Neoplasia Clincial effects and Spread of cancer

4,778 views

Published on

0 Comments
4 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
4,778
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
0
Comments
0
Likes
4
Embeds 0
No embeds

No notes for slide
  • Cachexia: Any general reduction in vitality and strength of body and mind resulting from a debilitating chronic disease
  • Amyloidosis: A disorder characterized by deposit of amyloid in organs or tissues; often secondary to chronic rheumatoid arthritis or tuberculosis or multiple myeloma
  • Image downloaded form: Dim CC, Akogu SP, Ezegwui HU, Olusina DB. Leiomyomatosisperitonealisdisseminata in a Nigerian woman. Niger Med J 2012;53:172-4
  • adenomatous polyposis coli (APC) protein
  • adenomatous polyposis coli (APC) protein
  • Neoplasia Clincial effects and Spread of cancer

    1. 1. NEOPLASIA Clinical effects and spread of cancer/ Molecular basis of cancer Dr. S. Parasuraman Faculty of Pharmacy, AIMST University
    2. 2. Clinical effects and spread of cancer • Management of neoplasia is based on – Tumour-host inter-relationship – Laboratory/ pathological diagnosis of cancer • Tumour-host inter-relationship depends upon host response against tumour and effect of tumour on host. • Laboratory/ pathological diagnosis of cancer mainly focus on histological and cytochemistry analysis
    3. 3. Clinical effects of cancer Tumour-host inter-relationship • Immune system can recognize tumour cells as ‘non-self’ and destroy them. • Immune surveillance exists is substantiated by increased frequency of cancers in immunodeficient host e.g. AIDS patients, post-transplant lymphoproliferative disease. • Tumour can produce ill-effects and this effect may be local or generalised and more widespread. Local effects depends on size/ location (local effects: compression, mechanical obstruction, tissue destruction, infarction, ulceration, haemorrhage).
    4. 4. Clinical effects of cancer Tumour-host inter-relationship • Systemic effect of cancer on the host – Fever: • Most common in Hodgkin’s disease, renal cell carcinoma and osteogenic sarcoma • Tumour cell themselves release pyrogens/ inflammatory cells in the tumor stroma, can produce interleukin-1 or TNF – Anorexia and weight loss • Paraneoplastic syndrome of anorexia, weight loss and cachexia is very common in patients with cancer – Endocrine syndromes • Cushing syndrome • Inappropriate antidiuresis • Hypercalcemia • Hypoglycemia
    5. 5. Clinical effects of cancer Tumour-host inter-relationship • Systemic effect of cancer on the host – Neurologic syndromes • Spinal cord: Subacute motor neuropathy • Peripheral nerves: Sensorimotor peripheral neuropathy – Skeletal muscle • Dermatomyositis or polymyositis (5-7 fold higher than normal person) – Hematologic syndromes • Erythrocytosis (particularly renal cell carcinoma, hepatocellular carcinoma, cerebellar hemangioblastoma); Anemiab (normocytic and normochromic anemia); leukocytes and platelets – Malabsorption – Renal syndromes: Nephrotic syndrome (consequence of renal vein thrombosis or amyloidosis) – Cutaneous syndromes (pigmented lesions and keratoses)
    6. 6. Clinical effects of cancer Pathological diagnosis of cancer – Histological methods – Cytological methods – Histochemistry and cytochemistry – Immunohistochemistry – Electron microscopy – Tumour marker – Other modern aids • Flow cytometry • Molecular diagnostic techniques • DNA microarray analysis of tumour
    7. 7. Spread of cancer Primary cancer (site of first cancer growth) Secondary cancer/ metastasis (spread form primary cancer) ? Direct extension (local spread) Metastatic spread (through the blood circulation, lymphatic system )
    8. 8. Spread of cancer • Direct extension (local spread) – Grows directly into nearby body tissues Benign  Dysplasia  In-situ Benign  Dysplasia nearby tissues  In-situ  Invasive  spread into – E.g. Peritoneal carcinomatosis (metastatic ovarian carcinoma)
    9. 9. Spread of cancer • Metastatic spread: – Transfer of malignant cells from one site to another through • Hematogenous metastases • Lymphatic metastases Stage I: Early disease (tumour confined) Stage II: tumour spread to movable ipsilateral axillary nodes Stage III: Locally advanced disease; involvement of ipsilateral mammary lymp nodes Stage IV: Advanced (metastatic) disease
    10. 10. Molecular basis of cancer Cancer Cell Do Not Grow Faster Than Normal Cells Rather, Their Growth is Just Uncontrolled
