Want to Read Currently Reading Read. Error rating book. Refresh and try again. Upcoming Events. No scheduled events. Note: Citations are based on reference standards. However, formatting rules can vary widely between applications and fields of interest or study. The specific requirements or preferences of your reviewing publisher, classroom teacher, institution or organization should be applied.
The E-mail Address es field is required. Please enter recipient e-mail address es. The E-mail Address es you entered is are not in a valid format. Please re-enter recipient e-mail address es. You may send this item to up to five recipients.
The name field is required. Please enter your name. The E-mail message field is required. Please enter the message. Please verify that you are not a robot. Would you also like to submit a review for this item? DOI: View PDF. Save to Library. Create Alert. Launch Research Feed. Each of these has to be separately standardized. One unit or minimum hemolytic dose of complement is defined as the highest dilution of guinea pig serum that lyses one unit volume of washed sheep erythrocyte in the presence of excess of hemolysin amboceptor within a fixed time usually 30 or 60 minutes and at a fixed temperature 37C Figs and Neutralization of bacteriophages can be demonstrated by the plaque inhibition test.
Neutralization of animal viruses can be seen in three systems: animal, eggs and tissue culture. Immunofluorescence Mechanismfluorescence is a property of absorbing light rays of one particular wavelength and emitting rays with different wavelengths.
Fluorescence dye can be conjugated to antibodies and such labelled antibodies can be used to locate and identify antigen in tissue. Usethis test can be used for identification of bacteria, viruses or other antigens using specific antisera labelled with fluorescence dyes. Dye usecommonly used dye is fluorescein isothio- cynate and lissamine rhodamine exhibiting blue-green and orange-red fluorescence respectively. Gupte S. Immunology 5th edn , Mosby, London, Samaranayake LP.
Essential Microbiology for Dentistry 2nd edn , Churchill Livingstone, Oncology is the study of neoplasm. Nomenclature There are mainly of two types neoplasm: benign and malignant. Benign tumors are designated by attaching oma to cell of the organ. Malignant tumors arising from mesenchymal tissues are known as sarcomas, like osteosarcoma. Malignant tumors of epithelial origin are called carcinoma, like adenocarcinoma and squamous cell carcinoma.
Normal Cell Cycle All renewing cells go through a series of events known as cell cycle. Successive phases of progression of cell cycle are described below Fig. G 1 phaseafter mitosis M phase , cells spend a variable period of resting G 1 phase where DNA synthesis is absent but the synthesis of RNA and protein continues.
Then the cells undergo replication or remain polypoid and eventually die. The proportion of cells population under- goes active proliferation in the cycle is termed as growth fraction. G 0 phasedaughter cells may continue to remain in cell cycle and divide further or may go out at the cell cycle in resting phase. Predisposing Epidemiologic Factor for Development of Neoplasm Hereditary Predisposition The risk of developing cancer in relatives of a known cancer patient is three times higher than control study.
Racial and Geographic Factors Cancers are largely due to the influence of environment and geographic differences affecting whole population such as climate, water, diet, habit. For example Black Africans commonly have cancers of skin, penis, cervix, and liver. Europeans and Americans commonly develop malignancies of lung, breast, and colon.
Nasopharyngeal cancer is common in south East Asians. Environmental and Cultural Factors We are surrounded by an environment of carcinogens which we eat, drink, inhale and touch Fig. For example Cigarette smoking is the etiology of cancer of oral cavity, pharynx, larynx, esophagus, lung, pancreas and urinary bladder.
Alcohol causes cancer of esophagus and liver. Alcohol and tobacco together accelerate the risk of developing cancer of upper aerodigestive tract. Betel nut chewing causes cancer of cheek and tongue.
Industrial and environmental materials are carcinogenic. This includes exposure to substances like arsenic, asbestos, benzene, and naphthylamine.
Overweight individuals, deficiency of vitamin A, people consuming foods rich in animal fats and low in fiber content have more risk of developing cancers like colonic cancer. Age Generally, it occurs in older individuals past 5th decade of life but, there is variation in age groups.
