Ateneo - UPO

1. the epidemiologic relevance of Cancer; the influence of the
environment and of the life style.
2. the main histopathologic characteristics of the tumours and their
classification
3. the molecular alterations responsible for the malignant behaviour of
tumour cells (loss of proliferative control; resistance to apoptosis;
invasiveness; altered metabolism of glucose, aminoacids and fatty acids;
altered proteome homeostasis); the role of autophagy and of cell death in
cancer
4. the role of genetics and epigenetics in cancer development and
progression; the genetic defects that predispose to cancer; genome
(chromosomal translocation) alterations and gene mutations (oncogenes,
oncosuppressors) associated with cancer
5. the origin and phenotypic characteristics of Cancer Stem Cells; the
genetic and metabolic re-programming leading to cancer
6. the mechanisms of metastasis formation; the role of proteolytic
enzymes
7. the inter-relationship between tumour cells and the tumour stroma,
with particular regard to the role of cancer associated fibroblasts and of
ruolo delle mutazioni genomiche, genetiche e epigenetiche; le alterazioni
del metabolismo (glicidico, aminoacidico e lipidico) della cellula tumorale;
le basi molecolari e metaboliche della cachessia neoplastica; nuovi
approcci diagnostici e terapeutici. Il punteggio massimo è 30 + Laude /
30.
NOTA: 1. il punteggio finale è concordato tra i due docenti dei moduli A e
B, tenuto conto delle valutazioni complessive; 2. se solo uno dei due
moduli (A o B) non è superato, lo studente deve ripetere l'esame per
entrambi i moduli (A e B) in una nuova sessione.
Per accedere all'esame lo studente deve aver compilato il form di
valutazione del docente.
Programma esteso Le malattie neoplastiche: definizioni e terminologia, classificazione e
derivazione istogenetica. Epidemiologia. Eziologia multifattoriale. Fattori
di rischio di natura chimica, fisica e biologica. Cancerogeni chimici.
Radiazioni e tumori. Virus oncogeni. Storia naturale delle neoplasie. La
cancerogenesi come processo multifasico. Ormoni nella cancerogenesi.
Stile di vita (alimentazioni, obesità, abitudini voluttuarie) e cancro. Eventi
genetici ed epigenetici nella cancerogenesi. STROMA E CANCRO. Ruolo
del processo infiammatorio. Ipossia. Angiogenesi nelle neoplasie.
Accrescimento infiltrativo/invasivo dei tumori maligni (adesione-motilità).
Le metastasi (proteasi). Transizione epitelio-mesenchima. CANCRO E
OSPITE La progressione neoplastica. Effetti sistemici del tumore
sull’ospite: la cachessia neoplastica. Immunità e Cancro. ONCOLOGIA
CELLULARE E MOLECOLARE Le Telomerasi e Cancro, MicroRNAs e Cancro,
La Riparazione del DNA e Cancro. Determinanti molecolari della
trasformazione neoplastica: oncogeni e geni oncosoppressori.
METABOLISMO DELLA CELLULA NEOPLASTICA Alterazioni del metabolismo
glicidico nelle cellule neoplastiche (l’effetto Warburg e la proliferazione
cellulare). Alterazioni del turnover proteico: Ubiquitina, autofagia e
cancro. CICLO CELLULARE – PROLIFERAZIONE – MORTE CELLULARE
apoptosi, senescenza cellulare e ‘dormancy’ . La cellula staminale
tumorale. Meccanismi di chemio resistenza Le terapie
antineoplastiche:convenzionali, molecolari.
Risultati di
apprendimento attesi
Conoscere le cause e i meccanismi di cancerogenesi e di progressione
tumorale. Saper interpretare, discutere e presentare i risultati
sperimentali di laboratorio o presenti in letteratura specificamente volti
alla descrizione e comprensione della trasformazione neoplastica e del
comportamento delle cellule tumorali.
immune cells;
8. the molecular and patho-physiological mechanisms responsible for the
cachexia syndrome.
9. the current techniques for Diagnosis (imaging, biomarkers) and the
therapeutic treatments available (chemical chemotherapy, biomolecular
therapy).
10. Novel therapeutic approach (epigenetics); novel paradigms for
carcinogenesis (microbioma);

The Molecular Biology of Cancer
S-Pelengaris and M. Khan
(Wiley-Blackwell edition)
Chapter 7 NEOPLASIA by Thomas P Stricker and V Kumar (from Robbins,
The molecular Basis of Disease)
A copy of the slides will be provided
http://www.insidecancer.org
http://www.oncolink.com/
http://www.cancer.gov

The course will provide students with fundaments of general oncology
and knowledge about cellular and molecular mechanisms involved in
carcinogenesis, as well as about experimental approaches in the field of
oncological research.

