Ch. 7: Pathophysiology

Grading

-A basic method for classifying cancers or cellular characteristics of the tumor. -Involves the microscopic examination of cancer cells to determine their level of differentiation and the number of mitoses. the closer the tumor cells resemble comparable normal tissue cells, both morphologically and functionally, the lower the grade, neoplasm

Staging

-A basic methods for classifying cancers or cellular characteristics of the tumor. -Cancers uses methods to determine the extent and spread of the disease. it is useful in determining the choice of treatment for individual patients, estimating prognosis and comparing the results of different treatment regimens. -Include the size of the primary tuor, its extent is local growth, lymph node involvement and presence of distant metastasis.

Cancer

-A disorder of altered cell differentiation and growth. -Is the second leading cause of death. - It can originate in almost any organ, with skin cancer being the most common site in persons in the US. -Excluding skin cancers, the prostate is the most common site in men and the breast is the most common in women.

Hematologic

-A type of malignant neoplasm -Involve cells normally found within the blood and lymph, therefore making them disseminated diseases from the beginning.

Solid Tumors

-A type of malignant neoplasm initially are confined to a specific tissue or organ. as the growth progresses, cells detach from the original tumor mass, invade the surrounding tissue and enter the blood and lymph system to metastasis.

Mutations in tumor-suppressor genes

-Are generally recessive, cells tend to behave normally until both genes are inactivated.

Malignant neoplasms

-Are less well differentiated tumors that have lost the ability to control both cell proliferation and differentiation. -They grow in a disorganized and uncontrolled manner to invade surrounding tissue, 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. -Grow rapid, invade and infiltrate nearby tissue and spread to other parts of the body. -Can gain access to blood and lymph channels

Fatigue and Sleep disorders

-Are two of the most frequent side effects experienced by persons with cancer. -Feelings of tiredness, weakness, and lack of energy and is distinct from the normal tiredness experienced by healthy individuals in that it is not relieved by rest or sleep. -Cause is multi-factoral -Categorized into two components: peripheral and central.

Benign Neoplasms

-Are well differentiated tumors that resemble the tissue of origin but have lost the ability to control cell proliferation. -do not cause death unless their location is such that it interrupts vital body function. -Slow, progressive rate of growth that may come to standstill or regress. -Remain localized -Can not metastasize to distant sites. -Grows by expansion.

Heredity

-Brest cancer, for example occurs more frequently in women whose grandmother, mothers and sisters have also have experienced a breast malignancy. -Tumor suppressor genes, called BRCA-1 and BRCA-2 have been implicated in a genetic susceptibility to breast cancers. Theses genes have also been associated with an increased risk of ovarian, prostate, pancreatic colon and other cancers.

genetic instability

-Considered to be a hallmark of cancer. -Uncorrected mutations in normal cells are rare due to many cellular mechanisms to prevent them. -Characteristics include: chromosomal abnormalities.

Molecular and cellular pathways

-Defects in DNA repair mechanism, disorders growth factor signaling pathways, evasion of apoptosis, development of sustained angiogenesis, and evasion of metastasis can cause development of cancer. -A relatively common pathway by which cancer cells gain autonomous growth is by mutations in genes that control signaling pathways. -The accumulation of cancer cells may result from the activation of growth-promoting oncogenes or inactivation of tumor-suppressor genes, but also from genes that regulate cell death through apoptosis. -Tumors can not grow with out angiogenesis to supply them with blood vessels.

Promotion

-Involves the induction of unregulated acceleration growth in already initiated cells by various chemicals an growth factors. -Is reversible if the promoter substance is removed.

Immune therapy

-Is a cancer treatment modality designed to heighten the patient's general immune responses so as to increase tumor destruction.

Apoptosis

-Is a form of programmed cell death that eliminates senescent cells, DNA, and damaged or unwanted cells. -Determines population. -Tumors can result from uncontrolled apoptosis.

