MedCosmos Surgery
Surgery Lecture Notes, Books, MCQ and Good Articles
Friday, September 5, 2008
Oncology MCQ
1. Cytotoxic T cells (CTL) are capable of recognizing:
A. Peptide antigens associated with major histocompatibility complex
(MHC) molecules.
B. Membrane-bound antigens.
C. Cytoplasmic antigens.
D. Nuclear antigens.
E. All of the above.
Answer: E
DISCUSSION: It was long thought that CTL recognize antigen
expressed on the surface of the target cell destined to be killed,
similar to the recognition of an antigen by an antibody; however, it
was found that the mechanism of CTL recognition of antigens was
fundamentally different from the mechanism of antibody recognition.
CTL can detect antigens derived from cell surface–associated proteins,
but in addition can recognize proteins that are normally in the
cytoplasm or in the nucleus. In fact, the normal location of the protein
can be anywhere within the cell.
To understand how a CTL can distinguish an antigen from a protein
that is normally located within the cytoplasm or nucleus of the cell,
investigators had to determine exactly what was being recognized by
the CTL. T cells were found to recognize short linear fragments of
processed or even denatured protein. It was found that proteins that
were synthesized endogenously were degraded within the cytoplasm
into 9– or 10–amino acid long peptides. These peptides were then
transported to the endocytoplasmic reticulum and associated with
newly synthesized MHC class I molecules. Certain peptides could fit
within the MHC class I molecule and were then transported to the cell
surface as a complex. It was this complex, consisting of a 9– to
10–amino acid peptide within a MHC class I molecule that was
presented to, and recognized by, CD8+ CTL.
2. Adoptive immunotherapy with lymphokine activated killer cells
,(LAK) and tumor infiltrate (TIL) cells are characterized by:
A. Nonspecific stimulation of effector cells.
B. Expansion ex vivo of large numbers of lymphocytes.
C. Infusion with interleukin 2 (IL-2).
D. Significant toxicity at high doses.
E. All of the above.
Answer: E
DISCUSSION: LAK cells, generated by short-term culture of peripheral
blood lymphocytes in the presence of high concentrations of IL-2, lyse
transformed target cells, and have minimal lytic activity for most
normal tissues. Up to 10 11 in vitro generated LAK cells have been
administered in a single intravenous infusion to cancer patients.
Therapeutic trials have also combined short courses of high-dose
systemic IL-2 administration with LAK cell transfer to promote LAK
function and viability, with apparently enhanced efficacy. The
shortcomings of LAK and IL-2 therapy included a larger degree of
toxicity (including pulmonary, renal, and hepatobiliary) with a
significant proportion of patients requiring intensive care unit
admissions and 2% to 5% treatment-related mortality. Despite this,
response rate remained relatively low.
Another therapy using in vitro expanded lymphocytes derived from a
TIL has been evaluated in clinical trials. In humans, TIL cell lines have
been generated by mincing tumor specimens and culturing eluted
lymphocytes with high concentrations of IL-2. TIL lines can be
expanded to 10 8 to 10 11 cells over 3 to 8 weeks in culture, and some
lines appear to function as T cells with lytic specificity for
autologous—but not allogeneic—tumor targets, whereas others
function as LAK cells and lyse both autologous and allogeneic tumor
targets. Adoptive transfer of 5 × 10 10 TIL alone has not been
associated with significant toxicity, and administration of 5 × 10 10 TIL
cells with concurrent systemic IL-2 has caused toxicities that are
attributable to the IL-2.
3. Previous clinical studies with cancer vaccines have:
A. Clearly demonstrated induction of tumor-specific immune
response.
B. Repeatedly demonstrated clinical response to large tumor burden.
C. Not clearly demonstrated induction of tumor-specific immune
response.
