Lesson 1 (2h) Introduction to Cancer. Definition, Epidemiology. Features overview of benign and malignant tumors. Solid tumors: parenchyma and stroma. Examples of tumors. Lesson 2 (2h) Introduction to Cancer. Natural history of cancer: multistage carcinogenesis, genetic and epigenetic modifications; clonal expansion; mutations, risk factors. Lesson 3 (2 h) Nomenclature, Histopathology. Classification, Staging, Grading. Lesson 4 (2h) Genetic and chromosome instability. DNA repair. Lesson 5 (2h) Familial and Genetic syndromes predisposing to cancer. Recap Lesson 6 (2h) Molecular Oncology 1: Oncogenes (classification). Main Oncogenes: c-MYC, RAS, BCL-2, BRAF, and others. Oncogene addiction. Signaling pathways Lesson 7 (2h) Molecular Oncology 2: Tumour Suppressors. Main Tumour Suppressor genes: TP53, PTEN, BECLIN1, BRCA1, TSC, and others. Signaling pathways Lesson 8 (2h) Epigenetics and Cancer. DNMT, HDAC, microRNAs. Recap Lesson 9 (2h) Cancer cell biology1: Control of cell proliferation, cell cycle; Telomerase Lesson 10 (2h) Cancer cell biology 2: Control of cell homeostasis; control of macromolecular turnover; Autophagy; Cancer cell biology 3: Control of Cell death (Apoptosis, Necrosis, Autophagic cell death). Lesson 11 (2h) Tumor Dormancy, cancer cell dormancy, cell senescence, Cancer Stem Cells.Lesson 12 (2h) Cancer cell metabolism: Glucose (Warburg effect), Amino Acids, Lipids. Lesson 13 (2h) Oncogenes and oncosuppressors and cancer cell metabolism. Recap of previous chapters Lesson 14 (2h) Tumour stroma. Cancer associated fibroblasts. Cancer inflammation. Immune response. Lesson 15 (2h) Cell adhesion. Invasion and Metastasis. Angiogenesis. Lesson 16 (2h) Aetiology; Gene – environment interaction; Lifestyle and Cancer (smoke, diet, alcohol). Recap Lesson 17 (2h) Aetiology of Cancer 2: Genotoxic and NON-genotoxic carcinogenesis (examples). Chemical Carcinogenesis. Indirect and Direct chemical carcinogens. DMS activation/excretion of chemical carcinogens. Nitrous Bases adducts. Lesson 18 (2h) Multistage carcinogenesis (initiation, promotion, progression. Cancer progression and Concept of clonal evolution Lesson 19 (2h) Infections and cancer; parasite infestation and cancer. Virus and carcinogenesis. Physical causes of cancer. Mineral fibers (Asbestos and mesothelioma pathogenesis). Radiation and cancer: direct and indirect effects. Ionizing radiation. UV radiation. Lesson 20 (2h) Chemotherapy and Mechanisms of chemoresistance. Recap Lesson 21 (2h) Cachexia and Anorexia in cancer patients. Cori’s cycle; adipose tissue metabolism.

A. Hematopoiesis and hematopoietic stem cell B. General concepts of myeloid neoplasia and chronic myeloid leukemia: general concepts, molecular pathology, molecular diagnostics and target treatment C. BCR/ABL negative myeloproliferative neoplasia (MPN): general concepts, molecular pathology, molecular diagnostics and target treatment D. General concepts on lymphoid neoplasia, Analysis of B-cell clonality, and Mantle cell lymphoma: general concepts, molecular pathology, molecular diagnostics and target treatment E. Follicular lymphoma: general concepts, molecular pathology, molecular diagnostics and target treatment F. Hairy cell leukemia and Burkitt lymphoma: general concepts, molecular pathology, molecular diagnostics and target treatment G. Lymphoplasmacytic lymphoma and Splenic marginal zone lymphoma: general concepts, molecular pathology, molecular diagnostics and target treatment H. Chronic lymphocytic leukemia: general concepts, molecular pathology, molecular diagnostics and target treatment I. Acute lymphoblastic leukemia and CAR T-cells: general concepts, molecular pathology, molecular diagnostics and target treatment J. Minimal residual disease (MRD); Precision Medicine, Clinical Trials and Benefit Sharing in Hematoncology

