Cell Metabolism/ Cancer

Cell Metabolism/Cancer

Cellular Regulation

  • Definition: The genetic and physiologic processes that control cellular growth, replication, differentiation, and function to maintain homeostasis.

  • Important Note: All cancer cells were once normal cells but lost the function of cellular regulation.

External Factors Causing Cancer

  • Chemical Carcinogenesis: 30% of cancers are related to tobacco use.

  • Physical Carcinogenesis: Includes exposure to radiation and chronic irritation.

  • Viral Carcinogenesis: Involves oncoviruses that can induce cancer.

Cancer Etiology and Genetic Risk

  • Factors influencing cancer development include:
      - Exposure to carcinogens.
      - Genetic predisposition.
      - Immunity.

Etiology - Unknown Factors

  • Examples of potential unexplained causes of cancer include:
      - Virus: Human papilloma virus linked to cervical cancer.
      - Ultraviolet Rays: Sunlight exposure related to skin cancer.
      - Environmental Factors: Smoking associated with lung cancer.
      - Immune Disorders: HIV/AIDS connection with Kaposi’s sarcoma.
      - Diet: High-fat, high-protein diets associated with colorectal cancer.
      - Genetic Factors: BRCA1 and BRCA2 gene mutations associated with breast cancer.

Genetic Testing for Cancer Predisposition

  • Purpose: Genetic testing does not diagnose cancer but provides risk information.

  • Important: Genetic counseling should involve both before and after testing.

Health Equity: Cancer Incidence

  • Access to care and socio-economic background significantly impact cancer development rates.

Health Promotion: Cancer Prevention

  • Primary Prevention:
      - Avoidance of known or potential carcinogens.
      - Modifying associated risk factors.
      - Removal of “at risk” tissue.
      - Chemoprevention strategies, such as using medications to reduce cancer risk.
      - Vaccination, e.g., HPV vaccination.

  • Secondary Prevention:
      - Regular screening: Although it does not reduce cancer incidence, it can lower cancer-related mortality.

Impact of Cancer on Physical Function

  • Effects on various bodily functions include:
      - Immune function and clotting processes.
      - Gastrointestinal (GI) function.
      - Peripheral nerve sensory perception.
      - Central motor and sensory deficits.
      - Respiratory and cardiac function.
      - Overall cancer pain and its impact on quality of life.

General Disease-Related Consequences of Cancer

  • Untreated cancer can lead to:
      - Destruction of normal tissue.
      - Impairment of immune function.
      - Alterations in GI tract structure and function.
      - Motor and sensory deficits.
      - Decreased respiratory function.
      - Ultimately, it may lead to death.

Development of Cancer

  • Development processes involving defects in cell mechanisms are as follows:
      - Defect in Cell Proliferation: The phases of the cell cycle are:
        - M Phase: Mitosis.
        - G0 Phase: Resting phase.
        - G1 Phase: Period of cellular growth before DNA replication.
        - S Phase: Synthesis of DNA.
        - G2 Phase: Preparation for mitosis, synthesis of components for mitosis.

Cancer Development: Defect in Cell Differentiation

  • Key concepts include malfunction of cell differentiation, such as:
      - Proto-oncogenes transforming into ONCOGENES.
      - Mutations in tumor suppressor genes that normally regulate cell growth and division.

Abnormal Cell Growth

  • Stages of cancer growth include:
      - Initiation: Begins the process of cancer development.
      - Promotion: Leads to the development of a critical mass; smallest tumor size detectable by MRI is approximately 0.5 cm.
      - Progression: Further advancement of the cancer state.

Characteristics of Cancer Cells

  • Features include:
      - Persistent proliferation.
      - Invasive growth into surrounding tissues.
      - Formation of metastases.
      - Immortality (ability to replicate indefinitely).

Normal Cells versus Cancer Cells

  • Normal Cells:
      - Exhibit small, uniformly shaped nuclei.
      - Relatively large cytoplasmic volume.
      - Conformance in size and shape; organized into discrete tissues.
      - Normal presentation of cell surface markers; clearly demarcated tissue boundaries.

  • Cancer Cells:
      - Display large, variably shaped nuclei.
      - Relatively small cytoplasmic volume.
      - Variation in size and shape; disorganized arrangements.
      - Loss of normal specialized features; elevated expression of abnormal cell markers.
      - High levels of dividing cells; poorly defined tumor boundaries.

