Published on February 27, 2014
NEOPLASM Neoplasia – process of new growth Neoplasm = new growth Oncology means study of tumor Cancer ---- common term of all malignant tumors.
DEFINITION Willis, definition of neoplasm A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue and persist in the same excessive manner after cessation of the stimuli which evoke the change.
WHY DOES A NEOPLASM OCCUR? Due to “heritable genetic changes that are passed down from the ‘changed’ (neoplastic) cell to the progeny of tumor cells The genetic change allows these group of cells to have excessive & unregulated proliferation that becomes almost completely autonomous
TUMORS ARE MONOCLONAL The entire population of cells within a tumor are one single cell that has incurred genetic change, and hence tumors are said to be “clonal” Clone= a group of cells arising from one single cell by asexual division and having the same structure and function as that of the parent cell
THE 5 PS OF NEOPLASIA A neoplasm is: Persistent Purposeless Parasitic Progressive PROLIFERATION
TYPES OF NEOPLASMS (TUMORS) Benign tumors They remain localized cannot spread to other sites and are amenable to local surgical removal and patient survives. Malignant tumors They invade and destroy adjacent structures and spread to distant sites to cause death of patient.
NOMENCLATURE Two basic components Parenchyma (proliferating neoplastic cell) Stroma (connecting tissue and blood vessels) Some tumors (sarcoma) stroma is scanty so neoplasm is soft and fleshy. Desmoplasia – Abundant colagenous stroma Schirrhous – Stony hard scirrhous
THREE BASIC GROUPS OF TUMORS I. Composed of one parenchymal cell type II. Composed of more than one parenchymal cell type arising from same germ layer . III. Composed of more than one germ layer arising from totipotential cells.
BENIGN TUMORS Benign mesenchymal tumors= - Oma as a suffix to cells of origin Epithelial: Adenoma, cystadenoma, papilloma, polyps
MALIGNANT TUMORS Sarcoma (sar= fleshy) -masanchymal tissue origin Carcinoma --- epithelial cell origin. Squmous cell carcinoma Adenocarcinoma
OTHER TERMS Melanoma Hepatoma Seminoma Chorsitoma Ectopic rest of normal tissue e.g. rest of adrenal cells under the kidney capsule. Hamartoma Mass of disorganised but mature specialized cells or tissue
Mixed tumor:- Divergent differentiation f a single line of parenchymal cells into an other tissue. These tumors arise from single germ layer. E.g. mixed tumor of salivary gland (pleomorphic adenoma) Teratoma :- Made up of variety parenchymal cell, arise from more than one germ layer. These tumors arise from totipotent cells e.g. Ovarian cyst teratoma (dermoidcyst)
BIOLOGY OF TUMOR GROWTH Four phases of malignant tumor Malignant changing in the target cell ---Transformation. Growth of transformed cells . Local invasion. Distant metastasis.
Differentiation Resemblance of neoplastic cells with normal cells , both morphologically and functionally . Anaplasia ( to form backward ) lack of differentiation.
MORPHOLOGICAL CHANGES OF ANAPLASIA Pleomorphism . Abnormal nuclear morphology . Increase mitotic figure Atypical mitotic figure Loss of polarity . Disorganization of tumor cells Tumor giant cells. Hyperchromatic Large nucleus and irregular Nucleoli present Mitosis . Variation in shape & size
Dysplasia Disorder growth . Reverse change may occur. Pleomorphism . Loss of orientation , hyperchromatic nuclei , increase mitotic activity. Mostly seen in epithelium . Carcinoma in situ, displastic changes are marked and involve the entire thickness of epithelium but the lesion remain confined to the normal tissue.
Papiloma of colon
Mixed tumor of the parotid gland
Adeno carcinoma of colon Adenoma of colon
Anaplastic tumor of the skeletal muscle
Carcinoma in situ
RATE OF GROWTH Rate of growth of tumor is determined by three main factor Doubling time of tumor cell. Fraction of tumor cells, the proportion of cells with in the tumor population that are in proliferative pool. Rate at which cells are shed and last in the growing lesion.
During early phase of cell growth transforms cells are in the proliferative pool. During growth of tumor , tumor cells leave the proliferative pool and goes nonproliferative pool (shading, apoptosis, differentiated and reversion to Go Most cells within tumor remain in the G0 or G1 phase. Leukemia,lymphoma , lung tumor high growth fraction.