Review of general topics of Molecular Biology relevant to the understanding of the course. Chromatin Remodeling: Histone Modifications, DNA methylation Structural classes of transcription factors (Myc, Fos) Epigenetic definition: epigenetic diseases and epigenetic therapies. Oncogenes and tumor suppressor genes. P53 function in normal and tumoral cells. MDM2 as an oncogene. pRb function. Heterogeneity of tumors, stochastic and hierarchical theories, properties of cancer stem cells, their isolation, asymmetric and symmetric divisions. Signaling Pathways activated in cancer stem cells, therapeutic implications of cancer stem cells. Reprogramming of somatic cells to pluripotency by somatic cell nuclear transfer (SCNT) into oocytes. Fusion between somatic and pluripotent cells and ectopic expression of defined transcription factors. Sheep cloned by nuclear transfer (Dolly sheep). Induced pluripotent stem cells (iPS cells); Yamanaka papers; reprogramming by transcription factors; causes of low reprogramming efficiency. Parallelisms between epigenetic reprogramming and cancer. Therapeutic use of iPS Cells and embryonic stem cells. Gender Integration: Interactive lesson and classroom discussion on the topic "Women in Science": what their contribution has been and how their entry into the world of science has impacted their integration into society. Stem cells, cellular reprogramming and use of these cells in cell therapy protocols in preclinical and potential applications in the clinic. Isolation, in vitro expansion and preparation of cells for experimental cell therapy. Vectors used for gene transfer: viral vectors and non-viral. Origin, construction and modification. Modulation of Expression cassettes: Constitutive and regulated expression. transcriptional or post-transcriptional expression regulation Immune response to vectors and transgenes used in gene transfer. Concepts of ex vivo and in vivo gene therapy. Clinical trials using cell and gene therapy strategies of target diseases.

Stem cells, cellular reprogramming and use of these cells in cell therapy protocols in preclinical and potential applications in the clinic. Isolation, in vitro expansion and preparation of cells for experimental cell therapy. Vectors used for gene transfer: viral vectors and non-viral. Origin, construction and modification. Modulation of Expression cassettes: Constitutive and regulated expression. transcriptional or post-transcriptional expression regulation Immune response to vectors and transgenes used in gene transfer. Concepts of ex vivo and in vivo gene therapy. Clinical trials using cell and gene therapy strategies of target diseases.