For example, acute leukemia occurs in children, neuroblastoma in infancy. Sex It is generally more common in men except cancer of breast, gallbladder, and thyroid. Acquired Preneoplastic Conditions These may be inflammatory, hyperplastic conditions or may be certain benign tumors. It includes chronic atrophic glossi- tis, leukoplakia of oral cavity, vulva and penis, cirrhosis of liver, chronic irritation and multiple neurofibromas.
Carcinogenesis Carcinogenesis or oncogenesis or tumorigenesis means induction of tumors; agents which can induce tumors are called carcinogens. Carcinogens are broadly divided into four groups Fig. Alkylating agents it includes, various chemotherapeutic drugs that have successfully cured, controlled or delayed recurrence of certain types of cancers only to later evoke a second form of cancer usually leukemia.
Various agents used are cyclophosphamide, chlorambucil, busulfan, melphalan, nitrosourea, -propiolactone and epoxides. This tragic consequence is called as Pyrrhic victory which becomes less of a victory when their initial use has been converted to cause later on second form of cancer. Acylating agentssubstances like acetyl imidazole. Indirect-acting carcinogens or procarcinogensthese are chemical substances requiring metabolic activation for becoming potent initial carcinogens.
Polycyclic aromatic hydrocarbons in tobacco, smoke, animal foods, industrial oil, and atmospheric pollutants. Important chemical compounds included are benzanthracene, benzapyrene, methylcholanthrene.
They may cause lung cancer, skin cancer, cancer of oral cavity, and sarcoma. Aromatic amines and azo dyesThese are -naphthyla- mine, benzidine, azo dyes used for coloring foods, and acetyl aminofluorene.
They may cause bladder cancer and hepatocellular carcinoma. Naturally occurring productAflatoxin, actinomycin-D, mitomycin-C, safrole, and betel nut. It can cause hepato- cellular carcinoma. Miscellaneousnitroso compounds, vinyl chloride monomer, asbestos, arsenical compounds, metals like nickel, lead, chromium, and insecticides, fungicides can cause gastric carcinoma, hemangiosarcoma of liver, bronchogenic carcinoma, epidermal hyperplasia, basal cell carcinoma, and lung cancer.
Promoters of Carcinogenesis Certain chemical substances lacking the intrinsic carcinogenic potential but helping the initiated cell to proliferate further are called promoter of carcinogenesis. They bind directly to DNA and RNA or cytoplasmic proteins to specific sites within molecule inducing miscoding error during transcription and replication. Factors affecting a carcinogenicity Dose dependentthe carcinogenicity of chemical agents is dose dependent and multiple traditional doses have same oncogenicity as a single comparative dose.
Administration of promotersthe carcinogenicity of chemical agents can be significantly enhanced by the subsequent administration of promoters. To be effective, the promoter must follow the initiator. Stage of Chemical Carcinogen The phenomenon of cellular transformation by chemical carcinogenesis is a progressive process involving two different stages. These are initiation and promotion. Initiation In this initiator carcinogen interact with DNA of target cell to induce mutation that is more or less irreversible to transform it into initiated cell.
Metabolic activationonly indirect acting carcinogen or procarcinogens require metabolic activation chiefly by mixed oxidases of cytochrome P system located in microsomal compounds of the endoplasmic reticulum or in the nucleus.
Reactive electrophilesthey are electron deficient protons, which bind to electron rich portions of other molecules of cell such as DNA, RNA or other protein. Target moleculesthe primary target is DNA, producing mutagenesis. Initiated cellthe unrepaired damage produced in the DNA of the cell becomes permanent, only if the altered cell undergoes at least one cycle of proliferation. Promotion It does not damage the DNA but enhances the effect of direct-acting carcinogen or procarcinogens.
The ultimate effect is further clonal proliferation of the initiated cell. Two or more initiators may be chemical, oncogenic virus or radiant energy may act in concert to induce malignant transformation referred to as cocarcinogens.
Physical Carcinogenesis It is divided into two groups. Radiation Carcinogenesis Forms of radiationradiation whenever in the form of UV light from sunlight, UV lamp, welders arc, or ionizing radiation like X-ray, , and ray, radioactive isotopes, protons and neutrons are established carcinogens.
