Oncology Flashcards
1
Q
CRITERIA SUGGESTIVE OF HEREDITARY CANCER
A
- Tumor development at a much younger age than usual 2. Presence of bilateral disease 3. Presence of multiple primary malignancies 4. Presentation of a cancer in less than affected sex. 5. Clustering of the same cancer type in relatives 6. Cancer associated with other conditions such as mental retardation and pathognomic skin lesion
1
Q
the gene mutated in multiple advanced cancers 1
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PTEN
1
Q
Metastases diagnosed at the initial cancer diagnosis
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SYNCHRONOUS METASTASES
2
Q
Activating mutations in BRAF causes:
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Melanoma Sporadic colorectal cancer Papillary thyroid cancer
3
Q
angiogenic oncogenes and tumor-suppressor genes
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Ras Myc HER2/ neu p53
3
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viral DNA can be integrated into the cellular chromosomal DNA, leading to transformation of cells to a neoplastic state
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Non Permissive Host
4
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Breast self-examination
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Monthly, starting at age 20
5
Q
Cells present in the blood that possess antigenic or genetic characteristics of a specific tumor type
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CA – CIRCULATING TUMOR CELLS
6
Q
PTEN ((phosphatase and tensin homologue)
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Cowden Disease (multiple hamartoma syndrome)
6
Q
Encodes for the human homologue of the yeast Cds1 and the RAD53 G2 checkpoint, whose activation by DNA damage prevents entry into mitosis
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hCHK2 gene
6
Q
Disappearance of disease and no evidence of new for a specified interval of 4 weeks
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Complete response
7
Q
Is a tumor related antigen that is elevated in colon and pancreatic ca; Measured at the start of therapy and every 1-3 mos while under treatment
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CA 19-9
8
Q
Step in Tumorigenesis that may lead a single cell to acquire a distinct growth advantage
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Initiation
8
Q
2 types of oncogenes
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Growth Factors Growth Factor Receptors
8
Q
other names for gene p16
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INK4A, CDKN1, CDKN2A, and MTS1
8
Q
3 groups of chemical carcinogens
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- Genotoxins 2. Co-carcinogens 3. Tumor promoters
8
Q
irradiated cells secrete cytokines and other factors that increase production of reactive oxygen species in bystander cells, may involve cell to cell communication via gap junction
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“By stander effect”
9
Q
Tumor cell-cycle regulators (in human) which are frequently mutated or altered in expression:
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INK4a INK4b KIP1
10
Q
Major cellular pathway for protein and organelle turnover
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Autophagy
11
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Progression step in tumorigenesis
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Repeated promoter application to acquire spontaneous mutation
11
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hereditary predisposition for colorectal cancer with early age of onset and an excess of synchronous and metachronous colonic cancers
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Lynch 1
12
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Tamoxifen
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Endometrial CA
13
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5q Mutation
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FAP (Familial Adenomatous Polyposis)
13
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A genetically regulated program to dispose of cells
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Apoptosis
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What are the types of Adjuvant Therapy?
Chemotherapy Hormonal therapy Immuno-therapy Biologic therapy Radiation Therapy
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What is formed when ligands are bound to the receptors
DISC (Death Inducing Signal Complex)
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50% or more decrease of the original size, determined by two observations (not less than 4 weeks apart); No appearance or progress of new lesion progression of any lesion demonstrated
Partial Response
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Benzene, Chlorambucil
Leukemia
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infection with an oncogenic DNA virus result in a productive lytic infection, leading to cell death and release of newly formed viruses
Permissive Host
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Ubiquitous proteins that are produced and secreted by cells locally which stimulates cell proliferation
Growth factors
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Steps in Tumorigenisis
Initiation Promotion Progression
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Types of Alkylating Agents
1. Classic alkylators 2. Nitrosoureas 3. Miscellaneous DNA-binding agents
20
Two types of epidemiological studies that are done most commonly
Cohort Study Case-control Study
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Glycoprotein encoded by MUC1 gene that tumor cells shed into the blood stream and useful in diagnosis of advanced breast CA
CA15-3
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Antitumor Antibiotic
Bleomycin
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Tumor suppressor that acts by binding CDK4 and CDK6 and inhibiting the catalytic activity of the CDK4-CDK6/cyclin D complex
p16
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CEA (Carcinoembryonic Antigen) is elevated specially in?
