkpoint blockers (ICBs), tumor recurrence and drug resistance remain key obstacles in achieving long term therapeutic success. Therefore, there is an urgent need to understand the cellular and molecular mechanisms of immune dysregulation in chemoresistant ovarian cancer in order to harness the host’s immune system to improve cancer survival. Early diagnosis and residual disease are key determinants of favorable survival in OVCA; however, CA125 which is the conventional marker is not reliable and has modest diagnostic accuracy. There is therefore an urgent need to discover reliable biomarkers to optimize individualized treatment and diagnostic recommendations. Plasma gelsolin (pGSN; an actin binding protein) is the secreted isoform of the gelsolin (GSN) gene implicated in inflammatory disorders, colon cancer and prostate cancer. Increased expression of total GSN is associated with poor survival of patients with gynecological cancers. As to whether this is due to pGSN is yet to be investigated. Increased expression of pGSN is significantly associated with the down-regulation of immune cell markers; however, the exact mechanism has not been explored. If and how pGSN is involved in the cellular and molecular mechanisms of OVCA remains to be determined. In our current research, we have demonstrated that pGSN is involved in the regulation of immune cells, early diagnosis, tumor recurrence and chemoresistance in OVCA, using standard in vitro techniques and human clinical samples (North America, Asia and public datasets). We have shown that pGSN is highly expressed and secreted in chemoresistant OVCA cells than their chemosensitive counterparts. pGSN, secreted and transported via exosomes, upregulated HIF1α–mediated pGSN expression in chemoresistant OVCA cells in an autocrine manner as well as conferred cisplatin resistance in otherwise chemosensitive OVCA cells. pGSN also induced the OVCA expression of the antioxidant and tumor growth promoter, glutathione (GSH), by activating Nuclear factor erythroid 2-related factor 2 (NRF2), a response that attenuated cisplatin (CDDP)-induced apoptosis. In human tumor tissues, increased pGSN mRNA and protein expressions were significantly associated with advanced tumor stage, suboptimal residual disease, tumor recurrence, chemoresistance and poor survival regardless of patients’ ethnic background and histologic subtypes. Increased Infiltration of CD8+ T cells was significantly associated with favorable patient survival; however, increased pGSN hindered the survival impact of these infiltrated CD8+ T cells. Further investigation revealed that pGSN induced CD8+ T cell death via caspase-3 activation, an action that resulted in decreased IFNγ levels. Increased epithelial pGSN expression was significantly associated with reduced survival benefits of infiltrated M1 macrophages, through caspase-3-dependent apoptosis as well as reduced production of TNFα and iNOS. The clinical application of circulatory pGSN as a biomarker for early detection and patients’ survival was investigated. Pre-operative circulating pGSN presented as a favorable and independent biomarker for early disease detection and residual disease prediction compared with CA125. The test accuracy of pGSN was significantly enhanced when combined with CA125 in multianalyte index assay. The findings suggest that pGSN is a potential target for chemoresistant OVCA and presents as a diagnostic marker for early stage disease and surgical outcomes, interventions that could maximize the therapeutic success of immunotherapies.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12945号 / 論医博第2097号 / 新制||医||1010(附属図書館) / 32204 / (主査)教授 髙橋 良輔, 教授 富樫 かおり, 教授 髙橋 淳 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Polycystic ovary syndrome is the single most common endocrine abnormality of women of reproductive age and is a leading cause of female infertility. Common clinical features include hirsutism, various ovarian abnormalities, obesity, and insulin resistance. Expert consensus recommendations on diagnostic criteria vary, but the most recent focus on the presence of clinical features of hyperandrogenism, hyperandrogenemia, polycystic ovaries, and ovulatory and menstrual dysfunction to the exclusion of alternative diagnoses. In adolescence, diagnosis is more difficult because of the frequent presence of individual clinical findings in otherwise "normal" individuals. Laboratory tests and pelvic ultrasound are necessary to confirm polycystic ovary syndrome and exclude other disorders that may mimic this syndrome. Treatment is centered on the clinical manifestations and should be initiated early to prevent/limit long-term complications, including the metabolic syndrome, diabetes, endometrial carcinoma, and infertility.

