THE BIOLOGY OF CANCER
Acknowledgement Ackn owledgement
I would like to express my special thanks of gratitude to our school principal Mr. Mr. Binod Kujur as well as my biology teacher Mr M r. Dinker Kumar who gave me the golden opportunity to do this wonderful project on the topic ‘he !iology of "ancer#$ which also helped me in doing a lot of %esearch and I came to know about so many new many new things I am really thankful to them.
&econdly I would also like to thank my parents my parents and friends who friends who helped me a lot in finali'ing this project within the limited time frame.
Certifcate This is to certify that _Sarthak Banerjee_; Roll Roll No. a student of Kendriya Kendriya Vidyalaya Fort illiam of class !""#A has done his/her full semester project during the academic year $%&'# $%&'# $%&( in the fullment of curriculum All India Senior Secondary Examination(CBSE! The project "or# entitled )*he Biology o+ Cancer, the original "or# done $y Sarthak Banerjee during his full semester project .
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/rinci0al,1 Signat2re
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The Biology of Cancer Cancer is a disease caused by b y the failure to control contr ol cell division. This results in cells that divide too often and eventually interfere with normal body function. Scientists view cancer as a disease caused by mutations in the genes that regulate cell division. The mutations can be inherited or caused by agents in the environment. For example, the tar from cigarette smoke has been directly linked to mutations in the p! gene. The tar in cigarette smoke is categori"ed as both a mutagen and a carcinogen. #utagens are agents that mutate, or chemically damage, $%&. Carcinogens are mutagens that cause cancer.
& coronal coronal CT scan showing a malignant malignant mesothelioma mesothelioma
Mutagenic and Carcinogenic Agents #any agents have been associated with higher rates of cancer. The one thing they all have in common is their ability to alter the se'uence of nucleotides in the $%& molecule. (hen damage occurs to $%&, the replication and transcriptional machinery may no longer be able to read the $%&)s $%&)s genetic information. This is a partial list of mutagens that are found in our environment. Radiation * rays and gamma rays, ra ys, +ltraviolet light, +-&, from tanning lamps +-B, +-B, the cause of sunburn Chemicals &rsenic Chemicals &rsenic /lemental form0 Ben"ene $ioxin 1olyvinyl chloride 1C0 Chemicals found in smoked meats and fish f ish &sbestos &lcohol Cigarette tar Food containing nitrates e.g., bacon0
Some viruses insert a copy of their genetic material into a cell)s $%&. (hen this insertion occurs in a gene involved with regulating the cell cycle, it creates an insertion mutation, which may disrupt the cell)s ability to control mitosis. #any of the viruses that are associated with higher rates of cancer are associated with a particular type of cancer.
Viruses Cancer 2epatitis B virus 2B0 3iver cancer 2erpes simplex virus 2S0 type 44 +terine cancer /pstein-Barr virus Burkitt)s lymphoma 2uman T-cell lymphotropic virus 2T3-50 3ymphomas and leukaemia 1apillomavirus Several cancers Because cancer is caused by changes in $%&, scientists have found that person)s genetic makeup may be linked to t o developing certain cancers. & predisposition to develop cancer can be inherited from one)s parents. The following cancers have been shown to t o be inherited6 3eukaemia Colorectal cancer Breast cancer 3ung cancer Stomach cancer 1rostate cancer Certain skin cancers 7etinoblastomas /ndometrial cancer (hen uncontrolled mitotic division occurs, a group of cells forms a tumor. & tumor is a mass of cells not normally found in a certain portion of the body. bod y. & benign tumor is a cell mass that t hat does not fragment and spread beyond its original area of growth. & benign tumor can become harmful, however, by growing large enough to interfere with normal bod y functions. Some tumors are malignant. #alignant tumors are harmful because they may spread or invade other parts of the body. Cells Cells of these tumors metastasi"e, or move from the original site and begin to grow new tumors in other regions of the body.
Epigenetics and Cancer <hough many cancers are caused by mutations, it is thought that epigenetic effects cause more cancers than mutations. /pigenetics causes changes in the expression of genetic mate- rial but do not alter mutate0 the $%&. Cells are constantly manipulating their $%& and histone proteins to regulate gene expression including those controlling cell division. For a variety of reasons, cells may perform these functions improperly. improperly. /pigenetic changes important to t o carcinogenesis are the result of certain chemical reactions that affect the nitrogenous base cytosine and histone proteins. Such chemical changes can lead to malfunctions of oncogenes or tumor-suppressor genes. This allows cells whose division rate had previously been regulated, to begin nonstop division8 a critical step in cancer development. These modifications to both $%& and histones are able to be passed on through mitosis and in some cases meiosis.
