Oncology

Differentiation

Differentiation

Process by which normal cells undergo physical and structural changes as they develop to form tissues

Hyperplasia

• Increased number of cells in tissue → increased tissue mass

• Can be normal physiological function → wound healing, callus forming

Neoplastic Hyperplasia

Increase in cell mass due to tumor formation

Dysplasia

• Disorganization fo cells in which an adult cell varies from its normal size, shape, or organization

  • May reverse itself or lead to cancer

Dysplasia is often caused by what?

Chronic irritation

Metaplasia

• Early dysplasia

• Reversible and benign but still an abnormal change

  • Ex:

    • Columnar epithelium of respiratory tract → squamous epithelium

    • Barrett’s esophagus

      • The squamous epithelium of the esophagus is replaced by the glandular epithelium of the stomach

Tumor

• “Neoplasms”

• Abnormal new growth of tissues that serves no functional purpose and may harm the host organism

  • Competes for blood supply and nutrients

  • Doesn’t respond to normal body function

Primary Tumor

Normally local to the given structure

Secondary Tumor

Cells have metastasized from another part of the body

Carcinogenesis

Process by which a normal cell undergoes malignant transformation

Oncogenesis

Transformation of normal cells into malignant cells, independently or incorporated with a virus. Focuses on the formation and growth of tumors.

TNM Staging for Tumors

Size of primary tumor (0-4)

TNM staging for Nodes

Regional lymph node involvement (0-4)

TNM staging for Metastasis

0 if no metastasis; 1 if metastases are present

Classifications of neoplasms

• Cell type

• Tissue of origin

• Degree of differentiation

• Anatomic site

• Benign/malignant

Stage 0 of Cancer

Carcinoma in situ (premalignant, preinvasive)

Heredity risk factors for cancer

• Disease of genes/mutations

• Only 5-10% of cancers are linked to heredity

  • Most are largely preventable

What is the median age of primary diagnosis?

66 years old for all ages and genders

What is the role of telomerase in cancer?

Allows for unlimited cell divisions

Cigarette smoking is linked to 90% of ______ cancers?

Lung

What reduces the immune system’s fight against genetic damage and is linked to 1/3 of cancer mortality?

Poor diet

What is linked with cancer of mouth, throat, liver, breast and increases absorption of tobacco-based carcinogens?

Alcohol

Incidence of different types of cancers varies ____________

Geographically

Precancerous lesion

May undergo later transformation into cancerous lesions and tumors

There is a link between biobehavioral and psychologic factors, like ________, and the progression of cancer.

Stress

Somatic mutation theory

Neoplasia originates in a single cell

tumor cells are characterized by __________ and ____________ chromosomal abnormalities

Numerical and structural

Numerical chromosomal abnormalities

Addition or deletion of entire chromsome

Structural chromosomal abnormalities

Translocations, deletions, inversions, and insertions of parts of chromosomes

Tumor suppressor genes can _________ growth and inhibit ________

Regulate; carcinogenesis

Defects in the oncogene occur simultaneously with the inactivation of _______-____________ _______.

Growth-suppressing genes

Steps of Metastasis

• Transformation/Proliferation

• Angiogenesis

• Intravasation

• Arrest/adherence

• Extravasation

• Tumor cell proliferation

Transformation/Proliferation

Step of metastasis in which normal cells transform into cancer cells with uncontrolled proliferation. Leads to formation of primary tumor

Angiogenesis

Step of metastasis in which new blood vessels form from pre-existing vessels. Tumors can now be supplied with nutrients and oxygen

Intravasation

Step of metastasis where cancer cells invade nearby blood vessels, gaining access to the circulatory or lymphatic system

Arrest/adherence

Step of metastasis where cancer cells encounter the challenge of staying alive and adhering to the endothelial lining of blood or lymphatic vessels

Extravasation

Step of metastasis, where cancer cells exit the circulation or lymphatic system and invade distant tissues at secondary sites

Tumor cell proliferation

Step of metastasis in which cancer cells now proliferate and establish metastases

What is the key factor to cure cancer?