Chemical Carcinogens

-Is an agent capable of causing cancer. -Chemical carcinogens can be divided into two groups. 1.) Direct-Reacting agents: which do not require activation in the body to become carcinogenic and 2.) indirect reacting agents, called pro-carcinogens or initiators which become active only after metabolic conversion. -The effects of carcinogenic agents usually are dose dependent (longer the exposure, the greater the risk that cancer will develop)

Cancer anorexia- cachexia syndrome

-Many cancers are associated with weight loss and wasting of body fat and muscle tissue, accompanied by profound weakness, anorexia, and anemia. -A common manifestation of most solid tumors -Probably multifactorial

Stages in development of a malignant neoplasm

-Normal cell -DNA damage -Activation of growth-promoting oncogenes, inactivation of tumor-suppressor genes, and alterations in genes that control apoptosis -Unregulated cell differentiation and growth -Malignant neoplasm.

Screening

-Represents a secondary preventing measure for the early recognition of cancer in an otherwise asymptomatic population. -Can be achieved through observation, palpation, and laboratory test and procedures. -It requires a test that will specifically detect early cancers or pre malignancies. -Early detection has led to improvement in outcomes.

Tumor

-Swelling that can be caused by a number of conditions, including inflammation and trauma. -Used to describe a neoplasm.

Radiation

-The effects of ionizing radiation in carcinogens have been well documented in atomic bomb survivors, in patients diagnostically exposed, and in industrial workers, scientist, and physicians who were exposed during employment. -They type of cancer that developed depended on the dose of radiation, the sex of the person, and the age at which exposure occurred. -can cause mutagenic effects in tees of causing chromosomal breakage, translocations, and, less frequently, point mutations.

Immunologic mechanisms

-The immune system in resistance against the progression and spread of cancer. -Plays a central role in resistance against the development of tumors. -Development of cancer might be associated with impairment or decline in immunity. -Tumor cells can be specifically recognized by immune T cells and be marked tumor antigens. -Virtually all of the components of the immune system have the potential for eradicating cancer cells, including T, B, NK, and macrophages.

Proliferation

-The process of cell division, is an inherent adaptive mechanism for cell replacement when old cells die or additional cells are needed. -Excessive and uncontrolled proliferation that is unregulated by normal growth is the fundamental to the origin of all neoplasms.

Differentiation

-The process of specialization whereby new cells acquire the structural, microscopic, and functional characteristics of the cells they replace.

Genetic events leading to Oncogene formation or activation

-There are a number of genetic events that can cause or activate oncogenesis. -Point mutation -Chromosomal translocations -Gene amplification: over exposure of genes can have higher than normal levels of proteins that increase cell proliferation.

Obesity

-There have been recent interest in obesity as a risk factor for certain types of cancers, including breast, endometrial, and prostate cancer. -Obesity has been associated with insulin resistance and increased production of pancreatic insulin, both of which can have a carcinogenic effect. -IGF-1 and insuline are anabolic molecules that can promote tumor development by stimulating cell proliferation and inhibiting apoptosis. -Obesity has been related to a condition of chronic inflammation characterized by abnormal production of inflammatory cytokines that can contribute to the development of malignant disease.

Host an environmental factors

-does not have a single cause. more likely cancers develop because of interactions among host factors and repeated exposure to chemical carcinogens, radiation, and microorganisms in the environment. -Heredity, hormones, obesity, immunologic mechanisms, chemical carcinogens, radiation, viral and microbial agents

Carcinogens as risk factors

1. Smoking or industrial exposure contains both pro carcinogens and promoters. It is associated with lung and laryngeal cancer. 2.Chewing tobacco increases the risk of cancers of the oral cavity and esophagus. 3.Benzo[a]pyrene and other polycyclic hydrocarbons are converted to carcinogens when food and fried in fat that have been reused multiple times. 4.Nitrosamines which are powerful carcinogens, found in foods that are smoked, salted, cured, or pickled using nitrites as preservatives. 5.Alcohol is associated with a variety of cancers and the mechanisms are very complex. Ethanol is acetaldehyde, a known carcinogen that interferes with DNA synthesis and repair can cause point mutations.

