Cancer Biology Jasmina Makarevic ATTA-UR-RAHMAN SCHOOL OF APPLIED BIOSCIENCES (ASAB) Cancer Biology Jasmina Makarevic Fall Semester 2016

Infection with Bacteria At the moment the best know infectins with bacteria causing cancer, are the infection of Clamydia trochamytis and Helicobacter pylori. Jasmina Makarevic

Clamydia Trochamytis Clamydia trochamatis deals as a possible cofactor of human papillomavirus which leads to cervical cancer. Chlamydia coat themselves with a growth factor made by the cells of the organism they are infecting. This disguise allows the bacteria to infect cells, much like a Trojan horse. Once inside, Chlamydia induces the host cell to turn out more of the growth factor. This production of excess growth factor enables more of bacteria to camouflage themselves and infect other cells creating a positive feedback loop which enhances bacterial infection and spread. The Pgp3 protein is a chlamydial virulence factor that is hypothesized to enhance the bug's ability to initially infect its human host and then evade host defenses. Jasmina Makarevic

Helicobacter pylori Two mechanisms are described: Up to 85% of people infected with H. pylori never experience symptoms or complications. Acute infection may appear as an acute gastritis with abdominal pain (stomach ache) or nausea. Where this develops into chronic gastritis. Individuals infected with H. pylori have a 10 to 20% lifetime risk of developing peptic ulcers and a 1 to 2% risk of acquiring stomach cancer. Two mechanisms are described: One mechanism involves the enhanced production of free radicals near H. pylori and an increased rate of host cell mutation. The other proposed mechanism has been called a "perigenetic pathway", and involves enhancement of the transformed host cell phenotype by means of alterations in cell proteins, such as adhesion proteins. H. pylori has been proposed to induce inflammation and locally high levels of TNF-α and/or interleukin 6 (IL-6). According to the proposed perigenetic mechanism, inflammation-associated signaling molecules, such as TNF-α, can alter gastric epithelial cell adhesion and lead to the dispersion and migration of mutated epithelial cells without the need for additional mutations in tumor suppressor genes, such as genes that code for cell adhesion proteins. Jasmina Makarevic

Growth Factors Jasmina Makarevic

Mutations Def.: Change in the genotype of a species that may involve an alteration in the nucleotide sequence of a DNA segment, the arrangement of a segment within a chromosome, the number of copies of a segment, the physical structure of a chromosome, or even the number of copies of a structural normal chromosome. What does this mean? Mutations are responsible: Changing content of a gene Converting one allel into anathor Creating a new allel frome one previosly widespreaded Wild-typeMutant Jasmina Makarevic

Mutations Jasmina Makarevic

Summary statistics (2012) Mutations Jasmina Makarevic

Mutations Jasmina Makarevic

Multi- Step Tumorgenesis Summary statistics (2012) Multi- Step Tumorgenesis Tumor progression: Process of multi-step evolution of a normal cell into a tumor cell. For this you need a initiation---a promotion---than it leeds to progression. Jasmina Makarevic

Adenoma-to-carcinoma Summary statistics (2012) Adenoma-to-carcinoma Jasmina Makarevic

Adenoma-to-carcinoma Jasmina Makarevic

Adenoma-to- carcinoma Summary statistics (2012) Adenoma-to- carcinoma Jasmina Makarevic

Summary statistics (2012) Clonal succession Jasmina Makarevic

Summary statistics (2012) Conclusion Jasmina Makarevic

Stem cells Def: Cell type within a tissue that is capable Summary statistics (2012) Stem cells Def: Cell type within a tissue that is capable of selfrenewal and is also capable of generating daughter cells that develope new phenotypes, including those that are more differentiated than the phanotype of stem cell. Jasmina Makarevic

Summary statistics (2012) Conclusion For the initiation promoting and progression of tumors mutation occurs in the germ cells and somatic cells. Mutation leeds to a change in proliferation and apoptosis balance. In the next lecture we will have a closer look: Stem cells What does it mean for cancer? Growth factors Jasmina Makarevic

Thank You for Your Attention! Jasmina Makarevic