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4.4h
| Question | Answer |
|---|---|
| It is often superficially believed that the only way gene expression can change is for the DNA base sequence to change—that is, through mutation. | It is clear, however, that other mechanisms called epigenetic effects can alter gene expression-reversibly activating or silencing genes without changes in base sequence. |
| Among these are variations in the higher-order packaging of chromatin, modification of the histones, | gene silencing by noncoding RNA (ncRNA), and DNA methylation-adding methyl (―CH3) groups to DNA bases, especially cytosine, with usually a gene-silencing effect. |
| Many epigenetic changes occur normally and affect such things as how stem cells end up as liver, nerve, or skin cells. | Different kinds of body cells are almost genetically identical, yet very different in structure and function because of epigenetic effects. |
| Some epigenetic changes, however, may trigger such diseases and disorders as cancer, obesity, diabetes mellitus, or heart disease. Epigenetics is thought to be a possible culprit, for example, in the hereditary disorder | Prader- Willi syndrome, 23 in which gene silencing leads to diverse effects including poor muscle tone, short stature, overeating, and childhood behavioral problems. |
| Particularly striking is the fact of epigenetic inheritance; we can pass on changes in gene expression to the next generation without changes in the base sequence of the genes themselves. | Our habits and experiences today may affect gene expression in our children and perhaps even grandchildren. |
| Anything from diet, smoking, or the use of recreational drugs to pollution, stress, epidemics, or famines can have epigenetic effects lasting for another generation or two. | In light of epigenetics, we must now view heredity as entailing not only the genes passed from one generation to the next, but also whether other factors have abnormally activated or silenced those genes. |
| Anyone awaiting the results of a tumor biopsy hopes for the good news: benign! | This means the tumor is slow-growing, contained in a fibrous capsule, and won't metastasize. In most cases, it's relatively easy to treat. |
| The dreaded news is that it's malignant, meaning it tends to grow rapidly, it's not encapsulated, | and it's prone to metastasize-to give off cells that seed the growth of multiple tumors elsewhere, such as colon cancer metastasizing to the lungs and brain. |
| Oncology is a medical specialty that deals with both benign and malignant tumors, but only malignancies are called cancer. The word cancer literally means "crab." | Hippocrates was the first to use the word this way, upon seeing a breast tumor with a tangle of blood vessels that reminded him of a crab's outstretched legs. |
| Energy-hungry tumors often stimulate such ingrowth of blood vessels-a phenomenon called tumor -----. | angiogenesis |
| Cancers | are named for the tissue of origin: |
| Carcinomas | originate in epithelial tissue |
| lymphomas | in the lymph nodes |
| melanomas | in pigment cells (melanocytes) of the epidermis |
| leukemias | in blood-forming tissues such as bone marrow |
| sarcomas in bone, other connective tissue, or muscle. | About 90% of malignancies are carcinomas. |
| Only 5% to 10% of cancers are hereditary, but cancer is always a genetic disease. This is not as contradictory as it may seem. | Most cases are due to mutations arising anew in the affected individual, not genes inherited from a parent. |
| Mutations can arise through errors in DNA replication every time cells divide, or from exposure to carcinogens-radiation such as ultraviolet rays and X-rays; | chemicals such as cigarette tar; and viruses such as human papillomavirus (HPV), hepatitis C, and type 2 herpes simplex. |
| Oncologists | are especially interested in two families of cancer genes called oncogenes and tumor suppressor genes. |
| An oncogene is analogous to a stuck accelerator on a car-it causes cell division to accelerate out of control, sometimes by | inducing the excessive secretion of growth factors that stimulate mitosis, or the production of excessive growth-factor receptors, making cells oversensitive to even a normal level of growth factor. |
| An oncogene called ras underlies about one-quarter of human cancers, and oncogene erbB2 is a common factor in breast | and ovarian cancer. Tumor suppressor (TS) genes inhibit cancer by opposing oncogene action, coding for DNA-repair enzymes, and other means. |
| Consequently, mutations that destroy their protective “braking” function can lead to cancer. | Mutation of a TS gene called TP53, for example, is involved in about 50% of cases of leukemia and colon, lung, breast, liver, brain, and esophageal tumors. |
| Many human cancers are associated, however, not with mutation but with aberrant -----, which can, for example, silence one's TS genes and turn off their protective function. | DNA methylation |