Programma esteso/Content PROGR_EST 8050 Sì Ripasso di argomenti generali di Biologia Molecolare rilevanti per la comprensione del corso. Rimodellamento della cromatina: modificazioni degli istoni, metilazione del DNA Fattori di trascrizione Definizione epigenetica: malattie epigenetiche e terapie epigenetiche. Oncogeni e geni oncosoppressori. Funzione di P53 nelle cellule normali e tumorali. MDM2 come oncogene. Funzione di pRb. Eterogeneità dei tumori, teorie stocastiche e gerarchiche, proprietà delle cellule staminali tumorali, loro isolamento, divisioni asimmetriche e simmetriche. Vie di segnalazione attivate nelle cellule staminali tumorali, implicazioni terapeutiche delle cellule staminali tumorali. Riprogrammazione di cellule somatiche a pluripotenza mediante trasferimento nucleare di cellule somatiche (SCNT) in ovociti. Fusione tra cellule somatiche e pluripotenti ed espressione ectopica di fattori di trascrizione definiti. Pecore clonate mediante trasferimento nucleare (pecora Dolly). Cellule staminali pluripotenti indotte (cellule iPS); papers di Yamanaka; riprogrammazione da fattori di trascrizione; cause di bassa efficienza di riprogrammazione. Parallelismi tra riprogrammazione epigenetica e cancro. Uso terapeutico delle cellule iPS e delle cellule staminali embrionali. Review of general topics of Molecular Biology relevant to the understanding of the course. Chromatin Remodeling: Histone Modifications, DNA methylation Structural classes of transcription factors (Myc, Fos) Epigenetic definition: epigenetic diseases and epigenetic therapies. Oncogenes and tumor suppressor genes. P53 function in normal and tumoral cells. MDM2 as an oncogene. pRb function. Heterogeneity of tumors, stochastic and hierarchical theories, properties of cancer stem cells, their isolation, asymmetric and symmetric divisions. Signaling Pathways activated in cancer stem cells, therapeutic implications of cancer stem cells. Reprogramming of somatic cells to pluripotency by somatic cell nuclear transfer (SCNT) into oocytes. Fusion between somatic and pluripotent cells and ectopic expression of defined transcription factors. Sheep cloned by nuclear transfer (Dolly sheep). Induced pluripotent stem cells (iPS cells); Yamanaka papers; reprogramming by transcription factors; causes of low reprogramming efficiency. Parallelisms between epigenetic reprogramming and cancer. Therapeutic use of iPS Cells and embryonic stem cells. Programma esteso/Content PROGR_EST 8050 Sì Ripasso di argomenti generali di Biologia Molecolare rilevanti per la comprensione del corso. Rimodellamento della cromatina: modificazioni degli istoni, metilazione del DNA Fattori di trascrizione Definizione epigenetica: malattie epigenetiche e terapie epigenetiche. Oncogeni e geni oncosoppressori. Funzione di P53 nelle cellule normali e tumorali. MDM2 come oncogene. Funzione di pRb. Eterogeneità dei tumori, teorie stocastiche e gerarchiche, proprietà delle cellule staminali tumorali, loro isolamento, divisioni asimmetriche e simmetriche. Vie di segnalazione attivate nelle cellule staminali tumorali, implicazioni terapeutiche delle cellule staminali tumorali. Riprogrammazione di cellule somatiche a pluripotenza mediante trasferimento nucleare di cellule somatiche (SCNT) in ovociti. Fusione tra cellule somatiche e pluripotenti ed espressione ectopica di fattori di trascrizione definiti. Pecore clonate mediante trasferimento nucleare (pecora Dolly). Cellule staminali pluripotenti indotte (cellule iPS); papers di Yamanaka; riprogrammazione da fattori di trascrizione; cause di bassa efficienza di riprogrammazione. Parallelismi tra riprogrammazione epigenetica e cancro. Uso terapeutico delle cellule iPS e delle cellule staminali embrionali. Review of general topics of Molecular Biology relevant to the understanding of the course. Chromatin Remodeling: Histone Modifications, DNA methylation Structural classes of transcription factors (Myc, Fos) Epigenetic definition: epigenetic diseases and epigenetic therapies. Oncogenes and tumor suppressor genes. P53 function in normal and tumoral cells. MDM2 as an oncogene. pRb function. Heterogeneity of tumors, stochastic and hierarchical theories, properties of cancer stem cells, their isolation, asymmetric and symmetric divisions. Signaling Pathways activated in cancer stem cells, therapeutic implications of cancer stem cells. Reprogramming of somatic cells to pluripotency by somatic cell nuclear transfer (SCNT) into oocytes. Fusion between somatic and pluripotent cells and ectopic expression of defined transcription factors. Sheep cloned by nuclear transfer (Dolly sheep). Induced pluripotent stem cells (iPS cells); Yamanaka papers; reprogramming by transcription factors; causes of low reprogramming efficiency. Parallelisms between epigenetic reprogramming and cancer. Therapeutic use of iPS Cells and embryonic stem cells.

Topic 1 Regulation of gene expression. Recall of the organization of genes in eukaryotes (enhancers, promoters, transcription initiation site, introns / exons, transcription termination sites). Control of gene transcription at the level of: a) transcription initiation rate, 2) alternative splicing and splicing, 3) mRNA stability, 4) interference between RNA and microRNA. Organization of transcription factors: structure of DNA binding and transactivation domains. Main DNA regulatory sequences. Assembly of the RNApolII transcription initiation complex and hints for other polymerases. Methods for studying the regulatory elements on DNA, the structure of the promoters and the binding sites of transcription factors. Transcription factors and chromatin structure, gene expression and chromatin remodeling. Post transcriptional modifications of histones and the histone code. DNA methylation. Other ways to regulate gene expression: alternative promoters, alternative splicing, mRNA stability control, mRNA translation control, miRNA and RNA interference. Topic 2 Control of gene expression by extracellular and intracellular signals. How the signal transduction pathways regulate gene expression: - the nuclear receptor family - the STAT family - ERK signaling for the serum response elements, NF-kB. Methods of studying signal transduction. Topic 3 mutations in transcription factors and cancer Mutations of P53 and tumorigenesis, Hif formation in response to hypoxia, myc and tumor amplification. Case studies: 1) transcription factors and tumor metabolism, 2) how alterations in metabolism (ie nutritional habits or cellular energy status) influence gene expression and chromatin status. Short simulated or face-to-face laboratory experiences on basic techniques.

Complexity of the human genome and role of non-coding elements in contributing to genome complexity. Definition of mammalian transcriptome and history of the discovery of lncRNAs Features of lncRNAs in comparison with those of protein-coding mRNAs Description of the experimental procedures used to discover lncRNA features Antisense transcription Description of lncRNA functions Therapeutic applications of lncRNAs: present and future prospects Seminar-type discussion on a newly discovered lncRNA: features and function (experimental details will also be discussed).