    11. 11. Molecular basis of cancer • Cancer is genetic disease – Non lethal Genetic damage is heart of carcinogenisis – Somatic mutation/in genes/ inherited in germline of persons leads to unregulated growth of cancer cells. – Most of cancers results form mutations in somatic cells – Some cancer are caused by mutations in germline cells – Mutations (by environmental mutagen or as consequence of normal cellular metabolism or by spontaneous errors in DNA replication and repair) in genes results in altered proteins • During cell division • External agents • Random event
    12. 12. Molecular pathogenesis of cancer • Monoclonality of tumors: – Most of the human cancer arise form a single clone of cell by genetic transformation or mutation. E.g. multiple myeloma (malignant of plasma cell) – due to inactivation of two X-chromosomes in female for G6PD isoenzyme. • Field theory of cancer: – Limited number of cells only grow into cancer after undergoing sequence of changes under the influence of etiological agents.
    13. 13. Molecular pathogenesis of cancer • Multi-step process of cancer growth: Carcinogenesis is multistep process at both the phenotypic and genetic level – A malignant neoplasm has several phenotypic attributes such as excessive growth, local invasiveness & distant metastasis – These characteristics are acquired in a stepwise fashion called tumor progression • Genetic theory of cancer: – Cell growth of normal as well as abnormal type is under genetic control. In cancer, there are either genetic abnormalities in the cell, or there are normal genes with abnormal expression.
    14. 14. Molecular basis of cancer • Genetic regulations of normal mitosis: – In normal cell growth has 4 regulatory genes – Proto-oncogenes are growthpromoting genes (they encode for cell proliferation pathway) – Anti-oncogenes are growthinhibiting or growth suppressor genets – Apoptosis regulatory genes – control the programmed cell death – DNA repair gene – normal gene regulate the repair of DNA damage during mitosis • In Cancer: • Fours classes of normal regulatory genes are the targets of genetic damage – Activation promoting of growthoncogenes (PDGF) – Inactivation of cancer suppressor genes (RB gene, NF-1 gene, p53 gene, WT-1 gene) – Abnormalities apoptosis regulatory genes (BCL-2 gene, p53 gene) – Failure of DNA repair gene
    15. 15. Molecular basis of cancer Proto-oncogenes may be converted to Oncogenes by 3 mechanisms 1. Point mutation 2. Chromosomal rearrangements 3. Gene amplification
    16. 16. Chromosomal changes in the genome of cancer cells Deletion Terminal Deletion Reciprocal translocation Duplication Insertion Inversion Ring Chromosome Robertsonian Translocation Isochromosomes http://www.tokyo-med.ac.jp/genet/cai-e.htm
    17. 17. Nucleotide changes in the genome of cancer cells Nucleotide Deletions Nucleotide Insertions Nucleotide Substitutions http://www.tokyo-med.ac.jp/genet/cai-e.htm
    18. 18. Important Oncogenes Type Proto-oncogene Mechanism Associated H. tumour GROWTH FACTOR PDGF-β TGF-α SIS RAS Overexpression Overexpression Gliomas, sarcoma Carcinomas, astrocytoma RECEPTORS FOR GROWTH FACTORS EGF receptors RET receptor ERB B1(HER 1) RET Overexpression Point mutation Squamous cell carcinoma lung NUCLEAR TRANSCRIPTION FACTORS C-MYC N-MYC MYC MYC Translocation Amplification Burkitt’s lymphoma CELL CYCLE REGULATORY PROTEINS CDKs CDK4 Amplification Glioblastoma, melanoma, sarcomas medullary Ca thyroid Neuroblastoma, small cell Ca lung
    19. 19. Important Tumour-suppressor anti-oncogenes Type Location Associated H. tumour RB Nucleus (13q) Retinoblastoma, osteosarcoma p53 (TP53) Nucleus (17p) Most human cancers, common in Ca lung, head and neck, colon, breast TGF–β and its receptor Extracellular Ca pancreas, colon, stomach APC and β-catenin proteins Nucleus and cytosol Ca colon Nucleus (BRCA1 17q21) Nucleus (BRCA2 13q12-13) Nucleus (3p) Nucleus (11p) Plasma membrane Ca breast, ovary Ca breast, ovary Renal cell carcinoma Wilms’ tumour Neurofibromatosis Others BRCA 1 BRCA 2 VHL WT 1 and 2 NF 1 and 2
    20. 20. Molecular basis of cancer
    21. 21. Major properties of cancer in terms of molecular carcinogenesis
    22. 22. DNA Loss in cancer cells
    23. 23. Clara_Jacobi-Tumor Thank you
    24. 24. Cushing syndrome Back
    25. 25. Dermatomyositis Back
    26. 26. cerebellar hemangioblastoma hemangioblastoma hemangioblastoma Back Erythrocytosis renal cell carcinoma renal cell carcinoma
    27. 27. Renal vein thrombosis Amyloid deposits in renal cells Back
    28. 28. Cutaneous syndromes Back

    ×