Med I: Cancer (Disturbances in Growth, Cellular Proliferation, and Differentiation)

Neoplasm

=A tumor: abnormal mass of tissue that forms when cells grow and divide more than they should. serve no physiologic purpose

can be benign or malignant

Carcinoma

malignant tumor/cancer from epithelial cells (80-90%)

Adenocarcinoma

carcinoma of the epithelial cells in glands

Lymphoma

malignant tumor/cancer from lymphocytes (5%)

Leukemia

malignant tumor/cancer from bone marrow cells (2.5%)

Benign tumor

Naming Based on Tissue Type Examples:

• adenoma (from glandular tissue); lipoma (tumor from fat); hemangioma (tumor from blood vessels); neuroma (tumor from nerve tissue)

polyp: benign tumor that grows from lining of the bowel (tubular adenoma)

Fibroid: grows from muscle layer of uterus (leiomyoma)

Characteristics

• Retain recognizable tissue structure and are well- organized and well-differentiated.

• Are encapsulated by connective tissue.

• Do not invade into other tissues.

• Do not spread to distant sites.

BUT can grow very large causing symp, overproduce hormones, undergo malignant transformation

Malignant tumor

Carcinomas → Epithelial Cells (80-90%)

• Adenocarcinoma (glands); Ductal carcinoma (ducts); squamous cell carcinoma squamous cells)

Sarcomas → Mesenchymal Cells (1% in adults)

Lymphomas → Lymphocytes (5%)

Leukemias → Bone Marrow Cells (2.5%)

Other types include: Melanoma (1.7%), Multiple Myeloma, Neuroendocrine, etc.

Charateristics:

• composed of undifferentiated (anaplastic) cells.

• Lose recognizable tissue structure; disorganized!

• Grow into and INVADE other structures.

• Spread to distant sites (metastasize).

if left untreated will become PRECANCEROUS LESIONS

• There are several abnormal histologic growth patterns that may eventually lead to cancer (hyperplasia (suggest incr/too freq cell growth) → often leads to dysplasia (abn growth) → carcinoma in situ (cells appearing cancerous BUT not metastasized)

TNM staging (ref breast cancer)

T: Tumor size

N: Lymph Node Status

• lymph node metastasis

M: Metastasis

• ANY spreading to another organ (M1) = Stg 4

Angiogenesis

The creation of new blood vessels

tips the balance so VEGF is more expressed = more blood vessels

• controlled by the balance of pro-angiogenic factors and inhibitors.

normal cells: the transcription factor hypoxia inducible factor-1α (HIF-1α) is triggered by hypoxic conditions to increase the expression of vascular endothelial growth factor (VEGF) which in turn promotes angiogenesis.

Cancer cells: HIF-1α is upregulated due to mutations in TP- 53, while angiogenesis inhibitors like thrombospondin-1 are down-regulated resulting in unchecked angiogenesis.

Telomeres

protective caps on ends of each chromosome (shorten w/ repliacation, will restrict number of times a cell is able to divide)

telomerase: enzyme!! able to restore size of telomeres

• cancer cells will TURN ON gene (incr production of telomerase)

Carcinogenesis

process (what causes) that turns reg cells into cancer cells

• genetic changes (DNA mutations, DNA damage, and epigenetic changes in HOW DNA expressed)

• oxidative stress: dev when too much ROS is formed → tissue damage and DNA mutagenesis

  • ROS (free radicals): generated by metabolic particles, too small to be used

Environmental-Lifestyle FactorsIinfluencing Carcinogenesis

Tobacco Use: via direct mutagenesis; inflammation/production of reactive oxygen species (ROS), epigenetic alterations (DNA methylation)

• cigarettes, pipe smoke, hookah smoke, oral forms, secondhand smoke

• 100/7000 chemicals carcinogenic

• ecig/marijuana: inhale in any form is inflammatory

Nutrition: DATA IS LACKING

• BOTH protect and carcinogenic

• box food bad/ fresh

  • Mediterranean diet (possible) redu cancer risk: nutrients and herb important for cellular processes, redu inflammation, acting as antioxidants (scavenge/bind free radicals)

  • processed foods, preservatives, saturated fats, grilled red meat carcinogenic

Obesity: definite associated with cancer, mechanisms unclear

• insulin-like growth factor effects (IGF-1): influences cell proliferation and apoptosis; altered expression and related receptors

• adipocyte derived cytokines: chemical junk from inflammation; lipolysis of saturated fats → PRO-inflammatory effects (macrophage activation and cytokine release)

• sex hormone production: adipose produces (estrogen via prod of aromatase enzyme)

Alcohol Consumption: promotes cancer growth and proliferation

• established carcinogen, NO SAFE LIMIT (moderation - no more than 1/night, no more that 3/wk)

• Methods: incr oxidative stress, incr DNA methylation, Histone modifications, aberrant microRNA expression

Physical Activity:

• proven to reduce risk

  • positive influence in ILGF, lowers obesity, decreases circulating sex hormones, improves immune syst func and redu inflammation, enhance CP450 activity (metabolizing potential carcinogens)

• 150 minutes/ week

Air Pollution: carcinogens: acids, organic and inorganic chemicals, metals, and dust particles

• induce oxidative stress, DNA Damage, inflammation

• Indoor (cooking, volatile organic compounds (VOCs) from cleaning supplies/pain/air conditioners, formaldehyde from furniture and glues, building materials

Ionizing Radiation: higher energy radiation altering electrons in substances it passes through (directly damage DNA)

• can lead to pro-cancer inflammation and oxidative stress

• RADON!! (#2 leading cause of lung cancer)

  • radioactive material from ground

• mantle radiation for lymphoma = high risk for breast cancer

UV Radiation: Increase BOTH squamous cell and basal cell carcinomas

• melanoma ← acute sunburns

• VIA induction of gene mutations, DNA methylation and histone modifications, incr inflammation and oxidative stress, redu immune surveillance

• Fairer skin = higher risk

Sexually Transmitted Infetions:

Agenesis

Anaplasia

undifferentialed cells

Hypoplasia

Metastasis

spread of malignant tumors to distant sites

Polyp (tubular adenoma)

benign tumor that grows from lining of bowel

Carcinoma in situ

cells that look like cancer under the microscope but don’t invade other structures and haven’t grown beyond their capsules (may do so!!)

Carcinogens