Yes / Background: The aim of this study was to investigate whether the prior consumption of 200mg of pure caffeine affected neuropsychological test scores in a group of elderly participants aged over 60 years. Method: Using a double blind placebo vs. caffeine design, participants were randomly assigned to receive 200mg of caffeine or placebo. A neuropsychological assessment testing the domains of general cognitive function, processing speed, semantic memory, episodic memory, executive function, working memory and short-term memory was carried out. Results: Significant interaction effects between age, caffeine and scores of executive function and processing speed were found; participants who had received caffeine showed a decline in performance with increasing age. This effect was not seen for participants who received placebo. Conclusion: The results highlight the need to consider and control prior caffeine consumption when scoring neuropsychological assessments in the elderly which is important for accuracy of diagnosis and corresponding normative data.

This critical synopsis of prior work by Luca Parisi is submitted in support of a PhD by Published Work. The work focuses on deriving accurate, reliable and explainable clinical decision support systems as minimum clinically viable solutions leveraging Machine Learning (ML) and evolutionary algorithms, for the first time, to facilitate early diagnostic predictions of Parkinson's Disease and hypothermia in hospitals, as well as prognostic predictions of optimal postoperative recovery area and of chronic hepatitis. Despite the various pathological aetiologies, the underlying capability of ML-based algorithms to serve as a minimum clinically viable solution for predicting early diagnosis and prognosis has been thoroughly demonstrated. Feature selection (FS) is a proven method for increasing the performance of ML-based classifiers for several applications. Although advances in ML, such as Deep Learning (DL), have denied the usefulness of any extrinsic FS by incorporating it in their architectures, e.g., convolutional filters in convolutional neural networks, DL algorithms often lack the required explainability to be understood and interpreted by clinicians within the context of the diagnostic and prognostic tasks of interest. Their relatively complicated architectures, the hardware required for running them and the limited explainability or interpretability of their architectures, the decision-making process – although as assistive tools - driven by the algorithms’ training and predictive outcomes have hindered their application in a clinical setting. Luca Parisi’s work fills this translational research gap by harnessing the explainability of using traditional ML- and evolutionary algorithms-based FS methods for improving the performance of ML-based algorithms and devise minimum viable solutions for diagnostic and prognostic purposes. The work submitted here involves independent research work, including collaborative studies with Marianne Lyne Manaog (MedIntellego®) and Narrendar RaviChandran (University of Auckland). In particular, conciliating his work as a Senior Artificial Intelligence Engineer and volunteering commitment as the President and Research Committee Leader of a student-led association named the “University of Auckland Rehabilitative Technologies Association”, Luca Parisi decided to embark on most research works included in this synopsis to add value to society via accurate, reliable and explainable, hence clinically viable applications of AI. The key findings of these studies are: (i) ML-based FS algorithms are sufficient for devising accurate, reliable and explainable ML-based classifiers for aiding prediction of early diagnosis for Parkinson’s Disease and chronic hepatitis; (ii) evolutionary algorithms-based optimisation is a preferred method for improving the accuracy and reliability of decision support systems aimed at aiding early diagnosis of hypothermia; (iii) evolutionary algorithms-based optimisation methods enable to devise optimised ML-based classifiers for improving postoperative discharge; (iv) whilst ML-based algorithms coupled with ML based FS methods are the minimum clinically viable solution for binary classification problems, ML-based classifiers leveraging evolutionary algorithms for FS yield more accurate and reliable predictions, as reducing the search space and overlapping regions for tackling multi-class classification problems more effectively, which involve a higher number of degrees of freedom. Collectively, these findings suggest that, despite advances in ML, state-of-the-art ML algorithms, coupled with ML-based or evolutionary algorithms for FS, are enough to devise accurate, reliable and explainable decision support systems for performing both an early diagnosis and a prediction of prognosis of various pathologies.