| Cancer seldom results from just one mutation. It usually requires 5 to 10 mutations at different gene loci. | It takes time for so many mutations to accumulate, which is why cancer is more common in the elderly than in the young. |
| In addition, as we age, we accrue more lifetime exposure to carcinogens, our DNA- | and tissue-repair mechanisms become less efficient, and our immune system grows weaker and less able to detect and destroy malignant cells. |
| Cancer typically begins with a single cell that has experienced multiple mutations, | leading it to divide out of control and grow into a larger and larger mass-the primary tumor. |
| The hallmark of cancer is metastasis- | the ability of malignant cells to spread from the primary tumor and seed the growth of new tumors elsewhere, detached from the primary one (fig. 4.22). |
| Motility and invasion are two key characteristics of metastasizing cells. | Depending on the type of cancer, malignant cells can travel in the lymphatic vessels, blood vessels, along nerves, or along the basal surfaces of epithelia, among other routes. |
| Recent research has shown that just prior to metastasis, primary tumors emit chemical signals (cytokines) that stimulate other tissues and organs to prepare for arriving metastatic cells. | Those tissues produce a modified cellular-biochemical environment that functions as a more favorable bed for metastatic cells to settle down and grow in. |
| The cancer behaves in some respects like a parasite, adapted to promote its own success, survival, and spread. | Unlike true parasites, however, cancer cannot spread from one person to another. |
| About one in five of us in the United States will die of cancer-one of the highest rates in the world- | with the five highest tolls taken by lung, colorectal, liver, stomach, and breast cancer, in descending order. If left untreated, cancer is almost always fatal |
| For one reason, malignant tumors replace functional tissue in vital organs. Kidney cancer can destroy most of the blood-filtering units (nephrons) of the kidneys, letting toxic wastes build up to lethal levels (fig. 4.23). | Lung cancer can destroy much of the gasexchange tissue (alveoli) of the lungs, making it increasingly hard to breathe, leading to a low blood oxygen level and multisystem organ failure as oxygen- starved, CO2-poisoned tissues die. • |
| Growing tumors can put lethal pressure on vital organs like the brain. | They can compress bronchi and prevent adequate ventilation of the lungs, or compress major blood vessels and shut down circulation |
| Ovarian tumors, for example, can grow to the size of oranges, even grapefruits, and larger. | In the crowded pelvic cavity, they can compress the major arteries and veins that serve the lower limbs, causing catastrophic circulatory failure. |
| The erosion of blood vessels by tumors can cause them to hemorrhage, | with vomiting or coughing up blood and unseen hemorrhaging into the body cavities. |
| Cancer weakens the immune system, leaving the body open to attack by opportunistic infections that a healthy person could ward off. | Leukemia, for example, produces a great overpopulation of white blood cells (WBCs) (see fig. 18.19) |
| ⚫ . Since WBCs are our disease-fighting cells, one might think this was a good thing. However, the leukemic cells are immature and can't perform that function. | A body overrun with leukemia is like a nation with a huge standing army, but composed of 10-year-old children who can't fight effectively to defend it. |
| Energy- and nutrient-hungry tumors outcompete healthy tissues, starving the body for energy. As muscle, fat, and other tissues atrophy, cancer victims can waste away to an alarmingly emaciated degree | called cachexia (ka-KEX-ee-ah), lapsing into fatigue, coma, and death from sheer exhaustion. |
| Cancer is usually treated with surgery, chemotherapy, or radiation therapy. In the worst cases, the body can become widely riddled with tumors, all of which started out as a single cell in someplace such as the lung, breast, skin, or colon. | At that point, a cure usually can't be achieved by surgery, and one's best hope may lie in something that acts body-wide such as chemotherapy, radiation therapy, or immunotherapy. |
| It is simplistic and misguided to hope for "a cure for cancer." Cancer isn't one disease and won't have one cure. | Many people have already been cured of some cancers, whereas other cancers haven't yet yielded to the skills of oncologists, and new forms of cancer are still evolving. |
| Some lively areas of cancer research today are drugs called angiogenesis inhibitors that prevent tumors from growing the dense plexus of blood vessels they need to survive; | cancer immunotherapy, programming one's own immune cells (T cells) to selectively recognize and attack tumor cells; and cancer genomics, tailoring treatment to the unique genetic makeup of each patient. |
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Russells3709