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Exam 2009-10-29
Molecular Oncology and Biostatistics
Biomedicine program, T5
Name:________________________
Code:__________________________
Good luck!
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Exam 2009-10-29
Molecular Oncology and Biostatistics
Biomedicine program, T5
Writing hours: 10.00-15.00
Code:________________________
Grading:
Basic questions
Maxpoints: 50p. To get an E-A grade at least 30p are
required.
Advanced questions
Maxpoints: 51p (F≤30, E:31-34, D:35-38, C:39-42, B:43-46,
A≥47)
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Good luck!
1. Explain the following tumor biological terms: (4p)
a)
Oncogene
b)
Restriction point
c)
Tumor progression
d)
Tumor angiogenesis
2. Explain the following clinical oncology terms: (4p)
a) Brachytherapy
b) Neo adjuvant treatment
c) Tumor grade
d) Tumor stage
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3. Cancer development is commonly associated with changes in
tumor suppressor genes (TSGs).
Please describe three conceptually different ways in which TSGs are
altered in tumor, and also describe how these three different types of
alterations can be detected at the molecular level (4.5p)
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4. A 59-year-old man who underwent a colonoscopy was found to
have a tumor that proves on biopsy to be moderately differentiated
adenocarcinoma.
a) Please describe under what circumstances this patient would
be likely to receive adjuvant therapy, and explain briefly why
some colon cancer patients are recommended adjuvant
treatment and others not (4p)
b) Unfortunately the patient got a relapse of his disease a year later.
In this setting targeted therapies against tyrosine-kinase receptors
may be beneficial. Drugs targeting tyrosine kinase receptor in cancer
have three principally different mechanisms of action. Please
describe those mechanisms. (3p)
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c) The response to therapy targeting tyrosine kinase receptors in
colorectal cancer can today partially be predicted using molecular
analysis of the tumor cells. Please give an example of such an
analysis and also give a plausible explanation of why you think
that the result of the analysis may predict the outcome of the
treatment. (2p)
5. A patient with breast cancer turns out to have metastasis in the left
lung as well as in the skeleton (in the breast bone, sternum). Please
reflect upon why this patient may have developed metastasis
specifically at these locations. (4.5p)
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6. Approximately 10% of all cancer patients have a clear hereditary
cause for their cancer. In colorectal cancer one gene causing
hereditary cancer is the APC gene.
a) Please describe the clinical picture in patients inheriting a mutant
APC gene. (2p)
b) Please describe briefly the normal molecular function of the
APC-protein. (5p)
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c) Please describe and reflect upon two ethical issues that may occur
in the handling of patients with hereditary cancer. (2p)
7. Cancer immunotherapy has mainly been successful using
monoclonal antibodies such as rituximab and alemtuzumab in
lymphoma treatment. Please describe two proposed mechanisms of
action for these antibodies. (1p)
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8. Last years Nobel Prize was awarded for discoveries concerning
two viruses, HIV and HPV. Infection with both of these viruses
increases the risk for cancer development. Please compare and
explain in what way these two viruses may promote cancer
development. (4p)
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9 Disease-related loss of weight is a common problem among cancer patients. Animal
studies have shown that intake of Eicosapentaenoic acid (EPA) can improve food
intake and prevent weight loss. Researchers have established a multi-center study to
see
whether
this
effect
can
be
seen
in
cancer
patients.
In this study, n=818 cancer patients with weight loss were randomized to either 2g
EPA per day (n=275), 4g EPA per day (n=272) or a placebo (n=271). Group
assignment was unknown to both patients and researchers during the study. Main
outcome was weight gain in kg after eight weeks. Shown below is a graphical
summary of the observed data (means and standard errors) and a preliminary analysis.