Colon, breast low growth fraction. Increased growth fraction tumor increase susceptibility to cancer therapy, decrease growth fraction decrease susceptibility to cancer therapy. Other factors like hormone , adequate blood supply and unknown influences may effect their growth.
LOCAL INVASION Benign tumor Localized Non-metastasize. Slow growth. Form fibrous capsule. Malignant tumor Progreesive infiltration, invasion and destruction . Poorly demarcated. Surgical resection is deficient.
METASTASIS Implantation of tumor cells from primary site to distant site . Three routes . Seeding of body cavities. Lymphatic spread Common e.g. Ca breast. Skip metastasis. Venous lymphatic anastomoses by inflammation . Radiation. Sentinel lymph node. First node in regional lymphatic system that received lymph flow from primary tumor.
HEMATOGENOUS SPREAD - Common in sarcoma. - Commonly through veins. - Lung and liver commonly involve .
FACTORS RESPONSIBLE FOR TUMOR Environmental factors Virus Radiation . Chemical agents. Cigarette smoking. Chronic alcoholism. Risk of cervical cancer increase with increase number of sex partner
GENETIC FACTOR Three categories Autosomal dominant inherited cancer syndrome. Point mutation in a single allele of tumor suppressor gene. Childhood retinoblastoma are common . Mutation of the RB tumor suppressor gene. Other e.g. osteogenic sarcoma. Familial adenomatous polyposis. Multiple endocrine neoplasia type I and II (MEN1and MEN2). Defective DNA repair syndrome. Autosomal recessive pattern of inheritance . Xeroderma pigmentosum. Ataxia telangectasia.
Hereditary non-polypoid colon cancer (HNPCC) Autosomal dominant condition caused by inactivation of DNA mismatch repair gene. HNPCC sydrome produce cancer in the colon, small intestine, endomatrium and ovaries. FAMILIAL Without clearly defined pattern of transmission. Ca colon , breast, ovary, brain and malinoma are common. Onset - early age. Tumor arise from two or more close relative. Some time bilatral or multiple tumor.
NON-HEREDITARY PREDISPOSING CONDITION Chronic inflmmation and cancer Ulcerative colitis , Crohn’s disease , helicobacter pylori gastritis , viral hepatitis, chronic pancreatitis. Unknown cause but (1) may be release of certain cytokinese which stimulate the growth of transforms cells. Chronic inflammation may directly promote genomic instability in cells through the production of reactive oxygen species (ROS).
PRE-CANCEROUS CONDITIONS Chronic atrophic gastritis of pernicious anemia . Solar keratosis of the skin. Chronic ulcerative colitis. Leukoplakia of oral cavity , vulva and penis. Some benign tumor like villpous adenoma of colon, liomymoma.
EPIDEMOLOGY Common tumors are: Ca lung Ca female breast Ca prostate Ca colon / rectum Ca liver
Common tumors of male are: Ca prostate Ca lung Ca colon / rectum Common tumors of female are: Ca breast Ca cervix Tumors of ovaries Ca lung
Common tumors due to alcohal Ca oropharnx Ca larynx Ca esophagus Ca liver Common tumors due to ciggrate smoking Ca lung 90% Ca mouth Ca pharynx Ca larynx Ca esophagus Ca parncreas Ca gall bladder
Common tumors of children Acute lymphoblastic leukemia Neuroblastoma Willm’s tumor Retinoblastoma Rhabdomyocarcoma Common tumors of old age Ca prostate Leukemias Ca pancreas
Normal physiology of cell proliferation Following steps Growth factor The binding of growth factor to its specific receptors generally located on the cell membrane. Transient and limited action of the growth factor receptor. Transmission of transduced signal across the cytosol to the nucleus via second messengers or by signal transduction molecules that directly activate transcription. Induction and activation of nuclear regulatory factors that initiate DNA transcription .
GENES Genetic damaged (or mutation) by environment agents such as chemicals, radiation, virus or it may be inherited . Tumor is formed by clonal expansion of a single precursor cells that has incurred the genetic damage. Four classes of normal regulatory gene. Growth promoting protooncogene. Growth inhibitory tumor suppressor gene. Gene that programmed cell death (apoptosis). Gene involve in DNA repair .
Oncogene . Protooncogene. That promote autonomus cell growth. Normal cellular counter part of oncogene. Protooncogene converted into cellular oncogene (Cone). That are involved in disease development. Oncoprotein . Product of oncogene is called as oncoprotein.
