Cancer Biology Exam 1

What is Fibrodysplasia Ossificans Progressiva (FOP)?

(Stone man disease) - fibrous connective tissue such as muscle, tendons, and ligaments turn into bone tissue Activation mutation in ACVR1, which encodes activin receptor type-1, a BMP type-1 receptor. BMP: bone morphogenetic protein

What is radiotherapy?

- 40-60% of patients receive radiation therapy at some point - - damaging DNA double strand breaks slow down growth leading to cellular death - curative if the tumor is localized to one area radiotherapy - External beam radiation therapy (linear accelerator) --- designed to deliver doses of radiation to cancer cells, not to normal tissues

What are cancer trends globally?

- Americans male and female develops skin cancer (i.e. tanning) - Japanese males and korean females develop stomach cancer (i.e., drinking)

how do nitrosamines and nitrosamides cause cancer?

- can cause cancer through a process that involves the formation of alkylated O^6-guanine derivatives in DNA. From exposure to tobacco and nitrite preservatives in food processing, including fish. METABOLISM: compounds are ingested or inhaled --> undergo metabolic activation in the body, primarily in the liver. This metabolic process can involve enzymes that convert nitrosamines and nitrosamides into highly reactive intermediates. FORMS ALKYLATED DNA ADDUCTS ON O^6 POSITION OF GUANINE BASES interfereS with DNA replication and repair processes. During DNA replication, when the cell attempts to copy the DNA strand containing these modifications, errors can occur, resulting in mutations in the DNA sequence. MUTATIONS CAN LEAD TO ONCOGENES -can drive uncontrolled cell proliferation (hallmark of cancer) TUMORS - accumulation of mutations and the altered regulation of cell growth can lead to the initiation of a tumor. This tumor may grow, invade nearby tissues, and potentially metastasize, resulting in advanced cancer.

What kind of environmental factors might influence cancer?

-Working condition: soot in chimney sweeps (chronic exposure) - nasal and scrotal cancer) - UV exposure --- skin cancer

what are some possible caveats to telomerase inhibitors?

-goal of telomerase inhibition: induce telomere dysfunction in cancer cells triggering apoptosis. -desirable outcome because it can lead to the selective elimination of cancer cells. -effectiveness of telomerase inhibitors depends on initial length of telomeres in cancer cells. -short telomeres --> more vulnerable to telomerase inhibition | longer telomeres --> less effect Telomerase inhibitors/telomere shortening, may not produce immediate results/relatively SLOW Telomerase has two main components: RNA (hTR) and catalytic protein (TERT). Inhibition strategies can target either of these components. For example: 1. Antisense oligonucleotides bind to hTR, preventing its interaction with TERT. 2. Ribozymes (catalytic RNA molecules) can cleave hTR, disrupting telomerase function. 3. Imetelstat - developed by Geron, a telomerase inhibitor. 13-mer oligonucleotide that binds to hTR. Nucleoside Analogs: Some telomerase inhibitors use nucleoside analogs like 6-thio-2'-deoxyguanosine (6-thio-dG) - incorporated into telomeres during DNA replication, disrupting telomere function.

What is included in cancer care?

-surgery -chemotherapy -immunotherapy -radiation therapy -precision therapy - specific care for their patients, based on the particular genes, proteins, and other substances in a person's bod

What are the four tissue types that comprise our bodies? Which one is most relevant to cancer?

1. Connective tissue 2. Epithelial tissue - 80-90% of cancer cases 3. Neuronal tissue 4. Muscle tissue

what are other techniques that can be used to probe for DNA-protein interactions?

1. DNase Footprinting: - identify protein binding sites on DNA. How it works: DNase I, an enzyme that cleaves DNA, is used to digest DNA that is not protected by protein binding. The DNA is then subjected to gel electrophoresis, revealing regions where proteins have bound and protected the DNA from digestion. These protected regions appear as "footprints" on the gel, indicating the binding sites of specific proteins. 2. Reporter Assay: - study the activity of a specific DNA sequence, often a promoter or enhancer, in controlling the expression of a reporter gene. How it works: A reporter gene, such as luciferase or green fluorescent protein (GFP), is placed under the control of the DNA sequence of interest. When the sequence is active, it drives the expression of the reporter gene, which can be easily detected and quantified. Reporter assays are used to study the regulation of gene expression and the impact of specific DNA sequences on that regulation. 3. ATAC-Seq (Assay for Transposase-Accessible Chromatin using Sequencing): - next-generation sequencing technique used to profile open chromatin regions in a genome. How it works: ATAC-Seq uses a transposase enzyme to insert sequencing adapters into open chromatin regions. These regions are more accessible to the enzyme because they are not bound by proteins. After adapter insertion, the DNA is sequenced, allowing researchers to identify and quantify regions of open chromatin. ATAC-Seq is valuable for studying gene regulation and identifying active regulatory elements. 4. ChIP-Seq (Chromatin Immunoprecipitation Sequencing): - identify protein binding sites on DNA, such as transcription factor binding sites or histone modifications. How it works: In ChIP-Seq, DNA-protein complexes are cross-linked, and the protein of interest is immunoprecipitated with an antibody specific to that protein. After purification, the associated DNA is sequenced, allowing the identification of genomic regions bound by the protein. ChIP-Seq is widely used for studying transcription factor binding, histone modifications, and other DNA-protein interactions.

