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- What is it like to be a first-year medical student at U of T?
- Cancer Therapies: Defeating the Enemy Within
- Kaplan: Analysis of the April 2000 MCAT
- Princeton Review: Report on the April 2000 MCAT
What is it like to be a first-year medical student at U of T?
ALan Fung
MD Candidate, University of Toronto and past president of Gadfly
A first-year medical student is exposed to a very different environment – academically and socially – from that of undergraduate or graduate studies. Some people may find it challenging, while others enjoy it a lot. The transition period may be especially stressful, as the first year curriculum begins with an intense 10-week block in anatomy and embryology. However, students will soon find out from the second-year students that second-year medical school is much less intense – and thus something that first-year medics could look forward to…[To Top]Demographics
The first-year class size from September 2000 on is 190 (previously 177).
The September 1999 entering class consisted of students with a great variety of academic backgrounds. Around 1/3 of the class had three-year university education (without degree or with three-year BSc); 1/3 with four-year BSc; 23% with Master’s degrees and 6% with PhD and/or post-doctoral experience; 4 students came from an engineering background and 5 students had BA degrees.
In the 1999 entering class, 41% attended U of T. Some have attended non-Canadian universities like Yale, Oxford and Paris.Academic life
Typical daily schedule is 8-5pm (sometimes maybe shorter but on average one should expect to spend more than 30 hours in class work per week).
The grading system is Honours (*80%) / Pass (60-79%) / Fail (<60%).At U of T, the first year medical curriculum consists of 4 main blocks:
- 10 weeks of gross anatomy and embryology
- 10 weeks of cardiac & respiratory physiology, biochemistry, molecular biology and histology
- 8 weeks of endocrinology, nutritional science, renal, G.I. and acid-base physiology, biochemisty and histology
- 8 weeks of neuroanatomy, neurophysiology and psychiatryThe first 20 weeks is grouped under the course "Structure & Function"; the next 8 weeks under "Metabolism & Nutrition" and the last 8 weeks "Brain & Behaviour".
One morning (4 hours) per week throughout the entire year is spent in a hospital learning medical interviewing and physical examination skills (Art and Science of Clinical Medicine; also known as ASCM; grading scheme is Credit/No credit).
Another 4 hours per week is spent on the Determinants of Community Medicine course (DOCH), which consists of lectures, seminars, field visits and projects in community health issues.
Problem-based learning (with around 7-9 students in each group) begins in November. Each case presents a real-life clinical scenario related to lecture topics and spans 2 or 3 two-hour sessions in which students develop clinical knowledge and skills of independent learning, presentation and teamwork.
Outside classrooms
As a first-year medic, there are lots of opportunities to take part in student societies, community services and interest groups.
Many students also look for mentors and elective experiences in the fields that they might be interested in for residency training.Tips (before medical school)
It would be very helpful to have taken an introductory course in each of human anatomy (e.g. ANA300Y at U of T) and human physiology (e.g. PSL 302Y).
At U of T, those who have taken human embyrology (ANA301H) may be exempted from the embryology exam in first year.
Take the summer (before first year medicine) off and enjoy life! First year medical school demands a lot of physical and emotional strength, so one should be well-rested beforehand.Beyond first year
Second year is similar to first year but is generally regarded as less intense, and is thus a good time to take part in student activities, community services and electives.
In clerkship (third and fourth years) students work in different health-care settings and departments full-time to try to learn as much as possible about each area.
Successfully completing the clerkship will bring you the M.D. degree; but after that you would undertake residency training – either in family medicine (2 years) or a specialty (usually 5 years but vary).