SEVEN FUNDAMENTAL CHANGES IN CELL PHYSIOLOGY TO PRODUCE MALIGNANCY Self sufficiency in growth signals –proliferation without stimuli Insensitivity to growth inhibitory signals Tumor may not respond to molecule that are inhibitory to the proliferation of normal cell. E.g. transforming growth factor β (TGF β). Direct inhibitor of cycline dependant kinase. Evasion of apoptosis Tumor resistance to programmed cell death by inactivation of P53.
Defect in DNA repair – By carcinogens or unregulated cellular proliferation . Limitless replicate potential . Unristicted proliferative capacity By maintance of telomer length and function. Sustained angiogenesis . By vascular endothelial growth factor (VEGF) . Ability to invasion and metastasis
1. Growth factor 2. Growth factor receptor 3. Signal transducing protein 4. Nuclear regulatory factor initiate DNA transcription 5. Cell cycle
1. GROWTH FACTOR: Many cancer cells acquire growth self sufficiency by synthesize some growth factor (PDGF, TGFα) Glioblastoma secrete PDGF and sarcomas TGF α) Growth factor gene it self not altered or muted but the product of other oncogene (e.g. RAS) caused over expression of growth factor gene, therefore secrete large amount of growth factor
2. GROWTH FACTOR RECEPTORS: Mutations and pathologic over expression of normal form of growth factor receptor have been detected in several tumors Over expression of ERBBI (EGF receptor) is over expressed in 80% of squamous cell carcinoma of lung HER2 receptor is amplified in 25-30% of breast cancer, adenocarcinoma of lung, ovary and salivary gland
3. SIGNAL TRANSDUCING PROTEIN: Signal protein receive signal from activated growth factor receptors and transmit them to nucleus Two important members RAS and ABL 30% of all human tumor contain mutated version of RAS Ca colon and ca pancreas, mutation of RAS is high
RAS GENE: When normal cell stimulated through growth factor receptor, inactivated (GDP-bound) RAS is activate to GTP bound state Activated RAS transmit signals to the nucleus Mutation of RAS, permanently activated leading to continuous stimulation of cells without external stimuli RAS gene is commonly activated by point mutation
4. NUCLEAR TRANSCRIPTION FACTOR : All signal transcription factors enter the nucleus and increase mitotic activity Excessive, abnormal growth occur when mutation of gene responsible for DNA transcription Most common oncogene are MYC, MYB, JUN, FOS and REL have been localized to the nuleus MYC gene is most commonly seen in human tumor
MYC gene: MYC protooncogene is expressed in all cells MYC protein is induced rapidly when quiescent cell receive signal to divide MYC protien bind to DNA causing transcription activation of several growth related gene (including cyclin dependent kinase) Oncogene version of MYC gene are over expressed and contribute to sustained proliferation Translocation of MYC gene seen in burkitts’ lymphoma, Bcell tumor Amplification of MYC is seen in breast, colon, lung and many other cancers
5. CELL CYCLE
Cell Cycle: After all growth promoting stimuli, the entry of quiescent cell into cell cycle Mutation of cyclin and CDKs favour excessive proliferation Cyclin D and CDK4 are commonly seen in neoplastic transformation Cyclin D over expression is seen in beast, Oesophagus, liver and lymphoma Amplification CDK4 gene occurs in melanoma, sarcoma and glioblastoma
Insensitivity to growth inhibitory signals (tumor suppressor gene) The growth of cell has to be controlled by many external signal to maintain the steady state (homeostasis) . Failure of growth inhibition is one of the fundamental alteration in the process of carcinogenesis . The genes brakes cell proliferation are called as tumor suppressor gene. The protein that apply brakes to cell proliferation are the product of tumor suppressor gene.
RB gene (Retinoblastoma ) First tumor suppressor gene RB gene discover from Retinoblastoma (childhood tumor) RB gene is also seen in breast cancer, small cell carcinoma of lung, bladder carcinoma. RB gene product is a DNA binding protein that is expressed in every cell. The main role of RB gene is active hypophosphorylated and inactive hyper phosphorylated state.