What are the hallmarks of cancer?

1. Evasion of growth inhibitory signals (ignoring signs that tell them to stop growing) 2. Avoiding immune destruction 3. Unlimited replicative potential 4. Tumor promoting inflammation 5. Invasion and metastasis 6. Angiogenesis 7. Genome instability and mutation 8. Evasion of cell death 9. Reprogramming energy metabolism 10. Growth signal autonomy

how do changes in chromatin structure, epigenetic modifications, and DNA methylation impact gene expression and drive tumorigenesis?

1. Mutations in Chromatin-Regulating Enzymes: ~50% of human cancers contain mutations in enzymes that regulate chromatin structure, disrupting the normal packaging of DNA into chromatin and affect gene expression. 2. SWI/SNF Mutations: - chromatin remodelers. Mutations are observed in about 20% of all human cancers. 3. Histone Modifications: - Alterations like acetylation and methylation are common in cancer. Changes in the activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs) impact gene expression. 4. p300 Inactivation: - p300, a histone acetyltransferase (HAT) is truncated or inactivated in epithelial cancers, acting as a tumor suppressor and is involved in regulating gene expression. 5. PML-RARA Fusion: The PML-RARA fusion protein found in acute promyelocytic leukemia (APL) leading to aberrant recruitment of histone deacetylases (HDACs), contributing to the disease. 6. Histone Mutations: Mutations in histones themselves, known as "oncohistones," can occur. These mutations can impact chromatin structure and gene regulation. 7. DNA Methylation: Aberrant DNA methylation, particularly hypermethylation of normally unmethylated promoters, can lead to gene silencing. Examples include BRCA1 promoter hypermethylation in breast cancer and the methylation of genes like RB, p16, APC, and DAPK. 8. DNMT Mutations: Mutations in DNA methyltransferases (DNMTs), such as DNMT3A, are observed in cancer. These mutations can lead to aberrant DNA methylation patterns and gene expression changes. 9. Cytosine Deamination: Methylated cytosines (5-methylcytosines) have a tendency to deaminate, leading to C-to-T mutations. This process can contribute to genetic mutations observed in cancer.

what are strategies that target DNA repair pathways, particularly those involving synthetic lethality and combination therapies?

1. Synthetic Lethality: situation where inhibiting the function of one gene (e.g., through targeted therapy) is cytotoxic (lethal) only in the presence of an additional mutation or specific genetic context. Example: inhibition of poly(ADP-ribose) polymerase (PARP) in cancer cells with defects in the BRCA1 or BRCA2 genes - These genes are involved in homologous recombination DNA repair. Inhibiting PARP in BRCA-deficient cancer cells leads to DNA damage accumulation and cell death because these cells heavily rely on alternative DNA repair mechanisms, such as PARP-mediated base excision repair. 2. Combination Therapies: PARP Inhibition + Chemotherapy/Radiation: Combining PARP inhibitors with chemotherapy or radiation therapy has been effective in certain cancer types, particularly those with DNA repair deficiencies.

When is the earliest evidence of cancer?

1500-1600 B.C

What was the First Induction of tumor by chemical carcinogen/mutagen?

1915, Katsusaburo Yamagiwa painted coal tars onto rabbit ears (660 days)

How do clinical trials works?

3 phases: Phase 1 - safety - 20-100 people Phase 2 - efficacy - hundreds of people Phase 3 - tests against conventional drugs - thousands ppl

How many organs, cells, units of DNA code/base pairs, chromosome pairs, and protein coding genes in the Human genome?

60 organs, 37 trillion cells, 3.2 billion DNA codes/base pairs 23 chromosomes pairs, 19-20K protein coding genes (2%)

Base Excision Repair (BER)

A DNA repair pathway that involves excision of a damaged base by DNA glycosylase, followed by cleavage of the DNA backbone adjacent to the site by an AP endonuclease. Nick translation, DNA polymerization, and ligation complete the repair. Oxidation: Oxidation of DNA bases can result from exposure to oxidative stress, such as reactive oxygen species (ROS). Guanine is particularly susceptible to oxidation and can be converted into 8-oxoguanine (8-oxoG). Deamination: Deamination is the removal of an amino group from a DNA base. It can lead to the conversion of adenine (A) to hypoxanthine or cytosine (C) to uracil (U). Alkylation: Alkylation involves the addition of alkyl groups (e.g., methyl or ethyl) to DNA bases, leading to altered base pairing and potential mispairing during DNA replication. Guanine Oxidation: G is prone to oxidation, especially by reactive oxygen species (ROS) can be converted into a lesion known as 8-oxoguanine (8-oxoG). Mimics Thymine (T): One of the key consequences of 8-oxoG is that it can pair with adenine (A) during DNA replication, effectively mimicking thymine (T). This is problematic because it introduces a mismatched base pair (8-oxoG:A) that is not corrected by the DNA polymerase enzyme during replication. G->T Transversion Mutation: If the 8-oxoG lesion is not repaired before DNA replication occurs, the 8-oxoG:A base pair can lead to a G-to-T (guanine to thymine) transversion mutation in the daughter strand. In other words, instead of the correct G-C base pair, you end up with a T-A base pair in the newly synthesized DNA strand. This G->T transversion mutation can be mutagenic and potentially lead to genetic changes, which, in certain circumstances, may contribute to cancer development or other diseases.

What is a teratoma?