To obtain a license to practice in Canada, one has to pass the two-part MCCQE (Medical Council of Canada Qualifying Exam) – first part at the end of medical school and second part 18 months into residency training.Useful websites
Official U of T medical student homepage: www.torontomeds.com
Official U of T Faculty of Medicine homepage: www.library.utoronto.ca/medicine/
Educational Computing (course resources and academic links for U of T medical students): http://icarus.med.utoronto.ca/Comments and enquiries on this article could be sent to
[email protected]
Cancer Therapies
Defeating the Enemy Within
Scott Lovitch
Cancer remains one of the deadliest diseases facing humanity. However, in the last several years, new therapies have been developed that are far more potent than traditional cancer treatments. These new drugs are the result of decades of research into just how cancer develops and invades the body.[To Top]Cancer is one of the most frightening of all human diseases. One reason for its capacity to instil fear in people is undoubtedly its widespread mortality. Cancer is currently the second most common cause of death in the United States, after heart disease; it kills 500,000Americans each year, and it has been estimated that one in six people alive today will develop some form of cancer. (1) Yet the real reason that cancer is such a frightening disease is the way that it invades the body from within. Bacteria and viruses enter cells from the outside and destroy them; we can fight them with antibiotics or vaccines that block them from invading. Cancer arises when a cell, suddenly and unpredictably, deviates from its genetic program and starts to grow and divide rapidly. As the deviant cells proliferate, more and more cells follow their destructive pattern. If bacterial infections are invasions of the body, cancer is more like an inner rebellion.
Not long ago, a diagnosis of cancer was a death sentence; unless a tumor could be removed surgically, doctors simply prescribed painkillers and allowed the rapidly proliferating cancer cells to continue their fatal growth. In the last thirty years, however, the development of new cancer therapies has brought cancer mortality to its lowest level ever. In 1971,the U.S. government announced that it had set a goal of curing cancer by the end of the decade. More than twenty-five years later, we still haven't reached that goal, but we have made major advances. Half the people treated for internal cancers today are cured of their disease (2).These new therapies work by several different mechanisms, but they have the same general strategy - they deliberately interfere with the mechanisms of human cell growth and proliferation, with the hope of killing cancer cells while minimizing damage to healthy cells. The prospect of discovering a general cure for all types of cancer is just as unlikely as it was in 1971, but with the continued development of new and more effective cancer therapies, it's possible that thirty years from now, cancer will be regarded as just another of the great killers of the past.
How Cancer Arises
The development of new cancer therapies has been the result of dedicated laboratory research into the basic biology of cancer. We now know more than ever about just what happens in cancer - what causes previously normal cells to go awry and begin randomly proliferating. Knowing this has allowed us to design therapies that specifically target these processes.
We now know that cancer is, fundamentally, a genetic disease. The nuclei of human cells contain approximately 100,000 genes located within46 chromosomes. A small subset of these genes control the life cycle of the cell - the pattern of growth and division characteristic of all cells.(3) This cycle differs among different cell types - hair follicle cells, for example, divide rapidly, while brain cells may never divide. (3) If these genes function properly, cell division is maintained at its proper rate and unchecked growth does not occur.
Cancer arises when a mutation in one of these genes causes a cell to initiate a program of inappropriate growth. Over a period of years, the aberrant cell will grow and divide, and further mutations can occur. Eventually, the mass of cells resulting from the original aberrant cell -what we call a tumor - will grow large enough to invade surrounding tissue. Cells can also break off from a tumor and be carried elsewhere in the body by the blood, a process called metastasis. (3) Eventually, the patient dies when tumors interfere with the function of vital organs.
Two general types of genes are capable of causing cancer when mutated. Proto-oncogenes code for proteins that play vital roles in signaling the cell to grow and divide. When mutated, they cause the signal for division to be constantly "on", so that the cell divides rapidly. One such gene codes for the protein Ras, which transmits stimulatory signals that trigger cell division; mutations in Ras are found in a quarter of human cancers. (3) Another class of genes involved in cancer is the tumor suppressor genes. These genes code for proteins that repair mutated DNA, or act as checkpoints to stop cell division if a mutation has occurred.(3) Mutations in these genes don't by themselves lead to cancer, but they increase the susceptibility of cells to mutation, and eventually, a mutation will strike a proto-oncogene and trigger cancerous growth.