The course deals with basic virology and virological terminology. The effect of virus infection at organism level is addressed. The focus of the course is on molecular virology, especially on virus replication in the infected cell and the molecular mechanisms of this. A selected set of relevant human viruses, differing in their genome structure (RNA versus DNA, circular versus linear) and in their virion architecture will be discussed, the content of the course being specialised with respect to molecular biology, molecular genetics, recombinational events, virus-host interactions and innate immunity. The focus is on medically important viruses, such as tumour viruses, hepatitis viruses, HIV and herpesviruses.

Cystic fibrosis: clinical diagnosis and principles of gene therapy The lung cancer (overview of gene therapy and targeted-therapy) Biotechnological aspects in the study of neuro-degenerative diseases Biotechnological aspects in the study of neuro-inflammatory diseases Aspects of the biotechnological treatment of viral hepatitis The biological basis of treatment of autoimmune diseases The biological basis of treatment of diabetes mellitus Pathophysiological aspects of paraneoplastic hypercalcemia Strategies for the use of biotechnology against doping in sport Use of new biomarkers in emergency medicine

General mechanisms of the endocrine system. Role of biotechnology for the classification, characterization, understanding and treatment of endocrine diseases. Molecular and genetic mechanisms of hypothalamic-pituitary pathologies and neuroendocrine tumors as a model of the use of biotechnologies in single and combination pharmacological targeting. Endocrine disruptors. Diseases of thyroid function, sporadic and hereditary thyroid tumors, characterization of the molecular targets of therapy. Adrenal pathophysiology, diseases of the adrenal cortex and medulla, genetic implications. Polygenic basis of metabolic diseases) obesity and diabetes), target central and peripheral endocrine-metabolic diseases. Gonadal dysfunction, hypogonadism, polycystic ovary syndrome.

1) evolution of reproduction (polytocic, monotocic, altricialiity, selection of the dominated follicle, meiosis, mitosis) 2) etiology of infertility (unexplained uterine tubal ovarian causes) 3) medical infertility therapy (clomiphene citrate, gonadotropins) 4) art techniques (seminal fluid preparation, IVF, icsi, oocyte freezing, embryonic freezing) 5) preimplantation genetics

The course aims to provide students with the fundamental principles of pharmacology, including: -the process of discovery, development, and approval of new drugs; -clinical trials and the collection of evidence regarding the benefits and risks of drugs; -general principles of drug action (pharmacodynamics); -pharmacokinetics (absorption, distribution, metabolism, excretion); -pharmacogenetic biomarkers; -general principles of pharmacovigilance; -description of the pharmacological profile of biotechnological drugs that have revolutionized pharmacological treatment in various pathological conditions, including oncological, neurological, metabolic, and cardiovascular diseases.

Introduction to metagenomics. Microbiome and Microbiota. The Human Microbiome Project. Alpha and Beta diversity. The human gut microbiota: composition, origin, and variations. Functions of the gut microbiota: protection against pathogens and metabolic functions. The microbiota and the gut-brain axis. Intestinal dysbiosis in aging, in metabolic diseases (obesity and type-2 diabetes), and neurological and neurodegenerative diseases (depression, autism, and Alzheimer’s Disease). Description of the main Next Generation Sequencing platforms (Illumina and Nanopore) and their applications in biomedical research and personalized medicine. 16S rRNA sequencing for microbiome analysis: advantages and disadvantages. Shotgun sequencing for microbiome analysis: advantages and disadvantages. Overview of the main bioinformatics tools for metagenomic data analysis. Introduction to metatranscriptomics. Presentation and discussion of scientific articles related to metagenomics.

Please, consult the program of each course. It should be noted that the integrated course also includes lessons and moments of reflection aimed at “gender integration”. In particular, the Forensomics course will address the issue of gender-based violence, and students will be invited to explore the topic in greater depth with supplementary material.

Forensic genomics: Crime Scene Investigation, characterization of evidence, forensic genetics (human identification, ancestry, phenotyping, DNA methylation) Microbiome and forensic sciences: human identification, estimation of PMI, causes of death, prediction of chronological age Forensic metabolomics and lipidomics: instruments and estimation of PMI Forensic proteomics: instruments and estimation of PMI, prediction of chronological age, human identification Forensic transcriptomics: RNA and body fluids identification, RNA and estimation of PMI. Thanatology: definition of death, algor, livor, rigor, post-mortal transformative phenomena, estimation of post-mortem interval. Anthropological identification of unknown corpses and living people: biological profile, age estimation, facial approximation, identification methods. Migrants and humanitarian forensic medicine. Gender-based violence: further exploration of this issue falls within the scope of ‘Gender mainstreaming’.

