Cellular regulation: Oncology

cellular regulation definition

Intracellular functions that support homeostasis including growth, replication & differentiation

normal division types

mitosis and meiosis

mitosis

-all cells capable of this (except egg and sperm)

-duplication: two identical “daughter” cells produced from single “parent” cell

-develop normal tissue or replace lost of damaged normal tissues

meiosis

-occurs only in cells that will become eggs in females and sperm in males

-Generates “daughter” cells distinct from one another and from “parent” cell

-used for sexual reproduction

proliferation

production of new cells

differentiation

specification of cellular functions

• less specialized cell becomes a specialized cell

apoptosis

programmed and normal cell death

normal cell growth

new cells created at same rate as old cells die

what os cell growth controlled by

molecular “stop” and “go” signals

how new cells are grew

Injured cells send “go” signals → activates intracellular proliferation pathways

“Stop” signals sent after new tissue formed

what can errors in the stop and go process result in

uncontrollled growth neoplasm

what has to happen for cells to become malignant

takes multiple errors compounded over time

how do new cells grow

cell cycle

cells can not

reverse process and go backwards once the cycle has started

interphases

chromosomes are copied, cell typically doubles in size

how many checkpoints are in a normal cell cycle

3

when can dna damage lead to neoplasm

during the cell cycle

what do checkpoints in the cell cycle do

check for any DNA issues or any issues with cell development

• the body is constantly assessing if the cell is reproducing as it should.

tumor suppressor genes

Normally inhibit cell replication

• stops cell proliferation when it needs to be stopped

proro-oncogenes

Regulates proliferation of cells – tissue healing

• go signal

mutator genes

DNA repair genes – check DNA or mismatched base pairs, or abnormalities

• signals apoptosis

what happens if there is a genetic mutation in Tumor Suppressor Genes, Proto-Oncogenes, Mutator Genes

can lead to cancer

Carcinogenesis

process where normal cells develop into cancer cells

Carcinogenesis: initiation

cancer cauing agent damaged cna

unsuccessful attempt at repair

permanent damage/ mutation to the cell

Carcinogenesis: promotion

carcinogen/ promoter introduced into the cell

clonal expansion

aquired mutation

benign tumor forms

Carcinogenesis: progression

accumulation of mutations

continue cellular transformation

malignant tumor forms

Carcinogens Risk Factors

• Age

• Smoking/tobacco

• Infectious agents

• Genetics

• Exposure to environmental carcinogens such as sunlight; pollutants in the air, soil, water, or food; or medical treatments such as medications or radiation

• Poor nutrition

• Sedentary lifestyle

When multiple errors occur, what happens to cells

mutations become fixed leading to neoplasia and formation of tumors

benign tumor

Groups of abnormal cells with excessive growth

benign tumors are

well differentiated→ Retain most of morphologic and functional characteristics

• look very closely to whatever organ or tissue is affected

• well differentiated: Grade 1 or 2

benign tumors are

Capable of replication and mitosis, not metastasis (doesn’t travel to other organs thru bloodstream= easier to treat)

what do benign tumors obstruct

body structures leading to pain, physiological dysfunction, death (brain tumors)

benign tumors are usally termed

adenomas

malignant tumors are

undefferentiated → Abnormal growth and abnormal function, can metastasize/ spread to other parts of the body

• undifferentiated: grade 3 or 4

malignant tumors are due to

unrepaired errors in multiple cancer-causing genes

what do cancer cells recruit

normal cells to contribute and support proliferation and invasion

what do malignant tumors develop

Tumor angiogenesis

some secrete growth factors impacting other tissues

Tumor angiogenesis

can take nutrients from healthy cells or survive through anaerobic metabolism

most cells are differentiated into a

specialized cell type

cells acquire functions different from

from parent cell

cell growth signaling

normally, when signaling mistakes occur, error is repaired or destroyed, If this system not working, malignancy can occur

histologic grading

grades neoplasm on degree of differentiation or how diff the neoplasm appears from tissue of organ

histologic grading scale

Grade I to Grade IV- anaplasia (worst prognosis)

tumor staging

TNM System (solid tumors)

TNM

T – tumor size and invasiveness

N – spread to regional Nodes

M – Metastasis to distant sites

oncology manifestations

CAUTION

CAUTION

Change in bowel or bladder habits

A sore that does not heal

Unusual bleeding or discharge

Thickening or lump in breast or any part of body

Indigestion or difficulty swallowing

Obvious change in mole

Nagging cough or hoarseness

oncology: local effects

increase in size of tumor and pressure it exerts on surrounding organs/tissues

oncology: systemic effects

tumor secretion of cytokines which cause fever, cachexia (lack of appetite), and fatigue.

