Chapter 26 (24) – Cancer Cells – Flashcards

question
Cancer
answer
means "crab" - describes disease in which tissues grow and spread unrestrained throughout the body
question
Carcinoma 758
answer
90% of all cancers, arise from epithelial cells that cover external and internal body surface
question
Sarcomas - 758
answer
Develop from supporting tissues like bone, cartilage, fat and muscle
question
Lymphoma / leukemia - 758
answer
Arise from cells of blood and lymphatic origin
question
Tumor characteristics - 758
answer
Not controlled by normal cell growth regulation Cell division isn't balanced with differentiation and cell death like in normal cells
question
Benign tumors - 758
answer
Grow in confined local areas and are rarely dangerous
question
Malignant tumors - 758
answer
Capable of invading surrounding tissues entering blood stream and spread to distant places in body
question
Anchorage-independent growth - 760
answer
Cancer cells can grow either unattached to anythin or in semi solid environment whereas normal cells cannot
question
Density-dependent inhibition of growth - 760
answer
Cell division stops or slows when the monolayer stage (surface is covered by single layer of cells) - cancer cells are less responsive to this
question
Why can cancer cells divide countless times - 761
answer
Produce telomerase to overcome the limitation placed on normal cells by the telomere - shortening prevents excessive proliferation Telomerase in cancer cells continuously add teleromers to the DNA Don't need growth factors in order to grow / divide by altering signaling pathways to create a constant signal to divide Don't respond to trigger checkpoints to limit growth in the cell cycle like normal cells Block pathways that signal apoptosis
question
What makes cancer so dangerous and deadly - 761
answer
The combination of ability to proliferate quickly and ability to spread throughout the body
question
Angiogenesis - 761
answer
Growth of blood vessels - tumors signal their own blood vessel network growth Tumors do this by increasing production of angiogenesis activators and decreasing in production of angiogenesis inhibitors
question
Vascular endothelial growth factor (VEGF) Fibroblast growth factor (FGF) - 762
answer
Proteins produced by cancer cells and released into surround tissue that bind to receptors on surface of endothelial cells Causes cells to divide and secrete protein-degrading enzymes called matrix metalloproteinases (MMP's)
question
MMP's = 762
answer
Secreted from endothelial cells that break down the extracellular matrix permitting the endothelial cells to migrate into surrounding tissues
question
Angiogenesis inhibitors - 762 exs: angiostatin, endostatin, thrombostatin
answer
Cancer molecules must overcome affects of these - that normally restrain the growth of blood vessels
question
Invasion and metasis - 762
answer
Invasion - Direct migration and penetration of cancer cells into neighboring tissues Metastasis - ability of cancer cells to enter bloodstream and travel to distant sites to form metastases - tumors not connected to primary tumor
question
Three main steps of metastasis - 762
answer
1 - Cancer cells invade surrounding tissues and penetrate through walls of lymphatic and blood vessels, gaining access to bloodstream 2 - Cancer cells are transported by circulatory system throughout body 3 - Cancer cells leave the bloodstream and enter various organs where they establish new matastatic tumors
question
What makes cancer cells able to invade surrounding tissues? - 763
answer
Changes in cell surface proteins that allow it to adhere to one another - in cancer these proteins are missing or defective allowing them to separate from main tumor cells more rapidly E-cadherin - cell-cell adhesive protein whose loss underlies reduced adhesiveness of many epithelial cancers Invasive cancers have less cadherin --Increased motility of cancer cells - stimulated by signaling molecules - chemoattractants Activation of Rho family GTPases plays central role in stimulation of cell motility --Ability of cancer to produce proteases - degrade protein-containing structures that would otherwise act as barriers to cancer cell movement
question
Basal lamina - 763
answer
