Gene TherapyThe future of cancer treatment *MD SAQUIB NASIR KHAN*STUDENT OF BIOINFORMATICS BHARATH UNIVERSITY
Cancer is a disease of cells. A single cell moves down thepath toward cancer as the result of a series ofenvironmentally induced changes to critical genes. Thegenes affected in cancer may fall into any of three classes(Craig, 1995). One class comprises the so-called―oncogenes‖, the genes that code for proteins that promotecell proliferation. Another class called tumor suppressorsencode proteins that provide a protective role in the body.A third class is represented by the gene Bcl-2 and consistsof genes that influ-ence cell viability or cell death. Thesignificance of the third class is that it suggests that cancercan result not only from the overgrowth of cells, but alsofrom a lack of cell death.1. Introduction Of Cancer
No. of % of all Rank Cause of Death deaths deaths 1. Heart Diseases 631,636 26.0 2. Cancer 559,888 23.1 3. Cerebrovascular diseases 137,119 5.7 4. Chronic lower respiratory diseases 124,583 5.1 5. Accidents (unintentional injuries) 121,599 5.0 6. Diabetes mellitus 72,449 3.0 7. Alzheimer disease 72,432 3.0 8. Influenza & pneumonia 56,326 2.3 9. Nephritis* 45,344 1.9US Mortality, 2006 10. Septicemia 34,234 1.4 *Includes nephrotic syndrome and nephrosis. Source: US Mortality Data 2006, National Center for Health Statistics, Centers for Disease Control and Prevention, 2009.
Japan, year 2000Annual deaths from smoking• Smoking kills about 113,000 people a year inJapan About 33,000 die in middle age from smoking Many of those killed in middle age would have lived on for 10, 20, 30 or more good years About 22 years of life are lost, on average, by those killed in middle age by smokingwww.deathsfromsmoking.net
(According to prevantionweb.net) No of events:157 No of people killed:8,568 Average killed per year:276 No of people affected:3,361,979 Average affected per year:108,451IN JAPAN NATURAL DISASTER
hereditary cancersDifficulties in studying hereditary cancers*Humans have small families*Generation times are long*Highly mobile; hard to keep in touch*Studies require cooperation **Consent for tests **Correct information on family members*Cancers are different diseases*Cancers can occur at random; hard to find affected families*More than one gene must be altered to get cancer
cellular and nuclear pleomorphism, they exhibit abnormal mitoses and chromosomal abnormalities. malignant transformation Hyperplasia Genome instability Incresed Angiogenisis Incresed motilityWhy its hard to identify cancer cell
Cancer is disease of Genes*Cancer is a genetic disease−Not monogenic like MD or CF, but multigenic*Cancer is caused by mutations in somatic cells*Cancer can be caused by mutagens, chemicals that damageDNA, or viruses*Cancer is caused by an accumulation of mutations in differentgenes in a single cell*Cancer is caused by altered expression of genes or byaccumulation of mutations in a single cell
Detection of cancers1.gene tests available: BRCA1: breast and ovarian cancer BRCA2: breast cancer p53: Li-Fraumeni syndrome APC: FAP colon cancer MLH1, MSH2 and other DNA repair genes: HNPCCcolon cancer2. Protein and enzyme tests
3. X-rays: Expose region to low dose X- rays, obtain image of more dense regions, including bones and the accumulation of minerals at tumor sites. ◦ improvements: minimize X-ray dose; ◦ standardize procedures and training to improve reliability; ◦ use high contrast dyes to localize regions4.CT or CAT scan--computed tomography-- computer analysis of scanning X-ray imagesCont…..
5.MRI--magnetic resonance imaging-- computer analysis of images that does not involve X-rays. Involves radiowaves and deflection by a powerful magnet; useful for tumors surrounded by bone.6.ultrasound--lower cost, lower resolution imaging. Widely used in breast cancer and prostate cancer to clarify results of initial tests.Cont….