Therapeutic irradiation can also induce carcinogenesis. Facts about radiation causing cancerradiant energy have potential of producing mutation and even killing cells. It can affect carcinogenesis by the following facts: Few tumors appear only after long latent period during which successive generation of clones are developed.
The radiation initiation is generally irreversible, but at a low dosage level is amenable to repair. The effect of radiation depends upon a number of factors such as type of radiation, dose, length of interval between the doses, capability of cells to repair in intervals and various host factors such as age, individual susceptibility, immune competence, hormonal influence and type of cell irradiated. Mechanismit induces cancer by following mechanism; Radiation may directly alter the cellular DNA and it may dislodge ions from water and other molecules of cell and result in the formation of highly reactive free radicals that may bring about the damage.
Radiation mutation may render cell vulnerable to other carcinogenic influence, i. Inhibition of cell division and inactivation of enzymes. Radiation might cause cell killing; permitting survivors to proliferate and thereby, become vulnerable to oncogenic influence. Non-radiation Physical Carcinogenesis Mechanical injury to tissues such as from stones in the gall bladder, stones in the urinary tract, and healed scars following burns or trauma has been suggested as causes of increased risk of carcinoma.
Implants of inert materials such as plastic, glass, etc. Hormonal Carcinogenesis Carcinoma is most likely to develop in organs and tissues which undergo proliferation under influence of excessive hormonal stimulation. Hormone sensitive tissues developing tumors are breast, endometrium, myometrium, vagina, thyroid, liver, prostate, and testis.
Estrogenin experimental animals, estrogen can cause induction of breast cancer in mice. Other cancers which can be induced in mice by estrogens are squamous cell carcinoma of cervix, connective tissue tumor of myo- metrium, tumor of kidney in hamsters, and benign and malignant tumors of liver in rats.
In case of human women receiving estrogen therapy and women with estrogen secreting granulosa cell, tumor of the ovary have increased risk of developing endometrial carcinoma.
Adenocarcinoma of the vagina is seen with increased frequency in adolescent daughter of mother who had received estrogen therapy during pregnancy. Contraceptive hormonesthere is increased risk of developing breast cancer, benign tumors of the liver and few patients have developed hepatocellular carcinoma. Anabolic steroidsconsumption of anabolic steroids by athletes to increase the muscle mass also increases the risk of developing benign and malignant tumor of the liver.
Hormone dependent tumorsit has been shown in experimental animals that induction of hyperfunction of adenohypophysis is associated with increased risk of developing neoplasia of the target organs following preceding functional hyperplasia. Biologic Carcinogenesis The epidemiological studies on different types of cancer indicate the involvement of transmissible biologic agents in their development, chiefly viruses. Therefore biological carcinogenesis is largely viral oncogenesis. A large number of viruses have been proved to be oncogenic in wide variety of animals and in certain types of cancers in humans.
The association of oncogenic virus with neoplasia was observed by an Italian physician Sanarelli in who noted association between myxomatosis of rabbit with poxvirus. Oncogenic viruses fall into 2 broad groups, i. Based on their activity to transplant target cells into neoplastic cells, they all are divided into three subgroups: Acute transforming virusesit includes Rous sarcoma virus in chickens, leukemia-sarcoma viruses of avian, feline, bovine and primate.
Slow transforming tumor virusesmouse mammary tumor virus MMTV that causes breast cancer in daughter mice. Adenovirusesit can cause upper respiratory infections and pharyngitis.
In man, they are not known to be involved in tumors but in hamsters they may induce sarcomas. Poxvirusin rabbits, it can cause myxomatosis and in humans, it can cause molluscum contagiosum and may induce squamous cell papilloma. Hepadnaviruseshepatitis B virus is a member of this family and it can cause acute hepatitis and is responsible for carrier state which can result chronic hepatitis.
In some cases, to progressing to hepatic cirrhosis and into hepatocellular carcinoma. The provirus is then integrated into the DNA of the host cell genome and may transform the cell into a neoplastic cell. Virus replication begins after integration of provirus into host cell genome.