A tumor that arises from all 3 germinal layers (ectoderm, mesoderm, endoderm)

How does Histone acetylation affects gene expression?

Acetylation of histone --- neutralizes the positive charge on K residues,relaxes chromatin folding (DNA: negative charge)

chemotherapy: Alkylating agents

Add covalent bonds via an alkyl group. Intra/inter strand cross-links in DNA

What are non-genotoxic carcinogens?

Agents that don't mutate genes, such as phenobarbital or arsenic --> global hypomethylation of DNA is associated with transformation.

How does alkylating agents cause cancer?

Alkylating agents can cause cancer by inducing DNA damage, including the formation of intra- and interstrand crosslinks. Mustard gas (WWI) is one such alkylating agent with a notorious history of use as a chemical warfare agent. Here's how alkylating agents like mustard gas contribute to cancer development: Alkylation of DNA: Alkylating agents are chemicals that can add alkyl groups (methyl, ethyl, etc.) to various cellular molecules, including DNA These crosslinks can occur either between two bases on the same DNA strand (intrastrand crosslinks) or between bases on opposite DNA strands (interstrand crosslinks). These abnormal structures can block DNA replication and transcription processes. Crosslinks are particularly challenging for repair mechanisms to resolve. Persistent DNA crosslinks can result in mutations, genetic instability, and cell death. Mutagenesis and Carcinogenesis: When DNA replication occurs in the presence of unrepaired DNA crosslinks, errors can be introduced into the DNA sequence. These errors may lead to mutations in critical genes that regulate cell growth and division. Oncogene Activation: Mutations caused by alkylating agents can activate oncogenes. Oncogenes are genes that, when mutated or overexpressed, can drive uncontrolled cell proliferation and contribute to the development of cancer. Tumor Formation: Over time, the accumulation of mutations and the proliferation of cells with damaged DNA can lead to the formation of a tumor. This tumor may grow locally, invade nearby tissues, and potentially metastasize, giving rise to advanced cancer.

One-step repair

Alkyltransferase: removes the alkyl group after alkylating carcinogen exposure.

how can estrogen be a contributing factor to the development of breast cancer?

BRCA1/2 Mutations: BRCA1 and BRCA2 are tumor suppressor genes -maintain integrity of the cell's DNA. When these genes are mutated (typically in the germline, meaning the mutation is present in all cells of an individual's body), they are less effective in repairing damaged DNA and regulating the cell cycle, INCREASING the risk of genetic mutations accumulating in cells, potentially leading to cancer. Individuals with inherited germline mutations in BRCA1 or BRCA2 have a significantly higher risk of developing breast cancer compared to the general population. Estrogen and Breast Cancer: Estrogen can stimulate the growth and division of breast cells. In individuals with BRCA1/2 mutations, the impaired DNA repair mechanisms make breast cells more vulnerable to the mutagenic effects of estrogen. The combination of genetic predisposition (BRCA mutations) and exposure to estrogen can increase the likelihood of genetic mutations occurring in breast cells. Transcription Regulation: BRCA1 and BRCA2 also play roles in transcription regulation, which involves controlling the expression of genes. Dysfunctional BRCA genes can lead to transcriptional changes that affect cell behavior, potentially contributing to cancer development.

Chemotherapy - Platinum based drugs

Binds to G/A, form covalent bonds via the platinum atom

Recombinational Repair (Homologous Recombination):

Breast Cancer 1/2 (BRCA1/BRCA2): involved in homologous recombination repair. Mutations linked to an elevated risk of breast and ovarian cancer. Homologous Recombination (HR): HR is a high-fidelity repair mechanism that primarily operates during the S and G2 phases of the cell cycle when a sister chromatid is available as a template. Process: The broken DNA ends are processed to generate single-stranded DNA overhangs. A search for a homologous DNA sequence (usually the sister chromatid) is initiated. The complementary single-stranded DNA from the intact sister chromatid invades the damaged DNA molecule. DNA synthesis proceeds using the intact sister chromatid as a template to fill in the gap and repair the break. After synthesis, the newly repaired DNA strand dissociates from the template and ligates with the other repaired end. Accuracy: HR is a highly accurate repair mechanism, as it uses an undamaged sister chromatid as a template for repair. Non-Homologous End Joining (NHEJ): NHEJ is a more error-prone but faster DNA repair mechanism that can occur throughout the cell cycle. Process: The broken DNA ends are recognized by a protein complex, and little or no homology between the ends is required. The DNA ends are trimmed, and any damaged bases are removed. The ends are then directly ligated together, often with the loss or addition of a few nucleotides. Accuracy: NHEJ is considered error-prone because it may introduce small insertions or deletions (indels) at the site of repair. These indels can lead to mutations. Choice between HR and NHEJ: The choice between HR and NHEJ is highly regulated and depends on various factors, including the cell cycle phase, the presence of a homologous template (sister chromatid), and the complexity of the DNA damage. HR is preferred when a sister chromatid is available and the DNA damage is more complex, such as in the case of two DSBs on different DNA strands. HR is a more conservative and accurate repair mechanism.

how are infectious pathogens cancerous?