The students must possess the basic knowledge in cell and molecular
biology and in biochemistry.

Interactive lesson continuously involving students with questions to
stimulate curiosity and verify the understanding of concepts.
Process illustration with practical examples. Discussion of relevant
scientific articles.

Students are welcome to spend a period in the laboratory of Molecular
Pathology to participate in the design, execution and discussion of
experiments. CFU will be assigned based on the duration of the stage.
Students will be involved in Journal Club meetings in which scientific
papers relevant for their preparation will be discussed.

The student can choose between two exam formats (“Basic” or
“Advanced”), according to the level of preparation they believe they have
reached. All written and oral questions are chosen from a list of questions
made available on the teacher's website, in order to allow the student to
take a self-assessment test.
The "Basic" format consists of a written test which is not followed by the
oral exam. The assignment consists of 5 “true or false statements” and
the student will have to answer 4 questions justifying the answer with a
supporting explanation in about 10 lines. You have 1 hour at your
disposal. The correct and exhaustive answer is worth 6 points (maximum
achievable score 24/30). The topics of the "Basic" program include
nomenclature, epidemiology, cytological and histological characteristics,
characteristics of the malignant phenotype, chemical and radiation
carcinogenesis, glucose metabolism.
The "Advanced" format includes a written assignment with 3 questions
(30 minutes) followed by an oral exam (3 questions) and the discussion of
a scientific article (as desired, from a list prepared by the teacher). The
"Advanced" exam program integrates the "basic" with an in-depth study
of the alterations of the molecular signaling pathways; cell cycle control;
telomerase; cancer stem cell; the role of genomic, genetic, and
epigenetic mutations; alterations in the (glucose, amino acid and lipid)
metabolism of the cancer cell; the molecular and metabolic bases of
neoplastic cachexia; new diagnostic and therapeutic approaches. The
maximum score is 30 + Laude / 30.
NOTE: 1. the final score is agreed between the two teachers of modules A
and B, taking into account the overall assessments; 2. if only one of the
two modules (A or B) is not passed, the student must repeat the exam for
both modules (A and B) in a new session.
NOTE:
To access the exam the student must have filled up the course
evaluation form.

Introduction to Cancer. Definition, Epidemiology. Features overview of benign and malignant tumors. Solid tumors: parenchyma and stroma. Examples of tumors.
Introduction to Cancer. Natural history of cancer: multistage carcinogenesis, genetic and epigenetic modifications; clonal expansion;
mutations, risk factors.
Nomenclature, Histopathology. Classification, Staging, Grading.
Genetic and chromosome instability. DNA repair.
Familial and Genetic syndromes predisposing to cancer.

Molecular Oncology 1: Oncogenes (classification). Main Oncogenes: c-MYC, RAS, BCL-2, BRAF, and others. Oncogene addiction. Signaling pathways

Molecular Oncology 2: Tumour Suppressors. Main Tumour Suppressor genes: TP53, PTEN, BECLIN1, BRCA1, TSC, and others. Signaling pathways

Epigenetics and Cancer. DNMT, HDAC, microRNAs. Cancer cell biology1: Control of cell proliferation, cell cycle; Telomerase 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).
Tumor Dormancy, cancer cell dormancy, cell senescence, Cancer Stem Cells.
Cancer cell metabolism: Glucose (Warburg effect), Amino Acids, Lipids.
Oncogenes and oncosuppressors and cancer cell metabolism.
Recap of previous chapters
Tumour stroma. Cancer associated fibroblasts. Cancer inflammation. Immune response.
Cell adhesion. Invasion and Metastasis. Angiogenesis.
Aetiology; Gene – environment interaction; Lifestyle and Cancer (smoke, diet, alcohol).
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.
Multistage carcinogenesis (initiation, promotion, progression. Cancer progression and Concept of clonal evolution. 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.
Chemotherapy and Mechanisms of chemoresistance.
Cachexia and Anorexia in cancer patients. Cori’s cycle; adipose tissue metabolism.
Microbiota and probiotics and cancer.

Knowing the causes and mechanisms of carcinogenesis and tumor
progression. Knowing how to interpret, discuss and present the
experimental laboratory results or found in literature, specifically aimed
at describing and understanding the neoplastic transformation and
behavior of tumor cells.