D. Not been performed to date.
Answer: C
DISCUSSION: Several different approaches in experimental animal
studies in the 1970s formed the basis for human clinical trials of SAI
against human cancers. Although several thousand patients have
, been injected with a variety of tumor cell preparations in this country
and elsewhere during the past 25 years, the complexity of the studies
has made it difficult to definitively assess the value of this approach to
cancer therapy. Nonetheless, a number of clinical trials have
suggested a therapeutic benefit of SAI. Most of these trials have two
features in common: (1) a therapeutic effect was not seen or, if seen,
has not been confirmed independently; and (2) no acceptable
information was provided on the presence of tumor antigens in the
vaccines and the immune response of patients to these antigens.
4. Which of the following statements is/are true of the epidemiology
and etiology of melanoma?
A. Most patients are diagnosed after age 60 years.
B. Skin color has no association with risk of melanoma.
C. Sun exposure is the only risk factor for melanoma.
D. The per capita incidence of melanoma is highest in Australia.
Answer: D
DISCUSSION: The median age at diagnosis is in the late forties; so, a
minority of patients are diagnosed after age 60. The risk of melanoma
is closely tied to skin color: Caucasians are at highest risk, and those
with a Celtic complexion at even higher risk. Australia has a large
Celtic population living near the equator, and it has the highest per
capita incidence of melanoma in the world. Sun exposure is believed
to be an important cause of melanoma, but the data remain
incomplete. Some melanomas arise in sites not exposed to the sun
(e.g., mucous membranes), so sun exposure is not the only risk factor.
5. Which of the following variables best predicts prognosis for patients
with a recent diagnosis of cutaneous melanoma and no clinical
evidence of metastatic disease?
A. Breslow thickness.
B. Clark's level.
C. Ulceration.
D. Gender.
E. Celtic complexion.
Answer: A
DISCUSSION: The prognosis for melanoma is best predicted by the
thickness, measured in millimeters (Breslow thickness). Clark's level
and ulceration are also predictive, but less so. Gender is a secondary
prognostic factor. Skin color may have a mild impact on outcome, but
it is primarily a risk factor for developing melanoma.
Surgery Lecture Notes, Books, MCQ and Good Articles
Friday, September 5, 2008
Oncology MCQ
1. Cytotoxic T cells (CTL) are capable of recognizing:
A. Peptide antigens associated with major histocompatibility complex
(MHC) molecules.
B. Membrane-bound antigens.
C. Cytoplasmic antigens.
D. Nuclear antigens.
E. All of the above.
Answer: E
DISCUSSION: It was long thought that CTL recognize antigen
expressed on the surface of the target cell destined to be killed,
similar to the recognition of an antigen by an antibody; however, it
was found that the mechanism of CTL recognition of antigens was
fundamentally different from the mechanism of antibody recognition.
CTL can detect antigens derived from cell surface–associated proteins,
but in addition can recognize proteins that are normally in the
cytoplasm or in the nucleus. In fact, the normal location of the protein
can be anywhere within the cell.
To understand how a CTL can distinguish an antigen from a protein
that is normally located within the cytoplasm or nucleus of the cell,
investigators had to determine exactly what was being recognized by
the CTL. T cells were found to recognize short linear fragments of
processed or even denatured protein. It was found that proteins that
were synthesized endogenously were degraded within the cytoplasm
into 9– or 10–amino acid long peptides. These peptides were then
transported to the endocytoplasmic reticulum and associated with
newly synthesized MHC class I molecules. Certain peptides could fit
within the MHC class I molecule and were then transported to the cell
surface as a complex. It was this complex, consisting of a 9– to
10–amino acid peptide within a MHC class I molecule that was
presented to, and recognized by, CD8+ CTL.
2. Adoptive immunotherapy with lymphokine activated killer cells
,(LAK) and tumor infiltrate (TIL) cells are characterized by:
A. Nonspecific stimulation of effector cells.
B. Expansion ex vivo of large numbers of lymphocytes.
C. Infusion with interleukin 2 (IL-2).
D. Significant toxicity at high doses.
E. All of the above.
Answer: E
DISCUSSION: LAK cells, generated by short-term culture of peripheral
blood lymphocytes in the presence of high concentrations of IL-2, lyse
transformed target cells, and have minimal lytic activity for most
normal tissues. Up to 10 11 in vitro generated LAK cells have been
administered in a single intravenous infusion to cancer patients.