Classification
Cancers are classified by the type of cell that cell that the tumor cells resemble and is therefore presumed to t o be the origin of the tumor. These types include6 •
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Carcinoma6 Cancers derived from epithelial Carcinoma6 epithelial cells. cells. This group includes many of the most common cancers, particularly in the aged, and include nearly all those developing in the breast breast,, prostate prostate,, lung lung,, pancreas pancreas,, and colon colon.. Sarcoma6 Cancers arising from connective Sarcoma6 tissue i.e. tissue i.e. bone bone,, cartilage cartilage,, fat fat,, nerve nerve0, 0, each of which develop from cells originating in mesenchymal mesenchymal cells cells outside the bone marrow. marro w. 3ymphoma and leukaemia 3ymphoma and leukaemia66 These two classes of cancer arise from hematopoietic blood blood-forming0 -forming0 cells that leave the marrow and tend to mature in the lymph nodes and blood, respectively. 3eukaemia 3eukaemia is the most common type of cancer in children accounting children accounting for about !9:.;<=> ?erm cell tumor 6 Cancers derived from pluripotent pluripotent cells, cells, most often presenting in the testicle testicle or or the ovary ovary seminoma seminoma and anddysgerminoma dysgerminoma,, respectively0. Blastoma6 Cancers derived from immature @precursor@ cells or Blastoma6 embryonic tissue. Blastomas are more common in children than in older adults.
Cancers are usually named using -carcinoma -carcinoma,, -sarcoma -sarcoma or or -blastoma -blastoma as as a suffix, with the 3atin or ?reek word for the organ organ or or tissue of origin as
the root. For example, cancers of the liver parenchyma parenchyma arising arising from malignant epithelial cells is called hepatocarcinoma hepatocarcinoma,, while a malignancy arising from primitive liver precursor cells is called a hepatoblastoma hepatoblastoma,, and a cancer arising from fat cells is called a liposarcoma liposarcoma.. For some common cancers, the /nglish organ name is used. For example, the most common type of breast cancer is is called ductal carcinoma of the breast . 2ere, the adAective ductal refers refers to the appearance of the cancer under the microscope, which suggests that it has originated in the milk ducts.
Benign tumors which tumors which are not cancers0 are named using -oma -oma as as a suffix with the organ name as the root. For example, a benign tumor of smooth muscle cells is called a leiomyoma the common name of this fre'uently leiomyoma the occurring benign tumor in the uterus is fibroid 0. 0. Confusingly, some types of cancer use the -noma -noma suffix, suffix, examples including melanoma melanoma and and seminoma seminoma.. Some types of cancer are named for the si"e and shape of the cells under a microscope, such as giant cell carcinoma, carcinoma, spindle cell carcinoma,, and small-cell carcinoma. carcinoma carcinoma.
Treatment Tr eatment Strategies The Surgical 7emoval of Cancer - nce cancer has been detected, it is often possible to eliminate the tumor. 4f the cancer is confined to a few specific locations, it may be possible to remove it surgically. #any cancers of the skin or breast are dealt with in this manner. The early detection of such cancers is important because early detection increases the likelihood that the cancer can be removed before it has metastasi"ed. 2owever, in some cases, surgery is impractical. 3eukaemia is a kind of cancer caused by the uncontrolled growth of white blood cells being formed in the bone marrow. 4n this situation, the cancerous cells spread through- out the body and cannot be removed surgically. Surgery is also not useful when the tumor is located where it can)t be removed without destroying necessary healthy tissue. For example, removing certain brain cancers can severely damage the brain. 4n such cases, other treatments may be used, such as chemotherapy and radiation therapy.