oncology: paraneoplastic syndromes

malignancy produces hormones, peptides when not supposed to, or reacts with normal tissue to cause symptoms distant from tumor site (i.e., hypercalcemia, SIADH)

Adenocarcinoma

Type of cancer that starts in the epithelial cells of glands that line the inside of the organs

when do Adenocarcinomas occur

when the glands that line the organs grow out of control

Adenocarcinomas are a common type of

colon cancer, breast cancer, prostate cancer, and lung cancer

breast cancer causes

genetic links Tp53 Gene, BRCA1 and BRCA2 gene mutation

breast cancer risk factors

age, gender, family history, obesity, smoking, overuse of alcohol

breast cancer process

Breast cancer cells with damaged DNA do not die off; continue replicating and becomes a malignancy

breast cancer symptoms

Mass: hard, fixed, non-mobile,

dimpling of, skin, inverted nipple, red, scaly rash

what assist in guiding treatment in breast cancer

ER+ and PR+

• estrogen and progesterone receptor positive

breast cancer treatment

triple screen: exam, imaging, biopsy

leading cause of cancer deaths

lung cancer, more than prostate, breast, and colon cancer combined

• no screening feature→ dicover cancer later making them harder to treat

lung cancer patho

Uncontrolled cell growth of lung tissues

most common type of lung cancer

non-small cell lung cancer

risk factor of lung cancer

Long-term exposure to cigarette smoke (85-90% of cases- MAJOR risk factor)

Linked to DNA mutations that damages Tp53 suppressor gene

lung cancer symptoms

Hemoptysis (coughing up blood), shortness of breath, coughing, weight loss (tumor metastases taking nutrients from body)

• if someone works in a certain environment these symptoms may not be abnormal so symptoms are advanced b4 getting treated

lung cancer paraneoplastic syndromes

secretion of PTH leading to hypercalcemia

colon cancer can

occur anywhere along the GI tract

colon cancer starts as

benign tumors formed from glandular structures in intestinal epithelium

• adenomas (polyps)

• precursor to cancers

colon cancer is a result of

genetic abnormalities and environmental factors (smoking, diet, obesity, lack of exercise)

• or Mutated tumor suppressor genes and oncogenes

colon cancer symptoms

Change in bowel habits, fatigue, weight loss, abdominal pain

prostate cancer characterisitcs

Grows slowly

rarely causes serious harm

where does prostate cancer tend to develop

on periphery of gland

prostate cancer symptoms

urinary frequency, weak flow, blood in urine, pain or burning on urination

prostate cancer screening

important to prevent late stages as it can metastasize to bones and lymph nodes

PSA and prostate cancer

is a blood test that if elevated can indicate cancer

sarcoma

Type of cancer that originates in the connective tissue (muscle or bone)

osteosarcoma

type of sarcoma that affects the bone

(osteo)sarcoma cancer is

Rare but do grow fast and metastasize quickly

where do (osteo)sarcoma mainly occur

femur, tibia, and humerus

osteosarcomarisk factos

-may be connected to periods of high bone growth or bone overstimulation

-Adolescents and young adults

-Radiation and bone marrow transplant increase risk

what does sarcoma/ osteosarcoma lead to

osteomyelitis leads to bone breakdown, fractures

what does sarcoma/ osteosarcoma tumor do

destroys bone tissue, interferes with bone blood supply

sarcoma symptoms

Deep bone pain, worse at night; muscle weakness and atrophy

• amputation as treatment

blastoma

cancer caused by malignancies in precursor cells (blasts)

type of blastoma

Nephroblastoma (Wilm’s tumor)

Nephroblastoma (Wilm’s tumor)

most common kidney cancer in children

what is Nephroblastoma (Wilm’s tumor) associated with

many genetic abnormalities (fam history)

Nephroblastoma (Wilm’s tumor) symptoms

Abdominal mass, swelling

Nephroblastoma (Wilm’s tumor) survial rate

90%

Hematologic cancers

genetically abnormal cells resulting in immature or ineffective hematopoietic cells (red, white, or platelet cell)

all blood cells rae derived from

multipoint hematopoietic stem cells → can differentiate into

any of 10 blood cell lines

lymphomas

abnormal cells that originate in lymphatic tissues

leukemias

originate in bone marrow or blood- forming cells

how many types of leukemias are there

4

what are leukemia types determined by

cell of origin and degree of differentiation

Acute Lymphocytic leukemia

impact blast cell phase of differentiation

• abnormal proliferation of blast cells

Chronic Lymphocytic leukemia

abnormal differentiation later on in cell development stage (more mature cells)

Acute myelogenous leukemia

abnormal growth of blast cells in any of the 9 other cell

chronic myelogenous leukemia

abnormal differentiation and growth of later stages of whatever cell is affected

Lymphocytic

results in abnormal lymphocyte development

myelogenous

any other 9 cell lines not lymphocytes are affected