a. Describe the design. (1p)
b. What kind of clinical trial is this? Motivate your answer. (1p)
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c. Interpret these results: Which statistical methods have been used? What are the
underlying hypotheses? What is your decision? How do the individual treatments
compare? (4p)
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Response: WeightGain
Df Sum Sq Mean Sq F value
Pr(>F)
Group
2
285.1
142.5 5.7301 0.003379 **
Residuals 815 20272.0
24.9
--Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
Pairwise comparisons using t tests with pooled SD
data:
WeightGain and Group
Placebo 2g EPA
2g EPA 1.0000 4g EPA 0.0069 0.0163
P value adjustment method: bonferroni
10. Researchers plan a study to assess the relationship between a dietary choice (either
vegan, lacto-ovo vegetarian, or neither) and cholesterol levels, where subjects will not
be randomized to a dietary group.
a. Is this an experimental or observational study? Motivate your answer briefly. (1p)
b. Suggest two potential confounders for which the study should be controlled.
Explain briefly what makes them confounders.
(3p)
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
Advanced questions:
I. i) A group of Swedish researchers has reported 19 different rodent
carcinogens in coffee, and shown that high intake of black coffee
caused ventricular cancer in mice. This caused headlines in the
Swedish tabloids.
You have decided to initiate a follow-up study to examine how this
translates to humans. The design is a case-control study where you
recruited cases from the cancer registry and chose random controls
matched on age and sex from the general population. The data is
collected with questionnaires.
Below, you see the results of the study. Since age is a strong risk
factor for all cancers, results and analysis are stratified by age (below
or above age 65).
Individuals <65 years
Daily intake of black Not daily intake of
coffee
black coffee
Cases
Controls
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Individuals >=65 years
Daily intake of black Not daily intake of
coffee
black coffee
180
135
220
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a. What would be a suitable measure of disease? (1p)
b. Calculate this measure in each age group, and for the whole study
population. (3p)
c. Interpret your results. (2p)
180
90
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ii) A colleague working in the same lab wants to compare the effect of
two different COX2 inhibitors on the proliferation rate of a
retinoblastoma cell line. In order to convince her skeptical
supervisor, she wants to conduct a statistical power analysis, and
asks for your help. Below, you see the settings she has chosen in a
suitable software package:
a. Describe the experiment that she has planned, including the type of analysis. (2p)
b. How big is her chance to get a significant result with this experiment?
(1p)
c. How can she (slightly) increase the power of the experiment
without changing the number of cell lines? (1p)
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a) II. This year’s Nobel prize in Physiology and Medicine was
awarded for the discovery of telomers and telomerase.
i.
Please describe an important process that is regulated by
telomers and telomerase, and also provide a reasonable
speculation on why evolution has developed the process
regulated by telomers and telomerase. (5p)
ii. Please hypothesize on the potential future use of the knowledge on
telomere biology in the management of cancer patients, and also
suggest and motivate a specific way to develop a novel anti-cancer
drug based on this knowledge. (8p)
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III. A deregulated cell cycle is thought to be a hallmark of cancer
cells.
i. Please describe the cell cycle machinery in a quiescent cell, and how
this is altered as the cell enters and traverses the G1-phase of the cell
cycle. (8p)
ii.
An over-expression of the onco-protein cyclin E is
frequently observed in many tumor types. Please discuss
possible mechanisms for such an over-expression. Please
also explain how you can define the specific mechanism
in a tumor cell line system. (6p)
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IV. ”Classification is the language of medicine.”
In the present lymphoma classification, ”WHO classification of
tumours of haematopoietic and lymphoid tissues”, are the diagnosis
based upon four different types of information.
a) Which four types of information? (2p)
b) Why is it so important to classify lymphomas in this way? (2p)
c) In most cases it is not possible for the physician to explain why the
patient got the lymphoma. But in some cases does the patient have a
clear risk factor. Mention two different types of major risk-factors
for lymphoma development, and suggest why they are risk factors.
(2p)
Follicular lymphoma (FL) and Burkitt’s lymphoma (BL) are
examples of lymphomas with different chromosomal aberrations,
biology, clinical picture and treatment.
Typical chromosomal aberrations in these diseases are t(14;18) in FL
and t(8;14) in BL.
Based on this information, please reflect upon:
d) The consequence of each aberration for; the affected lymphocytes,
the clinical picture, treatment strategy and treatment outcome. (8p)
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