Integration results in transcription of proviral genes or progenes into messenger RNA which then forms components of the virus particle, i. The three components of virus particles are then assembled at the plasma membrane of host cells and virus particles released by budding off from plasma membrane, thus completing the process of replication. DNA viral oncogenesis: ReplicationThe virus may replicate in the host cell with consequent lysis of infected cell and release of virions.
This results in neoplastic transformation of the host cell. Oxidative Mechanism of Carcinogenesis Active oxygen species and other free radicals have long known to be mutagenic. Further, these agents have emerged as mediators of the other phenotypic and genotypic changes that lead to form mutation to neoplasia.
Free radicals production is ubiquitous in all respiring organism and is enhanced by many disease states, by carcinogen exposure and under conditions of stress. Free radicals may therefore contribute widely to cancer development in humans.
Free radicals scavenging vitamins C and E have been shown to protect against cancer development in animal models. Biology of Tumor Growth The life cycle of malignant tumors can be divided into four phases. All etiologic factors ultimately affect the function of two sets of genes, one is proto- oncogenes or oncogenes and another one is anti- oncogenes or cancer suppressor genes.
Binding with DNAthe majority of carcinogens are mutagenes which bind the DNA directly or indirectly by undergoing enzymatic activation, inducing miscoding errors during transcription and replication. Production of growth factorsoncogenes may code for growth promoting factors and as a result, the tumor cells produce large amount of growth factors to which, only they can respond.
Multiple mutationscancer is a genetic disease that results when multiple mutations accumulate in the DNA of a cell and specific chromosomal abnormalities predispose to cancer. To produce a tumor of 10 12 cells, weighing 1 kg approximately, which is usually the maximum size compatible with life, the tumor cells have to undergo 10 further population doublings. So by the time the tumor is clinically detectable, it has already complete a major portion of its life cycle.
Factors affecting growth of cellsin tumor cells, there is an imbalance between cell production and cell loss, there- fore, the tumor grows progressively. The rate of tumor growth depends upon the growth fraction and the degree of imbalance between cell production and cell loss. Mechanism of Local Invasion and Distant Metastases Routes of metastasisthere are three routes through which metastases of tumor cells occur, i. Local invasionthe local invasion takes the path of least resistance and the tumor cells invade the surrounding tissue spaces.
Lymphatics spreadin case of oral malignancies, distant metastasis is mainly via lymphatics, either by lymphatic permeation or by lymphatic embolism. Blood vesselsrarely, it spreads through blood vessels and if this occurs, the tumor cells invade the lumen of blood vessels, the tumor emboli form, which are fragmented and the tumor cells are lodged into distant tissues. Theories of Carcinogenesis The Epigenetic Theory According to this theory, the carcinogenic agents act on the activators or suppressors of genes and not on the genes themselves and result in the abnormal expression of genes.
Genetic Theory Conceptthis is the most popular theory which suggests that cells become neoplastic because of alteration in the DNA.
It is suggested that, the secret of cancer lies within the normal cells themselves in the form of proto- oncogenes C-oncs. The mutated cells transmit their characters to the next progeny of cells. Inappropriate over expression of the gene or point mutation cause the cell to produce stimulating growth factors or in some way damages normal regulatory control. The qualitative and quantitative changes in the expression of genome may be brought about by carcinogenic influence, i.
OncogenesOncogenes are the transforming genes present in many tumor cells. Closely related genes are detected on normal animal and human cells and are called as proto-oncogenes or cellular oncogenes, abbreviated as c-oncs Cellular oncogenes of the host cells can transcribe its copies in the viral genome of acute transforming oncogenic retroviruses called as viral oncogenes or v-oncs.
An alternate mechanism is by anti-oncogenes in which, there is inactivation or deletion of genes that normally perform the function of suppressing cell proliferation, thus allowing them to proliferate. Feedback deletionaccording to genetic regulatory mechanism theory, primary change in the cell consists of a modification of repressor molecule which controls the functions of the gene. The repressor molecules are either RNA or protein. The modification of repressor molecules removes their orderly inhibitory control, which is responsible for normal morphogenesis and differentiation, and unearths the cell genetic potentiality for unrestricted growth.