Comparison of Normal and Abnormal Cells

Characteristic

Normal Cell

Benign Tumor Cell

Malignant Cell

Cell Division

None or slow

Continuous or inappropriate

Rapid or continuous

Appearance

Distinct recognizable appearance

Distinct recognizable appearance

Anaplastic

Nuclear-to-Cytoplasmic Ratio

Smaller

Smaller

Larger

Differentiated Functions

Many

Many

Some or none

Adherence

Tight

Tight

Loose

Migratory

No

No

Yes

Growth

Well regulated

Expansion

Aneuploida

Chromosomes

Diploid (euploid)

Diploid (euploid)

Yes

Mitotic Index

Low

Low

High (depends on the degree of malignant transformation)

Primary and Secondary Tumors

  • Primary Tumors: Identified by the tissue from which they arose (parent tissue).

  • Secondary Tumors (Metastatic): Cancer cells move from the primary location, break off, and establish remote colonies.

Steps of Metastasis

  • The steps of metastasis include:
      - Malignant transformation.
      - Tumor vascularization.
      - Blood vessel penetration.
      - Arrest and invasion into new tissues.

Cancer Metastasis Process

  1. Primary Tumor: Origin of cancer.

  2. Angiogenesis: Formation of new blood vessels to supply the tumor.

  3. Detachment/ Invasion: Tumor cells invade blood vessels.

  4. Embolism/Circulation: Tumor cells enter the bloodstream.

  5. Extravasation: Tumor cells adhere to vessel walls and migrate to other organs.

  6. Establishment of a Microenvironment: Creating favorable conditions for further growth.

  7. Proliferation/Angiogenesis: Continuous growth and new blood vessel formation to sustain tumor growth.

Cancer Classification

  • Major classes of cancer classification include:
      - Grading: Ability to assess differentiation of tumor cells.
      - Ploidy: Measurement of chromosome number abnormalities.
      - Staging: Includes clinical, surgical, pathologic methods.
      - TNM System: A standardized classification that includes:
        - T: Tumor size.
        - N: Node involvement.
        - M: Metastasis.
      - Consideration of doubling time and mitotic index.

Site Classification of Tumors

  • Site: Identified by the tissue type:
      - Epithelial Tissue Tumors:
        - Benign: -oma, e.g. Papilloma.
        - Malignant: -carcinoma, e.g. Carcinoma.
      - Connective Tissue Tumors:
        - Benign: -oma, e.g. Fibroma.
        - Malignant: -sarcoma, e.g. Fibrosarcoma.
      - Nervous Tissue Tumors:
        - Benign: -oma, e.g., Meningioma.
        - Malignant: -oma, e.g., Neuroblastoma.
      - Hematopoietic Tissue Tumors:
        - Lymphoid tissue lymphoma (e.g., Hodgkin’s, non-Hodgkin’s), plasma cell: multiple myeloma.

More Terms Relating to Tumors

  • Adenocarcinomas: Derived from glandular tissues.

  • Sarcomas: Connective, muscle, and bone origin tumors.

  • Gliomas: Tumors from brain and spinal cord tissue.

  • Melanomas: Origin from pigmented cells.

  • Myelomas: From plasma cells.

  • Lymphomas: Lymphatic tissue tumors.

  • Leukemias: Derived from leukocytes.

Histology Classification of Cancer

  • Grade X: Grade cannot be assessed (undetermined grade).

  • Grade 1: Well differentiated (low grade).

  • Grade 2: Moderately differentiated (intermediate grade).

  • Grade 3: Poorly differentiated (high grade).

  • Grade 4: Undifferentiated (high grade).

Clinical Staging of Cancer

  • Stage O: Carcinoma in situ (localized).

  • Stage I: Localized to primary tumor.

  • Stage II: Local metastasis.

  • Stage III: Extensive local invasion with lymph node involvement.

  • Stage IV: Distant metastasis.

TNM Classification Staging System

  • Primary Tumor (T):
      - T0: No evidence of primary tumor.
      - Tis: Carcinoma in situ.
      - T1-4: Ascending degrees of increase in tumor size and involvement.
      - Tx: Tumor cannot be measured or found.

  • Regional Lymph Nodes (N):
      - N0: No evidence of disease in lymph nodes.
      - N1-4: Ascending degrees of nodal involvement.
      - Nx: Regional lymph nodes unable to be assessed clinically.

  • Distant Metastases (M):
      - M0: No evidence of distant metastases.
      - M1-4: Ascending degrees of metastatic involvement, including distant nodes.
      - Mx: Metastatic disease cannot be determined.

CAUTION: Health Promotion-Disease Prevention

  • Key warning signs to observe:
      - C: Change in bowel or bladder habits.
      - A: A sore that does not heal.
      - U: Unusual bleeding or discharge.
      - T: Thickening or lump in breast or elsewhere.
      - I: Indigestion or difficulty swallowing.
      - O: Obvious change in wart, mole, or skin.
      - N: Nagging cough.

Additional Resources

  • For more information, visit: https://training.seer.cancer.gov/disease/categories/tumors.html