Aberrant cell Growth and cellular adaptations Unit-ivB Younas Masih RN, Post RN BSc.N Lecturer New Life College of Nursing Karachi 4/23/2017 Younas Masih ( NLCON)

Objectives By the end of this session the learners will be able to, Define the characteristics of the normal cell Describe the characteristics if the cancer cells Discuss the predisposing factors of the aberrant cell growth Differentiate between malignant and benign tumor Describe the TNM system Explain proto oncogene and anti oncogene 4/23/2017 Younas Masih ( NLCON)

Normal cell Cells are the smallest functional unit of the body They contain structures that are strikingly similar to those needed to maintain total body function The nucleus is the control center for the cell. It also contains most of the hereditary material. The organelles, which are analogous to the organs of the body, are contained in the cytoplasm. The cell membrane encloses the cell and provides for intracellular and intercellular communication, transport of materials into and out of the cell. 4/23/2017 Younas Masih ( NLCON)

Characteristics of the normal cell Normal body cells have a number of important characteristics. They can Reproduce themselves exactly Stop reproducing at the right time There is proper cell communication in between the cells Stick together in the right place Self destruct if they are damaged Become specialized or 'mature 4/23/2017 Younas Masih ( NLCON)

Normal cell cycle 4/23/2017 Younas Masih ( NLCON)

younas masih (new life college of nursing) Adaptations Adaptations are reversible changes in the number, size, phenotype, metabolic activity, or functions of cells in response to changes in their environment. There are following 4 types of teh adaptations Hyertrophy Hyperplasia Atrophy Metaplasia 4/23/2017 younas masih (new life college of nursing)

younas masih (new life college of nursing) Hypertrophy Hypertrophy is an increase in the size of cells resulting in increase in the size of the organ Hypertrophy occurs when cells have a limited capacity to divide It may be physiological or pathological It is caused either by increased functional demand or by growth factor or hormonal stimulation. 4/23/2017 younas masih (new life college of nursing)

younas masih (new life college of nursing) Hypertrophy Physiological The massive physiologic enlargement of the uterus during pregnancy occurs as a consequence of estrogen-stimulated smooth muscle hypertrophy and smooth muscle hyperplasia. Pathological An example of pathologic cellular hypertrophy is the cardiac enlargement that occurs with hypertension or aortic valve disease  4/23/2017 younas masih (new life college of nursing)

younas masih (new life college of nursing) Hyperplasia Hyperplasia takes place if the tissue contains cell populations capable of replication; it may occur concurrently with hypertrophy and often in response to the same stimuli It also may be Pathological and Physiological In both situations, cellular proliferation is stimulated by growth factors that are produced by a variety of cell types. 4/23/2017 younas masih (new life college of nursing)

younas masih (new life college of nursing) Hyeprplasia Physiological 1. Hormonal Exemplified by the proliferation of the glandular epithelium of the female breast at puberty and during pregnancy 2. Compensatory In which residual tissue grows after removal or loss of part of an organ. For example, when part of a liver is resected, mitotic activity in the remaining cells begins as early as 12 hours later, eventually restoring the liver to its normal weight 4/23/2017 younas masih (new life college of nursing)

younas masih (new life college of nursing) Hyperplasia Pathological It is caused by excessive hormonal or growth factor stimulation. For example, after a normal menstrual period there is a burst of uterine epithelial proliferation that is normally tightly regulated by stimulation through pituitary hormones and ovarian estrogen and by inhibition through progesterone. 4/23/2017 younas masih (new life college of nursing)

younas masih (new life college of nursing) Atrophy Shrinkage in the size of the cell by the loss of cell substance is known as atrophy. When a sufficient number of cells are involved, the entire tissue or organ diminishes in size, becoming atrophic Although atrophic cells may have diminished function, they are not dead. Causes: Causes of atrophy include a decreased workload (e.g., immobilization of a limb to permit healing of a fracture), loss of innervation, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, and aging (senile atrophy). Although some of these stimuli are physiologic (e.g., the loss of hormone stimulation in menopause) and others pathologic (e.g., denervation), the fundamental cellular changes are identical.  4/23/2017 younas masih (new life college of nursing)

younas masih (new life college of nursing) Atrophy The mechanisms of atrophy consist of a combination of decreased protein synthesis and increased protein degradation in cells. Protein synthesis decreases because of reduced metabolic activity. The degradation of cellular proteins occurs mainly by the ubiquitin-proteasome pathway 4/23/2017 younas masih (new life college of nursing)

younas masih (new life college of nursing) Metaplasia Metaplasia is a reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type Epithelial metaplasia is exemplified by the squamous change that occurs in the respiratory epithelium of habitual cigarette smokers  4/23/2017 younas masih (new life college of nursing)

younas masih (new life college of nursing) Metaplasia  The rugged stratified squamous epithelium may be able to survive the noxious chemicals in cigarette smoke that the more fragile specialized epithelium would not tolerate. 4/23/2017 younas masih (new life college of nursing)

younas masih (new life college of nursing) Dysplasia: This is the term which is used in pathology to refer to an abnormality of development or an epithelial anomaly of growth and differentiation in the cells. Example: Dysplasia of blood-forming cells, show increased numbers of immature cells in the bone marrow, and a decrease in mature, functional cells in the blood 4/23/2017 younas masih (new life college of nursing)