Killing Cells for your Own Good
So, cancer arises from mutations in genes critical to the regulation of cell growth. How, then, can we design drugs that stop this process? Unfortunately, we haven't yet figured out a way to prevent mutations from occurring -- you can minimize your risk by staying out of the sun and taking antioxidants, but some mutations will inevitably occur. But we can try to identify cells that are growing and dividing abnormally and kill them before they can spread or damage vital organs. That's the general strategy behind almost all cancer therapies. Cancer drugs target cells that are growing and dividing rapidly, the hallmark of a tumor cell, and kill them - either by interfering with the process of cell division, or by wreaking havoc with the cell's DNA, triggering a process known as apoptosis, or programmed cell death, in which the cell essentially commits suicide for the good of the organism. It's a dangerous strategy. Cancer cells aren't the only cells in the body that undergo rapid growth and division; many other types of cells must also proliferate rapidly in order to carry out their function. Cells in the bone marrow, for example, have to continuously grow and divide in order to be able to replenish the body's supply of red blood cells, which have short life spans. Hair follicle cells also divide rapidly, as do the cells in the inner lining of the digestive tract. Cancer therapies often kill these cells as well as their intended targets. This lack of specificity accounts for the devastating side effects of many cancer therapies: hair loss, anemia (from bone marrow depletion), and nausea(from stripping of the digestive lining), as well as other effects.
How Radiation Therapy Works
One cancer therapy, which has been used for decades, is radiation treatment. In this therapy, high-energy radiation in the form of X-rays or gamma rays is directed toward a tumor, or, in some rare cases, at the entire body. Radiation may be administered by an externally applied beam, or by implanting a radiation source in the region of the tumor. (2)
Radioactivity has a powerful mutagenic effect - it can cause extensive damage to DNA in the nuclei of cells. (Ironically, excessive exposure to ultraviolet light causes skin cancer by much the same process.)Specifically, radiation can break one or both strands of the DNA double helix, or can cause adjacent molecules of thymine - one of the four bases that specify the genetic information in DNA - to link together, by a process called dimerization. (2) This genetic damage triggers apoptosis, and the cell dies.
So how, then, does radiation therapy kill cancer cells without killing the patient? Again, the trick lies in targeting rapid cell division. Every time a cell divides, it makes a copy of its DNA. Damage to DNA induced by radiation prevents the cell's DNA replication machinery from working, so the cell can't divide. The more a cell divides, the more affected it will be by radiation-induced damage, so tumor cells will bear the brunt of the damage while healthy cells recover. Unfortunately, though, radiation falls prey to the same pitfalls as other types of therapy - cancer cells aren't the only cells in the body that divide rapidly, so radiation therapy inevitably kills some non-cancerous cells, resulting in severe side effects. (2)
Recently, advances in the way radiation treatment is administered have greatly increased its specificity and reduced its side effects. For example, the technique of conformal radiotherapy uses computer imaging along with a high-energy linear accelerator to deliver intense X-rays to the site of a tumor with precision unimaginable even a few years ago. Radiation therapy has also been used in combination with other therapies to increase specificity. (2)
How Chemotherapy Works
Another pitfall of radiation therapy is that since it must be confined to the precise region of a tumor, it can't be used to treat cancer that has already undergone metastasis and spread. In these cases, and in many other cancer cases, chemotherapeutic drugs are used. These drugs come in many forms, but all of them follow the same strategy previously described; they either interfere with the process of cell growth and division or cause catastrophic damage to DNA, triggering cell death by apoptosis. The majority of chemotherapeutic drugs are DNA damaging agents; they cause single- or double-strand breaks in DNA, making replication impossible and triggering apoptosis in a way similar to radiation therapy. Dynemicin is one example of such a DNA-damaging agent; it is administered orally or by injection, and enters cancer cells, causing double-strand breaks in DNA. (4) Other drugs damage DNA in other ways. For example, mitomycin C crosslinks adjacent molecules of guanine, another of the four bases that make up DNA. (4) The effect is the same - the replication machinery is blocked, resulting in cell death. Another class of chemotherapeutic drugs are known as DNA-alkylating agents. These drugs, rather than damaging DNA directly, cause the attachment of large, bulky molecules to the DNA. As a result, the double-helical structure of the DNA is disrupted; eventually, this has the same effect of blocking replication and causing cell death. Two commonly used chemo-therapeutic drugs, cyclophosphamide and chlorambucil, work in this manner.. (2) Until fairly recently, all chemotherapeutic drugs worked by inducing DNA damage. In the last several years, though, new drugs have been developed that act by blocking the cell cycle - they interfere with essential processes of growth and division, and prevent the cell from completing its life cycle, eventually resulting in apoptosis. One such class of cancer drugs are known as antimetabolites. These drugs interfere with normal metabolic processes in the cell that are required for cell growth and division to occur. (2) For example, methotrexate is an antimetabolic agent that binds to and inhibits an enzyme that normally converts folic acid to adenine and guanine, two of the bases in DNA. Deprived of these two bases, the cell's DNA cannot replicate, and the cell dies.
