Biology of Cancer, tumors, cancer epidemiology and manifestations Flashcards
Define Tumor
- can me benign or malignant.
*originally defined as swelling now refers to new growth - new growth of tissue from genetic changes that allow excessive and unregulated proliferation thus becoming AUTONOMOUS
TWO BASIC COMPONENTS:
1. parenchyma - tumor cells, constituted from the clonal neoplastic cells.
2: stroma - reactive supporting tissue for the parenchyma
Define Cancer
refers to a malignant tumor
Define Neoplasia
new growth, neoplasm
*neoplasm - abdnormal mass of tissue,
metastasis
distant spread of malignant tumor
Benign Tumor
BENIGN: grow slowly, well-defined capsule, not invasive, well differentiated, low mitotic index - dividing cells are rare, do not metastasize (spread)
- generally microscopic and gross characteristics are considered “relatively innocent” - it remains localized, generally amenable to surgical removal, patients generally survive
- designated with suffix OMA - fibroma (fibrous) , chondroma (cartilage), meningioma (meninges of the brain), lipoma (fat)
malignant tumor
- invade basement membrane of tissue
- lesions can invade and destroy adjacent structures and spread to distant sites and cause death
MALIGNANT: grow rapidly, not encapsulated, invade local structures and tissues, poorly differentiated (not able to tell if tissue or organ), high mitotic index (many dividing cells), can spread distantly, often through blood vessels and lymphatics. - Germ Layer Origin = called CARCINOMAS - squamous cell carcinoma (epithelial), adenocarinoma ( glands)
- mesenchymal tissue = SARCOMA - fibrosarchoma, chondromsarchoma, rhabdomyosarcom (bone, muscle, blood, connective tissue)
teratoma
- neoplasm containing recognizable mature or immature cells/tissues representative of more than one germ cell layr and sometimes all 3 - have the capacity to differentiate into to any of the cell types found in the adult body. benign and malignant exist
- tumors with teeth, hair inside of them!
mixed tumors
divergent differentiation of a single neoplastic clone alone two lineages will create a “plemorphic adenoma”
TNM Staging
*how we rate cancer levels now. Each category gets its own rating
Tumor, Nodes (lymphnodes), Metastasis
steps to malignancy
- normal cells
- dysplasia: abnormal changes in size, shape and organization of mature cells
- in situ neoplasm/carcinoma in situ (CIS): can remambe stable for a long time, can progress to invasive or metazoic cancer, or regress and disappear. can vary from low grade to high grade dysplasia
- invasive neoplasm/malignancy: goes through basement membrane layer
what is the most important parameter of all oncology screening?
relative change within a single patient
- weight loss/gain
- body temp
- fatigue
6 hallmarks of cancer
- self-sufficiency in growth signals - oncogene activation
- insensitivy to antigrowth signals - turmor suppresor gene goes away
- evading apoptosis - knocking out BCL-2
- Limitless replicative potential - after steps 1-3 there is not stopping it
- sustained angiogenesis: induces blood vessel growth
- tissue invasion and metastasis - malignancy cancer
oncogenes
mutant genes that in their NORMAL non-mutant state direct synthesis of proteins that positively regulate (accelerate) proliferation
- normal = proto-oncogene
1) MYC
2) RAS - if permanently turned on then cancer growth. move gene to diff. area of chromosome and proliferating and constantly turned on
tumor-suppressor genes
encode proteins that in their normal state negatively regulate (put the brakes on) proliferation
1) RB - retinablastoma gene (normally inhibits cell division but when activated allows for unchecked cell division)
2) P53 - “guardian of the human genome”. associated with over 50% of cancers. normally acts as a checkpoint in the cell cycle and prevents or initiates programmed cell death.
angiogenesis
- with blood vessel growth
- angiogenic factors that promote vascular growth and maturation = VEGF, PGDF, EGFL7, NRP1
- anti-NRP1 works to target NRP1 and inhibit angiogenesis
- same with Anti-VEGF, NRP1, EGFL7 = net decrease in vascular maturation
oncogenesis
the production of tumors
telomeres and cancer
- another mechanism of oncogenesis is the permanent activation of TELOMERASE which inhibits natural cell death via programmed loss of the telomere in each mitotic division
- at the end of DNA, long T repeats so that crucial DNA is not lost from apoptosis
- immortality to cancer cells*
Cancer Manifestations
- Pain: tumor can cause pressure on organs, etc. and cause pain but the tumor itself is not painful
- Fatigue: #1 symptom of cancer. the cancer growth uses a lot of your energy.
- Cachexia: shrink and waste away, decreased metabolism, weight loss, muscle atrophy, weakness
- anemia: low red blood cell count –> creates low o2 levels. symptom of chemo and radiation
- Leukopenia/thrombocytopenia: low white blood cell and platelet counts.
- INFECTION: more at risk with low white blood cell counts. Most common cause of ultimate death - body too weak to fight off infections
cancer incidence
- females: highest incidence of breast cancer but highest deaht rate from lung cancer
- males: highest incidence of prostate cancer but highest death of lung cancer
Primary Cancer Treatment Options
- chemotherapy - chemical destruction of cellular proliferation (8 major types)
- radiation therapy: a. proton therapy b. brachytherapy (internal radiation therapy)
- surgery - excision and cryosurgery
- immunotherapy -
- angiogenesis inhibitors
- bone marrow transplant
- gene therapy
- laser treatments: gama radiation, photodynamic therapy, hyperthermia (tissue destroyed via raising temp to 113F)
clonogenic cells post radiation
- pokes holes in DNA
1. if a cell faithfully repairs dan damage, then its clonal descendants will appear normal
2. if a cell is directly mutated by radiation then all its descendants will express the same mutation
3. radiation-induced genomic instability is characterizes by non clonal effects in descendant cells
