BIO 309 Midterm III

How long post-in vitro fertilization is the blastocysts used to make human ES cells?

4-5 Days

For each of the following genes involved in regulation of cell growth through the mTOR pathway, indicate whether the gene is activated (A) or inactivated (I) in cancer cells compared to normal healthy cells. Your answer would be a four-letter string composed of letters A and I only, e.g. AAAA. ( ) mTOR ( ) Akt ( ) PTEN ( ) PI3K

AAIA

_____________ are responsible for tissue repair and regeneration.

Adult Stem Cells

Which of these statements is false -The field of pluripotent stem cells began with cancer -Stem cells have similar properties to cancer cells -Adult stem cells are by definition safe

Adult stem cells are by definition safe

Loss of the gene encoding shugoshin in many multicellular organisms leads to sterility, suggesting defects in meiosis. What would you expect to occur in meiotic cells lacking shugoshin?

All chromatids separate prematurely in anaphase I.

The Rb gene in retinoblastomas is similar to the Apc gene in polyposis colon carcinomas in that both genes ...

All of the above

What defines stem cells?

All of the above

Which of the following can lead to p53 stabilization and activation?

All of the above

Which of the following events contributes to driving the mammalian cell past the restriction point of the cell cycle?

All of the above

Which of the following proteins activates the mitochondrial pathway of apoptosis?

All of the above

Mutation in which of the following genes is most prevalent in human colorectal cancer cells?

Apc

Compared to cells of a normal tissue, which of the following occurs less frequently in cells within a solid tumor?

Apoptosis

The Ames test is used to test the mutagenicity of a compound suspected to be a carcinogen. In a simple form of the test, the carcinogen is first mixed with a rat liver extract. A disc of filter paper is soaked with this mixture and placed on a culture of a strain of Salmonella typhimurium that is defective in a gene involved in the synthesis of histidine, an amino acid that is essential for cell growth and proliferation. The strain is thus normally unable to grow into visible colonies when the histidine in the culture medium is depleted. In the presence of a mutagen, however, mutations (often "reverse mutations" in the same gene) can enable the bacteria to produce histidine on their own, and therefore grow into colonies. The results of the Ames test for three compounds A, B, and C—each used at the same concentration—are shown in the schematic diagram below. Colonies are indicated with black dots, and the disc is indicated with a white circle at the center of each plate. Which compound (A to C) appears to be a stronger mutagen in this assay? Write down A, B, or C as your answer.

B

The microtubule-binding protein Patronin binds to the minus ends of microtubules at the spindle pole and protects them from the effect of catastrophe factors. If Patronin activity is inhibited by injecting an anti-Patronin antibody into Drosophila melanogaster embryos prior to cellularization, anaphase B is suppressed and the spindles are significantly shorter. Which of the forces (1 or 2) in the following schematic diagram do you think is mostly responsible for anaphase B in this organism at this stage? Does the effect of Patronin inhibition resemble that of kinesin-5 inhibition (I) or overactivation (O)? A. 1; I B. 1; O C. 2; I D. 2; O

B

Which of the molecules (A or B) in the following drawing is a more potent mutagen? Write down A or B as your answer

B

The Bcl2 family is comprised of anti-apoptotic (A), BH3-only (B), and effector (E) proteins. In the following diagram representing the regulation of the intrinsic pathway of apoptosis, what class of activated Bcl2 family proteins (A, B, or E) corresponds to boxes 1 to 3, respectively? Your answer would be a three-letter string composed of letters A, B, and E only, e.g. ABE.

BAE

In the following schematic diagram of a typical eukaryotic cell cycle, choose two major time points (among A to E) at which the cell-cycle control system normally arrests the cycle if DNA damage is detected. Your answer would be a two-letter string composed of letters A to E only in alphabetical order, e.g. CE.

BC

The following simplified diagram shows the typical sequence of genetic changes in a developing colorectal carcinoma. Indicate which event (A to C) corresponds to the following changes. Your answer would be a three-letter string composed of letters A to C only, e.g. CAB. ( ) Activation of K-Ras ( ) Loss of p53 ( ) Loss of Apc

BCA

PARP inhibitors can efficiently kill many breast cancer cells that lack functional Brca1 or Brca2 genes. How do these drugs accomplish this?

