Lecture recording CH 8

Neoplasia

Cancer cells are disorganized, disorderly arrangement, and problems with differentiation. When cells divide, the 2 new cells look like parent cell. That is why in the tissues, the cells look alike and do the same things. RBC’s, for example, should all look alike, have similar intracellular content, same size, same function ( which is to have large amount of hemoglobin to attract and hold on to oxygen). In cancer, cells differentiate a little differently. Differentation means specialization/maturation. The cell matures to look and do the work of current cell. But if cell becomes cancerous, it doesn’t do what its supposed to, looks different, and also loses capacity to do what it should be doing. Growth is uncoordinated. Cells need growth hormones/factors to grow, they stimulate cells until the time it has to stop growing, in which the hormone level decreases. But in cancer cells, they keep growing whether or not hormone/factor level decreases. Cell (----(?)ision) grow to a certain level and stop, but cancer cells do not respect cell --- division, just keep growing. The other catharsis(? Characteristics?) of cells is that whatever is the tissue that belongs to the (oncol???). Cancer cells have a way of anchoring where ever the cells are, they move away and carried in blood or lymph vessels. Where ever they can get into, and begin to multiply/spread = Metastasis. Normal cells do not leave where they belong. Cancer cells can metastastize. Growth uncoordinated, just keeps growing, and doesn’t listen to what growth factors are saying. So lack normal regalatory controls over their cell growth. Increase in size. Lawless.

Cell proliferation

Cell differentation/specialization/maturation

Apoptosis

Cell division/cycle has several steps. Cell stops and synthesize enough protein to support 2 cells. Some steps are when cell division stops and is checked for accuracy. If anything inappropriate happens- in quantity , the cell checks itself and can stop producing itself, because it doesn’t want copies that will be odd/unhealthy. Free radicals, chemicals that are prototons (?????) or that are toxic or carcinogenic that ruin normal process of the cell. When they divide, they do not check for accuracy. So rate that they divide is so much faster than normal cell develop. Cyclin, cyclin-dependent kinasesm cyclin dependent kinase inhibitors are responsible in checking that cell divisions goes on properly; incapacitated in cancer cells.

Different cell types

Blood, liver, skin cells are continually divided. That is why people can donate liver and the liver can grow into a full liver, and part of donated liver can grow back. Skin is always getting exfoliated/scrubbed off, so has to constantly grow and replace cell. Blood cells has lifespan and new ones are made. Neurons, skeletal and cardiac muscle cells are unable to divide and reproduce. Undifferentiated stem cells = stem cell research. Stem cells are in a primitive stage and capable to divide and become any cell they want with the help of growth hormone. If body needs more RBCs it is going to stimulate it. If infection, there will be a stimulation for production of more WBCs. There are some stem cells that can be treated to enter into the cell cycle and become a progenital cell. Progenitor cells are the ones that become what the body needs. If the cell is well differentiated it means the cell is well matured, well specialized and can do a specific function based on the cell it is and the tissue it is from. If cell is ill differentiated or not differentiated it means cell is not specialized. Cancer cells are not well differentiated. Regular cells are well differentiated. Some stem cells can only produce one kind of cell. Pluripotent stem cells can differentiate into different types of cells.

Tumors can be classified as malignant or benign. If a tumor is malignant it is cancerous and the cells will have cancer cells. If a tumor is benign, the cells will be more like regular cells. Tumor is an overgrowth of tissue.

If cells are malignant, will be undifferentiated, immature, will metastasize (spread), will overgrow and multiply rapidly. Have no clear boundaries. Can cause death bc it produces poison and toxins in tissues. Ex: Melanoma, adenocarcinoma, carcinoma, sarcoma. Grow rapidly and spread widely to metastasize. Have the potential to kill regardless of location. Some can be acute or chronic. Tend to compress blood vessels and outgrow their blood supply and use up blood from other tissues. Causes ischemia and tissue necrosis. Rob neighboring tissues of essential nutrients. Leukemia, cells multiply in the bone marrow so quickly and fills it, so blood has higher amount of cancer cells. Normal cells are squeezed out, become smaller, and cant carry enough oxygen becoming anemic. Liberate enzymes and toxins that destroy tumor tissue and normal tissue. Can cause ulcers because of damaged tissues.

Benign tumor is opposite. Well differentiated cells do not metastasize, do not overgrow and remain localized. Have clear boundaries, and are encapsulated. Normally wont cause death. Ex: Adenoma, Osteoma, papilloma. Benign are slow, progressive rate of growth that comes to a standstill or regress. Localized and inable to metastasize to distant sites. Composed of well differentiated cells that resemble their original tissues.

*** KNOW the DIFFERENCES

In cancer cell differentiation, anaplasia is used to describe the loss of cell differentiation in cancerous tissue. Anaplasia can not differentiate like they are supposed to specialize. Undifferentiated cancer cells are marked by morphologic changes including variations in size and shape = Pleomorphism. …???.... the lining of the surface is crypt and the cells are loose under the microscope. The normal leukophate(?) is what you are hoping to see. Early screening to pick up any slight or gradual changes. Look at family history. Looking at the nature of the cell can help the cytologist to say what is normal of the cell and normal changes.

Cancer can spread through invasion, just keeps growing into surrounding tissues. Or cancer cells can seed/slough off and be carried away to body cavities, or can be carried be lymph to distant site where it can stay. For instance, a lot of blood flows through liver and what it absorbed through GI tract must go through the liver before entering circulation. So liver is another site of metastasis and spreads through the blood.

