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.

The Molecular Biology of Cancer
S-Pelengaris and M. Khan
(Wiley-Blackwell edition)

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. Recognize the histopathological characteristics of the main human neoplasms;
Understand which molecular and cellular alterations determine
the neoplastic phenotype; Reason about the natural causes of carcinogenesis and
the factors that can determine tumor recurrence, keeping in mind the
role of defense systems at the molecular, cellular and organismal level;
Describe the distinctive characteristics (morphological, metabolic,
behavioral) of neoplastic stem cells. Know the
mechanisms responsible for tumor infiltration and metastasis;
Be able to illustrate how the stromal microenvironment that
surrounds the tumor changes and how this can favor neoplastic growth.
Recognize the clinical signs and be able to describe the molecular and
physiopathological mechanisms of neoplastic cachexia.
EXPECTED KNOWLEDGE AND SKILLS
At the end of the course the student must be able to tackle the
reading and analysis of scientific articles on the cellular and
molecular biology of neoplasms (during the course each student must present a
scientific article related to a topic covered).
Learning outcomes: Knowledge of the cellular
and molecular mechanisms underlying the carcinogenesis process. Dynamics
of neoplastic populations. Natural history of neoplasms. Risk
factors for the development of neoplasms.

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.

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.

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.