Another antimetabolite which recently received considerable media attention is taxol, a natural compound derived from the bark of the Pacific yew tree. (5) Taxol interferes directly with the process of cell division by binding to rod-shaped cellular structures called microtubules. Normally, microtubules assemble during cell division to form a spindle along which chromosomes are carried to opposite ends of the cell; the spindle then breaks down so that two new cells can form. When taxol binds to microtubules, they become extremely stable, so that breakdown does not occur, and the cell can't divide. (5) As a result, the cell dies through apoptosis.
One other class of drugs that work by blocking the cell cycle are known as topoisomerase inhibitors. (2) As the name suggests, these drugs inhibit the enzyme topoisomerase, which is necessary for DNA replication. During replication, the DNA double helix unwinds so that new strands can form; this unwinding supercoils the DNA directly in front of the site of replication, similar to the way a telephone cord coils up when twisted. To relieve this supercoiling, topoisomerase causes temporary single-strand breaks in the replicating DNA; the strands can then swivel to relieve the supercoiling. If topoisomerase is blocked, then either DNA replication cannot occur due to excessive supercoiling or numerous single-stranded breaks in DNA are formed (depending on exactly how inhibition occurs). (2)Either way, the cell can't divide. Since topoisomerase itself was only discovered in the early 1980s, these drugs are among the most recently developed. Doxorubicin and camptothecin are two topoisomerase inhibitors, which are just now entering clinical use.
Why Cancer Drugs Don't Kill You
All of these chemotherapeutic agents affect the mechanisms by which cells grow and divide - processes essential for cell survival. So, then, why don't they kill all cells in the body? In some cases (such as taxol, for example), the drug must be administered in low doses and directly to the tumor area, or else healthy cells would be killed, resulting in deadly side effects. But for most chemotherapeutic drugs, which are injected or taken orally, this isn't an option. Since the 1960s, then, cancer researchers have faced this problem: is there a way to make cancer drugs specific to tumor cells?
In 1977, Harold W. Moore, a professor at the University of California at Irvine, hypothesized that there was. Moore observed that while normal cells are arranged in an orderly manner and usually surrounded by blood vessels, cells in a tumor are often densely packed together. This dense packing hinders the formation of blood vessels, so tumor cells become oxygen-depleted from the lack of a blood supply. Oxygen is a very electron-hungry element, so molecules in normal cells tend to lose their electrons to oxygen (a so-called oxidizing element), whereas tumor cells have a reducing environment, in which electrons are more likely to be donated. So, Moore concluded, if a drug could be designed to be inactive in an oxidizing environment but active in a reducing environment, it would selectively attack tumor cells. This theory became known as bioreductive activation. (4)
Moore's hypothesis has been one of the guiding principles in the development of cancer drugs for the last twenty years; many currently used chemotherapeutic agents are bioreductively activated. In a way, bioreductive activation reverses the mechanism by which cancer-causing agents work. Many carcinogens are normally inactive, but when taken in by humans are transported to the liver for detoxification, where they are activated by the oxidizing environment and can damage DNA. In contrast, cancer drugs are activated by the reducing environment of cancer cells, and can block cell division or induce DNA damage, triggering apoptosis.(4) Doxorubicin, camptothecin, dynemicin, and mitomycin C are all examples of cancer drugs which are bioreductively activated.