Certain DNA viruses, such as human papillomavirus (HPV), Epstein-Barr virus (EBV), and hepatitis B virus (HBV), have the ability to integrate their genetic material into the host cell's DNA, disrupting normal regulation of host cell genes, leading to uncontrolled cell growth and potentially resulting in the formation of cancerous tumors. RNA Viruses: While RNA viruses do not integrate into the host genome in the same way as DNA viruses, some, like human T-cell lymphotropic virus type 1 (HTLV-1), can lead to cancer by promoting chronic inflammation, which can increase the likelihood of genetic mutations and the development of cancerous cells.

What are examples of PAHs?

Coal Tar: thick, dark liquid produced during the carbonization of coal, containing a complex mixture of organic compounds, including various high content of PAHs. Benzo[a]pyrene (BP): one of the most extensively studied PAHs, a well-known carcinogen found in tobacco smoke, grilled and charred foods, and polluted air. It can undergo metabolic activation in body to form reactive intermediates that can bind to DNA and cause DNA damage (lung cancer) 7,12-Dimethylbenz[a]anthracene (DMBA): exposure can lead to the development of tumors, particularly skin tumors, by causing DNA damage and mutations.

How does UVB damage DNA?

DIRECT DNA DAMAGE: It forms pyrimidine dimers like TT cyclobutane pyrimidine dimer which causes the DNA to bend in structure. During DNA Replication, DNA polymerase cannot read the structure so it just incorporates adenosine. This incorporation of incorrect nucleotides during DNA replication can introduce mutations into the DNA sequence. These mutations may disrupt normal cellular processes and potentially contribute to the development of cancer or other genetic diseases. These pyrimidine dimers represent direct physical alterations to the DNA structure, where two neighboring pyrimidine bases become covalently linked due to UVB exposure. This UVB-induced DNA damage can lead to mutations, disrupt normal DNA replication and transcription, and contribute to the development of skin cancers over time. To repair this direct DNA damage, cells utilize DNA repair mechanisms such as nucleotide excision repair (NER) to recognize, excise, and replace the damaged DNA sequences. NER is especially important in repairing UVB-induced DNA lesions, including pyrimidine dimers, to maintain genomic integrity and minimize the risk of skin cancer. GGCC to UV radiation and GGCC dimer to DNA polymerase and AACC to DNA polymerase and AATT. Ultimately CC to TT transition

what are some therapeutic strategies for targeting epigenetic modifications, such as DNA methylation and histone deacetylation?

DNA Methylation Inhibitors: 5'-Modified Analogs of Deoxycytidine: These are chemical compounds that are structurally similar to the DNA base cytosine but contain modifications at the 5' position. Examples include 5-azacytidine and 5-aza-2'-deoxycytidine (decitabine). Incorporation into DNA: These analogs can be incorporated into the DNA during replication because they are similar to natural cytosine. Once integrated into the DNA strand, they can act as traps for DNA methyltransferases (DNMTs). Crosslinking with DNMTs: These analogs can form covalent bonds with DNMTs when they attempt to methylate the modified cytosines. This effectively inhibits DNMT activity. Demethylation After Replication: During subsequent rounds of DNA replication, the analog-containing DNA strands can undergo passive demethylation because DNMTs are inhibited. This can result in the removal of methyl groups from previously methylated cytosines. DNA Instability and Apoptosis: The process of DNA demethylation and instability can lead to cell apoptosis, which is programmed cell death. This is a potential mechanism through which these inhibitors can kill cancer cells. HDAC Inhibitors: HDACs and Histone Acetylation: Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histone proteins, leading to chromatin condensation and gene silencing. In cancer, there can be aberrant histone deacetylation that contributes to the silencing of tumor suppressor genes. Reactivation of Tumor Suppressors: HDAC inhibitors can reactivate silenced tumor suppressor genes by preventing the removal of acetyl groups from histones. This leads to more open chromatin and increased gene expression. Binding to Catalytic Sites: HDAC inhibitors bind to the catalytic sites of HDAC enzymes, preventing them from deacetylating histones. Block Substrate Binding: Some HDAC inhibitors can block the binding of substrates to HDACs, further inhibiting their activity. Clinical Use: HDAC inhibitors, such as romidepsin and vorinostat, have been approved for the treatment of certain cancers, particularly hematological malignancies like cutaneous T-cell lymphoma (CTCL) and Sezary syndrome. They have also been investigated for their potential in treating solid tumo

chemotherapy: organic drugs

Doxorubicin: anthracycline chemotherapy drug that works by inhibiting topoisomerase II, an enzyme essential for DNA replication and repair. It does this by intercalating between DNA base pairs and forming stable complexes with topoisomerase II, preventing it from properly functioning. As a result, DNA strands become fragmented and cannot be properly resealed, leading to DNA damage and cell death. Vincristine and Vinblastine: Vincristine and vinblastine are chemotherapy drugs derived from plant extracts. They work by disrupting the formation of the mitotic spindle during cell division (mitosis). The mitotic spindle is responsible for segregating chromosomes into daughter cells during cell division. Tubulin Binding: These drugs specifically bind to microtubules, which are structural components of the mitotic spindle. By binding to tubulin, vincristine and vinblastine prevent microtubules from polymerizing properly. This disruption interferes with the assembly of the mitotic spindle and the proper segregation of chromosomes during cell division. Cell Cycle Arrest: As a result of the disrupted mitotic spindle, cells treated with vincristine and vinblastine often arrest in metaphase, a stage of mitosis where chromosomes are aligned in the middle of the cell. This arrest prevents the completion of cell division and leads to cell death

what's the difference between driver and passenger mutations?