Normal cell cycle G0, non dividing cell G1, cell growth; S, DNA replication; G2, protein synthesis; and mitosis, which lasts for 1 to 3 hours and is followed by cytokinesis or cell division. T, telophase A, anaphase M, metaphase P, prophase 4/23/2017 Younas Masih ( NLCON)

Cancer cells Cancer (Neoplasia) Cancer is a disorder of altered cell differentiation and growth. The resulting process is called neoplasia, meaning “new growth,” and the new growth is called a neoplasm. 4/23/2017 Younas Masih ( NLCON)

Characteristics of the Cancer cells Cancer cells are different to normal cells in several ways. They don't die if they move to another part of the body and Cancer cells don't stop reproducing (Unlike normal cells, cancer cells do not stop reproducing after they have doubled 50 or 60 times). Cancer cells don't obey signals from other cells (Something in the cancer cells overrides the normal signaling system. This may be because the genes that tell the cell to reproduce keep on and on firing. Or because the genes that normally tell the cell to stop reproducing have been damaged or lost. So the cancer cell keeps on doubling, regardless of the damage the extra cells cause to the part of the body where the cancer is growing). Cancer cells don't stick together Cancer cells don't specialize, but stay immature 4/23/2017 Younas Masih ( NLCON)

Normal Tissue renewal Normal tissue renewal and repair involves cell proliferation, differentiation, and apoptosis Proliferation Proliferation, or the process of cell division, is an inherent adaptive mechanism for cell replacement when old cells die or additional cells are needed. Cell proliferation is the process of increasing cell numbers by mitotic cell division. In normal tissue, cell proliferation is regulated so that the number of cells actively dividing is equivalent to the number dying or being shed 4/23/2017 Younas Masih ( NLCON)

Proliferation Apoptosis In humans, there are two major categories of cells: gametes and somatic cells. Apoptosis Apoptosis is a form of programmed cell death that eliminates senescent cells, cells with damaged DNA, or unwanted cells. 4/23/2017 Younas Masih ( NLCON)

Cell differentiation Cell differentiation is the process whereby proliferating cells become progressively more specialized cell types. This process results in a fully differentiated, adult cell that has a specific set of structural, functional, and life expectancy characteristics. For example, the red blood cell is a terminally differentiated cell that has been programmed to develop into a concave disk that functions as a vehicle for oxygen transport and lives approximately 120 days. 4/23/2017 Younas Masih ( NLCON)

Body cells can be divided into two large groups: Differentiation Body cells can be divided into two large groups: The well differentiated neurons and cells of skeletal and cardiac muscle that rarely divide and reproduce, Second is the progenitor or parent cells that continue to divide and reproduce, such as blood cells, skin cells, and liver cells. A third category of cells are the stem cells that remain quiescent until there is a need for cell replenishment, in which case they divide, producing other stem cells and cells that can carryout the functions of differentiated cells. 4/23/2017 Younas Masih ( NLCON)

Grade of the cancer cell Differentiation Cells can be well differentiated, moderately differentiated, or poorly differentiated Grade of the cancer cell The more normal a cancer cell looks, the lower its grade, The more abnormal or less well developed a cancer cell is, the higher its grade  Low, medium or high grade. It is also called grades 1, 2, or 3, where grade 1 is low grade. 4/23/2017 Younas Masih ( NLCON)

Tumors Tumor is a swelling that can be caused by a number of conditions, including inflammation and trauma, but more recently the term has been used to define a mass of cells that arises because of overgrowth. Although not synonymous, the terms tumor and neoplasm often are used interchangeably. Tumor Growth Once cells have an adequate blood supply, the rate of tissue growth in normal and cancerous tissue depends on three factors: (1) the number of cells that are actively dividing or moving through the cell cycle, (2) the duration of the cell cycle, and (3) the number of cells that are being lost relative to the number of new cells being produced. One of the reasons cancerous tumors often seem to grow so rapidly relates to the size of the cell pool that is actively engaged in cycling. 4/23/2017 Younas Masih ( NLCON)

Classification of the Tumor Tumors are classified as follows Malignant Benign Properties of the Benign tumor Benign neoplasms are well-differentiated tumors These resemble the tissues of origin These have loss of control of cell proliferation. They grow by expansion, These are enclosed in a fibrous capsule, and do not cause death unless their location is such that it interrupts vital body functions. 4/23/2017 Younas Masih ( NLCON)

Classification of the Tumors Properties of the Malignant tumors These are less well-differentiated These have lost the ability to control both cell proliferation and differentiation. They grow in a disorganized and uncontrolled manner to invade surrounding tissues, These have cells that break loose and travel to distant sites to form metastases, And inevitably cause suffering and death unless their growth can be controlled through treatment. 4/23/2017 Younas Masih ( NLCON)