Unfortunately, the distinction Moore drew between oxidizing and reducing environments is not perfect, and selectivity is still rather poor. So, while efforts are still underway to develop new bioreductively activated cancer drugs, cancer research in recent years has turned to other ways of targeting cancer cells, such as cancer immunotherapy and direct gene therapy.
Cancer Immunotherapy: The Cancer Drugs of the Future?
In December 1985, newspapers, magazines, and television programs around the world trumpeted the discovery of a potential cancer cure. The drug, a natural molecule of the immune system known as interleukin-2 (IL-2),could, according to the reports, transform the body's own white blood cells into powerful cancer fighters. (6) Reports of dramatic tumor shrinkage and even complete remission led thousands of cancer sufferers to call the National Cancer Society, which conducted the experiments on IL-2, demanding to know how they could get the drug.
Unfortunately, the IL-2 reports proved to be yet another example of media hype. It turned out that interleukin-2 therapy, although initially effective, has devastating - and sometimes even fatal - side effects, including liver dysfunction, kidney failure, and respiratory difficulty.(6) However, further research has led to more effective cancer therapies involving molecules of the immune system which lack the deadly side effects of IL-2. Cancer immunotherapy, as these treatments are called, is just now entering widespread clinical use and may become the most common method of cancer therapy in the near future.
The basic strategy of cancer immunotherapy is to strengthen the body's own immune system to attack cancer cells. (7) In response to bacterial and viral infections, the body produces chemical messengers that stimulate cells of the immune system to grow and attack the invader. These molecules, called cytokines, include IL-2, as well as other interleukins, interferon, and tumor necrosis factor (TNF). Increasing levels of these molecules in the blood, by direct administration of drugs like IL-2,boosts the immune system and makes it more able to fight tumor cells. (7)This type of therapy is called nonspecific immunotherapy. However, its fatal flaw is its lack of specificity. An artificially boosted immune system will indeed attack cancer cells, but it will also attack non-cancerous cells, which it would otherwise recognize as normal. (7) As a result, except in the most extreme of cases, nonspecific immunotherapy has been abandoned as too toxic for clinical use. More recently, research into cancer immunotherapy has focused on developing treatments that specifically target cancer cells. Cancer cells display specific molecules, called antigens, on their surface that identify them as "foreign" to the white blood cells of the immune system. Specific immuno-therapy works by stimulating the immune system to mount a specific immune response against these antigens, resulting in the elimination of tumor cells without the side effects of nonspecific therapies. (8) One method of specific immunotherapy involves isolating tumor antigens and then attaching them to molecules known to provoke an immune response; ideally, the immune system will mount an immune response against the antigen and the tumor cells that display it. (8) More recently, a new method for inducing a specific immune response has been developed. In this method, a small piece of tumor is removed and cells called tumor-infiltrating lymphocytes (TILs) are isolated. These cells are then genetically altered to make them more toxic to cancer cells, and reinjected into the patient, along with nonspecific immune system boosters like IL-2. Although this therapy has not yet entered widespread use, results of clinical trials indicate that it is one of the most promising new therapies developed.
Immunotherapy has also been combined with more conventional methods of therapy. For example, sources of radiation can be attached to antibodies, molecules of the immune system which bind specifically to cancer antigens. In this way, radiation can be delivered to cancer cells with precision not possible by conventional means. Certain chemotherapeutic drugs can also be targeted to cancer cells in this way.
The Prognosis for Cancer and Future Therapies
The development of chemotherapeutic drugs and immunotherapy have resulted in major improvements in cancer treatment and decreases in mortality. However, research continues into new methods of treating cancer. The most promising method currently under study is gene therapy. If defective proto-oncogenes or tumor suppressor genes could be replaced by functioning genes, then cancer could be stopped at its source. (9)
In particular, research into cancer gene therapy has focused on introducing functional tumor suppressor genes into cancerous cells. The gene p53, for example, is involved in DNA repair; mutations in this gene account for a wide variety of human cancers. Experiments have aimed at introducing the p53 gene into cells with p53 mutations. Although success has been observed in the laboratory, gene therapy is still several years from clinical use. (9)
More than twenty-five years have passed since the government's declaration of war on cancer. In that time, we have come to understand how cancer works at the molecular level, and to design drugs to block that function. But we have also come to realize that cancer is a disease that comes in many forms and that can use a variety of strategies. It is becoming more and more unlikely that a "magic bullet" to cure all types of cancer will be discovered. (1) However, continued development of drugs that specifically attack cancer cells, and further research into immunotherapy, holds the possibility of turning cancer from the widespread killer it is today into a manageable disease. The coming years should bring new and exciting developments in the field of cancer research.
