Chapter 10: biology of cancer Flashcards
_____ tumor: grow slowly with a well defined capsule
Benign
_____ tumor: grow rapidly and not encapsulated
Malignant
____ tumor: well differentiated and low mitotic index
Benign
____ tumor: poorly differentiated and high mitotic index
Malignant
Do benign tumors metastasize?
No. Malignant do.
Lipoma, Leiomyoma, and Meningioma are examples of which type of tumor?
Benign
Can benign tumors progress to cancer?
Yes
Which -oma cancers are malignant? (usually only benign tumors end in -oma)
Carcinoma, adenocarcinoma, sarcoma, and lymphoma
Carcinoma arises from
Epithelial tissue
Adenocarcinoma cancer arises from
ductal or glandular tissue
Sarcoma arises from
Mesenchymal tissue
Lymphoma arises from
Lymphatic tissue
Sarcoma. B or M?
Malignant
Carcinoma, B or M?
Malignant
Carcinoma in situ (CIS)
Pre-invasive epithelial malignant tumors of glandular or epithelial origin that have not broken through basement membrane or invaded the surrounding stoma
When is an epithelial malignant tumor considered in situ?
When the tumor has not broken through the basement membrane or invaded the surrounding stroma
What are possible outcomes of CIS?
- Remain stable
- Regress and disappear
- Become cancer
is CIS often treated?
Yes
What are the two foundational concepts for understanding biology of cancer cells?
- Cancer is a very complex genetic disease
2. Tumors exist in a complex microenvironment that contains both benign and cancerous cells.
The microenvironment affects tumors in what three ways?
- Tumor initiation
- Tumor promotion
- Tumor progression
Are multiple mutations required before oncogenes are activated?
Yes
Name three multiple mutations that are required before onco-genes are activated
- Small-scale DNA changes
- Large changes in chromosomes
- Epigenetic changes
After enough mutations, a normal cell transforms into a cancer cell. T or F
True
____ _____ means cancer cells accumulate faster than noncancer cells
Clonal proliferation
The cell acquires characteristics that allow it to have what over its neighbors?
Selective advantage
Increased growth rate or _____ apoptosis increases chances of survival for cancer cell
decreased
Hallmark of cancer: ________ immune destruction
avoiding
Hallmark of cancer: ______ growth suppressors
evading
Hallmark of cancer: ______ replicative immortality
Enabling
Hallmark of cancer: Inflammation that…
promotes tumors
Hallmark of cancer: Activating invasion and ______
metastasis
Hallmark of cancer: ________ ______ (mutator phenotype)
Genomic instability
Hallmark of cancer: inducing ______
angiogenesis
Hallmark of cancer: _____ cell death
resisting
Hallmark of cancer: ______ cellular genetics
de-regulating
Hallmark of cancer: ______ proliferative signaling
sustaining
What is tumor initiation when considering the complex microenvironment?
Produces an initial abnormal cancer cell
What is tumor promotion when considering the complex microenvironment that contains both benign and cancerous cells?
Cancer cells multiply and expand
What is tumor progression when considering the complex microenvironment that contains both benign and cancerous cells?
Tumor is spreading to local, regional, and distant sites (mets)
Cancer is predominantly a disease of ____ ____ ___ during aging
disease of cumulative genetic changes during aging
Which mutation refers to silencing or expression of genes?
Epigenetic changes
Cellular genes may become cancerous oncogenes as a result of _____ _____
epigenetic changes
Explain how inflammatory and immune cells help tumor growth
- non-malignant cells nearby release pro-inflammatory mediators.
- the i and i cells infiltrate and form the stroma (microenvironment) which helps the cancer suppress the immune system and evade
Stomal cells evolve to phenotypes that promote CA progression and ______
metastasis
Can cancer cells proliferate without growth factors?
Yes
______ ______: can grow without adhering to normal extracellular matrix (ECM)
Anchorage independence
What’s important to remember about anchorage independence?
Cancer cells can be grown outside the body/independence for the need of anchorage
_____ also known as cancer cells
oncogenes
_____: mutant proto-oncogenes or over-expressed p-o’s; always proliferating/uncontrolled cell death
Oncogenes
What genes encode proteins that, in their normal state, negatively regulate proliferation; independent of normal growth factors
Tumor-suppressor genes
Example of point mutations
in lung cancer, RAS gene converts from regulated to unregulated
_______: burkitt lymphomas. Chronic myeloid leukemia: results in an abnormal chromosome called the Philadelphia chromosome. Resulting in the uncontrolled growth of the myeloid
Translocations
What results in the inactivation of tumor-suppressor genes?
Mutations
Is Retinoblastoma gene a tumor supressor gene?
yes
Mutated RB leads to what?
Leads to persistent cell growth
What is the “guardian of the genome”?
Tumor protein p53
What does TP53 do?
Activates caretaker genes to repair damaged DNA and initiate apoptosis
_____ ______ may result from epigenetic silencing, or modulation of gene functioning
genomic instability
____ _______ leads to an increase in malignant cells
chromosome instability
______ cells are not _____, and can only divide a limited number of times before senescence or apoptosis
Somatic; immortal
______ are protective caps on each chromosome that germ and cancer cells target
Telomeres
In _____ cells, telomeres are held in place by telomerase which allows for longer cell division
germ
90% of what can activate telomerase?
cancer cells (unlimited division and proliferation)
______: growth of new vessels
angiogenesis
Advanced cancers activate this which leads to secretion of angiogenic factors
HIF-1alpha
Name the highlighted angiogenic factor from the powerpoints
Vascular endothelial GF
Normal cells generate ATP via oxphos, whereas cancer cells use _____ even under normal oxygen conditions
glycolysis
Why do some cancer cells also use oxphos along with CAF to under aerobic glycolysis?