replacement gene therapy knockout gene therapy suicide gene therapy immunomodulatory gene therapyGene therapy of Cancer
Replacement Gene Therapy=method for replacing a mutated or missing gene (usually a tumor suppressor gene) that serves to keep cell growth and division under control with a "healthy" (normal) copy of that gene.Replacement Gene Therapy
Knockout gene therapy primarily targets the products of oncogenes in an effort to inactivate them and reduce cellular proliferation. Several approaches are being tried: delivering a mutant oncogene that acts in a dominant manner to negate the effects of the cancer-causing oncogene inhibiting translation of the oncogene by gene therapyKnockout gene therapy
Suicide gene therapy—involves the transduction of a gene that transforms a nontoxic form of a drug (that is, a "pro- drug") into a toxic substance.Suicide gene therapy
Immunomodulatory gene therapy--is a method to induce cellular immune responses to metastatic tumors. The strategy involves injecting into the skin of a patient a suspension of irradiated tumor cells that have been transduced with a cytokine gene to stimulate a systemic immune response against tumor- specific antigens—in effect, vaccinating the patient against that specific cancer. The basic idea of immunotherapy is to: modify tumor cells outside the body with a cytokine gene transplant the cytokine-gene modified cells back into the patient (after the cells have been irradiated to prevent further cell division) let the hosts system create an antitumor immune responseImmunomodulatory gene therapy-
Nanomedicine is the medical application of nanotechnology .Nanomedicine ranges from the medical applications of nanomaterials,to nanoelectronic biosensor s, and even possible future applications of molecular nanotechnology. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials. One nanometer is one-millionth of a millimeter.Nanomedicine
Improving Cancer Treatment Traditional Treatment Nanotechnology Treatment Drugs Toxins Nanodevices CancerCancer cells Toxinscells Noncancerous cells Noncancerous cellsDead Deadcancer cancercells cells Dead noncancerous Intact noncancerous cells cells
Polymeric nanoparticles are shown as representativenanocarriers (circles). Passive tissue targeting is achievedby extravasation of nanoparticles (NP) through increasedpermeability of the tumor vasculature and ineffectivelymphatic drainage (EPR effect).Active cellular targeting (inset)can be achieved byfunctionalizing thesurface of NP withligands that promotecell-specific recognitionand binding. The nanoparticles can (i) release their contents in closeproximity to the target cells; (ii) attach to the membrane of the cell and actas an extracellular sustained-release drug depot; or (iii) internalize into thecell. Mechanisms by which Nanocarriers Can Deliver Drugs to Tumors
Nanotechnology Based Drug DeliverySystems for Cancer TherapySchematics - Reproduced from Sahoo and Labhasetwar, 2003 with kind permission from Drug DiscoveryToday.http://www.cancer-therapy.org/CT3A/HTML/13.%20Orive%20et%20al,%20131-138%20.html 2005
black raspberry are blueberries, blackberries, strawberries, and cranberries, These berries are high invitamin C, fiber, and ellagic acid, which can prevent skin cancer. Tenderstem, help prevent stomach, colon and lung cancers. Broccoli ,Some research has shown that a serving of broccoli every day can reduce the risk of colon cancer by almost 50 per cent. Cabbage ,Some scientists think cabbage is particularly good at protecting against colon cancer and breast cancer.Natural support for cancer
Watermelon ,Tomatoes, watermelons, guavas and grapefruit are rich in lycopene. This is a fat-soluble nutrient which appears to have a powerful action on the immune system by producing antioxidant activity in the body. Grapes ,An anti-fungal agent found in grapes my help to protect against cancer, according to researchers from De Montfort University in Leicester. Resveratrol is a molecule which helps grapes and other crops avoid fungus. Carrot ,help to prevent retina cancer , which is vary rear cancer Lemon is use to cure against NeuroblastomaCont……
Video Links Cancer Detection with Gold Nanoparticles – May 27, 2007 http://www.youtube.com/watch?v=uyhxRIvw_cY&feature=related Nanoparticle Carrying Capacity – March 27, 2008 http://www.youtube.com/watch?v=TVch-fDzet8&feature=related Nanotechnology In Drug Delivery - March 16, 2008 http://www.youtube.com/watch?v=ybK5TIGNNFA&NR=1 Nanomedicine for Brain Tumors – July 3, 2008 http://www.youtube.com/watch?v=gJgmi-D12pk Nanomedicine Cancer Drug Delivery from PlayGenSeriousGames – sponsored by Wellcome Trust http://www.youtube.com/watch?v=tPAO0WHoaX0 (1st) February 11, 2008 http://www.youtube.com/watch?v=DEcof9HlUvk (2nd) February 11, 2008 http://www.nanomission.org/ The Game Site Play