By inhibiting a DNA repair pathway

Indicate whether each of the following cancers can be best classified as a carcinoma (C), sarcoma (S), or neither of the two (N). Your answer would be a four-letter string composed of letters C, S, and N only, e.g. SSNC. ( ) Breast cancer ( ) Lung cancer ( ) Colorectal cancer ( ) Myeloma

CCCN

Indicate whether each of the following descriptions better applies to a cancer cell (C) or a normal adult cell (N). Your answer would be a four-letter string composed of letters C and N only, e.g. CCNC. ( ) Higher lactate production ( ) Higher oxidative phosphorylation ( ) Contact inhibition ( ) Anchorage independence

CNNC

What is the most accurate statement about human pluripotent cells?

Can make all types of human cells except extraembryonic tissues

A benign neoplasia of cartilage is called a

Chondroma

Stem cells can __________.

Divide and Differentiate

You are studying the rising incidence of a certain subtype of cervical cancer in Oceania, and are curious to know whether environmental factors are the dominant cause of the disease. You collect the incidence statistics from indigenous populations as well as from two different immigrant populations in three different countries, as shown in the following table. Do these data appear to be consistent with a dominant role of environmental risk factors (E) or a genetic background (G) for this type of cancer? Write down E or G as your answer.

E

Which of the following proteins is NOT encoded by a proto-oncogene?

E-cadherin

Which of the following sequential barriers to metastasis is the easiest to overcome for cancer cells in general?

Exit from the blood into a remote tissue or organ

Indicate true (T) and false (F) statements below regarding cytokinesis in animal cells. Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF. ( ) The force for cytokinesis is generated by kinesin motors on microtubule bundles that form the contractile ring. ( ) As the contractile ring constricts, its thickness increases to keep a constant volume. ( ) The midbody forms from bundles of actin and myosin II. ( ) Local activation of Ran GTPase triggers the assembly and contraction of the contractile ring.

FFFF

Indicate true (T) and false (F) statements below regarding cancer. Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF. ( ) Cancers become less and less heterogeneous as they progress. ( ) Knocking out Ras or Myc genes individually leads to a higher incidence of cancers in mice, and knocking out both genes simultaneously has an even stronger phenotype. ( ) Wnt signaling is important in colon epithelial cells and, correspondingly, mutations in genes in the Wnt pathway are present in most colorectal cancers. ( ) Genome destabilization in a subset of colorectal cancers that have defects in DNA mismatch repair takes the form of chromosome breaks, translocations, and deletions.

FFTF

Indicate true (T) and false (F) statements below regarding cell proliferation in human somatic cancer cells. Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF. ( ) Cancer cells show replicative cell senescence. ( ) Cancer cells maintain their telomeres by inhibiting the enzyme telomerase. ( ) Some cancer cells do not rely on telomerase for telomere lengthening. ( ) Most cancer cells lack telomeres.

FFTF

Indicate true (T) and false (F) statements below regarding the mutational landscape of cancer cells. Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF. ( ) In each cancer, usually there is one driver mutation and a large number of passenger mutations. ( ) It is estimated that about 20% of our genes are cancer-critical. ( ) Cancer-critical genes can encode metabolic enzymes or components of the RNA splicing machinery. ( ) The karyotype is often severely disordered in cancer cells.

FFTT

Indicate true (T) and false (F) statements below regarding programmed cell death by apoptosis. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF. ( ) Apoptosis is the final fate of almost all cells in an adult animal. ( ) Even perfectly healthy cells may undergo apoptosis. ( ) DNA damage that cannot be repaired inhibits apoptotic pathways. ( ) Apoptosis is the main form of programmed cell death in plant cells as well as in animal cells.

FTFF

Indicate true (T) and false (F) statements below regarding colorectal cancers. Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF. ( ) Observation of polyps in the colon epithelium of a patient is an indication of a malignant carcinoma. ( ) Progression of colorectal cancer is very slow and normally takes over 10 years to turn into malignancy. ( ) Colorectal cancers are usually diagnosed later in life. ( ) Invasive colorectal cancer cells usually metastasize to lymph nodes via lymphatic vessels and then into the bloodstream.

FTTT

Pluripotent stem cells can form extra-embryonic tissue

False

Which of the following cell populations in our body has the highest mitotic index?

Fibroblasts

Mammalian Cdk inhibitor proteins (CKIs) can be grouped into two families based on their structural and functional differences. The Cip/Kip family proteins (e.g. p21) have a broad binding specificity. These proteins bind preferentially to already formed cyclin-Cdk complexes and thus enhance complex formation. However, they inhibit the kinase activity of most complexes (e.g. S-Cdks), except in the case of G1-Cdk complexes where no inhibition occurs. Consequently, Cip/Kip family proteins have an overall positive effect on Cdk4/6 activity due to their help in bringing the subunits together. In contrast, the inhibitors of the INK4 family (e.g. p16) bind only to the Cdk subunit of G1-Cdks and prevent binding of both the G1 cyclins and the Cip/Kip family CKIs. Based solely on these findings, would you expect p16 to activate (A) or inactivate (I) the S-Cdks in the presence of limited amounts of p21?