Driver mutations --- usually located in cancer genes, confer growth advantage. Passenger mutations --- don't confer growth advantage.

what are some novel targets of cancer?

Driver/passenger mutations

Drugs resistance and heterogeneous cell sensitivity

Drug resistance is a significant challenge in cancer treatment, and it can occur with various types of chemotherapy drugs, including alkylating agents like doxorubicin. Resistance can be attributed to several mechanisms, including heterogeneous cell sensitivity. Heterogeneous Cell Sensitivity: One aspect of drug resistance is the presence of heterogeneity within a tumor, meaning not all cancer cells within a tumor are equally sensitive to the chemotherapy drug. Some cells may be highly sensitive and responsive to the treatment, while others may be inherently resistant or develop resistance over time. Drug Efflux Pumps: Cancer cells can develop mechanisms to pump chemotherapy drugs out of the cell, reducing their intracellular concentration and effectiveness. One well-known example is the P-glycoprotein pump, encoded by the MDR1 gene, which can pump drugs like doxorubicin out of cancer cells. DNA Repair Mechanisms: Alkylating agents like doxorubicin work by damaging DNA. Cancer cells with enhanced DNA repair mechanisms can more effectively repair the DNA damage caused by chemotherapy, making them resistant to the drug's effects.

what is 5-methoxy psoralen in sunscreen?

Early sunscreens had 5-methoxy psoralen When 5-methoxy psoralen comes into contact with the skin and is exposed to UV radiation, it can lead to a process called phototoxicity. Phototoxic reactions can cause a range of skin problems, including redness, inflammation, blistering, and burning sensations. These reactions are more severe when the skin is exposed to sunlight after applying products containing 5-methoxy psoralen, like bergamot oil. Due to the potential for phototoxicity and skin damage, 5-methoxy psoralen-containing products are not recommended for use on the skin before sun exposure. This is especially important in the case of sunscreens, as their primary purpose is to protect the skin from UV radiation.

What is ecDNA and how is it associated with cancer?

Extrachromosomal DNA (ecDNA) is CIRCULAR, double-stranded DNA molecules found outside the chromosomes in the nucleus of a cell. They are distinct from the linear DNA that makes up the cell's chromosomes. ecDNA often carries ONCOGENES, amplification --> uncontrolled cell growth and tumorigenesis. ecDNA can REPLICATE INDEPENDENTLY of the host cell's chromosomes --> increase ecDNA copy number and gene content. Tumor cells with ecDNA may exhibit greater ADAPTABILITY, potentially leading to resistance to therapies and tumor progression. Amplification of oncogenes on ecDNA can confer RESISTANCE to certain cancer therapies.

how do fibrous materials cause mesothelioma?

Fibrous minerals like asbestos and erionite can cause chronic inflammation when inhaled. Over time, this inflammation can lead to the development of mesothelioma, a type of cancer that affects the lining of the lungs and other organs. The exact mechanisms are not fully understood but likely involve DNA damage and other cellular changes caused by chronic inflammation.

Nucleotide Excision Repair (NER)

Helix-distorting lesions, such as pyrimidine dimers and bulky DNA adducts induced by UV, PAHs etc.

how do heterocyclic aromatic amines cause cancer?

Heterocyclic aromatic amines (HAAs) are a group of carcinogenic compounds that can form when meat, poultry, or fish are cooked at high temperatures, particularly through methods such as grilling, frying, or broiling. These compounds are associated with an increased risk of cancer, particularly colorectal, breast, prostate, and pancreatic cancers. Formation of HAAs: HAAs are not present in raw meat but are formed during the cooking process from precursors found in muscle tissues. The high heat of cooking, especially open flame or direct contact with hot surfaces, triggers chemical reactions that convert these precursors into HAAs. Metabolism: After ingestion, HAAs are absorbed into the body and undergo metabolism in the liver. This metabolic process involves enzymes like cytochrome P450, which can activate HAAs. DNA Damage: The activated HAAs can form reactive intermediates that can bind covalently to DNA. These DNA adducts can cause structural changes in the DNA molecule, leading to mutations during DNA replication. Mutation Accumulation: If the DNA damage is not adequately repaired by cellular DNA repair mechanisms, it can result in mutations in critical genes. Mutations can disrupt normal cell growth and division control, leading to uncontrolled cell proliferation—a hallmark of cancer. Oncogene Activation and Tumor Suppressor Gene Inhibition: Some of the genes affected by HAA-induced mutations may be oncogenes, which promote cell growth when mutated. Conversely, mutations in tumor suppressor genes, which typically inhibit cell proliferation, can also occur. Both scenarios can contribute to the development of cancer. Cell Transformation: HAAs can also induce changes in gene expression and signaling pathways within cells, further promoting tumor development. These changes can affect various cellular processes, such as apoptosis (cell death), cell cycle regulation, and inflammation. Tumor Initiation and Progression: The cumulative effects of DNA damage, mutations, and altered cellular processes can lead to the initiation of a tumor. Over time, this tumor can grow, invade nearby tissues, and potentially metastasize (spread to other parts of the body), resulting in advanced cancer.

Why is UVB radiation more effective than UVA radiation in being carcinogenic?