This concept of loss of growth control is described as feedback deletion. The concept of mode of action of virus has taken many forms- Act as parasitevirus is present as a parasite in all tumor cells and it is transmitted from cell-to-cell and stimulates extreme hyperplasia without affecting the genome cell.
Act as biologic carcinogenit acts as a biologic carcinogen on some cellular constituents to release or activate neoplastic potentialities normally present in cells. Auto synthesiscarcinogens of all kinds ultimately act by creating some new auto-synthesizing cytoplasmic constituents, probably an auto-catalytic protein, which can excite the cell to unlimited growth.
I mmune Surveillance Theory It suggests that an immune-competent host mounts an attack on developing tumor cells so as to destroy them while an immune-incompetent host fails to do so.
According to original immunological theory, normal cells contain specific self-marker identity proteins which is recognized by the normal growth regulating mechanism. These proteins serve as receptor for chemical carcino- gens hapten and the resulting complex is self-replicating. The complex complex antigen triggers off an immune response and the antibody free or cell bound combines with the self-marker carcinogen complex and eliminates it.
The new race of cells produced is deleted with self- markers and goes unrecognized by growth regulatory mechanism. The high incidence of cancer in AIDS patients is in support of this theory. Monoclonal Hypothesis Currently, there is strong evidence on studies of human and experimental animals that most of the cancers arise from single clone of transformed cell.
The best documentation of monoclonal origin of cancer cells come from the study of G 6 PD in women who are heterozygous for its two isoenzymes A and B.
It is observed that all tumor cells in benign uterine tumor leiomyoma contain either A or B genotype of G 6 PDi. Multistep Theory According to this theory, carcinogenesis is a multistep process which is substantiated in vitro by changes in experi- mental animals as well as in vivo by changes in human cancers.
In chemical carcinogenesis, there are two essential features, i. Many tumors arise from combination of activation or growth promoting oncogenes and inactivation of growth suppressing anti- oncogenes. In some cancers, there is initial dysplastic change that may progress into carcinoma in situ and then into invasive carcinoma.
This metastasis is the transfer of the disease from one organ or part to another not directly connected with it. If malignant cells did not metastasize, the surgical removal of primary neoplasm would completely cure the patient. Metastasis is fundamentally an embolic process. The invasiveness of malignant cells involves motility, which requires change in shape and adhesiveness and ability to degrade the matrix in order to penetrate it.
The metastatic process can be divided into several sequential steps although these steps are interconnected. Factors which control metastasis are proteolysis, cell adhesion, tumor angiogenesis, cell mediated immunity and genetic factor. Steps of Metastasis Breaking of cellsthe breaking of loose neoplastic cells from the parent tumor. Invasioninvasion of the matrix sarcoma , penetration of the basement membrane and invasion of connective tissue carcinoma.
Entering the blood vesselsit then entering the wall of blood and lymphatic vessels. Survivalsurvival of malignant cells in the bloodstream. Survival in the compatible tissue environment and induction of growth factor to stimulate new vessel formation to obtain nutrition. Emergence of cellsemergence of the malignant cells from the blood vessels in the form of the emboli and lodgment in other tissues.
Multiplicationmultiplication of neoplastic cells and growth to form secondary neoplasm at the new site. Control mechanismeach of these steps is probably controlled by different molecular mechanism and this may explain the differences in the behavior with reference to tumor metastasis. Neoplastic cells within a single tumor might differ in their ability to metastasize. A sub-population of cells preexists within the hetero- geneous primary tumor. The relative size of this sub- population in the primary tumor may vary with time between the neoplasms.
For example, mouth-to-neck nodes and breast- to-axillary nodes. Bloodstreamparticularly veins from gut via portal circulation to liver, from systemic sites through right heart to lung, from left heart to any systemic sites. Cavitiesalong epithelium lined cavities, for example: respiratory tract, gut, urinogenital tract etc. Otherstranscelomic spread, cerebrospinal fluid, tissue planes and through nerve sheath.