I

For each of the following proteins that are proteolytically cleaved in apoptosis, indicate whether the cleavage is first carried out by an initiator (I) or executioner (E) caspase. Your answer would be a five-letter string composed of letters I and E only, e.g. EEEII. ( ) The initiator caspase-2 ( ) The executioner caspase-3 ( ) The BH3-only protein Bid ( ) The endonuclease inhibitor iCAD ( ) The nuclear protein Lamin A

IIIEE

Indicate whether each of the following mutations would likely promote (P) or inhibit (I) apoptosis in cells harboring the mutation(s). Your answer would be a four-letter string composed of letters P and I only, e.g. PPPI. ( ) Mutations in the pro-apoptotic effector Bcl2 family proteins Bax and Bak that prevent their association with the outer mitochondrial membrane. ( ) A mutation in the BIR domain of the IAP protein DIAP1 that prevents binding to either caspases or anti-IAP proteins. ( ) A mutation in the anti-IAP protein Reaper that prevents its binding to the IAP proteins. ( ) A mutation in the CARD domain of caspase-9 that prevents its binding to Apaf1.

IPII

Indicate whether each of the following descriptions better applies to trastuzumab (T) which targets Her2, imatinib (I) which targets Bcr-Abl, or ipilimumab (P) which targets the CTLA4 protein. Your answer would be a three-letter string composed of letters T, I, and P only, e.g. TTP. ( ) It is NOT an antibody. ( ) It counters the immunosuppressive microenvironment of tumors. ( ) It does not bind to a cancer cell component.

IPP

Once the molecular aberrations in a cancer are understood, drugs can be designed with a rational approach to treat the cancer. Which of the following is NOT true regarding such drugs?

Imatinib is most effective in treating chronic myelogenous leukemia (CML) in its acute blast-crisis phase.

You have synchronized a culture of HeLa cells so that the cells are all at the same stage in the cell cycle. You then treat the cells with serum containing nutrients and growth factors in the presence or absence of the drug rapamycin. The distribution of cell sizes in the two cell populations is shown below. Based on these results, do you think rapamycin is an activator or inhibitor of the TOR complex? Is the S6 kinase expected to be up-regulated or down-regulated in the presence of rapamycin?

Inhibitor; down-regulated

Specifically which cells are harvested from the early embryo?

Inner Cell Mass

_______________ is used to generate embryonic stem cells.

Inner Cell Mass

v-FLIPs are viral proteins that were first identified as modulators of apoptosis; they contain two death effector domains, which are also found in some initiator caspases such as procaspase-8. These v-FLIP proteins can be recruited to the DISC through the binding of the death effector domain to similar domains in the adaptor proteins, but are otherwise catalytically inactive. What do you think is the effect of v-FLIP expression in the host cell?

It inhibits the extrinsic pathway of apoptosis.

Mutations in two important cancer-critical genes, encoding p53 and Rb, respectively, are commonly found in cancers. What type of mutations are these expected to be

Loss-of-function mutations in both genes

Among the following cancers, one is currently leading to the most number of deaths in the United States and in the rest of the world. In the United States, it contributes to cancer mortality more than the next three killing cancers combined. Worldwide, it claims more than 1.5 million lives every year. Which cancer is this?

Lung Cancer

Indicate whether each of the following descriptions better applies to mitogens (M), growth factors (G), or survival factors (S). Your answer would be a four-letter string composed of letters M, G, or S only, e.g. GMSG. ( ) They unblock cell-cycle progression ( ) They suppress apoptosis ( ) They trigger a wave of G1/S-Cdk activity ( ) They inhibit the degradation of cellular macromolecules

MSMG

Bone marrow stem cells are _____________stem cells that can differentiate into either the myeloid or lymphoid cells that become the blood vessels.

Multipotent

Suppose you are studying tumor heterogeneity in a certain type of melanoma. You have used fluorescence-activated cell sorting (FACS) to specifically isolate those melanoma tumor cells that either do (first category) or do not (second category) express a specific marker present in normal stem cells in the tissue of origin (i.e. the melanocyte stem cells). You implant the same number of cells from each of these categories into severely immunodeficient mice and compare the tumor-formation efficiencies after several weeks, which turn out to be significantly higher for the first category. You then analyze the new tumors using FACS, and find out that the majority of the cells in the tumors that originated from the first category of cells harbor the stem-cell marker, whereas the majority of the cells in the tumors that originated from the second cell category lack the marker, just like their respective founder cells. Do these observations support the existence of cancer stem cells? Write down Yes or No as your answer.