Dense layer of protein-containing material that separates epithelial layers from underlying tissues Usually acts as a barrier Must be breached Cancer cells secrete proteases that degrade proteins that form backbone of the basal lamina ex; plasminogen activator - enzyme that converts the inactive precursor plasminogen into active protease plasmin
question
Plasmin - 763
answer
Degrades components of basal lamina to allow tumor invasion Cleaves inactive precursors of matrix into active enzymes to degrade basal lamina and extracellular matrix
question
Clones - 764
answer
Cell populations derived from a single initial cell
question
Metastastis experiment with mice - 764
answer
Cells from the metastases where injected and reinjected and able to form more metastases than the original tumor cell Happens because the cell best suited for metastasizing were selected for in evolving cells
question
Tumors most frequently metastasize in: 764
answer
Capillaries and capillary beds
question
Optimal environment for tumor to metastasize - 764
answer
Blood flow patterns Prostate cancers usually metastasize in bone - bone cells produce specific growth factors that stimulate proliferation of prostate cancer cells
question
Immune system influence on cancer - 765
answer
Immune surveillance theory - immune destruction of cancer cells is a common event and cancer simply reflects the occasional failure of adequate immune response to be mounted against aberrant cells Rag2 - gene expressed only in lymphocytes - mice with no functional lymphocytes exhibit increased cancer risk Less helpful for protecting against against common types of cancer Cancer cells evade the immune response
question
Reasons cancer cells don't get attacked by immune system - 765
answer
Tumors are hetero that express antigens (substances that trigger immune response) - cells containing antigens requiring strong response are destroyed Cells that lack or have weakened immune response are selected for Cancer cells also produce molecules that inhibit functioning of T lymphocytes - may surround themselves with dense supporting tissue that shields them from immune attack Some divide too quickly to be killed
question
Tumor microenvironment influencing invasion and metastasis - 765
answer
Normal cells of immune system may attack cancer cells and other cells in tumor microenvironment produce TGFB - potent inhibitor of proliferation for many cell types --Cancer cells may develop mutations that allow them to continue to grow in presence of TGFB
question
Carcinogens - 767
answer
Cancer-causing agents Precarcinogens - chemical that is capable of causing cancer only after it has been metabolically activated cytochrome P450
question
Ames Test - 767
answer
Measuring a chemical's mutagenic activity Used bacteria as a test organism - histidine Possible mutagen Placed in dish with histidine If mutagenic - will trigger mutations some of which might restore ability to synthesize histidine More colonies = more mutagenic potency
question
DNA Damage from carcinogenic chemicals - 767
answer
bind to DNA, disrupt normal base-pairing, generate crosslinks between 2 strands of double helix, chemical links between adjacent bases
question
Multistep process of cancer development - 768
answer
DMBA causes cancer (coal and its components) Initiation - normal cells converted to a precancerous state Promotion - stimulates altered cells to divide and form tumors, gradual process requiring prolonged or repeated exposure to promoting agent DNA mutation Tumor progression - Tumor cell properties change over time as cells acquire more aberrant traits and become more aggressive Increase growth rate, invasiveness, ability to survive in bloodstream, resistance to immune attack - cells are selected for making them spread and strengthen
question
Ionizing radiation - 770
answer
X-rays and related forms of radiation emitted by radioactive elements - remove electrons from molecules Ultraviolet radiation - causes cancer by damaging DNA Triggers pyrimidine dimer formation - covalent bonds between adjacent pyrimidine bases
question
p53 - 770
answer
One of the first genes to be studied - known to be mutated in many human cancers --p53 Mutations DO NOT exhibit a distinctive UV signature
question
771
answer
Oncogenic virus - virus that causes cancer -- sarcomas - cancer in connective tissues Burkitt lymphoma - outbreaks of lymphocytic cancers of neck and jaw Epstein-Barr virus (EBV) cells can cause lymphomas Hepatitis C, HTLV, HPV H pylori - are all viruses that can cause cancer