Carcinogenesis The process by which carcinogenic (cancer-causing) agents cause normal cells to become cancer cells is hypothesized to be a multistep mechanism that can be divided into three stages: Initiation: (involves the exposure of cells to appropriate doses of a carcinogenic agent that makes them susceptible to malignant transformation.) Promotion: (involves the induction of unregulated accelerated growth in already initiated cells by various chemicals and growth factors. Promotion is reversible if the promoter substance is removed) Progression: (the process whereby tumor cells acquire malignant phenotypic changes that promote invasiveness, metastatic competence, autonomous growth tendencies, and increased karyotypic instability) 4/23/2017 Younas Masih ( NLCON)

Carcinogenesis There are following predisposing factors, Heredity (A hereditary predisposition to approximately 50 types of cancer has been observed in families. Breast cancer, for example, occurs more frequently in women whose grandmothers, mothers, aunts, or sisters also have experienced a breast malignancy) Hormones (Hormones have received considerable research attention with respect to cancer of the breast, ovary, and endometrium in women and of the prostate and testis in men) Immunological mechanisms (There is substantial evidence for the immune system’s participation in resistance against the progression and spread of cancer. The central concept, known as the immune surveillance hypothesis) 4/23/2017 Younas Masih ( NLCON)

Carcinogenesis Chemical agents (chemical carcinogens can be divided into two groups) (1) direct-reacting agents, which do not require activation in the body to become carcinogenic. (2) indirect-reacting agents, called procarcinogens or initiators, which become active only after metabolic conversion Radiations (The effects of ionizing radiation in carcinogenesis have been well documented in atomic bomb survivors, in patients diagnostically exposed, and in industrial workers, scientists, and physicians who were exposed during employment). 4/23/2017 Younas Masih ( NLCON)

On cogenesis This is the process through which the normal cells are transformed into cancer cells. This is a genetic mechanism This process involves the following , Proto-oncogenes Tumor suppressor genes Genes that control the program death of the cells or apoptosis Genes that repair the damage DNA 4/23/2017 Younas Masih ( NLCON)

On cogenesis Normally growth is controlled by Growth Promoting (Proto-oncogenes) and growth suppressing (anti-oncogenes). Cells that promote the autonomous cell growth in cancer cells are called oncogenes. These are derived from the mutations in the proto-oncogenes 4/23/2017 Younas Masih ( NLCON)

Development of the tumor cell Normal cell Carcinogenic agent DNA Repair genes DNA damage Failure of DNA repair Mutations in cell genes Growth promoting oncogenes Growth Suppressing antioncogenes Activation of apoptosis controlling genes Unregulated cell growth Neoplasm 4/23/2017 Younas Masih ( NLCON)

(Adamson, 1987; Weinstein & Joe, 2006) Proto oncogenes “Proto-oncogenes are a group of genes that cause normal cells to become cancerous when they are mutated “ (Adamson, 1987; Weinstein & Joe, 2006) Mutations in proto-oncogenes are typically dominant in nature, Mutated version of a proto-oncogene is called an oncogene. Often, proto-oncogenes encode proteins that function to stimulate cell division, inhibit cell differentiation, and halt cell death. All of these processes are important for normal human development and for the maintenance of tissues and organs. 4/23/2017 Younas Masih ( NLCON)

Oncogenes Oncogenes, however, typically exhibit increased production of these proteins, Thus leading to increased cell division, decreased cell differentiation, and inhibition of cell death; taken together, these phenotypes define cancer cells. Thus, oncogenes are currently a major molecular target for anti-cancer drug design. 4/23/2017 Younas Masih ( NLCON)

TNM staging system It is the system that classifies the various cancers into different anatomical forms, its regional lymph node involvement and distant metastasis. T: It is defined as the size of the primary tumor N: It tells the presence or absence of the tumor in the regional lymph nodes and lymph node drainage. M: It is the absence or presence to the distant spread or metastasis 4/23/2017 Younas Masih ( NLCON)

TNM staging system “T” Primary tumor: T0: No evidence of primary tumor T.is: Carcinoma in situ T1: Tumor < 2mm T2: Tumor >20 mm but less than 50mm T3: > 50mm T4: tumor of any size /to the chest wall or skin Tx: Primary tumor can not be assessed 4/23/2017 Younas Masih ( NLCON)

“N” Regional lymph nodes TNM Staging system “N” Regional lymph nodes N0: no regional lymph nodes involvement N1: Movable level( axiliary involvement) N2: Mammary lymph nodes,( not palpable axillary) N3: additionally supraclavical lymph nodes are involved Nx: can not be assessed 4/23/2017 Younas Masih ( NLCON)

TNM staging system “M” Distant Metastasis Mo: No distant metastasis M1: Metastasis present 4/23/2017 Younas Masih ( NLCON)

References Porth, C., Matfin, G., & Porth, C. (2009). Pathophysiology: Concepts of altered health states (8th ed.). Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins. purpose and principles of cancer staging. (2009, September 7). Retrieved from http://www.kliinikum.ee/ho/images/stories/attachments/102_Purpose%20and%20Principles%20of%20Cancer%20Staging.pdf Tumor node staging for breast cancer. (2010). Retrieved from http://www.sapycc.org/descarga/2010/UTD_Tumor_node_metastases.pdf 4/23/2017 Younas Masih ( NLCON)