Higher Energy: UVB radiation has higher energy levels than UVA. This higher energy allows UVB to directly damage the DNA in skin cells more efficiently. DNA Damage: UVB radiation is more effective at causing direct damage to the DNA in skin cells. This can lead to the formation of mutations and genetic changes that increase the risk of skin cancer. Formation of Thymine Dimers: UVB radiation is particularly efficient at causing the formation of thymine dimers in DNA. Thymine dimers are abnormal chemical bonds between adjacent thymine bases in the DNA strand, which can disrupt normal DNA replication and repair processes. Surface Penetration: While UVA can penetrate the skin more deeply than UVB, UVB primarily affects the outer layers of the skin, where most skin cancers originate.

how do hormones function as carcinogens?

Hormones, specifically certain sex hormones like estrogen, can indeed play a role as initiators or carcinogens in the development of various cancers, including breast, prostate, thyroid, ovarian, and testicular cancers. Promotion of Cell Proliferation: Estrogen, a female sex hormone, can stimulate the growth and division of cells in hormone-sensitive tissues, such as breast and prostate tissues. When cells divide more frequently, there are more opportunities for DNA replication errors to occur. These errors can lead to genetic mutations, some of which may be cancer-promoting. Estrogen Metabolites: Estrogen can be metabolized into various forms in the body, some of which can have carcinogenic effects. For example, estradiol-3,4-quinone is a metabolite of estrogen that can covalently bind to adenine (A) and guanine (G) bases in DNA. This can lead to the formation of DNA adducts, which are chemical modifications on the DNA molecule. These adducts can interfere with normal DNA replication and repair processes, potentially leading to mutations that initiate cancer. Exposure Time and Hormone Levels: The longer an individual is exposed to high levels of estrogen, the greater the potential for DNA damage and mutations to accumulate. Prolonged exposure to elevated estrogen levels can be a risk factor for hormone-related cancers. Breast Cancer: High lifetime exposure to estrogen, whether through early onset of menstruation, late menopause, hormone replacement therapy, or certain genetic factors, is linked to an increased risk of breast cancer. Estrogen can promote the growth of breast cells and contribute to the development of mutations. Prostate Cancer: While testosterone is the primary male hormone, it can be converted into estrogen in the body. Elevated estrogen levels or an imbalance in the ratio of testosterone to estrogen can influence prostate cell growth and potentially lead to the initiation of prostate cancer. Thyroid Cancer: Thyroid cancer is more common in women than in men, and there is evidence to suggest that estrogen exposure may contribute to thyroid cancer risk. However, the relationship between estrogen and thyroid cancer is complex and not fully understood. Ovarian Cancer: Ovarian cancer is inf

How does UVA damage DNA?

INDIRECT DNA DAMAGE UVA (Ultraviolet A) radiation primarily induces DNA damage indirectly through the generation of reactive oxygen species (ROS) and other free radicals. Unlike UVB radiation, UVA photons have lower energy and are less effective at directly causing DNA mutations by forming pyrimidine dimers. Instead, when UVA radiation penetrates the skin and is absorbed by cellular components, it can trigger the production of ROS within cells. These ROS are highly reactive molecules that can damage cellular structures, including DNA. The DNA damage induced by UVA radiation is often in the form of oxidative DNA lesions, such as oxidized bases and single-strand breaks. UVA-induced DNA damage is considered more subtle and less directly mutagenic than the damage caused by UVB radiation. However, it can still contribute to cellular dysfunction, premature aging of the skin (photoaging), and an increased risk of skin cancers over prolonged exposure. Additionally, UVA radiation can have harmful effects on other cellular components and processes beyond DNA. To repair UVA-induced DNA damage and maintain genomic integrity, cells employ various DNA repair mechanisms, including base excision repair (BER) for oxidative lesions and other repair pathways for single-strand breaks. Characteristic mutation: G->T transversions

How does a tumor suppressor gene lead to abnormal growth?

If it is a growth inhibitor, then it recessively loses the autonomy to stop growing. if it is a DNA repair protein, then it is haplosufficient and a lower gene done leads to abnormal growth. when a lower gene dose occurs due to mutations or loss of the remaining normal allele, it can disrupt the normal DNA repair mechanisms. As a result, DNA damage may accumulate within cells, and this can increase the risk of abnormal cell growth, tumor formation, and ultimately cancer.

how do Chemotherapy and radiation therapy prevent cancer?

Induces DNA damages to trigger apoptosis in cancer cells.

what is External beam radiation therapy (linear accelerator)?

Ionizing radiation --> react with H2O in the cells to generate ROS --> DNA damage supply of O2 matters. Hypoxia (low oxygen)--> decrease efficacy

How does radiation cause cancer?

It damages DNA directly or indirectly for example when UV penetrates the cell and damages the DNA by breakage or translocation

Why is ionizing radiation more carcinogenic than UV radiation?

It emits more energy due to the smaller wavelengths leading to more DNA damage. ionizing DNA or H2O leads to ROS which leads to DNA damage

How does PAH get metabolized to form the ultimate carcinogen?