Review of basic concepts on the structure, organization and functioning of the human genome. The Ensembl database, description and operation. Structure of a human gene in Ensembl, sequence information retrieval, protein structure, functional and clinical annotations. The UCSC browser genome, description and operation. UCSC structure and annotation of a human gene, retrieval of functional and expression information. Introduction to NGS Sequencing. Illumina sequencing methodology. Introduction to RNA-seq methodology. Design of an RNA-seq experiment and related bioinformatics data analysis. Cancer genomics and the TCGA project. Introduction to systems biology and network theory. Examples of networks in biology and genomics. Basic elements of the Python programming language. The Google Colab environment. Examples of research articles available on Pubmed discussing topics related to arguments related to the course.

See content of the single modules

Nano-structured particles and materials, nano and micro porosity, surface textures and their effects on tissue engineering and regeneration. Sensors Drug Delivery Systems Systems for gene delivering

Introduction to biomaterials and classification Metals and alloys in biomedical applications Ceramics, glasses, and glass-ceramics Polymers and hydrogels Composites and biohybrid materials Biofabrication techniques (additive manufacturing, coatings, conventional processing) Mechanical, chemical, and biological characterization methods Case studies and clinical applications

1. basics on biomechanics of the osteoarthroarticular system 2. functional anatomy of the heart and cardiovascular system

- Brief summary of body organization (cells, tissues, organs) - Stem cells and regeneration - Main stem cells characteristics and functions: embryonic and adult stem cells, induced pluripotent stem cells - Stem cell localization and differentiation in different tissues (symmetric and asymmetric division) - Embryonic and adult stem cell isolation, characterization and maintenance in culture - Regulation of stem cell differentiation - Biology and applications of hematopoietic, mesenchymal and neural stem cells - Stem cell-based therapies: nowadays and future applications

The role of immune system in tissue regeneration. Innate and adaptive immunity. The phases of tissue healing and immune cell polarization. Tissue regeneration: methods involving stem cells, biomaterials, drug delivery systems

Lesson 1 (2h) Introduction to Cancer. Definition, Epidemiology. Features overview of benign and malignant tumors. Solid tumors: parenchyma and stroma. Examples of tumors. Lesson 2 (2h) Introduction to Cancer. Natural history of cancer: multistage carcinogenesis, genetic and epigenetic modifications; clonal expansion; mutations, risk factors. Lesson 3 (2 h) Nomenclature, Histopathology. Classification, Staging, Grading. Lesson 4 (2h) Genetic and chromosome instability. DNA repair. Lesson 5 (2h) Familial and Genetic syndromes predisposing to cancer. Recap Lesson 6 (2h) Molecular Oncology 1: Oncogenes (classification). Main Oncogenes: c-MYC, RAS, BCL-2, BRAF, and others. Oncogene addiction. Signaling pathways Lesson 7 (2h) Molecular Oncology 2: Tumour Suppressors. Main Tumour Suppressor genes: TP53, PTEN, BECLIN1, BRCA1, TSC, and others. Signaling pathways Lesson 8 (2h) Epigenetics and Cancer. DNMT, HDAC, microRNAs. Recap Lesson 9 (2h) Cancer cell biology1: Control of cell proliferation, cell cycle; Telomerase Lesson 10 (2h) Cancer cell biology 2: Control of cell homeostasis; control of macromolecular turnover; Autophagy; Cancer cell biology 3: Control of Cell death (Apoptosis, Necrosis, Autophagic cell death). Lesson 11 (2h) Tumor Dormancy, cancer cell dormancy, cell senescence, Cancer Stem Cells.Lesson 12 (2h) Cancer cell metabolism: Glucose (Warburg effect), Amino Acids, Lipids. Lesson 13 (2h) Oncogenes and oncosuppressors and cancer cell metabolism. Recap of previous chapters Lesson 14 (2h) Tumour stroma. Cancer associated fibroblasts. Cancer inflammation. Immune response. Lesson 15 (2h) Cell adhesion. Invasion and Metastasis. Angiogenesis. Lesson 16 (2h) Aetiology; Gene – environment interaction; Lifestyle and Cancer (smoke, diet, alcohol). Recap Lesson 17 (2h) Aetiology of Cancer 2: Genotoxic and NON-genotoxic carcinogenesis (examples). Chemical Carcinogenesis. Indirect and Direct chemical carcinogens. DMS activation/excretion of chemical carcinogens. Nitrous Bases adducts. Lesson 18 (2h) Multistage carcinogenesis (initiation, promotion, progression. Cancer progression and Concept of clonal evolution Lesson 19 (2h) Infections and cancer; parasite infestation and cancer. Virus and carcinogenesis. Physical causes of cancer. Mineral fibers (Asbestos and mesothelioma pathogenesis). Radiation and cancer: direct and indirect effects. Ionizing radiation. UV radiation. Lesson 20 (2h) Chemotherapy and Mechanisms of chemoresistance. Recap Lesson 21 (2h) Cachexia and Anorexia in cancer patients. Cori’s cycle; adipose tissue metabolism.