Pattern of Metastatic Spread Mechanistic theorythe capillary bed of the first organ which encounter viable neoplastic cells is the preferred site of metastasis. Seed and soil hypothesisit suggests that availability of fertile environment the soil in which compatible tumor cells the seed can grow is important.
Ewing suggested that varying pattern of metastasis is due to fact that different tumor cells thrive in certain biological sites soils but not in the other sites. Cell interactioninteraction between cell surface protein of malignant cells and organ specific protein, e.
Grading and Staging of Tumors Grading The grading features are those indicative of proliferation and differentiation. It is defined as, macroscopic and microscopic degree of differentiation of tumor. Grading depends mainly on two histologic features, the degree of anaplasia and the rate of growth.
Different types of grading systems are as follows: Broders Classification System Fig. Grade II Moderately differentiated, i. Usually, the invasion is poorly delineated from the stroma. Grade III Moderately differentiated, i. CI N Grading Alternative classification for grading of dysplasia and carcinoma in situ together is cervical intraepithelial neoplasia CIN.
Depending on thickness of squamous epithelium involved by atypical cells According to this, grading of dysplasia is as follows: Mild Moderate Severe Staging It is the extent of spread of tumor within patients.
Assessment It is assessed by following ways: Clinical examinationstaging can be assessed clinically by the size and extent of primary lesion. Investigationinvestigation like radiology, sonography can lead to staging of disease. Pathological examinationthis is very important part while staging of neoplastic process is done.
Mainly biopsy, cytology are used. Infiltrationdegree of infiltration of primary lesion should be carried out. Metastasispresence or absence of metastasis to regional lymph nodes. Presence and absence of distant meta- stasis. Involvement of contralateral or ipsilateral node. Whether node are fixed or not. Objectives Treatment planningit aids clinician in the planning of treatment.
Prognosisto give some indication of prognosis. Evaluation of treatmentto assist in evaluation of the result of treatment. Exchange of informationto facilitate the exchange of information between treatment centers. Investigationto contribute to the continuing investi- gations of human cancer. Primary tumor T : local extent is major factor contributing to prognosis. T x : primary tumor cannot be assessed. T 0 : no evidence of primary tumor. T is : carcinoma in situ.
T 1 : tumor 2 cm or less in diameter. T 2 : tumor cm in diameter. T 3 : tumor more than 4 cm in greatest diameter. T 4 : tumor of any size in which tumor invades adjacent structure e. Regional lymph nodes N N x : regional lymph node cannot be assessed.
N 0 : no regional lymph node metastasis. N 1 : metastasis in single ipsilateral lymph node less than 3 cm in diameter. N 1 a: nodes considered not contain to tumor growth.
N 2 a: Single ipsilateral lymph node more than 3 but less than 6 cm. N 2 b: multiple ipsilateral lymph nodes less than 6 cm. N 2 c: Bilateral or contralateral lymph node less than 6 cm in greatest dimension. N 3 : metastasis in lymph node more than 6 cm and it is fixed. N 3 aipsilateral nodes at least one greater than 6 cm. N 3 bbilateral nodes greater than 6 cm. N 3 ccontralateral nodes at least one greater than 6 cm. Distant metastasis M M x : Distant metastasis cannot be assessed.
M 0 : No distant metastasis. M 1 : Distant metastasis. Category M 1 may be further specified according to the notation. S 2 lip mucosa. S 3 tongue. S 4 cheek. S 5 palate. S 6 floor of mouth.
S 7 alveolar process. S 8 antrum. S 9 central carcinoma of bone. Size of tumorit is denoted by T T 1 less than 2 cm in diameter. T 2 between 2 cm and 4 cm in diameter. T 3 between 4 cm and 6 cm in diameter and extending beyond the primary region and extending through adjacent periosteum. T 4 greater than 6 cm in diameter and extending to involve adjacent structures.
Regional nodes were grouped as N 0 no palpable nodes. N 1 equifocal node enlargement. N 2 clinically palpable homolateral regional nodes, not fixed. N 3 same as N 2 but fixed.