question
772
answer
Oncogenes - gene whose presence can trigger development of a cancer - some introduced by cancer-causing viruses, others arise from mutations --Rous sarcoma virus - src 3T3 cells - transfection - uptake of foreign DNA into cells and incorporates it into their chromosomes RAS --> Ras first human oncogene discovered ---together w other oncogenes that target p53 pathway will cause cancer Multiple mutations are required to convert normal cell into a cancer cell
question
772
answer
Proto-oncogenes - Mutation from normal cellular genes (proto oncogenes) - not harmful alone Mutations that cause cancer: 1 - Point mutation - single nucleotide sub 2 - Gene amplification - increases # of copies like ERBB2 gene 3 - Chromosomal translocation - portion of 1 chromosome physically removed and joined to another i.e. Burkitt lymphoma, EBV MYC is moved from 8 to 14 Philadelphia chromosome - abnl 22 --> BCR-ABL 4 - Local DNA rearrangements - base sequences altered by deletions, insertions, inversions, transpositions ex: NTRK1 and TPM3 TRK oncogene --> coiled oil 5 - Insertional mutagenesis - Retroviruses cause cancer - integrate their genes into host chromosome - insertional mutagenesis - integration of viral DNA converts host cell proto to oncogene
question
774 - 777
answer
Categories of proteins produced by oncogenes: 1 - Growth factors - Cell possesses an oncogene that produces growth factor and stimulates its own proliferation ex: v-sis gene simian sarcoma virus form of PDGF 2 - Receptors - code for mutant versions of receptors - tyrosine kinase activity is permanently activated regardless of presence of growth factor TRK, v-erb-b, EGF, ERBB2, Jak-STAT pathway, myeloproliferative leukemia virus, v-mpl, thrombopoietin 3 - Plasma membrane GTP-binding protein - Hyperactive Ras protein that retains bound GTP instead of hydrolyzing it - permanently activated state 4 - Nonreceptor protein kinase - enzymes that catalyze intercellular phosphorylation reactions - MAP kinases, BRAF, Src, Jak, Abl protein kinases 5 - Transcription factors - Alter gene expression, produce mutant forms of transcription factors in excessive quantities - Myc --> Burkitt lymphoma, 6 - Cell cycle and apoptosis regulators - Coding for cyclins, cyclin-dependent kinases (Cdk's), CDK4, CYCD1 - CDk-cyclin, inhibit apoptosis, Bcl-2, MDM2 --> destroys p53 pathway
question
777
answer
Tumor suppressor genes - Restrain cell proliferation - if they are damaged it can lead to cancer --As long as hybrid cells retain both sets of original chromosomes - ability to form tumors is suppressed can overcome effects of RAS oncogene
question
778
answer
hereditary retinblastoma - first tumor suppressor gene found studying this RB gene - the missing gene leading to retinoblastoma E7 protein - suppresses Rb gene and prevents HPV
question
778
answer
p53 gene - most frequently mutated tumor suppressor gene in humans - helps with apoptosis - when damaged cell division cannot be stopped
question
779
answer
APC gene - associated with inherited disease familial adenomatous polyposis - develops polyps in colon Wnt pathway - role in controlling cell proliferation during embryonic development - B-catenin, axin, glycogen synthase kinase 3 (GSK3) Wnt proteins APC-axin-GSK3, TCF transcription factor,
question
780
answer
Genetic instability - cancer cells thousands of times higher than normal --Disruptions in DNA repair, --Mismatch repair --> HNPCC Xeroderma pimentosum - defects in excision repair --Mutant in BRCA1 or BRCA2 -- defects in repairing double strand breaks Defects in mitotic spindle checkpoints - normal chromosome separation
question
782
answer
Mad or Bub proteins - components of mitotic spindle checkpoint Gatekeepers - like RB, p53, APC - loss directly opens gates to excessive cell proliferation and tumors Caretakers - genes involved in DNA repair and chromosome sorting - maintain genetic stability but are not directly involved in controlling cell proliferation and survival
question
782 - How cancers develop
answer
Typically involves mutations in about 50-75 different protein-coding genes Breaks must be released - tumor suppressor genes Accelerator held on - oncogenes
question
783 - KRAS
answer
Oncogene accompanied by loss of function mutations in suppressors APC, SMAD4 and p53
question
784 - Epigenetic changes
answer
