Human Health and Disease

1. Human Health and Disease Lecture 7

2. Cancer Therapy • Surgery: Removal of cancerous tissue/cyst/organ • Radiation Therapy: Use of high doze of radiation to kill cancer cells and shrink tumors • Chemotherapy: Use of drugs to induce apoptosis in cancerous cells. • Immunotherapy: Helps immune system to fight cancer. • Hormone therapy: Slows or stops the growth of cancerous cells that use hormones to grow.

3. Cancer therapy • Stem cell transplant: Procedures that restore blood-forming stem cells in people who have their destroyed by high doses of cancer treatments, such as chemotherapy and radiation therapy. • Gene Therapy: Use of viral and non-viral vector to replace mutated genes.

4. Cancer Biopsy • An incisional biopsy is the removal of a piece of the suspicious area for examination. • An excisional biopsy is the removal of the entire suspicious area, such as an unusual mole or a lump. • After a biopsy, the tissue removed is examined under a microscope by a pathologist. The pathologist provides a pathology report to the surgeon or oncologist, who makes the diagnosis of the type and stage of cancer.

5. Cancer Surgery • Tumor removal, also called curative or primary surgery. • The tissue surrounding the tumor is called the margin. • Tumor removal may be the only treatment, or it may be combined with chemotherapy, radiation therapy or other treatments, which may be given before or after surgery. • Conventional surgery requires large cuts, called incisions, through skin, muscle, and sometimes bone. • However, in some situations, surgeons can use surgical techniques that are less invasive, which may speed recovery and reduce pain afterwards.

6. Cancer Surgery • Debulking. When the complete removal of a tumor is not possible or might cause excessive damage to the body, surgery is used to remove as much of the tumor as possible. • Other treatments, such as radiation therapy or chemotherapy, may sometimes also be used to shrink the remaining cancer.

7. Cancer Surgery • Palliation. Palliative surgery is used to relieve side effects caused by a tumor. It plays an important role in improving quality of life for patients with advanced cancer or widespread disease. Examples include the following: • Surgery may be used to help relieve pain or restore physical function if a tumor presses on a nerve or the spinal cord, blocks the bowel or intestines, or creates pressure or blockage elsewhere in the body. • Surgery may be used to help stop bleeding. Certain cancers are more likely to cause bleeding because they occur in areas with a high concentration of blood vessels, such as the uterus, or organs in which the tumors are fragile and can easily bleed when food and waste products pass through, such as the esophagus, stomach, and bowel. In addition, bleeding may be a side effect of some drugs used to treat cancer. When surgery is needed to stop bleeding, a common technique is suture ligation, which involves tying blood vessels using surgical thread. • Surgery may be used to insert a feeding tube or tubes that deliver medications. If the cancer or cancer treatment has made it difficult to eat, a feeding tube may be inserted directly into the stomach or intestine through the abdominal wall. Or a tube may be inserted into a vein to deliver pain medication or chemotherapy. • Surgery may be used to prevent broken bones. Bones weakened by cancer or cancer treatment can break easily and often heal slowly. Inserting a metal rod may help prevent fractures of weak bones and relieve pain during healing.

8. Cancer Surgery • Reconstruction. After primary cancer surgery, surgery may be an option to restore the body's appearance or function. This is called reconstructive or plastic surgery. • Reconstructive surgery may be done at the same time as surgery to remove the tumor. • Or, it may be done later after a person has healed or received additional treatment. • Examples of reconstructive surgery include breast reconstruction after a mastectomy and surgery to restore a person’s appearance and function after surgery to the head and neck area.

9. Cancer Surgery • Prevention. Some surgery is performed to reduce the risk of developing cancer. • For example, doctors often recommend the removal of precancerous polyps in the colon to prevent colon cancer. • In addition, women with a strong family history of breast or ovarian cancers or known mutations to the BRCA1 and BRCA2 breast and ovarian cancer genes may decide to have a mastectomy, which is the removal of the breast, or an oophorectomy, which is the removal of the ovaries, to lower the risk of developing breast or ovarian cancer in the future.