Other factors affecting tumor growth… Tumor cells have a cell cycle, divide very quickly, bc they don’t check to see any errors. High turnover rate. The number of cells dividing or moving through the cell cycle is very large, unlike regular cells. The number of cells that are being lost compared to the number of cells being produced are less. Cancer cells are “immortal”- meaning that they live longer and divide more rapidly than normal cells, and don’t die when they are supposed to- they stay longer. Growth fraction= ratio of dividing cells to resting cells in a tissue mass is higher. *Doubling time- time it takes for the tumor to increase by 2; time it takes for tumor to grow twice in size. Very short for malignant tumors. Benign takes longer.

Steps in changing a normal cell into a cancer cell:

Initiation= cell exposed to carcinogenic agents (radiation, toxic chemicals…) will become more susceptible to changes or malignancy.

Promotion- cells exposed and now producing various chemicals and growth factors that make the bad change to continue.

Progression- Tumor cells acquire certain characteristics that make them become invasive, metastasize, and keep growing.

Environmental factors include: heredity/genetics; hormones; carcinogens – in food accumulation; oncogenic viruses; immunologic mechanisms- HIV that advances to AIDS makes patient more prone to some cancers than normal, decreased immune system exposes cells to not be able to correct changes;

Signs/Manifestations of Cancer:

Tissue integrity can be compromised, like ulcer formation or wound. Cancer cachexia can cause weight loss, body wasting of fats and muscle tissues, profound weakness and anemia. Paraneoplastic syndromes where inappropriate hormones are released. Neurologic factors and other changes occur that are related to unusual hormonal activities. Has to do with extensive weight loss fatty and muscle tissue losses. Result of cancer cells releasing toxins/chemicals into surrounding tissues causing erosion of blood vessels and tissues.

Labwork includes pap smear- scraped cervix; biopsy- take piece of tissue and look at cells to see if differentiated or not; cytologic studies- tissue biopsy; endoscopic exams- tissue color changes; ultrasound; xray; MRI.

**Tumor markers are chemicals, hormones, molecules that are released uniquely by tumors. So if level in blood is high, it is an indication of strong tumor activity. For example: Cancer in the prostate there is PSA (prostate specific antigen) level will rise much higher than normal and can tell by value how many times the quantity has increased. Shows that there is a lot going on in the gland and it is not good. Only need a blood test to look at the markers.

Staging and Grading tumors

Staging determined by asking: Has it metastasized to lymph nodes around the area? Is it in another part other than the original organ? Original stage means it has not spread anywhere and still contained in the organ = Best stage. So that radiation, chemo, etc can be related to one area. Is it one specific site or all over? That’s when the outcome, depending on kind of cancer, can become dicey.

Grading is asking what are the cellular characteristics?Do they look differentiated? Or are cells all over the place? So the longer the tumor has been there, the more undifferentiated the cells will look. That is why a biopsy will help in characterizing the tumor and stage. Doctor uses this to decide best treatment; can be radiation, chemotherapy, or combination… sometimes used to shrink the tumor before surgery is done. All depends on whether spread or not.

**Early detection observation example in breast cancer- is there any secretions from the nipples (unless breastfeeding), palpation should not feel lump, should be uniform in texture. Laboratory tests includes mammogram to examine the breasts, blood tests for tumor markers, cytological studies like taking samples for biopsy.

Treatment Goal is:

Curative: Was found on time, still contained in one site, get rid of organ.

Control: control spread – stop growing. Controlling that by monitoring regularly.

Palliative: reduce number and cancer activity so that normal blood will return, person will have enough (?), and have good quality life.. Also controlling by monitoring regularly.

Remission: Blood picture is similar to what it used to be before the person had cancer. If cancer activity is non detectable (i.e. PSA level is back down to normal level) means that person is responding to treatment. Still want to monitor for anything that is going on.

Treatment modalities:

Radiation

hormonal therapy

targeted therapy- goes to one site to kill tissue without damaging everything. Risk is directed to that source. Issue is that the tissue around may be damaged.

Biotherapy:

Immunotherapy- using immune system to fight

Biologic response

Types of Surgery:

Cryosurgery- uses liquid nitrogen to instill in tumor through a probe

Chemosurgery- uses a corrosive paste frozen and applied to tumor

Laser surgery

Laparoscopic surgery- Performed through 2 small incisions. Can be used for other things besides cancer.

Stem Cell transplantation because stem cells are capable of growing into progenitor cells according to what the body wants with the help of growth factors given to patient (i.e. erthropoeitin- platelet stimulating hormone). Peripheral blood stem cell transplantation can be used to treat for leukemia and other types of cancer so the normal cells replace the bad cells… But before that is done there has to be destruction of cancer cells and decrease in immune response (immunosuppression) so that normal cells do not get attacked.

Radiation therapy is beneficial except in young infants because can kill all cells. Radiation therapy uses high energy particles or waves to destroy cancer cells. The absorption of this is tissues can lead to ionization and increase in free radicals (damaging to cells). So radiation can also effect indirectly by interacting with water, which produces free radicals and damages regular cell functions. Therefore not recommended in infants or young children.

Adverse effects of radiation affects normal tissue that is dividing rapidly. Tissues within the treatment field may be affected especially the skin, GI tract, bone marrow.

COMPLETE CHAPTER

-DIRECT&INDIRECT DNA INTERACTING AGENTS

-CELL CYCLE DRUGS

-LONG TERM EFFECTS OF TADIATION AND CHEMO

- CHILDHOOD CANCER CHARACTERISTICS

KNOW WAYS CANCER CELLS ARE DIAGNOSED, CHARACTERISTICS, TREATMENTS

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pathophysiology