colon cancer
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Anti-metabolites
Folate analogues Methotrexate Purine analogues Azathioprine Mercaptopurine Thioguanine Cladibrine (2-chlorodeoxyadenosine) Fludarabine Pentostatin Pyrimidine analogues Capecitabine Cytarabine Floxuridine Gemcitabine Ribonucleotide reductase inhibitors Hydroxyurea
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25% or greater increase in size or appearance of new lesions
Progressive
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Classifications of Biopsy
1. Mucosal biopsy via endoscopic exam 2. Palpable external lesions a. Needle biopsy - Fine needle biopsy - Core needle biopsy 3. Open biopsy (When needle biopsy is questionable) - Incision biopsy - Excision biopsy
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Breast Cancer Global Statistics
2ND LEADING CANCER IN THE WORLD 5th MOST COMMON CAUSE OF CANCER DEATH
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Physical Carcinogens cause cancer either by:
a. Induction of inflammation and cell proliferation b. Exposure induces DNA damages and mutation
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Administration before surgery of tumor considered initially inoperable
preoperative chemotherapy, neoadjuvant chemotherapy, or induction therapy
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hMLH1; hMSH2; hMSH6;PMS1; hPMS2
Hereditary nonpolyposis colorectal cancer
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What is the primary goal of PRIMARY / DEFINITIVE THERAPY?
Local and regional control of cancer
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Block caspase 3 activation
Inhibitors of Apoptosis Proteins (IAPs)
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rb
Retinoblastoma
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Uses of Cancer Staging
1. Selection of therapy – basis for selection of therapy 2. Estimation of prognosis 3. Evaluation of treatments 4. Exchange of information among tx centers 5. Continued investigation of human cancers
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It is detected by staining bone marrow aspirates with monoclonal antibodies to cytokeratin.
Bone marrow Metastases
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Surgical ablation of organs producing the hormones- oophorectomy for breast cancer
Hormonal Therapy
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Not a single cell but rather a large number of cells in a target organ may have undergone the initiating genetic event
Field Theory
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Indications for Chemotherapy
1. Established / documented distant metastatic disease: 2. Therapy given for patient with high risk for distant metastasis known as adjuvant chemotherapy.
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Treatment for breast cancer which work by targeting bcr-abl, c-kit, and HER2/ neu,
Trastuzumab (Herceptin)
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Cells that have the ability to perpetuate themselves through self-renewal and to generate mature cells of a particular tissue through differentiation
Cancer stem cells
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Benzidine
Bladder cancer
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Plant Alkaloids
VInca alkaloids Vinblastine Vincristine Vindesine Vinorelbine Epipodophyllotoxins Etoposide Teniposide Taxanes Paclitaxel Docetaxel
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stimulate hydrolysis of the bound GTP to return RAS to its inactive form
GTPase activating proteins (GAP's)
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Compare a group of patients affected with a disease to a group of individuals without the disease for a given exposure
Case-Conrol Study
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Heat shock proteins
hsp27, hsp70
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Promoters include:
Hormones Growth Factors Cytokines \*Chronic Smoking
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System describing the extent malignancy
Cancer Staging
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Cells exhibit reduced sensitivity to drugs-by virtue of their cell cycle distribution
Kinetic Resistance
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Spread from the primary site and formation of new tumor in distant sites
Metastasis
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Bind to the DISC & inhibit activation of caspase 8
FADD-like interleukin-1 protease-inhibitory proteins (FLIPs)
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hereditary predisposition for colorectal cancer with early age of onset and an excess of synchronous and metachronous colonic cancers and has a high risk for: carcinoma of the endometrium transitional cell carcinoma of the ureter and renal pelvis carcinomas of the stomach, small bowel, ovary, and pancreas
Lynch 2
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Mechanisms of Viral Oncogenes
a. Interfere cell-cycle check points and DNA repair b. Expression of cytokines and other growth factors c. Alteration of immune system
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Hepatocellular carcinoma
Hepatitis B Hepatitis C
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Miscellaneous Agents
Asparaginase Estramustine Mitotane
