MicroBio 160 1st Edition Lecture 13Outline of Last Lecture I. Breast Cancer Staging II. Sentinel Lymph Node BiopsyIII. Sentinel Lymph Node DetectionIV. Surgery for Breast Cancer V. Radiation Therapy vs. Brachytherapy:VI. Hormone Therapy VII. Tamoxifen, the first SERM:VIII. Raloxifene, an alternative SERM:IX. How your body makes Estrogen after MenopauseOutline of Current Lecture I. Facts about Addiction to Nicotine II. What’s in Cigarettes?III. Linking Cigarettes to CancerIV. Mutations of p53 and K-ras in Lung CancerV. Non-small Cell Lung Cancer: VI. Small Cell Carcinoma VII. Renal Cell Carcinoma and SmokingVIII. Diagnosis IX. Treatments X. Exposure to SmokingXI. Electronic CigarettesCurrent LectureFacts about Addiction to Nicotine:- Nicotine is the tobacco plant’s natural protection from being eaten by insects - Within 8 seconds of first puff, nicotine arrives at the brain’s reward pathways (producing more dopamine—telling brains that we are happy so don’t quit)- Once inside the brain, nicotine gains direct and indirect control over the flow of more than 200 neurochemicals These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- Men who don’t quit smoking lose an average of 13.2 years of life, while smoking women lose even more—an average of 14.5 years What happens when you smoke:- Falling blood nicotine levels- Brain generates craving- Inhale new nicotine- Brain releases dopamineWhat is in cigarettes? Cigarette Tar: it is the sticky brown substance which causes yellow-brown stains on fingers, teeth, clothes and furniture- The more you smoke—carcinogens get into lungs and they will have effects on your DNAand immune system (if they are no longer protecting us we are at higher risks)- Tar is a mixture of substances that together form a sticky mass in the lungs- Tar in cigarettes also paralyzes the cilia, the small hairs which protect and clean the lungs- The last puff can contain more than twice as much tar as the first puffLinking Cigarettes to Cancer1. Burning tars in cigarettes create the chemical benzo (a) pyrene (BP) which is absorbed bylung tissue2. Within the cell’s nucleus, BP is modified to BPDE and binds to the tumor-suppressing gene p533. Benzopyrene (BP) causes mutations at three specific “hot spots” on the p53 gene, which results in unrestricted cell division (cancer)Mutations of p53 and K-ras in Lung CancerAs you can see, the graph shows that as tar concentration increases, the amount of DNA damage in rat thymocytes increases. As we have discussed previously, damage to your DNA can increase your risk ofcancer.P53:- P53 works at 2 cell cycle checkpoints- P53 detects DNA damage and signals the cell to stop dividing, allowing time for a mutation to be repaired before it is passed on to daughter cells - It is also the primary protein that starts apoptosisK-ras (it’s an oncogene that needs to receive a growth factor in order to send signals—accelerator- The protein produced by the K-ras gene is a tumor “activator” - K-ras is analogous to a car accelerator, because its overactivity contributes to tumor development - The K-ras protein resides on the inner side of the cell membrane, where it conducts growth signals from cell-surface receptors to the nucleus (signal transduction) o Mutations K-ras gene result in a K-ras protein that is essentially stuck in an “on” position—signaling cascade in the absence of any signal from a growth factorNon-small Cell Lung Cancer: 3 types: - Adenocarcinoma (cancer originating in the lung gland)o Usually develops on the outer boundaries of the lungs and is more commonly found in women than in meno Cause 40% of lung cancers in the US- Squamous cell carcinoma (thin flat layer of cells like the skin, organs, and tissues)o Commonly starts in the bronchi and may not spread as rapidly as other lung cancers (30%)- Large cell carcinoma (the cells are larger than normal cells) o Causes 15% of all lung cancer in USSmall Cell Carcinoma: aka oat cell carcinoma; more deadly—when the cell is smaller than normal cells and is a very aggressive cancer that often spreads to other parts of the body- Mutations in the p53 gene are found in 70% of lung tumors, the highest rate for any cancer- The p53 protein is a tumor suppressor, analogous to car brakes, because its activity helps counter tumor development o P53 occupies a “checkpoint” in the cycle of cell division, where it “senses” DNA damage or mutations o The cell cycle is composed of 4 stages- It can create its own hormones, which alters body chemistry- Smoking tobacco is the major risk factor for developing small cell lung cancer- SCC of the lung has the most aggressive clinical course of any type of pulmonary tumor, with a median survival from diagnosis of only 2-4 months without any treatmento It has a greater tendency to be widely spread by the time of diagnosis, which is much more responsive to chemotherapy and irradiationRenal Cell Carcinoma and Smoking: renal cell carcinoma is the most common form of kidney cancer- Studies show that smokers are twice as likely as nonsmokers to develop this type of kidney cancer- In addition to RCC, smokers are more likely to develop:o Renal failure: causes kidneys to shut down—life-threatening conditiono Renal sarcomas: rare and attack the kidney’s connective tissueo Transitional cell carcinomas:less common form of kidney cancer found in connecting tubes in the kidneys and bladder—Tobacco is a leading cause of this type of cancerWhy do you think this is?- Increases blood pressure and heart rate.- Reduces blood flow in the kidneys- Increases production of angiotensis II (hormone produced in kidney)- Narrows the blood vessels in the kidneys- Damages arterioles (branches of arteries)- Forms arteriosclerosis (thickening and hardening) of the renal arteries.- Accelerates loss of kidney function.Diagnosis: - There are many ways including chest x-ray, CT scan, MRI, lung biopsy, sputum cytology, positron emission tomography (PET), bronchoscopy, mediastinoscopy, bone scan for lungcancer, ct scan of the brain for lung cancer, thoracentesis for lung cancer.o Complications: excessive bleeding can occur when taking a biopsy or performing bronchoscopy, thoracentesis, or mediastinoscopy.o Exposure to X-raysTreatment:- Stage 1A—Good prognosis; 49-75%o Stage IA—tumor 3cm or less- Stage 1B—45-55%o Stage
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