Chemotherapy and 7adiation- Therapy Scientists believe that chemotherapy and radiation therapy for cancer take advantage of the cell)s ability to monitor cell division at the cell cycle c ycle checkpoints. By damaging $%& or or preventing its replication, chemotherapy chemotherap y and radiation cause the targeted cancer cells to stop dividing and die. ther
chemotherapeutic agents disrupt parts of the cell, such as the spindle, that are critical for cell division. #ost common cancers cannot be controlled with chemotherapy alone. Chemotherapy is often used in combination with radiation therapy therap y. 7adiation therapy uses powerful *rays or gamma rays tto o damage the $%& of the cancer cells. &t times, radiation can be used when surgery surger y is impractical. This therapy can be applied from outside the body or by implanting radioactive seedsD into the tumor. 4n both cases, a primary concern is to protect healthy tissue from the radiation)s harmful effects. (hen radiation r adiation is applied from outside the body, a beam of radiation is focused on the cancerous cells and shields protect as much healthy tissue as possible. +nfortunately, Chemotherapy and radiation therapy can also have negative effects on normal cells. Chemotherapy may expose all the body)s cells to the toxic ingredients and then weaken the body)s bod y)s normal defense mechanisms, because it decreases the body)s bod y)s ability to reproduce new white blood cells by mitosis. &s a precaution against infection, cancer patients undergoing chemotherapy must be given antibiotics. The antibiotics help them defend against dangerous bacteria that might invade their bodies. ther side effects of chemochemo- therapy include intestinal disorders and hair loss, which are caused by damage to the healthy cells in the intestinal tract and the skin that normally divide by mitosis.
(hole-Body 7adiation- (hole-body radiation is used to treat some leukaemia patients, who have cancer of the blood-forming cells located in their bone marrow8 however, not all of these cells are cancerous. & radiation therapy method prescribed for some patients involves the removal of some of their bone marrow and isolation of the noncancerous cells. The normal cells can then be grown gro wn in a laboratory. &fter these healthy cells have been cultured and increased in number, the patient)s whole body is exposed to high doses of radiation sufficient to kill all
the cancerous cells remaining in the bone marrow. Because this treatment can cause significant damage to the immune system, it is potentially deadly. &s a precaution the patient is isolated from all harmful sub- stances and infectious microbes. They are fed sterile food, drink sterile water, and breathe sterile air while being closely monitored and treated with antibiotics. The cultured noncancerous cells are inAected back into the patient. &s if the cells had a memory, they migrate back to their origins in the bone marrow, marro w, establish establish residence, and begin regulated cell division all over again. Because radiation damages healthy cells, it is used very ver y cautiously. 4n cases of extreme exposure to radiation, people develop radiation sickness. The symptoms of this disease include hair loss, bloody vomiting and diarrhoea, and a reduced white blood cell count. omiting, nausea, and diarrhoea occur because the radiation kills many of the cells lining the gut and interferes with the replacement of the intestine)s lining, which is constantly being lost as food travels through. 2air loss occurs because radiation prevents cell division at the hair root8 these cells must divide for the hair to grow. gro w. 7adiation reduces white blood cells because it prevents prevent s their continuous replacement from cells in the bone marrow and lymph nodes. (hen radiation strikes these rapidly dividing cells and kills them, the lining of the intestine wears away and bleeds, hair falls out, and there are very few new white blood cells to defend the body against infection.
%anoparticle Therapy- The use of nanoparticle cancer therapy is being explored in many research labs. %anoparticles cover a range between 5 and 599 nanometres in diameter and can be synthesi"ed so that they attach only to specific cancer cells taken from a patient. They can be combined with cancer specific, anticancer proteins. (hen inAected into an organism, these combination particles travel throughout the body without causing harm or being reAected until they attach to their targeted cancer cells. (hen they combine with cell surface molecules, the anticancer drug is delivered and the cancer cell destroyed. (hile still in the research phase, nanoparticle cancer therapy has been shown to stop the growth of prostate, breast, and lung tumors in rodents.
Signs and symptoms (hen cancer begins it invariably produces no symptoms with signs and symptoms only appearing as the mass continues to grow or ulcerates. The findings that result depends on the type and location of the cancer. Few symptoms are specific, with many of them also fre'uently occurring in individuals who have other conditions. Cancer is the new @great imitator@. Thus it is not uncommon for people diagnosed with cancer to
have been treated for other diseases to which it was assumed their symptoms were due.