In it s active state, RB brake the cell proliferation from G1 to the S phase of the cell cycle. If RB protein is absent or mutation , the molecular brakes on the cell cycle are released and cell move into S phase. Various growth factor promote the formation of the D/CDK4 complex like EGF, TGFα, HGF, PDGF. Growth inhibitor inhibit the above process (TGFβ, P53, and other )
P53 (Guardian of the genome) Located on chromosome on 17P13 A, and it is the most common target for genetic alteration in human tumors. 50% of human tumor contain mutations in this gene . Most commonly seen in Ca lung, Ca breast, and Ca colon. P53 also called as gate keeper or molecular policeman against the formation of cancer, that prevent the propagation of genetically damage cells P53 protein is a DNA binding proteins localized to the nucleous.
Main function is to control the transcription of several other gene. Mutation RB (transforming protein of several DNA virus) and MDM2 degrade the formation of P53. The main function of 53 proteins are cell cycle arrest and initiation of apoptosis in response to DNA damage. P53 apply emergency brakes when DNA is damage by irradiation, ultraviolet light and chemicals. P53 also help in the repair process directly by inducing the transcription of GADD45 (growth arrest and DNA damage ) which encodes proteins involved in DNA repair.
When DNA repaired successfully P53 activate MDM2, whose product degrade P53, thus releiving the cell cycle brake. If DNA damage not successfully repair P53 send the cell to the grave yard by inducing the activation of apoptosis gene (BAX) BAX binds to and antagonizes the apoptosis inhibiting protein BCL-2 thus promote cell death. In view of these activities P53 right fully called ‘guardian of genome’.
APC gene Tumor suppressor gene that responsible for down regulation of growth promoting signals (β-catenin) In the cell nucleous β catenin form a complex with TCF (transcription factor) that up regulation of cellular proliferation by transcription of cell promote gene (MYC)
To be Contd:
EVASION OF APOPTOSIS Cell growth in regulated by growth promoting and growth inhibitory gene, cell survival is conditioned by gene that promote and inhibit apoptosis. The accumulation of tumor cells may occur due to mutation in the gene that regulated apoptosis. BCL-2 BCL-2 protect cell from apoptosis Translocation of BCL-2 results over expression therefore protect tumor cells from apoptosis e.g. B-cell lymphoma of follicular type.
P53 P53 Increase transcription of pro-apoptotic gene such as BAX Lack of P53 by mutation reduced apoptotic activity MYC MYC and BCL2 may collaborate in tumor genesis MYC triggers proliferation and BCL2 prevent cell death.
DNA repair defect and genomic instability in cancer cell. DNA damaging agents are ionizing radiation, sunlight , dietary carcinogens and oxidative stress. DNA of normal dividing cell is susceptible to alteration resulting from error that occur spontaneously during DNA replication . Such mistake is not repair properly , therefore push the cell into neoplastic transformation . Those born with such defective gene, are at high risk of developing cancer. These conditions are K/a genomic instability syndrome. DNA repair gene themselves are not oncogene, but their abnormalities allow mutation in other gene during the process of normal cell division.
Three types of DNA repair systems Mismatch repair Nucleotide excision repair Recombination repair.
Mismatch repair Mismatch repair gene act as spell checkers of strand of DNA . For example if there is some error in pair of G with T , rather than the normal A with T. The mismatch gene correct this defect. Without these corrections errors slowly accumulate in several gene including protooncogene and tumor suppressor gene. Mutation in at least five mismatch repair gene have been found in hereditary non Polyposis cancer syndrome (HNPCC)
Defect in nuclutide excision repair In xeroderma pigmentosum, defective DNA repair genes, are at increased risk for the development of skin cancer, when exposed to UV rays in sun light . UV rays causes cross linking of pyrimidine residues , this preventing normal DNA replication . Such DNA damage is repaired by the nucleotide excision repair (NER) system . Several protein and gene are involve in the NER, and on inherited loss of any one can give rise to xeroderma pigmentosum.
Inherited disease with defect in DNA repair by hemologous recombination In this DNA repair system two important gene are BRCA1 , BRCA2 Mutation in two genes are seen in 80% of familial breast cancer. BRCA1 Mutation also produce ovarian cancer in female and prostate cancer in male.