NO

Embryonic stem cells can become

Nearly any type of cell in the body

What are the near term clinical applications of stem cells?

Only A and B

The immortalized non-malignant mouse cell line NIH-3T3 was derived from normal mouse fibroblasts in the early 1960s. These cells are able to readily take up exogenous DNA and are prone to transformation by cancer-causing agents, including some retroviruses. DNA extracted from a human bladder carcinoma line is able to transform these cells, as judged by a significant increase in the number of foci (cell clumps) in the cell-culture plates when the DNA is added. The malignant cells contain human DNA, and the DNA can be shown by sequence analysis to contain a single mutant gene that is present in the original bladder carcinoma cell line. The gene codes for a monomeric G protein and was one of the first cancer-critical genes to be identified in this way. The protein encoded by this gene is

Ras

Retinoblastoma is an early-onset cancer of the retina with a rapid progression, and is mostly diagnosed in children. In its hereditary form, multiple eye tumors usually arise in both eyes, while the nonhereditary form usually causes fewer tumors in only one eye. Treatment may involve a combination of chemotherapy, radiotherapy, and other therapies and the majority of patients can be cured if given the right treatment. However, survivors of one form of retinoblastoma (and not the other form) have a markedly increased frequency of subsequent neoplasms that can lead to other cancers later in life, especially soft-tissue sarcomas. These patients should therefore be closely monitored throughout their lives. Which gene is affected by the primary driver mutation in this cancer as well as the later sarcomas? Which form of retinoblastoma do you think is associated with a higher risk of subsequent neoplasms?

Rb; hereditary

Dolly was created by ___________

Reproductive cloning

Which of the following is estimated to be the leading cause of death from cancer in the United States?

Smoking

What does the acronym SCNT stand for?

Somatic cell nuclear transfer

The homologous chromosome pairs in our cells do not carry identical sequences in all loci. This heterozygosity (difference between the two copies) can be altered in cancer: in fact, loss of heterozygosity at many loci is observed in cancer cells, through an increase in either homozygosity (two identical copies) or hemizygosity (i.e. loss of one copy). Researchers can take advantage of this loss of heterozygosity in cancer cells to identify genomic loci that contain cancer-critical genes. What type of gene would you expect to find in chromosomal regions with a loss of heterozygosity? Proto-oncogenes (P) or tumor suppressor genes (T)? Write down P or T as your answer.

T

Indicate true (T) and false (F) statements below regarding apoptosis in disease. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF. ( ) Either excessive or insufficient apoptosis can contribute to disease. ( ) Excessive apoptosis, in many cases, leads to autoimmune disease and cancer. ( ) In about half of human cancers, the tumor suppressor protein p53 is mutated. ( ) Drugs that interfere with the function of Bcl2 family proteins such as Bax and Bak may treat cancers by stimulating apoptosis.

TFTF

Indicate true (T) and false (F) statements below regarding cancer incidence and cancer prevention. Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF. ( ) Over half of all cancers are preventable by lifestyle changes. ( ) The age-adjusted cancer death rates have increased steadily since 1900, mostly due to the industrial way of life. ( ) Currently, more than half of all cancer patients survive at least five years post-diagnosis. ( ) About half of all cancers are thought to arise by infection with viruses, bacteria, or parasites.

TFTF

Indicate true (T) and false (F) statements below regarding the properties of cancer cells. Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF. ( ) Cancer cells invade and colonize territories that normally belong to other cells. ( ) Unlike in normal tissues, cell death is extremely rare in tumors. ( ) Cancer cells grow and proliferate in defiance of normal restraints. ( ) Malignant tumors are composed of cells that grow and proliferate, but still have not acquired invasiveness.

TFTF

Indicate whether each of the following descriptions better applies to proto-oncogenes (P) or tumor suppressor genes (T). Your answer would be a four-letter string composed of letters P and T only, e.g. PPPT. ( ) Cancer mutations in these genes are usually recessive. ( ) Cancer mutations in these genes include gene duplications. ( ) Cancer mutations in these genes are responsible for most hereditary cancers. ( ) Cancer mutations in these genes are commonly in the form of nonsense (truncating) mutations that abort protein synthesis.

TPTT

Indicate true (T) and false (F) statements below regarding cancer. Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF. ( ) Cancer can be induced by infectious agents such as viruses. ( ) The earlier a cancer is diagnosed, the better the chances are for a cure. ( ) Most cancers originate from a single aberrant cell. ( ) A single mutation is NOT enough to turn a normal cell into a cancer cell.