3ocal effects- 3ocal symptoms may occur due to the mass of the tumor or its ulceration. For example mass effects from lung cancer can cause blockage of the bronchus resulting in cough or pneumonia, esophageal cancer can cause narrowing of the esophagus making it difficult or painful to swallow, and colorectal cancer may lead to narrowing or blockages in the bowel resulting in changes in bowel habits. #asses of breast or testicles may be easily felt. +lceration can cause bleeding which, if it occurs in the lung, will lead to coughing up blood, in the bowels to anemia or rectal bleeding, in the bladder to blood in the urine, and in the uterus to vaginal bleeding. <hough locali"ed locali"ed pain may occur in advanced cancer, the initial swelling is usually painless. Some cancers can cause buildup of fluid within the chest or abdomen.
Systemic symptoms- ?eneral symptoms occur due to distant effects of the cancer that are not related to direct or metastatic spread. These may include6 unintentional weight loss, fever, being excessively tired, and changes to the skin. 2odgkin disease, leukaemia, and cancers of the liver or kidney can cause a persistent fever of unknown origin. Specific constellations of systemic symptoms, termed paraneoplastic termed paraneoplastic phenomena, may occur with some cancers. /xamples include the appearance of myasthenia gravis in thymoma t hymoma and clubbing in lung cancer.
Symptoms of cancer metastasis metastasis depend depend on the location of the tumor
#etastasis-- Symptoms of metastasis are due to the spread of cancer #etastasis to other locations in the t he body. They can include enlarged lymph nodes which can be felt or sometimes seen under the skin and are typically hard0, hepatomegaly enlarged liver0 or splenomegaly enlarged spleen0 which can be felt in the abdomen, pain or fracture of affected bones, and neurological symptoms.
Diet and exercise $iet, physical inactivity, and obesity are related to approximately !9E !: of cancer deaths . 1hysical inactivity is believed to contribute to cancer risk not only through its effect on body weight but also through negative effects on immune system and endocrine s ystem. $iets that are low in vegetables, fruits and whole grains, and high in processed or red meats are linked with a number of cancers. & high salt diet is linked to gastric cancer, aflatoxin B5, a fre'uent food contaminate, with liver cancer, and Betel nut chewing with oral cancer.
Physical agents
Some substances cause cancer primarily through their physical, rather than chemical, effects on cells. & prominent example of this is prolonged exposure to asbestos, naturally occurring mineral fibers which are a maAor cause of mesothelioma, a type of cancer of the serous membrane. ther substances in this category, c ategory, including both naturally occurring and synthetic asbestos-like fibers such as wollastonite, attapulgite, glass wool, and rock wool, are believed to have similar effects. %onfibrous particulate materials that cause cancer include powdered metallic cobalt and nickel, and crystalline silica 'uart", cristobalite, and tridymite0. +sually, physical carcinogens must get inside the body such as through inhaling tiny pieces0 and re'uire years of exposure to develop cancer. 1hysical trauma resulting in cancer is relatively rare. Claims that breaking bone resulted in bone cancer, for example, have never been proven. Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer, or brain cancer. ne accepted source is fre'uent, long-term application of hot obAects to the body. 4t is possible that repeated burns on the same part of the body, such as those produced by kanger and kairo heaters charcoal hand warmers0, may produce skin cancer, especially if carcinogenic chemicals are also present. Fre'uently drinking scalding hot tea may produce esophageal cancer. ?enerally, ?enerally, it is believed that the cancer arises, or a pre-existing cancer is encouraged, during the process of repairing the trauma, rather than the cancer being caused directly by the trauma. 2owever, repeated inAuries to the same tissues might promote excessive cell proliferation, which could then increase the odds of a cancerous mutation. There is no evidence that inflammation itself causes cancer.
Hormones Some hormones play a role in the development of cancer by promoting cell proliferation. 2ormones are important agents in sex-related cancers
such as cancer of the breast, endometrium, prostate, ovary, and testis, and also of thyroid cancer and bone cancer. &n &n individuals hormone levels are mostly determined genetically, so this may at least partly explains the presence of some cancers that run in families that do not seem to have any cancer-causing genes. For example, the daughters of women who have breast cancer have significantly higher levels of estrogen and progesterone than the daughters of women without breast cancer. These higher hormone levels may explain why wh y these women have higher risk of breast cancer, even in the absence of a breastcancer gene. 2owever, non-genetic factors are also relevant6 obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers. (omen who take hormone replacement therapy have a higher risk of developing cancers associated with those hormones. n the other hand, people who exercise far more than average have lower levels of these hormones, and lower risk of cancer. steosarcoma may be promoted by growth hormones. Some treatments and prevention approaches leverage this cause by artificially reducing hormone levels, and thus discouraging hormone-sensitive cancers.
