extent to which tumor cells resemble normal cells

the more normal looking the cell-"well differentiated"

type of mesenchymal tumors

-leukemia

-lymphoma

-myeloma

adenoma (gland like)

papilloma (finger-like projections)

malignant epith. tumors

(lung,breast cancers)

carcinomas

-adenicarcinoma (gland like)

-squamous cell carcinoma (plate like)

further classified by tissue of origin:

bronchogenic carcinoma-lung

hepatocellular carcinoma-liver cancer

lung

breast

prostate

colon

biggest killer of people (cancer)

1.most diagnosed cancer in men

2....in women

1. prostate

2. breast

1. healthy and cancer cells multiply by mitotic cell cycle

2. controlled by cell signals and events

3. dysregulation of cell cycle contol is pathognomonic of all cancer cells

-gets stuck in cycle

-enter cycle much too often

-do cycle to quickly

1. oncogenes

2. tumor suppressor genes

1. over expression causes cells to continue proliferating

2. under expression causes cells to cont. proliferating

MAIN POINT of cancer proliferation:

tissue cell number = cell proliferation - cell death

area of control:

cell death: apoptosis genes, anti-apotosis genes

cell proliferation: oncogenes, tumor suppressor genes

dont know how to work properly

grow out of control

forget to die

travel

abnormal genes

large variation in size and shape

large immature nucleaus

prominent nucleoli

high nuclear to cytoplasmic ration

high micotic activity

bizarre mitotic figures

1. Genetic factors

2. Environmental factors-chem, radiation, infect agents

3. lifestyle choices-tob, alcoho,uv,diet

4.immune dysfunction

familial clustering of cancer- oncogenes or tumor suppressor geens

specific chromosomal abnormalities-down syndrome

1. tissue that is most sensitive to radiation

2. latent period of radiation:

-leukemia:

-soild tumors:

1.bone marrow, breast, and thyroid

2. leuk- 2-5yr

solid 5-10+ yr

fungal aflatoxin - liver

hep a and c - live

H. pylori -stomach

schistosoma infection worm- bladder

HTLV-1 - tcell lymphoma, leukemia

HPV- uterine cervix

BV - lymphoma, nasopharynx

1. transplant pts

2. HIV infection

3. congenital immune deficiency

Seven warning signs

many different ways cancer can show up

Change in bowel or bladder habit

A sore that doesnt heal

Unusual bleeding or discharge

Thicking or lump

Indigestion or difficulty swallowing

Obvious change in wart or mole

Nagging cough or hoarseness

Asbestos alone

Asbestos exposure + smoking

Epstein-barr with mono:

1. Asbestos alone: 4-5 fold cancer

2. Asbestos and smoking Combo: 50-90 times

3. Burkitts lymphoma, nasopharyn, hodgkins, cns lymphoma

1. Obliteration of normal tissue

2. Compression of normal structures

3. Pressure/stretching in nerve fibers --> pain

Remote effects common to all tumors:

1. Paraneoplastic syndrome

2. Other sytemic effects:

1. caused by substances secreted by tumor cells

2. Anorexia, weight loss, cachexia (skin-and-bones), fever, itching

Metastasis: Types

important for drug development

series of steps:

1.transformation

2. Angiogenesis-new blood suply (food, highway out)

3. Motility and invasion

4. embolism and circulation

5. arrest in capillary beds

6. adherence

7. extravasation into organ parenchyma

8. response to microenvironment: tumor cell proliferation and angiogenesis

9. metastases

diagnosis and staging of cancer

Pathologic examination of tissue samples

-only way to exclude inflammatory process, hyperplasia, benign tumors

-only way to select therapy

T= primary tumor (inc size)

N= regional lymph nodes (inc #)

M= distant metastasis (M1=stage 4)

Stage of tumor (I-iV) is based on TNM

Stage correlates with prognosis and response to treatment

Tumor markers

Funx

substances which can be measured in blood and are indicatibe of tumor activity

-screen high risk

-establishing specific diagnosis

-monitor effectiveness of treatment

-early dection of recurrent disease

1. surgery is MC

-provides tissues for diagnosis

-allows staging

-best chance for cure in most solid tumore

-also palliation (comfort)

used alone or in combo with surgery and chemo

damages dna

effects last 4-6 wks

also for palliation

+++brain can sustain the most radiation

++poison given in sub lethal doses, rapid cell dividing most sensitive, normal cells can recover malignant cant, diferent tumors respond different, drugs used in combo

systemic tx

work through a variety of mechanisms

-may be used for cure, improvement in survival, and palliation

most at rapidly dividing cells:

1. hair

2. lining of GI tract

3. bone marrow

++other toxicity based on drugs- heart, kidney etc

give chemo even when cancer isnt visible:

-Breast and colon cancer!

= many times microscopic disease left behind-likely in lymph nodes

-

sucessful tumors escape immune detection and elimination

Boosts patients immune respone against the tumor

+++used for melanoma, renal cell carcinoma, and some hematologic malignancies

tumor vaccines

(PROVENGE-boost up white blood cells)

drugs tha target specific cell processes required for cell growth, survival, and/or metastasis

++enzyme inhibitors andiogenesis inhibitors, apoptosis-indusing durgs

rx: Gleevec (imatinib)

attach to cell surface proteints and direct immune attch or deliver another drug

RX: Rituxan (rituxumab)