It is a process called biotransformation. The ultimate carcinogenic form of many PAHs is typically generated through a series of enzymatic reactions in the liver. Phase I Metabolism: In the initial phase of biotransformation, enzymes called cytochrome P450s (CYPs) oxidize PAHs like BP (a procarcinogen). These enzymes introduce oxygen molecules into the PAH structure, converting them into more reactive intermediates. This phase can result in the formation of epoxides (oxiranes) or dihydrodiols. Formation of Epoxides: Epoxides are highly reactive and can form covalent bonds with DNA. . Phase II Metabolism: In the second phase of biotransformation, enzymes conjugate the reactive intermediates (e.g., epoxides) with other molecules helping detoxify the intermediates and making them more water-soluble for excretion. DNA Binding: Despite phase II detoxification, some of the reactive intermediates can escape and bind to DNA molecules. This can result in the formation of DNA adducts, where the carcinogenic intermediates covalently bond to the DNA structure. Mutations and Tumor Formation: If the DNA adducts are not repaired, they can lead to mutations during DNA replication. Accumulation of mutations in critical genes can ultimately result in uncontrolled cell growth and tumor formation. intercalates in DNA and attack guanine bases G->T transversions

what are some classic targets of cancer?

Kinases - catalysing the transfer of phosphate p53 - promotes apoptosis/cell cycle arrest Ras - protooncogenes -molecular switches regulating pathways responsible for proliferation and cell survival. Rb - prototype tumor suppressor gene, inhibitor of cell proliferation

What are long ncRNAs?

Long non-coding RNAs (lncRNAs) are a class of RNA molecules that are longer than 200 nucleotides in length and do not code for proteins, meaning they do not have significant open reading frames (ORFs) that can be translated into functional proteins. Instead, lncRNAs play important roles in gene regulation and various cellular processes through a variety of mechanisms. Diverse Functions: LncRNAs have diverse functions in the cell. They can act as regulators of gene expression, epigenetic modifiers, scaffolds for protein complexes, guides for chromatin-modifying factors, and more. p21-Associated lncRNA (lncRNA-p21): This lncRNA is an example of a non-coding RNA molecule that plays a role in the regulation of gene expression. It is downstream of the p53 signaling pathway and functions to repress the expression of certain genes. Its dysregulation can be associated with various cellular processes, including cell cycle control and apoptosis. HOTAIR: HOTAIR (HOX Transcript Antisense RNA) is a well-known lncRNA that guides chromatin-modifying factors to specific genomic loci. It is involved in epigenetic regulation and has been implicated in cancer. Dysregulation or overexpression of HOTAIR is often linked to cancer progression and metastasis. Epigenetic Regulation: Many lncRNAs are involved in epigenetic modifications of the genome. They can recruit chromatin-modifying complexes to specific genomic regions, leading to changes in histone modifications and DNA methylation, which, in turn, affect gene expression. Cancer and Disease: Dysregulation of lncRNAs has been implicated in various diseases, including cancer. Aberrant expression of lncRNAs can contribute to tumorigenesis, metastasis, and drug resistance in cancer cells. Consequently, lncRNAs have become important targets for cancer research and potential therapeutic interventions. Emerging Roles: Research into lncRNAs is ongoing, and many new lncRNAs with specific functions continue to be discovered. They have been found to play roles in development, immune response, neurobiology, and other biological processes. Molecular Mechanisms: LncRNAs can exert their effects through multiple mechanisms, including acting as molecular scaffolds to bring proteins toge

What are the trends with lung cancer?

Lung cancer has decreased over the years

What is microRNA?

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, typically composed of 18-25 nucleotides, that play a significant role in post-transcriptional gene regulation. They are involved in various cellular processes and can exert their regulatory effects by targeting messenger RNAs (mRNAs). Size: MiRNAs are small RNA molecules, usually 18-25 nucleotides in length. Despite their small size, they can have a profound impact on gene expression. Targeting mRNAs: MiRNAs primarily function by binding to the 3' untranslated region (3'UTR) of target mRNAs. This binding can lead to mRNA degradation or translational repression, ultimately reducing the expression of the target gene. Broad Impact: Each miRNA has the potential to repress the expression of hundreds of target genes. This ability to target multiple genes allows miRNAs to fine-tune complex regulatory networks. Roles in Cancer: MiRNAs can play both oncogenic and tumor-suppressive roles in cancer. Some miRNAs, known as oncomirs, are upregulated or amplified in cancer and target tumor suppressor genes, promoting tumorigenesis. Conversely, other miRNAs act as tumor suppressors by normally repressing oncogenes; their loss or dysregulation can contribute to cancer development. Dysregulation: Dysregulation of miRNAs in cancer can occur through various mechanisms, including genetic mutations, deletions, and aberrant epigenetic modifications. These changes can lead to an imbalance in the expression of specific miRNAs, contributing to cancer progression. Regulation by Oncogenes: Oncogenes can influence the expression and activity of miRNAs. Some oncogenes may upregulate certain miRNAs that target tumor suppressor genes, contributing to the oncogenic process. Pseudogenes: Pseudogenes are non-functional copies of genes. In some cases, the 3'UTR of pseudogenes can act as decoys for miRNAs, sequestering them and preventing them from binding to their intended target mRNAs.

What kind of lifestyle factors might influence cancer?

No kids in reproductive life - breast cancer, HPV, HIV Diet, exercise - decrease rates alcohol --- classified as a carcinogen in 2007! smoking - lung cancer metabolism - create byproducts of mutagenic oxygen radicals

where are the majority of cancer related SNPs located?

Non-coding region

Can any mutation cause cancer?

Not all mutations cause cancer. While mutations are a common feature of cancer development, specific mutations in certain genes, known as oncogenes or tumor suppressor genes, are more likely to contribute to cancer. Cancer typically results from a combination of genetic mutations, environmental factors, and other influences. Mutations alone do not always lead to cancer, but they can increase the risk of developing cancer when they affect critical genes involved in cell growth, division, and regulation.

how can TF cause cancer?