Changes in genetic sequence that doesn't involve original gene sequence --DNA methylation - CG sites near gene promoters Extensive methlyation --> epigenetic silencing of tumor suppressor genes MicroRNA's - bind to and silence translation of thousands of individual mRNA's - bind to and silence translation of mRNA's miR-155 Can either be overproduced or underproduced Can influence histone modification reactions
question
785 - Carcinogenesis
answer
Multistep series of events that convert normal cells into cancer cells Hallmarks of cancer: 1 - Self-sufficiency of growth signals 2 - Insensitivity to antigrowth signals 3 - Evasion of apoptosis 4 - Limitless replicative potential 5 - Sustained angiogenesis 6 - Tissue invasion and metastasis
question
Diagnosis and screening - 786
answer
Microscopic examination of tissue specimens (biopsy) Tumor grading - assignment of numbered grades to tumors based on differences in appearance Pap smear - screening and detection of cervical cancer Mammography, colonoscopy PSA test - measures how prostate-specific antigen is present in bloodstream
question
Treatment - 788
answer
Radiation Chemotherapy - uses drugs that kill dividing cells: 1 - antimetabolites - inhibit metabolic pathways 2 - Alkylating agents - inhibit DNA function 3 - Antibiotics - inhibit DNA function 4 - Plant-derived drugs - disrupt microtubules of mitotic spindle Multi-drug resistance transport proteins (ABC transporters - actively pump a wide range of chemically dissimilar hydrophobic drugs out the cell Immunotherapy - Exploiting immune system to recognize cancer cells - BCG, antibodies, Provenge
question
Molecular targeting - 790
answer
Drugs designed to specifically target proteins critical to the cancer cell Herceptin - ERBB2, Erbitux, Avastin, rational drug design, small molecule inhibitors, Gleevec, BCR-ABL Anti-angiogenic therapy - angiogenesis inhibitors to reverse blood vessel formation for tumors - Avastin, VEGF
question
Individualizing treatment 790
answer
Personalized medicine - choices made based on individual characteristics of patients, Transcriptome analysis - use of DNA microarrays to determine which genes are being transcribed Oncotype DX - test to measure activity of certain genes Iressa,
1 of

Unlock all answers in this set

Unlock answers
question
Cancer
answer
means "crab" - describes disease in which tissues grow and spread unrestrained throughout the body
question
Carcinoma 758
answer
90% of all cancers, arise from epithelial cells that cover external and internal body surface
question
Sarcomas - 758
answer
Develop from supporting tissues like bone, cartilage, fat and muscle
question
Lymphoma / leukemia - 758
answer
Arise from cells of blood and lymphatic origin
question
Tumor characteristics - 758
answer
Not controlled by normal cell growth regulation Cell division isn't balanced with differentiation and cell death like in normal cells
question
Benign tumors - 758
answer
Grow in confined local areas and are rarely dangerous
question
Malignant tumors - 758
answer
Capable of invading surrounding tissues entering blood stream and spread to distant places in body
question
Anchorage-independent growth - 760
answer
Cancer cells can grow either unattached to anythin or in semi solid environment whereas normal cells cannot
question
Density-dependent inhibition of growth - 760
answer
Cell division stops or slows when the monolayer stage (surface is covered by single layer of cells) - cancer cells are less responsive to this
question
Why can cancer cells divide countless times - 761
answer
Produce telomerase to overcome the limitation placed on normal cells by the telomere - shortening prevents excessive proliferation Telomerase in cancer cells continuously add teleromers to the DNA Don't need growth factors in order to grow / divide by altering signaling pathways to create a constant signal to divide Don't respond to trigger checkpoints to limit growth in the cell cycle like normal cells Block pathways that signal apoptosis
question
What makes cancer so dangerous and deadly - 761
answer
The combination of ability to proliferate quickly and ability to spread throughout the body
question
Angiogenesis - 761
answer
Growth of blood vessels - tumors signal their own blood vessel network growth Tumors do this by increasing production of angiogenesis activators and decreasing in production of angiogenesis inhibitors
question