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3 stages of Adenomas:
Increase size Dysplasia Villous content
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HPV type 16 and 18
Cervical cancer Anal cancer
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Metastasis diagnosed after a disease-free interval
METACHRONOUS METASTASES
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Nitrosoureas
Carmustine (BCNU) Lomustine (CCNU) Semustine (MeCCNU) Streptozocin
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EBV (Epstein Barr Virus)
Burkitt's lymphoma, Hodgkin's disease Immunosuppression-related lymphoma Sinonasal angiocentric, T-cell lymphoma, Nasopharyngeal carcinoma
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3rd most common cause of cancer death
Colorectal Cancer
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if tumor is small, instead of removal of the whole breast, you only remove one quadrant
Conservative surgery
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To induce or potentiate inherent anti-tumor immunity to destroy cancer cells
Immune therapy
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Medullary thyroid carcinoma and pheochromocytoma (in 50%) or parathyroid adenoma (in 20%)
MEN2A
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p53
Li-Fraumeni syndrome
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Potentially best tumor marker available
PSA (Prostate Specific antigen)
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Failure to kill cells is due to insufficient drug concentration occurs when tumor cells are located in sites where effective drug concentrations are difficult to achieve
Pharmacologic Resistance
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The intent is not for cure because of the nature of the disease
Palliative surgery
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Glycoprotein that is ideal for tumor marker
PSA (Prostate Specific antigen)
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Adult T-cell leukemia or lymphoma
Human T-cell lymphotropic viruses
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Follow a group of people who initially do not have a disease over time and measure the rate of development of a disease
Cohort Study
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Metastatic process involves
1. Access to circulation 2. Survival 3. Lodge in new organ 4. Initiate growth 5. Establish vascularization for survival
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aberrations in the apoptotic program in human cancers:
1. Increased expression of -Fas and TRAIL decoy receptors -anti-apoptotic Bcl-2 -IAP-related protein surviving -c-FLIP -growth factors and growth factor receptors activation of the PI3-K/Akt survival pathway 2. Mutations or downregulation of -proapoptotic Bax -caspase-8 -APAF1 -XAF1 -CD95, TRAIL-R1, and TRAIL-R2 (death receptors) 3. Alterations of the p53 pathway
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Pathognomonic features of Cowden disease
Trichilemmomas, benign tumors of the hair follicle infundibulum, and mucocutaneous papillomatosis
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Mammography
Annual, starting at age 40
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Links Ras to activation of protein kinase C and calcium mobilization
Phospholipase C
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Exploits the molecular difference between normal and cancer cells; Directed at the processes involved in tumor growth rather than directly targeting the tumor cells
Biological Therapy
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Neither complete or partial response nor
Minimal or stable response
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PSA (Prostate Specific antigen) sensitive for
prostate cancer benign prostate hypertrophy prostatis
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Miscellaneous DNA-binding agents
Carboplatin Cisplatin Dacarbazinw (DTIC) Hexamethylmelamine Procarbazine
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this cancer has the highest age-adjusted incidence in JAPAN
Stomach/Gastric Cancer
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For large lesion done directly overlie the area to be removed than tunneling.
Incision Biopsy
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five groups of human carcinogens
(1) Proven carcinogens (2A) Probable carcinogens (suggestive epidemiological evidence; no causality evidence and inadequate) basis (2B) Possible carcinogen (3) Not classifiable as to carcinogenicity in human but carcinogenic in animals (4) Probably not carcinogenic humans
70
Tumors that appear to lie exclusively above the basement membrane
In situ Cancer
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Substances detected in higher levels produced either by cancer or body response to cancer can be both prognostic or predictive values
Tumor Markers
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plays an important role in cell-cell interactions, cell adhesion, regulation of β-catenin, and maintenance of cytoskeletal microtubules
APC
71
Beryllium Cadmium
Lung cancer
71
identification of metastases that had formerly been silent and unidentified→stage migration→ perceived improvement in chances of survival
"Will Rogers effect"
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TWO CRITERIA USED TO ASSESS THE EFFICACY OF A SENTINEL LYMPH NODE BIOPSY:
1. Sentinel lymph node identification rate 2. False-negative rate
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Performed using isosulfan blue dye, technetium-labeled sulfur colloid or albumin or a combination of both techniques to detect sentinel nodes which may improve the capability of detecting sentinel lymph nodes
LYMPHATIC MAPPING
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Drive a quiescent cell from G0 into the cell cycle
Mitogenic Growth Factors
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These are closely related to the death receptors but lack a functional death domain
Decoy receptors
76
What are the stimuli for the Mitochondrial Pathway of Apoptosis
o DNA damages o ROS o Withdrawal of survival factors
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Eradication of micrometastatic disease with the intent of decreasing relapse rates and improving survival rates
Adjuvant Therapy (goal)
79
MEN1
Multiple endocrine neoplasia type 1
81
2 of the best studied oncogenes
1. HER2/Neu (c-erb B-2) 2. RAS
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PSA level of \_\_\_\_\_should be used as threshold for performing prostate biopsy
4ng/mL
83
Classic alkylators
Busulfan Chlorambucil Cyclophosphamide Ifosfamide Mechlorethamine (nitrogen mustard) Melphalan Mitomycin Triethylene thiophosphoramide (thiotepa)
85
Downstream pathways activated by RAS-GTP
Serine-Threonine Kinase RAF PI3K RAS-related RAL protein Phospholipase C
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Performed for lesions for which either core biopsy is not possible or the results are nondiagnostic
Open Biopsy
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Stimulate the formation of RAS-GTP (active form)
Guanine nucleotide exchange factors (GEFs)
89
Criteria for classic LFS in an individual (the proband):
a. A bone or soft tissue sarcoma when younger than 45 years b. A first-degree relative with cancer before age 45 years c. First- or second-degree relative with either a sarcoma diagnosed at any age or any cancer diagnosed before age 45 years
90
Attachment to glycoproteins of the ECM such as fibronectin, laminin, and collagen is mediated by
tumor cell integrin receptors
91
A family of proteases (Cysteine-dependent and aspartate-directed proteases) that effects the apoptosis
Caspases
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Sometimes referred to as a second form of programmed cell death
Autophagy
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Normal cellular gene that contributes to cancer when abnormal
Oncogene
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defines the cancer in terms of the anatomic extent of disease and is based on assessment of three components; applies only to tumors that have been microscopically confirmed to be malignant
TNM staging
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Surgeon in Oncology should:
1. be responsible for the initial diagnosis and management of solid tumors 2. have knowledge of cancer epidemiology, etiology, staging and natural history since it is required for initial assessment and determination of optimal surgical therapy
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ADJUVANT THERAPY primary goal
1. Systemic control by treatment of distant foci of subclinical disease 2. Prevent distant recurrence
100
Types of Initiator Caspases:
Caspase 8 Caspase 9 Caspase 10
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Procedure to remove a small area of diseased or problematic tissue with a margin of normal tissue
Excision Biopsy
102
States that lymphadenectomy is important for staging and survival; More extensive lymphadenectomy yielding of nodes reduces the risk of regional recurrence
Traditional Halsted View
102
First node to receive drainage from the tumor site
Sentinel Node
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determines the tumor histology and grade and thus assists in definitive therapeutic planning
Biopsy
105
Process Involved in Invasion
1. Changes in adhesion 2.Initiation of Motility 3. ECM proteolysis
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Global Statistics of Lung Cancer
NO. 1 LEADING CANCER IN THE WORLD NO. 1 MOST COMMON CAUSE OF CANCER DEATH
108
What are the type of activation of the following genes? abl c-myc ras HER-2/neu
abl (Translocation) c-myc (Promoter insertion) ras (Mutation) HER-2/neu (Amplification)
109
Achieved with the help of MMP, proteinases, serine and cysteine and plasminogen activator
ECM proteolysis
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Chemotherapy administered to a patient who is at high risk for distant recurrence but has no evidence of distant disease
Adjuvant Therapy
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generally used to describe molecular markers that predict disease-free survival, disease-specific survival, and overall survival
Prognostic Markers
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Types of Executioner Caspases:
Caspase 3 Caspase 6 Caspase 7
114
Usually is expressed as the number of new cases per 100,000 persons per year
Incidence
115
Another factor limiting optimal killing for drug-sensitive cancers; Dose reduction of 20% because of drug toxicity = decline in the cure rate by as much as 50%
IMPROPER DOSING
117
What are the 6 hallmarks of Cancer?