Eradicating metastases

What stimulates proliferation of vascular cells

Endothelial and fibroblast growth factors

What are the most important predictors of recurrent cancer

Stage at the time of initial therapy and histologic findings

Which cells kill cancer cells without previous exposure to the tumor?

Natural killer cells

T/F: Macrophages kill tumor cells

True

Antibodies ___________ complement-dependent cytotoxicity against tumor cells. IgM is an example.

Mediate

Which cells are the major immunologic barrier against tumors that recognize tumor antigens and lyse tumor cells?

Cytotoxic CD8+ T cells

How do know that cancer is linked to the immune system?

• Higher incidence of cancer after immunosuppression or in immunodeficiency

• Infiltration of tumors by lymphocytes and macrophages

• Lymphocyte proliferation in response to tumors

• Regression of metastases after ablation of the primary tumor

• Immune-Mediated Spontaneous regression of human tumors

How does cancer evade the immune system?

• Loss of immunogenicity

• Antigenic modulation

• Induction of immune suppression

What role does the loss of immunogenicity play in how cancer evades the immune system?

• Tumors mutate antigenic peptides, so that they can’t be loaded onto the class I MHC and be presented to CD8+ T cells

• Cytotoxic T cells can’t make contact with the tumor cell and undergo the remaining steps of triggering its killing mechanism

What role does antigenic modulation play in how cancer evades the immune system?

Tumor antigens are internalized or downregulated so that antibodies can’t bind

Antigenic Modulation

Loss of surface antigen

What role does the induction of immune suppression play in how cancer evades the immune system?

Tumors produce suppressive factors that inhibit NK and T cells directly

Common diagnostic associated with cancer

• Biopsy

• Biomarkers

• Molecular profiling

Incisional/Open Biopsy

Making an incision and removing only a portion of the abnormal tissue

Excisional/Lumpectomy

Making an incision to excise all gross, abnormal tissue that is visually apparent or identified using a needle to localize the lesion

When is a re-excision performed?

When specimen contains tumor cells within the margin. Must obtain a negative margin before proceeding

Resection without ________ _________ has the potential to causes metastasizing as new blood vessels form during the healing process.

Clear margins

Biomarkers

• Diagnostic but can signal malignancies (ex: carcinoembryonic antigen)

• Substances produced and secreted by tumor cells may be found in the blood

What seems to correlate with the extent of the disease?

Level of tumor marker

What is used more frequently rather than individual tumor marker evaluations?

Test panels

Molecular profiling

Specific cancer biomarkers can help determine the aggressiveness of the tumor, potential response to treatment, and prediction of risk for cancer diagnosis within a family

Treatments associated with cancer

• Surgery

• Irradiation Therapy

• Chemotherapy

• Pharmaceutical interventions

• OT/PT/SLP

Surgery

Most often in combination with other therapies; micro metastases require additional treatment (chemo-radiation)

Goals of irradiation therapy

• Destroy the dividing cancer cells by destroying hydrogen bonds between DNA strands within the cancer cells

• Limit damage to resting normal cells

When paired with surgery, irradiation therapy …

• Can be used to shrink a tumor, making it operable, while preventing further spread of disease during surgery

• Once wound heals, postoperative doses prevent residual cancer cells from multiplying or metastasizing.

Chemotherapy

• Kills cancer cells by affecting DNA synthesis/function

  • Bind to DNA and prevent replication

  • Bind to DNA: distort structure

  • Block cell growths

  • Inhibit enzymes responsible for DNA structure

  • disrupt mitosis

  • Direct cancer cell death

• After treatment-sensitive cells are destroyed, resistant cells may develop

Factors that influence prognosis of cancer

• Type of cancer

• Stage and grade of disease at diagnosis

• Availability of effective treatment

• Response to treatment

• Factors related to lifestyle such as smoking, alcohol consumption, diet, nutrition, and exercise.

Improved survival rates occur with what?

Screening and early detection/treatment

The cancer prognosis is poor for who?

Anyone with advanced, disseminated cancer

T/F: People considered “cured” are NOT left with physical limitations and movement dysfunctions that interfere with their daily lives

False

In terminally ill individuals, what is more important than absolute measure, as an indicator of survival?

Rates of change