Vascular endothelial growth factor (VEGF) Fibroblast growth factor (FGF) - 762
answer
Proteins produced by cancer cells and released into surround tissue that bind to receptors on surface of endothelial cells Causes cells to divide and secrete protein-degrading enzymes called matrix metalloproteinases (MMP's)
question
MMP's = 762
answer
Secreted from endothelial cells that break down the extracellular matrix permitting the endothelial cells to migrate into surrounding tissues
question
Angiogenesis inhibitors - 762 exs: angiostatin, endostatin, thrombostatin
answer
Cancer molecules must overcome affects of these - that normally restrain the growth of blood vessels
question
Invasion and metasis - 762
answer
Invasion - Direct migration and penetration of cancer cells into neighboring tissues Metastasis - ability of cancer cells to enter bloodstream and travel to distant sites to form metastases - tumors not connected to primary tumor
question
Three main steps of metastasis - 762
answer
1 - Cancer cells invade surrounding tissues and penetrate through walls of lymphatic and blood vessels, gaining access to bloodstream 2 - Cancer cells are transported by circulatory system throughout body 3 - Cancer cells leave the bloodstream and enter various organs where they establish new matastatic tumors
question
What makes cancer cells able to invade surrounding tissues? - 763
answer
Changes in cell surface proteins that allow it to adhere to one another - in cancer these proteins are missing or defective allowing them to separate from main tumor cells more rapidly E-cadherin - cell-cell adhesive protein whose loss underlies reduced adhesiveness of many epithelial cancers Invasive cancers have less cadherin --Increased motility of cancer cells - stimulated by signaling molecules - chemoattractants Activation of Rho family GTPases plays central role in stimulation of cell motility --Ability of cancer to produce proteases - degrade protein-containing structures that would otherwise act as barriers to cancer cell movement
question
Basal lamina - 763
answer
Dense layer of protein-containing material that separates epithelial layers from underlying tissues Usually acts as a barrier Must be breached Cancer cells secrete proteases that degrade proteins that form backbone of the basal lamina ex; plasminogen activator - enzyme that converts the inactive precursor plasminogen into active protease plasmin
question
Plasmin - 763
answer
Degrades components of basal lamina to allow tumor invasion Cleaves inactive precursors of matrix into active enzymes to degrade basal lamina and extracellular matrix
question
Clones - 764
answer
Cell populations derived from a single initial cell
question
Metastastis experiment with mice - 764
answer
Cells from the metastases where injected and reinjected and able to form more metastases than the original tumor cell Happens because the cell best suited for metastasizing were selected for in evolving cells
question
Tumors most frequently metastasize in: 764
answer
Capillaries and capillary beds
question
Optimal environment for tumor to metastasize - 764
answer
Blood flow patterns Prostate cancers usually metastasize in bone - bone cells produce specific growth factors that stimulate proliferation of prostate cancer cells
question
Immune system influence on cancer - 765
answer
Immune surveillance theory - immune destruction of cancer cells is a common event and cancer simply reflects the occasional failure of adequate immune response to be mounted against aberrant cells Rag2 - gene expressed only in lymphocytes - mice with no functional lymphocytes exhibit increased cancer risk Less helpful for protecting against against common types of cancer Cancer cells evade the immune response
question
Reasons cancer cells don't get attacked by immune system - 765
answer
Tumors are hetero that express antigens (substances that trigger immune response) - cells containing antigens requiring strong response are destroyed Cells that lack or have weakened immune response are selected for Cancer cells also produce molecules that inhibit functioning of T lymphocytes - may surround themselves with dense supporting tissue that shields them from immune attack Some divide too quickly to be killed
question
Tumor microenvironment influencing invasion and metastasis - 765
answer