BRCA2 mutation increase risk of Ca breast in man and women and cancer of ovary, prostate, pancreas, bile duct, stomach and melanocyte. Main function of these two gene are regulate DNA repair Cell that lack these genes develop chromosomal breaks BRCA1 is a part of multi protein complex that is crucial for repair of double strands breaks in chromosomes
Limitless replicative potential . Telomerase After fix number of division , normal cell become arrested in non-dividing steps. It has been noted that with each cell division some shortening of specialized structure of cell called telomers at the end of chromosome . Loss of telomer resulting activation of P53 dependent cell cycle check point causing proliferate arrest or apoptosis . Germ cell telomer shorten is prevented by enzyme telomerase
Loss of telomerase means loss of replication ability . In tumor cell reactivation of telomerase. Telomerase is detected in more then 90% of tumors . Telomerase activity and maintain of telomer length are essential for the replicative potential in cancer cell.
Development of sustained angiogenesis Tumor stimulate the growth of host blood vessels called as angiogenesis. Essential for supply a nutrient to the tumor. Two factor produce by tumor cells are VEGF and bFGF.
Invasion and metastasis Detachment (“ loosening up”) of the tumor cells from each other. Attachment to matrix components. Receptors of lamina and fibronectin of ECM. Degradation of ECM. E. adherins. Catenine. MMPs (Matrix metaloprotenasis) – type IV colegenase. Migration of tumor cells. CD44.
WHY TUMOR SPREAD IN PARTICULAR ORGAN OR TISSUE? Adhesion molecule whose ligands are expressed on the endothelial cells of the target organ. Chemokines have important role in spread of tumor in particular organ or tissue .e.g. some breast cancer expressed the chemokine receptors CXCR4 and CCR7 . Chemokines that bind to these receptors are highly expressed in tissue to which breast cancer commonly metastasize . Some target organ may liberate chemoattractants that tend to recruit tumor cell to the site.
CARCINOGENIC AGENTS Chemical carcinogenesis Radiation carcinogenesis. Microbial carcinogenesis.
CHEMICAL CARCINOGENESIS - Initiations –exposure of cells to a sufficient dose of a carcinogenic agents (initiator). (DNA damage and mutation ) - Initiated cell is altered making it potentially capable of giving rise to a tumor. - Initiation is not sufficient for tumor formation. - Promotor – these are chemicals which them selves are noncarcinogenic but induce tumor in initiated cells. (Clonal expansion of mutated cells)
INITIATION OF CHEMICAL CARCINOGENESIS 1. 1. Direct acting compound Do not require metabolic conversion to become carcinogenic 2. Indirect acting compound (Pro carcinogene) Which require metabolic conversion to become carcinogenic
Carcinogenic are highly reactive electrophiles (have electron deficient atom) that can react with nucleophilic (electron rich) in the cell. These reaction are non enzymatic and result in the formation of covalent adducts (addition product) between the chemical carcinogenic and a nucleotide in DNA . Electrophlic reaction may attack DNA, RNA and proteins of target cell .
Radiation carcinogenesis Ultra-violet rays E.g UV rays of sunlight. Squamous cell carcinoma. Basal cell carcinoma. Malignant malanoma. Ionizing radiation. X-rays Atomic rays. Skin cancer. Thyroid cancer. Leukemia. Thyroid cancer. Ca breast. Ca Colon . Ca lung. Radio nucleotide. Lung cancer.
MICROBIAL CARCINOGENESIS Viral carcinogenesis DNA virus The genome of oncogenic DNA form stable association with host cell genome.The virus is enable to complete its replicative cycle because the viral gene essential for completion of replication are interrupted during the integration of viral DNA .Thus virus can remain in a laten state for years. Those viral gene that are transcribed early in the viral life cycle (early gene) are important for transformation and are expressed in transformed cells. E.g.
HUMAN PAPILOMA VIRUS (HPV) Benign squamous papiloma (warts) . Squamous cell carcinoma of cervix . Oral and laryngeal cancer. E6 and E7 protein product of HPV viral gene bind and neutralize the RB and P53 suppressor gene . E7 also interfere with P53 transcriptional activity and also inactivate P21. Net effect of E6 and E7 is to block apopotsis and excessive cell proliferation .
EPSTEIN - BARR VIRUS (EBV) Burkitt’s lymphoma Post- transplant lymphoproliferate disease Primary central nervous system lymphoma is AID patients Sub set of other AID related lymphoma Sub set of hodgkin lymphoma Nasopharyngeal carcinoma LMP-1 gene (EBV encoded gene) act as oncogene, promote B cell proliferation by activating signaling pathways. LMP-1 also prevent apoptosis by activating BCL-2. EBNA-2 EBV encoded gene –transactivate several host gene including cyclin D and Src family genes.