TTTT

Apoptotic cells are efficiently phagocytosed by neighboring cells or macrophages. Which of the following DOES NOT normally happen in this process?

The apoptotic cell releases some of its cytoplasmic content to induce a local inflammatory response.

Which of the following morphological changes is NOT typically seen in a cell that is undergoing apoptosis?

The cell swells.

What is the Niche?

The home of stem cells

Which of the following is false about human embryonic stem cells? -They can only be made from human embryos -Their production must destroy a human embryo -They are most often derived from material produced in a lab that would otherwise be most often be medical waste -Adult human stem cells were discovered decades before human ES cells

Their production must destroy a human embryo

Which of the following is true of embryonic stem cells but not of adult stem cells?

They can give rise to all cell types in the organism

What is so special about stem cells?

They can make other types of cells

What is the scientific challenge in developing a new therapy based upon embryonic stem cell replacement?

Tissue rejection and tumor formation

Adult stem cells can become only a particular type of cell

True

Autologous stem cells are derived from patient's own body or his or her cord blood.

True

Cell therapy can be compared to transplanting cells instead of organs

True

There is no ethical problem in using adult stem cells for therapy.

True

iPSCs are made in laboratory turning somatic cells into stem cells to differentiate.

True

Somatic cell nuclear transplant uses material from a (n) _________ cell.

Wrong (Not embryonic or surrogate )

Formin nucleates the growth of parallel actin bundles in the cell. Additionally, myosin motor activity is positively regulated by phosphorylation. The monomeric G protein RhoA is important in cytokinesis, because it directly or indirectly

activates formins and inactivates myosin light-chain phosphatase

What is the name of early embryo at 5-6 days?

blastocyst

Carcinoma of the uterine cervix in humans

can be largely prevented by vaccination.

Embryonic stem cells to specialized cell types in the adult involves

cell differentation

Fill in the blank: In the intrinsic pathway of apoptosis, a protein called ... is released from the mitochondria into the cytosol and binds to the adaptor protein Apaf1, causing it to oligomerize into a wheel-like assembly called an apoptosome, which then recruits initiator caspase-9 proteins.

cytochrome c

Carcinoma cells that have acquired malignancy and started local invasiveness to begin metastasis ...

decrease the expression of E-cadherin and undergo epithelial-mesenchymal transition.

How does the potency change as cells become more specialized?

decreases

What is an argument in favor of using embryonic stem cells over adult stem cells?

embryonic stem cells can differentiate into many more types of cells

Stem cell treatments are risk-free if they come from your own body

false

Adult cells altered to become pluripotent stem cells called:

iPS

Eggs are retrieved from ovary and fertilized in a dish embryos are introduced into the uterus by process called:

in vitro fertilization

What cells produced by therapeutic cloning are used to culture new tissue?

inner cell mass

The cell cycle can be arrested in mitosis when a single sister-chromatid pair is mono-oriented on the mitotic spindle. If at this point a glass microneedle is used to pull the mono-oriented chromosome toward the pole to which it is not attached, the cell proceeds to anaphase. This observation confirms that

lack of mechanical tension at the kinetochore in at least one chromosome prevents entry into anaphase

What is the potency of adult stem cells?

multipotent

Most DNA tumor viruses inhibit the products of

p53 and Rb

The effect of the deletion of one copy of the gene encoding p53 is different from the effects caused by other p53 mutations. For example, some loss-of-function mutations in the DNA-binding domain of p53 cripple its function as a transcription regulator. Such a mutation in only one copy of the p53 gene can be enough to confer a p53 loss-of-function phenotype, even when the other copy of the gene on the homologous chromosome is wild type. This is because ...

p53 forms a tetramer.

What is the potency of embryonic stem cells?

pluripotent

____________ stem cells differentiates into cells from any of the three germ layers?

pluripotent

Genetically knocking out both copies of the p53 gene in rats

results in a higher rate of cancer onset, but the rats are otherwise seemingly normal.

Initiator and executioner caspases share all of the following features EXCEPT that

their inactive form is a monomer

What is a disadvantage of adult stem cells over embryonic stem cells?

they are difficult to locate

According to the cancer stem-cell model for tumor growth and propagation

transit amplifying cells constitute the great majority of the cells in the tumor.

Cells which can produce only one cell type - but are still capable of self-renewal are:

unipotent

What is the most common source of embryo for stem cell harvest?

unused embryos from fertility clinics

Stem cell obtained from different species are called:

xenogenic