A. Hematopoiesis and hematopoietic stem cell B. General concepts of myeloid neoplasia and chronic myeloid leukemia: general concepts, molecular pathology, molecular diagnostics and target treatment C. BCR/ABL negative myeloproliferative neoplasia (MPN): general concepts, molecular pathology, molecular diagnostics and target treatment D. General concepts on lymphoid neoplasia, Analysis of B-cell clonality, and Mantle cell lymphoma: general concepts, molecular pathology, molecular diagnostics and target treatment E. Follicular lymphoma: general concepts, molecular pathology, molecular diagnostics and target treatment F. Hairy cell leukemia and Burkitt lymphoma: general concepts, molecular pathology, molecular diagnostics and target treatment G. Lymphoplasmacytic lymphoma and Splenic marginal zone lymphoma: general concepts, molecular pathology, molecular diagnostics and target treatment H. Chronic lymphocytic leukemia: general concepts, molecular pathology, molecular diagnostics and target treatment I. Acute lymphoblastic leukemia and CAR T-cells: general concepts, molecular pathology, molecular diagnostics and target treatment J. Minimal residual disease (MRD); Precision Medicine, Clinical Trials and Benefit Sharing in Hematoncology

Lesson 1 (2h) Introduction to Cancer. Definition, Epidemiology. Features overview of benign and malignant tumors. Solid tumors: parenchyma and stroma. Examples of tumors. Lesson 2 (2h) Introduction to Cancer. Natural history of cancer: multistage carcinogenesis, genetic and epigenetic modifications; clonal expansion; mutations, risk factors. Lesson 3 (2 h) Nomenclature, Histopathology. Classification, Staging, Grading. Lesson 4 (2h) Genetic and chromosome instability. DNA repair. Lesson 5 (2h) Familial and Genetic syndromes predisposing to cancer. Recap Lesson 6 (2h) Molecular Oncology 1: Oncogenes (classification). Main Oncogenes: c-MYC, RAS, BCL-2, BRAF, and others. Oncogene addiction. Signaling pathways Lesson 7 (2h) Molecular Oncology 2: Tumour Suppressors. Main Tumour Suppressor genes: TP53, PTEN, BECLIN1, BRCA1, TSC, and others. Signaling pathways Lesson 8 (2h) Epigenetics and Cancer. DNMT, HDAC, microRNAs. Recap Lesson 9 (2h) Cancer cell biology1: Control of cell proliferation, cell cycle; Telomerase Lesson 10 (2h) Cancer cell biology 2: Control of cell homeostasis; control of macromolecular turnover; Autophagy; Cancer cell biology 3: Control of Cell death (Apoptosis, Necrosis, Autophagic cell death). Lesson 11 (2h) Tumor Dormancy, cancer cell dormancy, cell senescence, Cancer Stem Cells.Lesson 12 (2h) Cancer cell metabolism: Glucose (Warburg effect), Amino Acids, Lipids. Lesson 13 (2h) Oncogenes and oncosuppressors and cancer cell metabolism. Recap of previous chapters Lesson 14 (2h) Tumour stroma. Cancer associated fibroblasts. Cancer inflammation. Immune response. Lesson 15 (2h) Cell adhesion. Invasion and Metastasis. Angiogenesis. Lesson 16 (2h) Aetiology; Gene – environment interaction; Lifestyle and Cancer (smoke, diet, alcohol). Recap Lesson 17 (2h) Aetiology of Cancer 2: Genotoxic and NON-genotoxic carcinogenesis (examples). Chemical Carcinogenesis. Indirect and Direct chemical carcinogens. DMS activation/excretion of chemical carcinogens. Nitrous Bases adducts. Lesson 18 (2h) Multistage carcinogenesis (initiation, promotion, progression. Cancer progression and Concept of clonal evolution Lesson 19 (2h) Infections and cancer; parasite infestation and cancer. Virus and carcinogenesis. Physical causes of cancer. Mineral fibers (Asbestos and mesothelioma pathogenesis). Radiation and cancer: direct and indirect effects. Ionizing radiation. UV radiation. Lesson 20 (2h) Chemotherapy and Mechanisms of chemoresistance. Recap Lesson 21 (2h) Cachexia and Anorexia in cancer patients. Cori’s cycle; adipose tissue metabolism.