HEPATITIS B VIRUS Hepato cellular carcinoma Mode of action of this virus in tumor production is not fully known. Chronic liver cell injury and regeneration, HBV predisposes the cell to mutations, caused possibly by environment agents e.g. dietary toxin HBV encoded regulatory element called HBx. HBx disrupts normal growth of infected liver cell by transcripitional activation of several growth control genes .
RNA virus Retrovirus transform cell by two mechanism 1. Acute transforming virus contain viral oncogenes, transduced human protooncogenes . 2. Slow transforming virus Do not contain viral oncogene but proviral DNA are found near a cellular oncogene . Under the influence of a strong retroviral promotor, the mutated or normal cell oncogene is over expressed. This mechanism of transformation is called insertional mutagenesis e.g. Human T – cell leukemia virus type I (HTLV-1)
HTVL-1 Produce T cell leukemia / lymphoma HTLV-1 has tropism for CD4+ T-cell and this subset of T cells is the major target for neoplasm trasnformation. Infected T cell spread via sexual intercourse, blood product and breast feeding. Pathogenesis HTLV-1 infected many T-cells causes polyclonal proliferation activated by TAX gene. TAX neutralize growth inhibitory signals by attaching P53 . Ultimately monoclonal T leukemia / lymphoma.
HELICOBACTER PYLORI Peptic ulcer Gastric carcinoma . Gastric lymphoma (B-cell origin) H.Pylori infection leads to the formation of H.Pylori reactivity T-cells which causes polyclonal B cell proliferation . Gastric carcinoma ------ first chronic gastritis followed by gastric atrophy, intestinal metaplasm of the epithelial linning, displasia and cancer. This sequence takes decades to complete and occurs in only 3% of infected patient .
Tumor Immunity (host defense against tumor immunity) Tumor antigens Antigen that elicit immune response. Two types Tumor specific antigen Present on tumor cell and induce immune response to a tumor it self e.g. testicular carcinoma melanoma medullary carcinoma of breast.
Tumor associated antigen. These are present in tumor cells and some normal cells. they do not induce immune response but their detection is of value in detection of certain tumor. e.g. 1. Embryonic antigen (oncofetal antigen) . (a) alpha fetoprotein . (b) carcinoembryonic antigen. 2. Differentiation antigen produced by tumor cell at a specific differentiation stage eg. CD10 –expressed in B cell lymphoma, prostatic specific antigen – Ca prostate .
Anti-tumor effecter mechanisms 1.Cytotoxic T- lymphocyte (CTLs) Play a protective role against virus associated neoplasma e.g. EBV induced Burkitt’s lymphoma Important role for CD8+ cytotoxic T cells in tumor immunity CTLs recognized peptide antigen present on the tumor cell surface by MHC class I molecule. 2.Natural Killer cells (NK) Lymphocyte that destroy tumor cells without prior sensitization IL-2 activate NK cells and lyse the tumor cells NKG2D protein expressed on NK cells and some T lymphocyte are important triggering receptors. They recognize antigen expressed mainly on tumor cells. NK cells can also participate in antibody dependant cellular toxicity.
3. Macrophages Activation of macrophages by interferon gamma. this cytokine produce by T-lymphocyte and natural killer cells. Activated macrophages kill tumor cell by production of reactive oxygen metabolites or by secretion of tumor necrosis factor (TNF) . 4. Antibodies. Antibodies formed by various tumor antigen . Antibody kill tumor cell by activating complement or by antibody dependant cell mediated cytotoxicity .
Immune surveillance Prevention of tumor from immune system 1. Selective out growth of antigen negative variants, During tumor pregression, strongly immunogenic sub clone may be eliminated. 2. Loss or reduced expression of histo compatibility antigen . 3. Lack of costimulation Sensitization of T cell require two singles, one by forign peptide presented by MHC and the other by costimulatory molecules . Tumor cell do not expressed constimulatory molecule (B7-1). B7-1 prevents sensitization of T cell but also T cell under go apoptosis
CLINICAL FEATURES OF TUMOR Local pressure on adjacent structure Hormone or hormone like substance release from tumors ------ para neoplastic syndrome Bleeding and infections, when tumor ulcerated E.g. Pressure of adenoma of pitutray gland -----Hypopitutrism Neoplasm of gut ------ Intestinal obstructions E.g. tumors of skin and gut Symptoms result from rupture or infarction Cachexia or wasting
Cancer cachexia Progreessive loss of body fat and lean body mass accompanied by profound weakness , anorexia and anemia . Cachexia result for the action of soluble factor such as cytokines produce by tumor and by the host in response to the tumor. TNF IL-1 Interferon gamma
PARANEOPLASTIC SYNDROME Symptoms complex other than cochexia that appear in patient of cancer due to secretion of hormones or hormone like substances from tumors. Endocrinopathy ------ Ectopic hormone production
GRADING AND STAGING OF TUMOR Grading Degree of differentiation of the tumor cell and number of the mitosis within tumor. 1. Well differentiated . 2. Moderate differentiated. 3. Poorly differentiated. 4. undifferentiated.