1. self sufficiency of growth signals 2. Insensitivity to growth-inhibiting growth factors 3. Evasion of apoptosis 4. Potential for limitless replication 5. Angiogenesis 6. Invasion and Metastasis
118
Encodes small GTP-binding proteins that regulate several cellular processes
RAS
120
what are the 2 functions of Heat Shock Proteins in Apoptosis?
1. Blocking formation of the apoptosome complex 2. Inhibiting release of cytochrome c from the mitochondria
122
Revised Criteria for Hereditary Nonpolyposis Colon Cancer (HNPCC) (Amsterdam Criteria II):
3-2-1-0 3 or more relatives with an HNPCC-associated cancer (colorectal cancer, endometrial cancer, cancer of the small bowel, ureter, or renal pelvis), one of whom is a first-degree relative of the other two At least 2 successive generations affected At least 1 case diagnosed before age 50 y Familial adenomatous polyposis excluded (0) Tumors verified by pathologic examination
123
BRCA1,BRCA2
Breast-ovarian syndrome
124
Response to Chemotherapy
Progressive Minimal or stable response Partial Response Complete response
126
Promoters enhance cell replication by:
1. Interacting with self-surface receptors (to effect intracellular pathway) 2. Altering Gene expression
128
4 Phases of Cell cycle
S phase G1,G2 G0 M phase
130
Monitor trends in cancer incidence and mortality
Epidemiological Studies
131
infection of the cell is permanent (DNA or RNA virus)
RNA (Retro virus)
133
hCHK2
Li-Fraumeni syndrome and hereditary breast cancer
135
cell-cycle regulators which suppresses cell-cycle inhibitors like p27
cyclin D1
137
Characteristics of abnormally proliferating cells (5)
1. Loss of contact inhibition 2. Altered Appearance and poor adherence to cells and substartum 3. Loss of Anchorage 4. Immortalization 5. Gain of Tumorigenicity
138
Proportion of patients in whom a sentinel lymph node was identified and removed among all patients undergoing an attempted sentinel lymph node biopsy
Sentinel lymph node identification rate
139
Normal gene that becomes an oncogene due to mutation or increased expression
Proto-Oncogenes
141
2nd most common cause of cancer death
Gastric cancer
142
Affect cell by binding to tubulin S phase Blocks microtubule polymerization impairing mitotic spindle formation M phase. Inhibits enzymes necessary to synthesize DNA.
Plant Alkaloids
143
cancer cells initially grow rapidly (exponential growth phase), then the growth slows down owing to hypoxia and decreased nutrient supply
GOMPERTZIAN MODEL
145
p53 gene is located in?
p arm of Chromosome 17 (17p)
146
Location of the following: HRAS KRAS NRAS
HRAS (Ch 11) KRAS (Ch 12) NRAS (Ch 1)
148
Establishment of new blood vessels from a preexisting vascular bed
Angiogenesis
149
Disadvantage of Fine Needle Biopsy
Cannot differentiate between invasive and noninvasive tumor.
150
this cancer is related mainly to dietary differences in consumption of animal fat, meat, and fiber.
Colorectal Cancer
152
Constitutive activation of RAF is common in some tumors such as:
Non–small cell lung cancer Renal cell carcinoma Hepatocellular cancer
153
Aflatoxins
Liver cancer
154
H. Pylori plays a major role in what cancer development?
Stomach/Gastric Cancer
155
the first breast cancer susceptibility gene identified
BRCA1
156
Primary modality of therapy for distant metastatic disease
Chemotherapy
158
What happens in Heterodimerization with HER2/neu?