References
1. The enemy with a thousand faces." The Economist, August 5, 1989,pp. 69-72.
2. Hellman, Samuel, and Everett E. Vokes. "Advancing current treatments for cancer." Scientific American, September 1996, pp. 118-123.
3. Weinberg, Robert A. "How Cancer Arises." Scientific American, September 1996, pp. 62-70.
4. Moore, Harold W. "Bioactivation as a Model for Drug Design Bioreductive Alkylation." Science, August 5, 1977, pp. 527-532.
5. Nicolaou, K. C., Rodney K. Guy, and Pierre Potier. "Taxoids: New Weapons Against Cancer." Scientific American, June 1996, pp. 94-98.
6. Langone, John. "Cautious Optimism." Discover, March 1986, pp.36-46.
7. Old, Lloyd J. "Immunotherapy for Cancer." Scientific American, September 1996, pp. 136-143.
8. Cowley, Geoffrey. "The Quest for a Cancer Vaccine." Newsweek, October 19, 1982, pp. 74-76.
9. Oliff, Allen, Jackson B. Gibbs, and Frank McCormick. "New Molecular Targets for Cancer Therapy." Scientific American, September 1996, pp.144-149.
Scott Lovitch was a Biochemistry concentrator at Harvard University, Class of 1999. This article was originally published in the Harvard Science Review.
ANALYSIS of the April 2000 MCAT
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Overview
Most Kaplan students agreed that they were very prepared for the test. Many noted that they completed the Physical Sciences section with more time to spare than on the Kaplan proctored exams. Students reported that Kaplan’s Full Length 4 was more challenging than the actual MCAT. They also indicated that the Verbal Reasoning section was the most difficult part of the test. Students identified at least 7 different test forms. As usual, there were passages that were common across several forms. Some of the passages have appeared in previous administrations of the test, as well as in Kaplan materials.Verbal Reasoning
The Verbal Reasoning section consisted of nine passages (60-75 lines), each followed by 6-10 questions. The usual menagerie of question types were observed, with special emphasis on logic, inference, and implied detail, as has been true for the past several administrations of the test.The topics included:
* The role of methane in the regulation of environmental oxygen
* Archeology and environmental studies
* Gothic literature
* The energetics of hopping in kangaroos
* The concept of freedom of speech
* Symbolism and religion
* Allegory and the use of pageantry in 19th-century America
Students reported that the level of difficulty was on par with that of the Kaplan materials.Physical Sciences
Kaplan students found the Physical Sciences section to be relatively easy. Knowledge of formulas was de-emphasized in favor of conceptual understanding of the principles involved. Calculation-intensive questions were not common: questions involving calculations could be easily answered with judicious approximation. Quite a few questions were based purely on outside knowledge.Passage topics included:
* Factors contributing to the strength of ionic bonds
* Thermochemistry of glucose oxidation
* Polywater
* Sonar
* Fuel cells
* Quarks and the Millikan oil-drop experiment
* Five important physical constants
* Recovery of copper from circuit boards
Discrete questions were very straightforward ones dealing with concepts such as neutralization, half-life, and hydrogen bonding.Writing Sample
The two prompts on the Saturday administration of the exam were:
* A business’s main purpose should be to make a profit.
* Youth and innovation are sometimes more beneficial in politics than age and experience.For the Sunday administration, the prompts were:
* Caution is often the best guide for government.
* Scientific inquiry is rooted in the desire to discover, but there is no discovery so important that in its pursuit a threat to human life can be tolerated.Biological Sciences Students found the Biological Sciences section of the test challenging when compared to AAMC’s released materials. Despite the level of difficulty, students felt that the Kaplan had prepared them for the section. It was noted that the breakdown between Biology and Organic Chemistry varied from test form to test form.