INTRODUÇÃO: Os relatos do desenvolvimento motor de recém-nascidos prétermo (RNPT) extremo são razoavelmente bem documentados, mas pouco se sabe sobre o desenvolvimento de RNPT Tardios (RNPT T). OBJETIVOS: Analisar o desenvolvimento motor de RNPT T desde o nascimento até a idade corrigida de termo e comparar ao de recém-nascidos de termo (RNT) ao nascer. MÉTODOS: Foi realizado um estudo de coorte, prospectivo, com 29 RNPT Te 88 RNT de 4 hospitais credenciados à rede pública de saúde no município de Cuiabá/MT. OS RNPT T foram submetidos à avaliação motora através do Test of Infant Motor Performance (TIMP) ao nascer, realizaram US de crânio nas duas primeiras semanas de vida e repetiram o TIMP a cada duas semanas até a idade equivalente ao termo, bem como as medidas de peso, comprimento e perímetro cefálico. Ao termo, foi realizada uma avaliação neurológica pelo método de Dubowitz. Os RNT foram submetidos à avaliação motora pelo TIMP e neurológica de Dubowitz ao nascer. ANÁLISE ESTATÍSTICA: O tamanho da amostra definiu 29 crianças no grupo RNPT T, considerando um poder de teste de 80% e nível de significância de 5%. As análises basearam-se nos testes Exato de Fisher e Qui Quadrado e para comparação das variáveis quantitativas, os testes t de Student para duas amostras pareadas e teste t de Student para duas amostras independentes. Para análise dos fatores preditores do TIMP ao T foi realizada Regressão Múltipla Linear. RESULTADOS: Dos 29 RNPT T avaliados, 23 (79,3%) apresentaram US de crânio dentro da normalidade, 2 (6,9%) hemorragia intracraniana (HIC) grau I e 4 (13,8%) HIC grau I bilateral. O escore total do TIMP aumentou significativamente a partir de 38 - 39 semanas no grupo RNPT T (51,9 ± 5,8 às 34-35 sem, 53,6 ± 6,4 às 36-37 sem, 57,7 ± 7,3 às 38-39 sem e 62,6 ± 5,2 às 40 sem) (p < 0,05). As médias dos escores do TIMP de RNPT T em idades equivalentes às dos RNT ao nascer foram, às 38- 39 sem, de 57,7 ± 7,3 e 59,8 ± 6,4 e, às 40 sem, de 62,6 ± 5,2 e 61,7 ± 5,0,respectivamente, sem diferenças estatísticas entre estes. Por análise de regressão múltipla linear foram identificados a idade materna e o perímetro cefálico como preditores do TIMP em RNPT T em idade equivalente ao termo. Não foram encontradas diferenças ao comparar os escores das avaliações neurológicas pelo método Dubowitz de RNPT T aos de termo ao nascer. CONCLUSÃO: RNPT T de baixo risco podem apresentar evolução motora com aumento significante a partir de 38-39 semanas pós-termo, alcançando desempenho motor em idade equivalente ao termo, semelhante ao de RNT ao nascer. A idade materna e o PC foram identificados como preditores do escore do TIMP em RNPT T à idade corrigida de termo / INTRODUCTION: Reports on the motor development of extremely preterm infants are frequent in the literature, but little is known about the development of late preterm infants (LPI). OBJECTIVES: To analyze the motor development of LPI from birth until term-corrected age, and compare with that of term infants (TI) at birth. METHODS: A cohort study was performed, in which the Test of Infant Motor Performance (TIMP) was administered to 29 LPI at birth and repeated every two weeks until term-corrected age, as well as the anthropometric measures of weight, length and head circumference. A cranial ultrasound (US) in the first two weeks of age and a Dubowitz neurological assessment were administered to LPI at term corrected age. The TIMP and the Dubowitz neurological examination were administered to TI at birth. STATISTICAL ANALYSIS: The sample size was defined as 29 LPI, considering a test power of 80 % and a significance level of 5. Qualitative variables were compared using the Fisher exact test and Chi Square and Student\'s t test for two samples and paired Student\'s t test for two independent samples for quantitative variables. The multiple linear regression was performed for analysis of predictors of TIMP at term time. RESULTS: Among the 29 LPI evaluated, 23 (79.3%) had a cranial US within normal limits, 2 (6.9%) intracranial hemorrhage (ICH) grade I, and 4 (13.8%) bilateral ICH grade I. The mean TIMP score and standard deviation of LPI was 51.9 ± 5.8 at 34-35 weeks and 62.6 ± 5.2 at 40 weeks. There was a significant increase at 38-39 weeks in the LPI group (p < 0.05). There were no significant differences