A. Hematopoiesis and hematopoietic stem cell B. General concepts of myeloid neoplasia and chronic myeloid leukemia: general concepts, molecular pathology, molecular diagnostics and target treatment C. BCR/ABL negative myeloproliferative neoplasia (MPN): general concepts, molecular pathology, molecular diagnostics and target treatment D. General concepts on lymphoid neoplasia, Analysis of B-cell clonality, and Mantle cell lymphoma: general concepts, molecular pathology, molecular diagnostics and target treatment E. Follicular lymphoma: general concepts, molecular pathology, molecular diagnostics and target treatment F. Hairy cell leukemia and Burkitt lymphoma: general concepts, molecular pathology, molecular diagnostics and target treatment G. Lymphoplasmacytic lymphoma and Splenic marginal zone lymphoma: general concepts, molecular pathology, molecular diagnostics and target treatment H. Chronic lymphocytic leukemia: general concepts, molecular pathology, molecular diagnostics and target treatment I. Acute lymphoblastic leukemia and CAR T-cells: general concepts, molecular pathology, molecular diagnostics and target treatment J. Minimal residual disease (MRD); Precision Medicine, Clinical Trials and Benefit Sharing in Hematoncology

Review of basic concepts on the structure, organization and functioning of the human genome. The Ensembl database, description and operation. Structure of a human gene in Ensembl, sequence information retrieval, protein structure, functional and clinical annotations. The UCSC browser genome, description and operation. UCSC structure and annotation of a human gene, retrieval of functional and expression information. Introduction to NGS Sequencing. Illumina sequencing methodology. Introduction to RNA-seq methodology. Design of an RNA-seq experiment and related bioinformatics data analysis. Cancer genomics and the TCGA project. Introduction to systems biology and network theory. Examples of networks in biology and genomics. Basic elements of the Python programming language. The Google Colab environment. Examples of research articles available on Pubmed discussing topics related to arguments related to the course.

1. Introduction to clinical trials -Role of experimental studies in biomedical research -Observational vs experimental designs -Overview of clinical trial phases 2.Formulation of the research question -From hypothesis to trial design -PICO framework -Clinical vs surrogate endpoints 3.Main trial designs -Parallel-group randomized trials -Cross-over trials -Cluster randomized trials -Pragmatic vs explanatory trials 4.Internal validity and bias -Selection bias -Information bias -Confounding in experimental studies -Randomization, allocation concealment, blinding 5.Key design elements -Eligibility criteria -Control groups (placebo vs active comparator) -Definition and hierarchy of endpoints -Feasibility and ethical considerations 6.Modern clinical trial designs -Adaptive trials: concept and main features -Platform trials and master protocols -Basket and umbrella trials -Advantages, limitations, and applicability.

Cystic fibrosis: clinical diagnosis and principles of gene therapy The lung cancer (overview of gene therapy and targeted-therapy) Biotechnological aspects in the study of neuro-degenerative diseases Biotechnological aspects in the study of neuro-inflammatory diseases Aspects of the biotechnological treatment of viral hepatitis The biological basis of treatment of autoimmune diseases The biological basis of treatment of diabetes mellitus Pathophysiological aspects of paraneoplastic hypercalcemia Strategies for the use of biotechnology against doping in sport Use of new biomarkers in emergency medicine

The frequency distribution. Measures of Central Tendency and dispersion. Properties of Probability. Probability distribution: the Poisson and normal distribution. Sampling distribution. Distribution of the sample mean. Confidence interval. Hypothesis testing: a single population mean, the difference between two population means, a single population proportion. Type I and type II error and the power of a test. Chi-square test. Odds ratio. The correlation coefficient and the regression model. Survival analysis.