Pathophysiology
Cancers are caused by a series of mutations. /ach mutation alters the behaviour of the cell somewhat. Cancer is fundamentally a disease of failure of regulation of tissue growth. 4n order for a normal cell to transform into a cancer cell, the genes which regulate cell growth and differentiation must be altered. The affected genes are divided into two broad categories. ncogenes are genes which promote cell growth and reproduction. Tumor suppressor genes are genes which inhibit cell division and survival. #alignant transformation can occur through the formation of novel oncogenes, the inappropriate over-expression of normal oncogenes, or by the under-expression or disabling of tumor suppressor genes. Typically, Typically, changes in many genes are re'uired to transform a normal cell into a cancer cell. ?enetic changes can occur at different levels and by different mechanisms. The gain or loss of an entire chromosome can occur through errors in mitosis. #ore common are mutations, which are changes in the nucleotide se'uence of genomic $%&. 3arge-scale mutations involve the deletion or gain of a portion of a chromosome. ?enomic amplification occurs when a cell gains many copies often G9 or more0 of a small chromosomal locus, usually containing one or more oncogenes and adAacent genetic material. Translocation Translocation occurs when two separate chromosomal regions become abnormally fused, often of ten at a characteristic location. & wellwellknown example of this is the t he 1hiladelphia chromosome, or translocation of chromosomes = and GG, which occurs in chronic myelogenous leukaemia, and results in production of the BC7-abl fusion protein, an oncogenic tyrosine kinase. Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter region of a gene and affect its expression, or may occur in the genes coding se'uence and alter the function or stability of its protein product. $isruption of a single gene may also result from integration of genomic material from a $%& virus or retrovirus, and resulting in the expression of viral oncogenes in the affected cell and its descendants.
7eplication of the enormous amount of data contained within the $%& of living cells will probabilistically result in some errors mutations0. Complex error correction and prevention is built into the process, and safeguards the cell against cancer. 4f significant error occurs, the damaged cell can @self-destruct@ through programmed cell death, termed apoptosis. 4f the error control processes fail, then the mutations will survive and be passed along to daughter cells. Some environments make errors more likely to arise and propagate. Such environments can include the presence of disruptive substances called carcinogens, repeated physical inAury, heat, ionising radiation, or hypoxia
The errors which cause cancer are self-amplifying and compounding, for example6 mutation in the error-correcting machinery of a cell might cause & mutation that cell and its children to accumulate errors more rapidly. & further mutation in an oncogene might cause the cell to reproduce more rapidly and more fre'uently than its normal counterparts. & further mutation may cause loss of a tumour suppressor gene, disrupting the apoptosis signalling pathway and resulting in the cell becoming immortal. & further mutation in signalling signalling machinery of the cell might send error causing signals to nearby cells. The transformation of normal cell into cancer is akin to a chain reaction caused by initial errors, which compound into more severe errors, each
progressively allowing the cell to escape the controls that limit normal tissue growth. This rebellion-like scenario becomes an undesirable survival of the fittest, where the driving forces of evolution work against the bodys design and enforcement enfor cement of order. nce cancer has begun to develop, this ongoing process, termed clonal evolution drives progression towards more invasive stages.
Pathology The tissue diagnosis given by the pathologist indicates the type of cell that is proliferating, its histological grade, genetic abnormalities, and other features of the tumor. Together Together,, this information is useful to evaluate the prognosis of the patient and to choose the best treatment. Cytogenetics and immunohistochemistry are other types of testing that the pathologist may perform on the tissue specimen. These tests may provide information about the molecular changes such as mutations, fusion genes, and numerical chromosome changes0 that has happened in the cancer cells, and may thus also indicate the future behaviour of the cancer prognosis0 and best treatment. &n invasive ductal carcinoma of the breast pale area at the centre0 surrounded by spikes of whitish scar tissue and yellow fatty fatt y tissue &n invasive colorectal carcinoma top centre0 in a colectomy specimen & s'uamous cell carcinoma the whitish tumor0 near the bronchi in a lung specimen & large invasive ductal carcinoma in a mastectomy specimen showing a huge lump above the top left side of nipples. 1athological staging- 1T!-1%*-1#5
An invasive ductal carcinoma o carcinoma o the !reast "#ale area at the center$ surrounded !% s#i&es o 'hitish scar tissue and %ello' att% tissue(
An invasive colorectal carcinoma "to# carcinoma "to# center$ in a colectom% colectom% s#ecimen( s#ecimen(
A s)uamous*cell carcinoma "the 'hitish tumor$ near the !ronchi !ronchiin in a lun+ s#ecimen. s#ecimen .
