Published on May 31, 2014
CANCER AND METASTASIS Speaker :Sandeep kumar
Tumor Or Neoplasm An abnormal cell that grow and proliferate out of control Benign Tumor As long as neoplastic cells do not become invasive A Tumor is considered a Cancer only if it is malignant i.e. Invasiveness is a essential characteristic of cancer cell
•M o r e s e l f - s u f f i c i e n t t h e n n o r m a l c e l l s f o r g r o w t h a n d p r o l i f e r a t i o n •I n s e n s i t i v e t o a n t i - p r o l i f e r a t i v e e x t r a c e l l u l a r s i g n a l s •L e s s p r o n e t o u n d e r g o a p o p t o s i s •D e f e c t i v e i n i n t r a c e l l u l a r c o n t r o l m e c h a n i s m s t h a t n o r m a l l y s t o p c e l l d i v i s i o n p e r m a n e n t l y i n r e s p o n s e t o s t r e s s o r D N A d a m a g e •I n d u c e a n g i o g e n e s i s •M e t a s t a s i z e •G e n e t i c a l l y u n s t a b l e •E i t h e r p r o d u c e t e l o m e r a s e o r a c q u i r e o t h e r w a y s o f s t a b i l i z i n g t h e i r t e l o m e r e s . General Behaviors of Cancer Cell
Types of Cancer Carcinoma - cancer that begins in the skin or in tissues that line or cover internal organs e.g. adenocarcinoma, basal cell carcinoma and transitional cell carcinoma. Sarcoma - cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia - cancer that starts in blood-forming tissue such as the bone marrow Lymphoma and myeloma - cancers that begin in the cells of the immune system. Central nervous system cancers - cancers that begin in the tissues of the brain and spinal cord.
Carcinogens Any agent that provoke the development of cancer is called carcinogenic Carcinogenesis is linked to the Mutagenesis(i.e. cause mutations) Carcinogens are classified into 2 classes 1) Chemical carcinogen: Typically cause simple local changes in nucleotide sequence and 2) Radiations such as x- Rays: Typically cause chromosomal breakage and Translocation & UV Rays: Cause specific DNA base alteration i.e. Point mutation
CANCER AND THE CELL CYCLE In cancer cells CDK4 and CyclinD is either Mutated or over-expressed
A GENETIC BASIS FOR CANCER Oncogene : genes whose products play important roles in the regulation of biochemical activities within cells, including those activities related to cell division First discovered in the genomes of RNA viruses-called υ-onc Later, the cellular counterparts of these viral oncogenes were discovered in many different organisms, ranging from Drosophila to humans called c-onc/normal celluar oncogene/proto-oncogene
Rous sarcoma virus: First tumor-inducing virus discovered in 1910 by Peyton Rous Contains 4 different genes: Gag- which encodes the capsid protein of the virion; pol-which encodes the reverse transcriptase; Env- which encodes a protein of the viral envelope; v-src- which encodes a protein kinase that inserts into the plasma membranes of infected cells, responsible for tumor formation v-src gene produces 100 times as much tyrosine kinase as the c-src gene, oversupply of the kinase upsets the delicate signaling mechanisms that control cell division, causing unregulated growth
Structure of Rous Sarcoma Virus
MUTANT CELLULAR ONCOGENES AND CANCER
CHROMOSOME REARRANGEMENTS AND CANCER Translocated chromosome9 22 Philadelphia chromosome causes chronic myelogenous leukemia (CML) The Tyrosine kinase function of the c-Abl protein has been constitutively activated by the bcr/c-abl gene fusion White blood cells grow and divide uncontrollably.
Tumor Suppressor Genes Genes that are normally involved in the restraint of cell growth, also called anti-oncogenes
Molecular Biology of Cancer Cell
Molecular Biology of Cancer Cell The pathway by which Rb controls cell cycle entry
Molecular Biology of Cancer Cell This system becomes abnormally activated early in tumor progression
What is cancer metastasis? Metastasis is the process by which a tumor cell leaves the primary tumor, travels to a distant site via the circulatory system, and establishes a secondary tumor Metastatic tumors
Preferential metastatic sites Primary tumor Common distant site (s) Breast’ adenocarcinoma Bone, brain, adrenal Prostate adenocarcinoma Bone Lung small cell carcinoma Bone, brain, liver Skin cutaneous melanoma Brain, liver, Bowel Thyroid adenocarcinoma Bone Kidney clear cell carcinoma Bone, liver, thyroid Testis carcinoma Liver Bladder carcinoma Brain Neuroblastoma Liver, adrenal
5 major steps in metastasis 1. Invasion and infiltration of surrounding normal host tissue with penetration of small lymphatic or vascular channels; 2. Release of neoplastic cells, either single cells or small clumps, into the circulation; 3. Survival in the circulation; 4. Arrest in the capillary beds of distant organs; 5. Penetration of the lymphatic or blood vessel walls followed by growth of the disseminated tumor cells.
Steps in the Process of Metastasis
Molecular Changes in Metastatic Cancer Cell Over expression of Rho-family GTPase RhoC, mediate actin- based cell mobility Epithelial to Mesenchymal transition: change in expression of E- cadherin gene,required for cell cell adhesion
Tumor induce Angiogenesis To grow , a tumor needs an adequate blood supply to get sufficient O2 and nutrients so form new blood vessels(Angiogenesis), and lymphatic vessels (Lymphangiogenesis) Hypoxia HIF-1α(gene regulatory protein) VEGF(pro-angiogenic factor) Attract endothelial cells and stimulate growth of new blood vessels Vessels not only supply nutrients & O2 but also provide escape route for its cells to metastasize
How organisms adapt and survive in different environment.
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