Normal cells of immune system may attack cancer cells and other cells in tumor microenvironment produce TGFB - potent inhibitor of proliferation for many cell types --Cancer cells may develop mutations that allow them to continue to grow in presence of TGFB
question
Carcinogens - 767
answer
Cancer-causing agents Precarcinogens - chemical that is capable of causing cancer only after it has been metabolically activated cytochrome P450
question
Ames Test - 767
answer
Measuring a chemical's mutagenic activity Used bacteria as a test organism - histidine Possible mutagen Placed in dish with histidine If mutagenic - will trigger mutations some of which might restore ability to synthesize histidine More colonies = more mutagenic potency
question
DNA Damage from carcinogenic chemicals - 767
answer
bind to DNA, disrupt normal base-pairing, generate crosslinks between 2 strands of double helix, chemical links between adjacent bases
question
Multistep process of cancer development - 768
answer
DMBA causes cancer (coal and its components) Initiation - normal cells converted to a precancerous state Promotion - stimulates altered cells to divide and form tumors, gradual process requiring prolonged or repeated exposure to promoting agent DNA mutation Tumor progression - Tumor cell properties change over time as cells acquire more aberrant traits and become more aggressive Increase growth rate, invasiveness, ability to survive in bloodstream, resistance to immune attack - cells are selected for making them spread and strengthen
question
Ionizing radiation - 770
answer
X-rays and related forms of radiation emitted by radioactive elements - remove electrons from molecules Ultraviolet radiation - causes cancer by damaging DNA Triggers pyrimidine dimer formation - covalent bonds between adjacent pyrimidine bases
question
p53 - 770
answer
One of the first genes to be studied - known to be mutated in many human cancers --p53 Mutations DO NOT exhibit a distinctive UV signature
question
771
answer
Oncogenic virus - virus that causes cancer -- sarcomas - cancer in connective tissues Burkitt lymphoma - outbreaks of lymphocytic cancers of neck and jaw Epstein-Barr virus (EBV) cells can cause lymphomas Hepatitis C, HTLV, HPV H pylori - are all viruses that can cause cancer
question
772
answer
Oncogenes - gene whose presence can trigger development of a cancer - some introduced by cancer-causing viruses, others arise from mutations --Rous sarcoma virus - src 3T3 cells - transfection - uptake of foreign DNA into cells and incorporates it into their chromosomes RAS --> Ras first human oncogene discovered ---together w other oncogenes that target p53 pathway will cause cancer Multiple mutations are required to convert normal cell into a cancer cell
question
772
answer
Proto-oncogenes - Mutation from normal cellular genes (proto oncogenes) - not harmful alone Mutations that cause cancer: 1 - Point mutation - single nucleotide sub 2 - Gene amplification - increases # of copies like ERBB2 gene 3 - Chromosomal translocation - portion of 1 chromosome physically removed and joined to another i.e. Burkitt lymphoma, EBV MYC is moved from 8 to 14 Philadelphia chromosome - abnl 22 --> BCR-ABL 4 - Local DNA rearrangements - base sequences altered by deletions, insertions, inversions, transpositions ex: NTRK1 and TPM3 TRK oncogene --> coiled oil 5 - Insertional mutagenesis - Retroviruses cause cancer - integrate their genes into host chromosome - insertional mutagenesis - integration of viral DNA converts host cell proto to oncogene
question
774 - 777
answer
Categories of proteins produced by oncogenes: 1 - Growth factors - Cell possesses an oncogene that produces growth factor and stimulates its own proliferation ex: v-sis gene simian sarcoma virus form of PDGF 2 - Receptors - code for mutant versions of receptors - tyrosine kinase activity is permanently activated regardless of presence of growth factor TRK, v-erb-b, EGF, ERBB2, Jak-STAT pathway, myeloproliferative leukemia virus, v-mpl, thrombopoietin 3 - Plasma membrane GTP-binding protein - Hyperactive Ras protein that retains bound GTP instead of hydrolyzing it - permanently activated state 4 - Nonreceptor protein kinase - enzymes that catalyze intercellular phosphorylation reactions - MAP kinases, BRAF, Src, Jak, Abl protein kinases 5 - Transcription factors - Alter gene expression, produce mutant forms of transcription factors in excessive quantities - Myc --> Burkitt lymphoma, 6 - Cell cycle and apoptosis regulators - Coding for cyclins, cyclin-dependent kinases (Cdk's), CDK4, CYCD1 - CDk-cyclin, inhibit apoptosis, Bcl-2, MDM2 --> destroys p53 pathway