A lar+e invasive ductal carcinoma in a mastectomy s#ecimen s#ecimen..
Preention Cancer prevention is defined as active measures to decrease the risk of cancer. The The vast maAority of cancer cases are due to environmental risk factors, and many, but not all, of these environmental fact ors are controllable lifestyle choices. Thus, cancer is considered a largely preventable disease. ?reater than !9: of cancer deaths could be prevented by avoiding risk factors including6 tobacco, overweight H obesity, an insufficient diet, physical inactivity, alcohol, alcohol, sexually transmitted infections, and air pollution. %ot all environmental causes are controllable, such as naturally occurring background radiation, and other cases of cancer are caused through hereditary genetic disorders, and thus it is not possible to prevent all cases of cancer.
Cancer Screening +nlike diagnosis efforts prompted by symptoms and medical signs, cancer screening involves efforts to detect cancer after it has formed, but before any noticeable symptoms appear. This may involve physical examination, blood or urine tests, or medical imaging. Cancer screening is currently not possible for many types of cancers, and even when tests are available, they may not be recommended for everyone. +niversal screening or mass screening involves screening everyone. ev eryone. Selective screening identifies people who are known to be at higher risk of developing cancer, such as people with a family history of cancer. Several factors are considered to determine whether the benefits of screening outweigh the risks and the costs of screening.
These factors include6 1ossible harms from the screening test6 for example, *-ray images involve exposure to potentially harmful ioni"ing radiation. The likelihood of the test correctly identifying cancer. The likelihood of cancer being present6 Screening is not normally useful for rare cancers. 1ossible harms from follow-up procedures. (hether suitable treatment is available. (hether early detection improves treatment outcomes. (hether the cancer will ever need treatment. (hether the test is acceptable to the people6 4f a screening test is too burdensome for example, being extremely painful0, then people will refuse to participate. Cost of the test.
!esearch Because cancer is a class of diseases, it is unlikely that there will ever be a single @cure for cancer@ any more than there will be a single treatment for all infectious diseases. &ngiogenesis &ngiogenesis inhibitors were once thought to have potential as a @silver bullet@ treatment applicable to many types of cancer, but this has not been the case in practice. /xperimental cancer treatments are treatments that are being studied to see whether they work. Typically, Typically, these are studied st udied in clinical trials to compare the proposed treatment to the best existing treatment. They may be entirely new treatments, or they may be treatments that have been used successfully in one type of cancer, and are now being tested to see whether they are effective in another type. #ore and more, such treatments are being developed alongside companion diagnostic t ests to target the right drugs to the right patients, based on their individual biology. biology. Cancer research is the intense scientific effort to understand disease processes and discover possible therapies. 7esearch about cancer causes focuses on the following issues6 &gents e.g. viruses0 and events e.g. mutations0 which cause or facilitate genetic changes in cells destined to become cancer. The precise nature of the genetic damage, and the genes which are affected by it. The conse'uences of those genetic changes on the biology of the cell, both in generating the defining properties of a cancer cell, and in facilitating additional genetic events which lead to further progression of the cancer.
Bibliography /very satisfactory work is build by means of substantial references. 4 hereby state to have legitimately exploited following sources in the making of my proAect- ?uaytton and Sutton)s Textbook Textbook of #edicinal ncology #illenium /dition, I Froth Silk 1ublishers, Boston - Comprehensive 1ractical Biology J Class *44 & biology biology practical plus proAects textbook by 3axmi 1ublications 1vt. 3td. - (ikipedia.com The nline /ncyclopedia - 4CBS/ nline 2elp Forum http6HHwww.proAects.icbse.comHmain.aspx - TCKonline.com & world world class educational and tutorial site on the web - #eritnation.com