Staging Staging of cancer is based on the size of the primary lesion , spread of regional lymph node and presence or absence of metastasis . TNM system (UICC). (a) To --- Ca in situ . T1 --- T4 size of primary tumor. (b) N--- regional lymph node involvement No,N1,N2,N3/ (c) M--- Mo no metastasis. M1, M2 ---- metastasis. 1. 2. AJC system. In this tumor are divided in to stage o – IV, incorporating , size of primary lesion , as well as presence of nodal spread and of distant metastasis .
LABORATORY DIAGNOSIS OF CANCER Histologic and cytologic methods Histologic examination is the most important method of diagnosis is greatly aided by Availability of all relevant clinical data. Adequate preservation and sampling of the specimen. In some cases examination of the frozen specimen to detect cell surface receptors. In addition to the usual fixed and paraffin embedded section, quick frozen secretion are employed to obtain a rapid diagnosis while the patient is still under
FINE NEEDLE ASPIRATION Fine needle aspiration involves aspiration of cell and fluids from tumors or masses that occur in readily palpable sites e.g, breast thyroid lymph nodes. The aspiration cells are smeared stained and examined.
CYTOLOGIC PAPANICOLAOUS SMEARS Cytologic or papanicolaou smear involve examination of cancer cell that are readily shed exfolitive cytology is ude most commonly in the diagnosis of dyplasia carcinoma in situ and invasive cancer of uterine cervix and tumors of the stomach bronchus and urinary bladder. Interpretation is based chiefly in changes in the appearance of individual cells.
IMMUNOCYTOCHEMISTR Y Immunocytochemistry involves detection of cell products or surface markers by monoclonal antibodies . The binding of antibodies can be revealed by fluorescent labels or chemical reactions that result in the generation of a colored product. This technique is useful in the following settings. Diagnosis of undifferentiated tumors . catagerazaion of leukemaias determination of site of origin of metastasis . Detection of molecules that have prognostic or therapeutic significance .
DNA probe analysis DNA probe analysis involves polymerase chain reaction (PCR)or FISH analysis. This technique is currently used in the diagnosis of lymphoid neoplasm due to association of these tumors with chloral rearrangements of T –cells and B – cells antigen receptor genes . Detection of oncogenes e.g.N – myc in assessing the prognosis of certain tumors . Diagnosis of chronic myeloid leukemia by detection of bcr – abl fusion gene product even in the absence of philadelphia chromosome. Specific translocation can distinguish b/w similar appearing tumors e.g. small round cell tumors in children
Heredetary predisposition to certain tumor e.g breast cancer and endocrine neoplasm can be detected by mutilational analysis of BRC A – 1, BRC A-2 and RET genes .
FLOW CYTOMETRY Measurement of the DNA containt of tumor cell by flow cytometry is useful due to relationship b/w abnormal DNA content and prognosis. Flowcytometry is of value in the diagnosis of leukemia and lymphoma .
TUMOR MARKERS These are tumor derived are tumor associated molecules that can be detected in blood or other body fluids. They are not primary methods of diagnosis but help in the diagnosis. They are also valuable in determining the response to therapy . Examples : Carcinoembryonic antigen (CEA) normally produced by fetal gut , liver and pancreas, may be elaborated by Ca: colon , pancreas stomach and breast. Alpha fetoprotein is normally produced by fetal yolk sac and liver ,markedly increased in Ca: liver and testicular embryonic carcinoma .
Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal's breadth ...
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Neoplasia ist eine wissenschaftliche Fachzeitschrift, die vom Neoplasia-Verlag veröffentlicht wird. Derzeit erscheint die Zeitschrift mit zwölf Ausgaben ...
Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth ...
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