Passage topics included:
* Epoxide ring-opening
* IgA deficiency
* Sickle-cell anemia
* Diels-Alder reactions
* Permeability of cell membranes
* The Ritter reaction
* Osteoblasts
* Cystic fibrosis
Discrete questions in this section dealt with stereocenters, protein structure, viruses, etc.
Understanding Colorectal Cancer
Clement Zai
[To Top]Adenocarcinoma of the colon and the rectum is the second leading cause of death in Canada. It is caused by abnormal cell growth (tumor formation) in the large intestine. The tumor is benign if it remains at its original site, and it is malignant if it spreads to and invades other parts of the body. Colon cancer is very common in men and women, with people above the age of 60 have highest chances of developing this disease. History of inflammatory bowel diseases such as chronic ulcerative colitis that damages the intestine increases the probability of acquiring colon cancer.
Most cases of colon cancer are sporadic with no family history, but genes have been shown to be associated with the familial form (2 to 5% of all) colon cancer. The families affected by this disease have large numbers of affected members with a young age of cancer onset. One of these genes is APC (adenomatous polyposis coli) gene. It is involved in signal tranduction pathways that control cell proliferation. A dominant inherited mutation in (one of the two copies of) this gene results in multiple tumors forming in the colon. Although these polyps are benign, they represent a larger number of targets for subsequent random mutations that may give rise to malignancy. Another form familial colon cancer is HNPCC (hereditary non-polyposis colorectal cancer). People with HNPCC have a higher likelihood of developing not only colon cancer but also cancer of the ovaries, uterus, and stomach. HNPCC has been linked to several genes involved in DNA repair. Therefore, if a mutation that give cells a growth advantage, the DNA repair machinery (with only one normal copy of the genes) will not be able to handle the workload, giving rise to more mutations. The stability of the entire genome can be affected. The result is full cancer development.
For the cases of sporadic colon cancer, the genetic evidence is less clear. Hence, it has been proposed that sporadic colon cancer is caused by mutations within a series of genes that normally regulate the orderly process of cell proliferation and differentiation in the large intestine. To understand how sporadic colon cancer (and possibly other cancers) occurs, we must first understand how the normal colonic crypt grows and differentiates. The lower two thirds of the colonic crypt is where proliferation takes place. Cells migrate up toward the luminal surface where they are terminally differentiated to function in the intestine. The growth of these differentiated cells then ceases and they go through programmed cell death (apoptosis) as their debris are removed in the lumen. Newly proliferated and differentiated cells from the lower parts of the crypt balance their loss.
A genetic model for the development of colorectal carcinoma follows the sequence:
(1) Normal epithelium
Loss of or mutation within proto-oncogenes that normally regulate cellular proliferation (such as APC)
(2) Hyperproliferative epithelium
DNA hypomethylation
(3) Early adenoma
Mutation causing constant activation of oncogenes in signal transduction pathways (such as k-ras, c-src)
(4) Intermediate adenoma
Loss or mutation of DCC
(5) Late adenoma
Loss or mutation of genes involved in cell-cycle control or apoptosis (such as p53)
(6) Carcinoma
Loss or mutation of genes that express cell-adhesion molecules or mutations that will result in the destruction of the basement membrane allowing the migration of tumor cells (such as further k-ras mutations)
(7) MetastasesA recent discovery from a mouse and human cell culture experiment pointed the cause of colon cancer to the loss of protein p110gamma. The role of this protein in the development of colon cancer still requires further investigation. For members in families with history of colorectal cancer, genetic screening has been developed for mutations in genes like APC and DNA repair genes associated with HNPCC. For sporadic colon cancer, genetic testing is not feasible as many genes can be involved in the development of the multi-stage cancer. Environment does undoubtedly play a role also. In these cases, other diagnostic tools for colorectal cancer exist:
Rectal Examination The physician inserts a gloved finger into the anus to feel for abnormalities.
Testing for blood in stool Stool from patients on meat-free diet tested for blood.