Therapeutic trials have also combined short courses of high-dose
systemic IL-2 administration with LAK cell transfer to promote LAK
function and viability, with apparently enhanced efficacy. The
shortcomings of LAK and IL-2 therapy included a larger degree of
toxicity (including pulmonary, renal, and hepatobiliary) with a
significant proportion of patients requiring intensive care unit
admissions and 2% to 5% treatment-related mortality. Despite this,
response rate remained relatively low.
Another therapy using in vitro expanded lymphocytes derived from a
TIL has been evaluated in clinical trials. In humans, TIL cell lines have
been generated by mincing tumor specimens and culturing eluted
lymphocytes with high concentrations of IL-2. TIL lines can be
expanded to 10 8 to 10 11 cells over 3 to 8 weeks in culture, and some
lines appear to function as T cells with lytic specificity for
autologous—but not allogeneic—tumor targets, whereas others
function as LAK cells and lyse both autologous and allogeneic tumor
targets. Adoptive transfer of 5 × 10 10 TIL alone has not been
associated with significant toxicity, and administration of 5 × 10 10 TIL
cells with concurrent systemic IL-2 has caused toxicities that are
attributable to the IL-2.
3. Previous clinical studies with cancer vaccines have:
A. Clearly demonstrated induction of tumor-specific immune
response.
B. Repeatedly demonstrated clinical response to large tumor burden.
C. Not clearly demonstrated induction of tumor-specific immune
response.
D. Not been performed to date.
Answer: C
DISCUSSION: Several different approaches in experimental animal
studies in the 1970s formed the basis for human clinical trials of SAI
against human cancers. Although several thousand patients have
, been injected with a variety of tumor cell preparations in this country
and elsewhere during the past 25 years, the complexity of the studies
has made it difficult to definitively assess the value of this approach to
cancer therapy. Nonetheless, a number of clinical trials have
suggested a therapeutic benefit of SAI. Most of these trials have two
features in common: (1) a therapeutic effect was not seen or, if seen,
has not been confirmed independently; and (2) no acceptable
information was provided on the presence of tumor antigens in the
vaccines and the immune response of patients to these antigens.
4. Which of the following statements is/are true of the epidemiology
and etiology of melanoma?
A. Most patients are diagnosed after age 60 years.
B. Skin color has no association with risk of melanoma.
C. Sun exposure is the only risk factor for melanoma.
D. The per capita incidence of melanoma is highest in Australia.
Answer: D
DISCUSSION: The median age at diagnosis is in the late forties; so, a
minority of patients are diagnosed after age 60. The risk of melanoma
is closely tied to skin color: Caucasians are at highest risk, and those
with a Celtic complexion at even higher risk. Australia has a large
Celtic population living near the equator, and it has the highest per
capita incidence of melanoma in the world. Sun exposure is believed
to be an important cause of melanoma, but the data remain
incomplete. Some melanomas arise in sites not exposed to the sun
(e.g., mucous membranes), so sun exposure is not the only risk factor.
5. Which of the following variables best predicts prognosis for patients
with a recent diagnosis of cutaneous melanoma and no clinical
evidence of metastatic disease?
A. Breslow thickness.
B. Clark's level.
C. Ulceration.
D. Gender.
E. Celtic complexion.
Answer: A
DISCUSSION: The prognosis for melanoma is best predicted by the
thickness, measured in millimeters (Breslow thickness). Clark's level
and ulceration are also predictive, but less so. Gender is a secondary
prognostic factor. Skin color may have a mild impact on outcome, but
it is primarily a risk factor for developing melanoma.