To secrete usable metabolites, which allow cancer cells to replicate quickly
Apoptosis is controlled by the balance of pro-apoptotic and anti-poptotic members of what family?
Bcl-2 family
What two pathways trigger apoptosis?
- Intrinsic in response to cellular stress; especially if the DNA is damaged
- Extrinsic, via activation of death receptor
Dysregulation of intrinsic or extrinsic pathways in most cancers provide resistance to ______
apoptotic cell death
Is chronic inflammation an important factor in the development of cancer?
yes
Example of chronic inflammation and its association of cancer?
Helicobacter pylori: peptic ulcer disease, stomach carcinoma, and mucosa-asociated lymphoid tissue lymphomas
Name three viruses associated with cancers
Epstein-Barr virus, Kaposi sarcoma, and HPC (cervical cancer)
Cancer cells recruit _____ cells to decrease host immune response
immune
Treg cell function is manipulated in tumors and used to produce high levels of which immunosuppressive cytokine?
Interleukin-10
Tumors using interleukin 10 suppresses what two things?
Antigen recognition, and the ability of CD8+ T cells to recognize and kill tumor cells
Increased treg cells and decreased T cells in the tumor microenvironment also makes the tumor more resistant to what?
Chemo treatment and xrt
Once cells become malignant, they enhance _______
inflammation
what is TAM?
Tumor associated macrophage
_____ cells turn acute inflammatory response on its head from “rejection” to “regeneration” respons
cancer
the presence of tumor-associated macrophages frequently…
frequently correlates with a worse prognosis
TAM mimic M1 phenotype of _____, a phenotype that induces cellular proliferation
macrophages
TAM have a diminished ____ response
cytotoxic
TAM block T-cytotoxic cells and NK cell functions, and produce cytokines that are advantageous for….
tumor growth and spread
Direct invasion of contiguous organs is known as ____ ____
local spread
Metastases to distant organs…cancer is traveling through the _____ and ____
Lymphatics and blood
Activation and metastasis requires great _____ and occurs late
efficiency
Epithelial mesenchymal transition is the mode that changes fixed cancer cells to
metastatic cancer cells
Initially, tumors spread locally through “direct extension” t or f
True
After growing, tumors spread by invasion into surrounding tissues through the release of _____ ____
lytic enzymes
Concerning metastases, some cancer cells bind to _____
platelets
Breast cancer goes into the _____ and lymphomas migrate to the _____
bone; spleen
Can metastatic cancer cells enter dormancy?
Yes
Early signs of cancer?
Unexplained weight loss. Skin changes, nagging cough, indigestion, and change in bowel habits
New growth is called ________ syndromes
Paraneoplastic syndromes
Paraneoplastic syndromes are commonly caused by ______ and _____.
Serotonin and bradykinin.
Serotonin and bradykinin are released from _______ tumors
carcinoid
Hypoxia
No oxygen
Hypoxemia (like anemia)
No oxygen in the blood (is a type of hypoxia)
Are paraneoplastic syndromes common? Arise late or early?
Not common. arise late.
Malignancy has little or no pain during what stage
early
What is pain from cancer influenced by?
Fear, anxiety, sleep loss, fatigue, and overall physical deterioration
Name the mechanisms of pain from cancer
- pressure
- obstruction
- invasion of sensitive structures
- tissue destruction
- inflammation/infection
What is the most frequently reported symptom of cancer?
Fatigue
What is syndrome of cachexia?
Most severe form of malnutrition
What do you treat anemia with?
Exogenous erythropoietin
Mechanism of anemia
Chronic bleeding resulting from iron deficiency
Direct tumor invasion to the bone marrow causes ______ and ______
leukopenia and thrombocytopenia
Chemotherapy drugs are toxic to the _____ ____
bone marrow
Risk of infection increases when the absolute _____ and ______ count falls
neutrophil and lymphocyte
How do they test for cancer
Biopsy, aspiration collection, and exfoliative cytology (i.e pap smear)
Microscopic analysis for staging cancers is based on presence of _________
metastasis
Stage I
no metastasis
Stage II
Local invasion
Stage III
Spread to regional structures
Stave IV
Distant metastasis
Tumor cell markers are substances produced by ____ ___
cancer cells
Tumor cell markers are found on or in tumor cells, in the ____, ____, or ____
blood, CSF, or urine
What are tumor markers used to do?
Screen and identify individuals at high risk for cancer
Tumors are classified based on __________ analysis of protein expression for improved treatment
Immunohistochemical
_____ chemotherapy is for shrinkage or disapperance of tumors
induction
______ chemotherapy : eliminate micrometastasis after surgery
adjuvant
______ therapy: given before localized treatment to shrink tumor
Neoadjuvant
Cancer tx: gene therapy
Patients own T-cells are genetically modified with a new gene for a protein that directs T-cells to target and kill leukemia cells