Sigmoidoscopy A hollow tube with a light inserted into the colon allows a visual examination of the rectum. A biopsy is taken if an abnormality if found.
Colonoscopy A flexible instrument is inserted through the rectum and extended to the beginning of the large intestine to allow visual examination and biopsy if necessary.
Barium Enema A barium solution is given as an enema, allowing visualization of any abnormalities in the bowel lining with X-ray.Symptoms of colorectal cancer that can be observed include changes in bowel habits, diarrhea or constipation, blood in stool, discomfort/pain/swelling of the abdomens, weight loss, and exhaustion.
Some recommendations from the American Cancer Society:
(1) Avoid alcohol, salt-cured, smoked, and nitrite-preserved foods
(2) Limit fat intake
(3) Maintain desirable body weight
(4) Eat more foods with high fiber content; ex., vegetables, fruits, whole-grain cereals, and legumes
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[To Top]Well, the MCAT’s over, and we congratulate you for all your hard work and tireless effort! You should be receiving your scores around June 14th, so relax and trust that the knowledge and experience which you gained over the course of the program allowed you to do your best.
Overall, the April 2000 exam offered no surprises and was comparable in difficulty to AAMC’s MCAT Practice Test IV, but, as usual, different forms had varying difficulty levels for the subtests. We identified three test series—G, H, K—with as many as six forms in each. Although most of the passages were reported as new, our course materials contained a number of passages and questions which helped to provide valuable practice for, and confidence with, those that appeared on the actual MCAT.
Verbal Reasoning:
All forms contained nine passages, with source credits collected all at the end of the booklet. Topics included discussing animals in biomedical research, physical anthropology, egret sibling aggression, linguistics, the Renaissance, philosophy, art, political science, and even the hopping speed of kangaroos. There were several questions of the strengthen/weaken, support/challenge, agree/refute variety, as well as many that asked how the author would respond to new information. Inference questions and main-idea questions were also popular. Passage length (60-70 lines) and difficulty were consistent with that in AAMC Practice Test IV.Physical Sciences:
The breakdown of passages most often favoured Physics slightly over G-Chem: with 5 G-Chem and 6 Physics, but the free-standing questions heavily favoured Chemistry. Most (but certainly not all) of the General Chemistry passages were reported as straightforward, with graphs and tables of data that often provided the answers without scrutinizing the passage text, although reading the passages that centred on an experiment was particularly helpful. Acid/base chemistry and solubility were most popular, with periodic trends and electrochemistry not far behind. The most popular Physics topics were kinematics, sound, light reflection and refraction, and E&M (circuits). As usual, there were many conceptual questions. However, with calm and confidence and a mastery of the fundamentals—and checking back to the equations in the passage or the data in the graphs—the questions could be successfully attacked. As usual, the percentage of questions requiring mathematical calculation was low (less than 20%). The free-standing questions were generally regarded as straightforward.Writing Sample:
As promised, the two Writing Sample items came from the list published by the AAMC in their MCAT 2000 Announcement (the MCAT Registration booklet). The first item was the last prompt in the first column on page 47 of the 2000 Announcement, and the second item was the seventh prompt in the first column on page 55.Essay Topic #1:
"A business’s main purpose should be to make a profit."Essay Topic #2:
"Youth and innovation are sometimes more beneficial in politics than age and experience."Biological Sciences:
The split between Bio and O-Chem favoured Biology, with the most common breakdown being 7 Bio passages and 4 O-Chem. The free-standing questions also leaned much more toward Biology than O-Chem and offered no surprises. The BioSci section of this April’s MCAT was generally regarded as comparable to AAMC Practice Test IV. Biology passage topics included discussions of endorphins released in long-distance runners, sickle-cell anemia, differentiation during fetal development, immune deficiencies, kidney function and osmolarity, and genetics. The O-Chem looked intimidating but the questions were considered fair. Passage topics included SN1 reactions, isoelectric focusing of proteins, epoxide reactions, and the breakdown of triglycerides by lipase and cholic acid. Passages often presented lots of structures and mechanistic steps.All the best,
The Staff of The Princeton Review – Canada
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