question
777
answer
Tumor suppressor genes - Restrain cell proliferation - if they are damaged it can lead to cancer --As long as hybrid cells retain both sets of original chromosomes - ability to form tumors is suppressed can overcome effects of RAS oncogene
question
778
answer
hereditary retinblastoma - first tumor suppressor gene found studying this RB gene - the missing gene leading to retinoblastoma E7 protein - suppresses Rb gene and prevents HPV
question
778
answer
p53 gene - most frequently mutated tumor suppressor gene in humans - helps with apoptosis - when damaged cell division cannot be stopped
question
779
answer
APC gene - associated with inherited disease familial adenomatous polyposis - develops polyps in colon Wnt pathway - role in controlling cell proliferation during embryonic development - B-catenin, axin, glycogen synthase kinase 3 (GSK3) Wnt proteins APC-axin-GSK3, TCF transcription factor,
question
780
answer
Genetic instability - cancer cells thousands of times higher than normal --Disruptions in DNA repair, --Mismatch repair --> HNPCC Xeroderma pimentosum - defects in excision repair --Mutant in BRCA1 or BRCA2 -- defects in repairing double strand breaks Defects in mitotic spindle checkpoints - normal chromosome separation
question
782
answer
Mad or Bub proteins - components of mitotic spindle checkpoint Gatekeepers - like RB, p53, APC - loss directly opens gates to excessive cell proliferation and tumors Caretakers - genes involved in DNA repair and chromosome sorting - maintain genetic stability but are not directly involved in controlling cell proliferation and survival
question
782 - How cancers develop
answer
Typically involves mutations in about 50-75 different protein-coding genes Breaks must be released - tumor suppressor genes Accelerator held on - oncogenes
question
783 - KRAS
answer
Oncogene accompanied by loss of function mutations in suppressors APC, SMAD4 and p53
question
784 - Epigenetic changes
answer
Changes in genetic sequence that doesn't involve original gene sequence --DNA methylation - CG sites near gene promoters Extensive methlyation --> epigenetic silencing of tumor suppressor genes MicroRNA's - bind to and silence translation of thousands of individual mRNA's - bind to and silence translation of mRNA's miR-155 Can either be overproduced or underproduced Can influence histone modification reactions
question
785 - Carcinogenesis
answer
Multistep series of events that convert normal cells into cancer cells Hallmarks of cancer: 1 - Self-sufficiency of growth signals 2 - Insensitivity to antigrowth signals 3 - Evasion of apoptosis 4 - Limitless replicative potential 5 - Sustained angiogenesis 6 - Tissue invasion and metastasis
question
Diagnosis and screening - 786
answer
Microscopic examination of tissue specimens (biopsy) Tumor grading - assignment of numbered grades to tumors based on differences in appearance Pap smear - screening and detection of cervical cancer Mammography, colonoscopy PSA test - measures how prostate-specific antigen is present in bloodstream
question
Treatment - 788
answer
Radiation Chemotherapy - uses drugs that kill dividing cells: 1 - antimetabolites - inhibit metabolic pathways 2 - Alkylating agents - inhibit DNA function 3 - Antibiotics - inhibit DNA function 4 - Plant-derived drugs - disrupt microtubules of mitotic spindle Multi-drug resistance transport proteins (ABC transporters - actively pump a wide range of chemically dissimilar hydrophobic drugs out the cell Immunotherapy - Exploiting immune system to recognize cancer cells - BCG, antibodies, Provenge
question
Molecular targeting - 790
answer
Drugs designed to specifically target proteins critical to the cancer cell Herceptin - ERBB2, Erbitux, Avastin, rational drug design, small molecule inhibitors, Gleevec, BCR-ABL Anti-angiogenic therapy - angiogenesis inhibitors to reverse blood vessel formation for tumors - Avastin, VEGF
question
Individualizing treatment 790
answer
Personalized medicine - choices made based on individual characteristics of patients, Transcriptome analysis - use of DNA microarrays to determine which genes are being transcribed Oncotype DX - test to measure activity of certain genes Iressa,