Heterodimerization potentiates recycling of receptors rather than degradation
159
Proangiogenic factors
1. VASCULAR ENDOTHELIAL GROWTH FACTORS (VEGF) 2. Platelet Derived Growth Factors (PDGF's) A,B, C, D 3. ANGIOPOIETINS
161
TWO OPPOSING VIEWS REGARDING THE ROLE OF LYMPHADENECTOMY:
1. The traditional Halsted view 2. The opposing view
162
factors responsible for initiating motility
autocrine motility factor autotaxin, scatter factor TGF-α EGF Insulin like GF
164
Components of Apoptosome
Cytochrome c Procaspase 9 Apoptotic protease activating factor 1 (Apaf-1)
165
Medullary thyroid carcinoma, marfanoid habitus, mucosal neuromas, and ganglioneuromatosis
MEN2B
166
Stages of Evaluation of Cancer Patient
1. Cancer risk assessment 2. Cancer screening 3. Diagnosis 4. Cancer staging
167
APC
Familial adenomatous polyposis (FAP)
168
p16;CDK4
Familial melanoma
169
model uses risk factors such as an individual's age, age at menarche, age at first live birth, number of first-degree relatives with breast cancer, number of previous breast biopsies, and whether the biopsy results revealed atypical ductal hyperplasia
GAIL MODEL
170
Treatment for chronic myelogenousleukemia and gastrointestinal stromal tumors
Imitanib Mesylate, Gleevec
172
Hallmark of HNPCC
microsatellite instability - unrepaired mismatches and small insertion or deletion loops
173
CDH1
Hereditary diffuse gastric cancer
174
tumor cells are genetically unstable and tend to mutate to form different cell clones
Goldie-Coldman hypothesis:
175
Best known agent of physical carcinogenesis
Radiation
176
HIV-1
Kaposi's sarcoma Non-Hodgkin's lymphoma
178
Tumors demonstrating ability to breach the basement membrane, penetrating into surrounding stroma
Invasive Cancer
179
En-bloc resection with adequate margins of normal tissues and regional nodes in some cases
PRIMARY / DEFINITIVE THERAPY
181
Autophagy is involved in:
o Starvation o Cellular differentiation o Cell death o Aging
182
cell that has a proliferative advantage by bypassing quiescence stage
Tumor Cell
183
Major groups of targeted therapy
Inhibition of growth factor receptors Intracellular signal transduction Cell cycle inhibitors Apoptosis based therapy Anti angiogenic compounds
185
RET
Multiple endocrine neoplasia type 2
186
SURGICAL GOLD STANDARD
negative surgical margins
187
Defined on the basis of observed clustering of malignancies, including early-onset breast cancer, soft tissue sarcomas, brain tumors, adrenocortical tumors, and leukemia
LI-FRAUMENI SYNDROME (LFS)
189
One of the best characterized tyrosine kinases because it is the preferred partner in heterodimer formation with all the other EGFR family
HER2/Neu (c-erb B-2)
190
Develop hundreds to thousands of polyps in the colon and rectum
FAMILIAL ADENOMATOUS POLYPOSIS (FAP)
191
Most common cancer in men
Prostate Cancer
192
Types of Cancer screening tests
1. Physical examination 2. Laboratory 3. Imaging procedures 4. Genetic tests 5. BIRADS VI
193
Number of deaths occurring
Mortality
194
Colorectal CA Procedures for screening
Fecal occult blood test (FOBT) Flexible sigmoidoscopy Fecal occult blood test and flexible sigmoidoscopy Double-contrast barium enema (DCBE) Colonoscopy
195
Anti-angiogenesis Factors
thrombospondin-1 angiostatin
196
2 FOLD EFFECT OF APPROPRIATE STAGING ON SURVIVAL:
1. Patients with nodal metastases may be offered adjuvant therapy, which improves their survival chances 2. improved staging can improve perceived survival rates through a "Will Rogers effect"
197
Combining cell cycle specific and cell cycle nonspecific agents
Combination Therapy
198
CEA (Carcinoembryonic Antigen)
Glycoprotein found in embryonic endodermal epithelium, that is associated with the plasma membrane of tumor cells, from which may be released in the blood
199
Uniform goal for all oncologic operations
achieving widely negative margins with no evidence of macroscopic or microscopic tumor at the surgical margins
200
often is used in the context of predicting response to certain therapies. The markers are markers that can prospectively identify patients who will benefit from certain therapy
Predictive Marker
201
The predominant change in Colorectal Cancer (Molecular)
Mutational Inactivation of Tumor Suppressor Genes
202
Compatibility between cancer biology and its new microenvironment
Seed and soil theory
203
HER2/Neu (c-erb B-2) is amplified in what common types of tumors?
(LOBOG) Lung Oral Breast Ovarian Gastric
204
Proportion of patients with regional lymph node metastases in whom the sentinel lymph node was found to be negative
False-negative rate
205
FACTORS CAUSING DISTURBANCE OF REGULATORY MECHANISMS
CKI&CKI-kinase inhibitors Cell cycle proteins Growth Factors GF receptors Intracellular signal transduction proteins Nuclear transcription Factors