11. Chemotherapy

13. Side effects of Chemotherapy • Fatigue • Headaches • Muscle pain • Stomach pain • Pain from nerve damage, such as burning, numbness, or shooting pains, usually in the fingers and toes • Mouth and throat sores • Diarrhea • Nausea and vomiting • Constipation • Blood disorders

14. Side effects of Chemotherapy Nervous system effects. Some drugs cause nerve damage. This can cause the following nerve or muscle symptoms: • Tingling • Burning • Weakness or numbness in the hands, feet, or both • Weak, sore, tired, or achy muscles • Loss of balance • Shaking or trembling • Stiff neck, headache, or problems seeing, hearing, or walking normally. These symptoms usually get better with a lower chemotherapy dose or after treatment. Changes in thinking and memory. Some people have trouble thinking clearly and concentrating after chemotherapy. Cancer survivors often call this chemo brain. Your doctor might call it cognitive changes or cognitive dysfunction.

15. Why does chemotherapy cause side effects? • Chemotherapy works on active cells. Active cells are cells that are growing and dividing into more of the same type of cell. Cancer cells are active, but so are some healthy cells. These include cells in your blood, mouth, digestive system, and hair follicles. Side effects happen when chemotherapy damages these healthy cells.

16. Spherical vesicles with a phospholipid bilayer What is a liposome? Hydrophilic Hydrophobic

17. Uses of Liposomes Chelation therapy for treatment of heavy metal poisoning Diagnostic imaging of tumors Study of membranes Enzyme replacement therapy Drug/Gene Delivery

18. Liposome with DNA or Drug

19. Entry into the cell • A liposome has an aqueous solution core surrounded by a hydrophobic membrane, in the form of a lipid bilayer. • Hydrophilic solutes dissolved in the core cannot readily pass through the bilayer. • Hydrophobic chemicals associate with the bilayer. • A liposome can be hence loaded with hydrophobic and/or and hydrophilic molecules. • To deliver the molecules to a site of action, the lipid bilayer can fuse with the cell membrane, thus delivering the liposome contents. • Thus preparation of liposomes in a solution of DNA or drugs (which would normally be unable to diffuse through the membrane) they can be (indiscriminately) delivered past the lipid bilayer.

20. Entry into the cell

21. Nano-liposomes • Composition:Nano-Liposomes are made up of lipids, most of which occur naturally within the body. • Size and stability: Typically 60-80 nanometers,Nano- Liposomes are stable in blood, circulate well, and easily enter tumor cells to deliver their payloads, destroying cancer cells. • Active ingredients:  both water-loving (hydrophilic) and water-hating (hydrophobic) compounds can be loaded into NanoLiposomes. • Protection: Actives are stored either within the liposomal core or lipid bilayer, preventing degradation during circulation. • Delivery:NanoLiposomes are stable during circulation and release payloads intracellularly following membrane fusion. • Targeting:NanoLiposomes can be targeted through size and surface charge, or a wide range of targeting materials can be attached to the surface.

22. Cationic Liposome • Cationic liposomes are structures that are made of positively charged lipids and are increasingly being researched for use in gene therapy due to their favourable interactions with negatively charged DNA and cell membranes. They can be administered efficiently, safely, and repeatedly for direct gene transfer for the treatment of human diseases. An ideal cationic liposome is capable of targeting tumor vessels and tumor cells.

23. Current liposomal drug preparations Type of Agents Examples Duanorubicin, Doxorubicin*, Epirubicin Methotrexate, Cisplatin*, Cytarabin Anticancer Drugs Anti bacterial Antiviral DNA material Enzymes Radionuclide Fungicides Vaccines Triclosan, Clindamycin hydrochloride, Ampicillin, peperacillin, rifamicin AZT cDNA - CFTR* Hexosaminidase A Glucocerebrosidase, Peroxidase In-111*, Tc-99m Amphotericin B* Malaria merozoite, Malaria sporozoite Hepatitis B antigen, Rabies virus glycoprotein *Currently in Clinical Trials or Approved for Clinical Use

24. Doxil • Chemotherapy drug doxorubin • Anemia, damage to veins and tissue at injection, decrease • platelet and WBC count, toxic to the body Treats cancer tumors • Modifications of liposome “stealth” • keeps doxorubin in blood for 50 hours instead of • 20 minutes • concentrates at KS lesions and tumors *approved by FDA in 2000*

25. Problems with Liposomal Preparations of Drugs Price • Fungizone $40.58 Amphotec $2334 • Doxil $1200 per treatment, twice the cost of normal protocol • of chemotherapy and drugs Lack long term stability (short shelf life) Physical and chemical instability Freeze dry and pH adjustment Low “Pay Load” - poor encapsulation Polar drugs and drugs without opposite charge