Good manufacturing practice (GMP) procedures and the regulatory framework; differences and similarities between GMP facilities, cell factories, clean rooms, etc., and the laws governing their activities; therapeutic procedures requiring a GMP facility; the Technical Director of a GMP facility and his or her characteristics; innovative processes leading to drug development (GCP); the design and phases of clinical trials for new drugs; certification/accreditation of diagnostic laboratories and procedures for developing a diagnostic kit; internal and external quality controls; general criteria and regulatory framework for patent procedures; biobanking and the preservation of biological samples; informed consent.

- Health concept -Promotion and prevention - Determinants and risk factors Tools for measuring health -Epidemiology - frequency measurements - association measures - bias, confounding Critical reading of a scientific article and in particular: - identification of the knowledge on which the work is based; - hypotheses and objectives of the research; - recognition of the research design - transversal - cohort - case-control - experimental

A. Introduction to Clinical Trials in Hematology B. Clinical Study Design C. Hematologic Endpoints D. Regulatory Considerations and Ethics E. Safety and Pharmacovigilance F. Advanced Technologies G. Disease-Specific Trials H. Role of the Clinical Trial Unit.

General mechanisms of the endocrine system. Role of biotechnology for the classification, characterization, understanding and treatment of endocrine diseases. Molecular and genetic mechanisms of hypothalamic-pituitary pathologies and neuroendocrine tumors as a model of the use of biotechnologies in single and combination pharmacological targeting. Endocrine disruptors. Diseases of thyroid function, sporadic and hereditary thyroid tumors, characterization of the molecular targets of therapy. Adrenal pathophysiology, diseases of the adrenal cortex and medulla, genetic implications. Polygenic basis of metabolic diseases) obesity and diabetes), target central and peripheral endocrine-metabolic diseases. Gonadal dysfunction, hypogonadism, polycystic ovary syndrome.

1. Computer Architecture & Data Representation 1a. The Hardware Layer: How the CPU, RAM, and Storage interact during data processing. 1b. Binary & Logic: How biological information (like DNA sequences) is translated into 0s and 1s. 1c. Memory Management: The difference between volatile memory (RAM) and permanent storage (SSD/Cloud). 2. Systems & Networking 2a. Operating Systems (OS): The role of the kernel and file systems in organizing research data. 2b. The Internet & APIs: How "The Cloud" works. Understanding how to request data from remote biomedical servers (like NCBI) using the HTTP protocol. 2c. Virtual Environments: Introduction to Jupyter Notebooks and Google Colab as research workstations. 3: Programming Logic with Python 3a. Foundations: Variables, data types (Integers, Floats, Strings), and basic arithmetic. 3b. Control Flow: Using if statements for decision-making and for loops to process lists of patient records. 3c. Functional Thinking: Writing basic functions to make code reusable across different datasets. 4. Data Manipulation & Matrix Analysis 4a. NumPy: Understanding "Vectorization"—why math is faster when done on entire arrays at once. 4b. Pandas: Learning the "DataFrame" structure. How to load, filter, and group tabular clinical data. 4c. Data Cleaning: Handling missing values (NaN) and correcting sensor errors in experimental results. 5. Data Science & Visualization 5a. Exploratory Data Analysis: Using .describe() and .groupby() to find trends in biological populations. 5b. Visualization with Seaborn/Matplotlib: Creating histograms, scatter plots, and boxplots. 5c. Reproducible Reporting: Best practices for documenting code and results so other scientists can verify the findings.

Introduction to data management, data formats, importing/exporting in Excel and R, data cleaning, variable transformation, filters and pivot tables, introduction to R and RStudio, dataset handling, derived variable creation, descriptive analysis and basic plots, practical exercises with biomedical datasets.

The cell: structure and function. Differences between prokaryotic and eukaryotic cells. Nucleoid and organization of genetic material in bacteria. Nucleus and nuclear envelope in eukaryotic cells. Reorganization of genetic material, and how post-transcriptional modifications influence the transcriptional process. Cytoplasm and structure and function of organelles: endoplasmic reticulum, Golgi apparatus, mitochondrion, and peroxisomes. Cytoskeleton with microfilaments, intermediate filaments, and microtubules. Extracellular matrix: cell-cell and cell-matrix adhesion. Secretory vesicles. Chloroplasts and vacuoles in plant cells. Passive and active transport across the plasma membrane. Transport of proteins from the nucleus to the cytosol. Mechanisms of replication, transcription, and translation. Role of protein-coding and non-coding RNAs.