Tumor antigens

1.) unique tumor specific antigens: found only on tumor cells 2.) Tumor associated antigens: found on tumor cells and on normal cells.

Diagnostic Methods

A number of procedures are used in the diagnosis of cancer including blood test for tumor markers, cytological studies ad tissue biopsy, endoscopic examinations, ultrasound, x-ray studies, magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography (PET) scans.

P53

A well-known tumor-suppressor gene The most common target for genetic alterations in human cancers. mutations in this gene can occur in virtually every type of cancer. Most common: lung, breast, and colon. -Normally senses DNA damage and assists in DNA repair by causing arrest of the cell cycle.

Retinoblastoma (RB)

A well-known-suppressor gene represents a model for other genes that act similarly. In persons carrying an inherited mutation, all somatic cells are perfectly normal, except for the high risk of cancer.

Viral and microbial agents

An oncogenic virusis one that can induce cancer. Many DNA viruses that proved to be oncogenic. -Examples: human papilloma virus (HPV), Epstein-Barr virus (EBV), hepatitis B virus (HBV), and human herpesvirus 8 (HV-8)

Proto-oncogenes

Associated with gene overactivity; these are normal genes that can become cancer-causing oncogenes if mutated.

Abnormal chromosomes

Benign: normal chromosomes Malignant cells display aneuploidy (abnormal number of chromosomes)

Cancer-Associated Genes

Can be classified into two broad categories based on whether genes have overactivity or under activity that increases the risk for cancer.

Functional Features

Cancer cells tend to function on a more primitive level than normal cells, retaining only those functions that are essential for their survival and proliferation.

Childhood cancers

Cancer in children is relatively rare. Usually involve the hematopoietic system, nervous system, soft tissues, bones and kidneys. A number of childhood cancers are mainly genetic related. Many childhood cancers are curable. The number of children who survive are increasing, Unfortunately, radiation and chemotherapy may produce late sequel, such as impaired growth, neurology dysfunction, hormonal dysfunction, cardiomyopathy, pulmonary fibrosis, and risk for second malignancies. Vital organs such as the heart and lungs may be affected by cancer treatment.

Paraneoplastic syndromes

Cancer that can produce manifestations in sites that are not directly affected by the disease. -Some of these manifestations are caused by the elaboration of hormones by cancer cells, and others result from the production of circulating factors that produce hematopoietic, neurologic, and dermatologic syndromes. -Most common with lung, breast and hematologic malignancies. -May be the earliest indication that a person has cancer, and should be regarded as such.

Invasion

Cancers grow and spread by sending crablike projections into the surrounding tissues; cancer spreads by invasion and expansion. Benign tumors: grow by expansion and usually are surrounded by a capsule

Micro RNA genes

Do not encode proteins. instead, the products of these genes consist of a single RNA strand that serves to regulate gene expressions. -Can pair with mRNA and therefore blocking protein translation or degradation of the mRNA. -Can be a tumor suppressor if in a given cell its critical target is a tumor-suppressor gene.

Ultraviolet radiation

Emits relatively low-energy rays that do not deeply penetrate the skin. -Causes skin cancer

Lymphatic spread

In many types of cancers, the first evidence is the presence of a tumor cells in the lymph nodes that drain the tumor area. the tumor cells lodge first in the initial lymph node (sentinel node) that receives drainage from the tumor site. If they survive and grow, the cancer cells may spread from more distant lymph nodes.

Anaplasia

Means to "Form backward" to an earlier dedifferentiated state.

Metastatic Spread

Metastatic tumors frequently retain many of the microscopic characteristics of the primary tumor from which they were derived. -Can be spread by one of two pathways: lymph vessels or blood vessels

Growth properties

Most normal cells require a complex growth media and survive for only a limited time in vitro. In the case of cancer cells, the addition of serum, which is rich in growth factors it is unnecessary for the cancers to proliferate. -Some cancer cells make their own growth factors while others have abnormal receptors or signaling proteins that may activate signaling pathways within cells.

tumor-suppressor gene function

Normal cells have regulatory genet mechanisms that protect them against activated or newly acquired oncogenesis. These genes are called tumor suppressor genes. -When this type of gene is inactivated a genetic signal that normally inhibits cell proliferation is removed, and therefore causing unregulated growth to begin.