in the motor evaluations between LPI at the age equivalent to TI at birth (38-39 weeks and 40 weeks). The growth of LPI until term was adequate in relation to Alexander curve. After multiple linear regression we found that maternal age and head circumference were predictors of TIMP in LP at term age. No differences were found when comparing the scores of neurological assessments by Dubowitz between LPI and T infants. CONCLUSION: Low risk LPI presented a gradual progression of motor development until the term-corrected age, but differences with TI at birth were not detected. Maternal age and head circumference were identified as predictors of TIMP score at term in LPI

Cânceres de pele não melanoma (CPNM) representam 95% das neoplasias cutâneas, dentre as quais o carcinoma espinocelular (CEC) é a forma mais agressiva devido a seu padrão de crescimento invasivo e possivelmente metastático. O padrão ouro para o diagnóstico é o exame clínico e avaliação histopatológica, que são subjetivos e dependem da experiência do médico e patologista envolvidos no procedimento. Considerando que o diagnóstico precoce é fundamental para alcançar um tratamento com resultados favoráveis, o presente trabalho utilizou a espectroscopia FTIR (Fourier transform infrared spectroscopy) para avaliar as alterações bioquímicas em pele normal causadas por lesões neoplásicas precursoras de carcinoma espinocelular. Para isto, as lesões foram induzidas quimicamente no dorso de camundongos Swiss via aplicação tópica de 9,10-dimetil-1,2-benzantraceno (DMBA) e 12-tetradecanoforbol-13-acetato (TPA) por um período de 28 semanas. Os espectros de absorção no infravermelho por transformada de Fourier foram coletados na região do infravermelho médio (4000-400 cm-1) no modo de reflexão total atenuada (ATR) e pré-processados para análise posterior. Considerou-se a amplitude da segunda derivada dos espectros de absorção como critério de comparação entre os grupos, nos quais foi observado redução de fibras colágenas e glicogênio no tecido neoplásico, assim como o aumento na intensidade de absorção de modos vibracionais associados a ácidos nucleicos e conteúdo proteico. A técnica de análise por agrupamento (HCA) foi utilizada para classificação dos espectros de tecidos normal e neoplásico, na qual obteve-se 92,6% de acurácia na discriminação dos dados. Diante disso, conclui-se que a espectroscopia FTIR associada a análise por agrupamento apresenta-se como uma potencial ferramenta para complementar a análise histopatológica na rotina clínica durante o diagnóstico de carcinoma espinocelular. / Nonmelanoma skin cancers represent 95% of cutaneous neoplasms, which squamous cell carcinoma (SCC) is the more aggressive form due to its invasive growth pattern and potentially metastatic. Histopathologycal analysis and clinical exam are the gold standard for diagnosis, which are subjective and depend on the experience of the physician and pathologist involved in the procedure. Considering that early diagnosis has fundamental importance to achieving a treatment with favorable results, this study used FTIR spectroscopy (Fourier transform Infrared spectroscopy) to assess the biochemical changes in normal skin caused by neoplastic lesions precursors of squamous cell carcinoma. For this, the lesions were chemically induced in the back of Swiss mice by topical application of 9,10- dimethyl-1,2-benzanthracene (DMBA) and 12 tetradecanoforbol-13-acetate (TPA) for a 28- week period. Fourier transform infrared spectra from normal and neoplastic tissue were collected in the mid-infrared region (4000-400 cm-1) using attenuated total reflection (ATR) sampling mode and pre-processed for group comparison. The amplitude of second derivative was considered as criteria for group comparison, which showed a reduction of collagen fibers and glycogen content in the neoplastic tissue, as well as increasing in the vibrational modes associated with nucleic acids and protein content. Hierarchical Cluster Analysis (HCA) was used for classification of spectra from neoplastic and normal tissue and obtained an accuracy of 92,6% sorting the data. In this sense, we conclude that FTIR spectroscopy associated with HCA presents as a potential tool for complementary histopathological analysis in the clinical diagnosis of squamous cell carcinoma.