Repair

Normal renewal involves two components: cell proliferation and differentiation.

Differentiation

Refers to the extent to which the cells of a tumor resemble their normal origin: morphologically and functionally. Malignant neoplasm: poorly differentiated or undifferentiated cells. (Anaplastic) Benign tumors: are composed of cells that resemble the tissue from where they have arisen. -Have a higher grade on the 1-4 grade.

Metastasis

Spread to distance sites. -describes the development of a secondary tumor in a location distant for the primary tumor.

Tumor-suppressor genes

The category of cancer-assocaited under activity genes includes these genes. which, by being less active create an environment which is cancer promoted.

Cancer Treatment

The goals of cancer treatment methods fall into three categories: curative, control and palliative. The most common modalities are surgery, radiation, chemotherapy, hormonal therapy, and biotherapy.

Tumor cell transformation

The process by which carcinogenic agents cause normal cells to become cancer cells is hypothesized to be a multistep mechanism that can be divided into three stages 1. initiation, promotion, and progression.

Neoplasm

The resulting process of cancer. "new growth" Benign or malignant.

Oncology

The study of neoplasms.

Epigenetic Mechanisms

There are molecular and cellular mechanisms that involve changes in the patterns of gene expression with out a change in the DNA. -Can silence genes such as tumor-suppressor genes

Clinical manifestations

There probably is not a single body function left unaffected by the presence of cancer. The initial manifestations of cancer usually reflect the function of the primary site of involvement. Systemic Manifestations: anorexia, cachexia, fatigue, sleeping disorders, and paraneoplastic syndromes

Seeding of cancer cells

This occurs when a tumor erodes and sheds cells into body cavities. common with ovarian cancer. -Surgery is a concern during removal of cancers, where is is possibly inadvertently introduce free cancer cells into a body cavity.

Angiogenesis

Tumor cells as well as other cells in the microenvironment secrete angiogenesis factors that enable the development of new blood vessels within the tumor.

Tumor cell characteristics

Whether a tumor is benin or malignant is determined by examination of its cells. -Differentiation and Anaplasia -Genetic instability and chromosomal abnormalities -Growth properties -Functional Features

Hormones

With respect to breast, ovary and endometrium cancer hormones are said to have a link. The link is unclear but it has been suggested that it may reside the ability of hormones to drive the cell division of a malignant phenotype.

Causes of cancer

can be viewed from two perspectives: 1.) the genetic and molecular mechanisms that characterized there transformation of normal cells into cancer cells and 2.) the external and more contextual factors such as age, heredity and environmental agents that contribute to its development and progression.

Undifferentiated State

cancer cells are marked by a number of morphologic changes. The cell changes variation in size and shape. Benign tumors: are composed of cells that resemble the tissue from where they have arisen. Have a lower grade on the 1-4 grade.

Hematogenous spread

cancer cells commonly invade capillaries and venules. Thicker wall arteries are resistant.The liver and lungs are the most common for hematogenous spread.

Tumor growth

depends on three factors: 1) the number of cells that are actively dividing or moving through 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. -Cancer growth cells prevent them from the dying part of the cell cycle.

Difference between benign and malignant tumors

determined by 1) the characteristics of the tumor cells 2) the rate of growth 3) local invasions, and 4) the ability to metastasize.

Initiation

involves the exposure of cells to appropriate doses of a carcinogenic agent that makes them susceptible to malignant transformation.

Molecular pathogenesis

of most cancers is thought to originate from genetic damage or mutation with resultant changes in cell physiology that transforms a normally functioning cell into a cancer cell.

Progression

the process whereby tumor cells acquire malignant phenotyping changes that promotes invasiveness, metastatic competences, autonomous growth tendencies, and increases karyotypic instability.