OVEREXPRESSION: c-JUN, c-FOS, (AP1 transcription factors) can transform normal cells inculture to cancer cells. Frequently overexpressed in cancer MUTATION/CHROMOSOMAL TRANSLOCATION RAR (retinoic acid receptor) - In the absence of RA --> repressor - In the presence of RA --> activate target genes. PML-RARA fusion (RARA=RAR-alpha ) - resulted from translocation, drives leukemia. Dominant negative inhibitor, inhibit the expression of genes required forhematopoietic differentiation. -Add "all-trans retinoic acid", PML-RARA changes conformation, and releases its binding to the corepressors --> allowing gene expression towards differentiation. MUTATION OF TF-BINDING DNA SEQUENCES (PROMOTERS, ENHANCERS, SUPER ENHANCERS) Insertional mutation, created a binding site for MYB --> upregulates TAL1 expression

What are Genomic Alterations in Cancer?

Point mutations Deletions Amplifications translocations - fuse sequence from different chromosomes

what are Polycyclic aromatic hydrocarbons (PAH) and how are they related to cancer?

Polycyclic aromatic hydrocarbons (PAHs) are a group of organic compounds composed of multiple fused aromatic rings, which are hexagonal carbon rings with alternating single and double bonds. PAHs are found in various environmental sources, including fossil fuels, tobacco smoke, grilled or charred foods, and polluted air and water. They are also produced naturally through processes like forest fires and volcanic eruptions. PAHs have been linked to cancer and are considered carcinogenic to humans. This association arises because some PAHs have the potential to damage DNA and disrupt normal cellular processes. Specifically, PAHs can undergo metabolic activation within the body to form reactive intermediates that bind to DNA, forming DNA adducts. These adducts can lead to mutations in critical genes, potentially initiating the development of cancer. Several PAHs, such as benzo[a]pyrene, have been extensively studied and are known carcinogens. They are commonly found in tobacco smoke and are associated with lung cancer. Additionally, PAH exposure through contaminated air, water, or diet has been linked to various types of cancer, including lung, skin, bladder, and gastrointestinal cancers. Reducing exposure to PAHs, such as by avoiding tobacco smoke, consuming grilled foods in moderation, and living in areas with low air pollution, can help mitigate the risk of cancer associated with these compounds.

What is the 98% of non-coding DNA comprised of?

Pseudogenes, ncRNA, introns and untranslated regions of mRNA, Regulatory DNA sequences, Repetitive DNA sequences (~50%), Mobile genetic elements (transposons) and their relics - DNA sequences found within an organism's genome that have the ability to move or "transpose" to different locations within the genome

Where can dysregulation of gene expression include alterations in?

Quantity, Timing, Localization of gene products.

What is the therapeutic index?

Ratio of a drug's toxic level to the level that provides therapeutic benefits - measuring the min. effective dose vs max. tolerated dose

What are example of endogenous carcinogenic reactions within the body that can lead to the development of cancer?

Reactive Oxygen Species (ROS): highly reactive molecules generated during normal cellular processes, such as oxidative respiration and lipid peroxidation play important roles in various cellular functions but excessive or uncontrolled production of ROS can damage DNA, proteins, and lipids, leading to mutations and chromosomal abnormalities. APOBEC Enzymes: APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) enzymes are involved in DNA and RNA editing processes. Overexpression of certain APOBEC enzymes has been linked to carcinogenesis. They produce mutations, particularly C->T (cytosine to thymine) transitions, by deaminating cytosine residues in DNA, resulting in genetic mutations that drive the development of cancer, especially in specific sequence contexts like TCA/TCT sequences where it produces uracil. DNA Replication and Recombination Errors: DNA replication is a complex and highly accurate process, but errors can occur. Mistakes in DNA replication, such as base substitutions, insertions, or deletions, can lead to genetic mutations that may initiate cancer. Similarly, errors during DNA recombination, which is important for repair and maintenance of DNA, can also contribute to genetic changes that increase cancer risk.

what are some Nutrition deficiencies that lead to cancer?

S-adenosyl-methionine (SAM) levels in the cells is affected by the nutritional levels of methionine, choline. SAM serves as a methyl donor in many cellular methylation reactions, where it transfers a methyl group to target molecules, including DNA, RNA, proteins, and lipids. The levels of SAM in cells can be influenced by nutritional factors, particularly the availability of certain nutrients, such as methionine and choline. Methionine: Methionine is an essential amino acid and a precursor to SAM. Cells use methionine to synthesize SAM through a series of enzymatic reactions known as the methionine cycle. Adequate dietary intake of methionine is essential for maintaining SAM levels. When there is a shortage of methionine in the diet, it can lead to a decrease in SAM levels, which, in turn, can affect various methylation reactions in the cell. Choline: Choline is a water-soluble nutrient that can be converted into betaine in the body. Betaine, in turn, participates in a biochemical pathway known as the "methionine cycle" or "one-carbon metabolism." Choline contributes to SAM levels indirectly by providing methyl groups through the production of betaine. Adequate choline intake supports the generation of SAM and helps maintain its cellular levels. Both methionine and choline are essential nutrients that play roles in various biological processes, including the regulation of SAM levels and methylation reactions. Proper dietary intake of these nutrients is important for ensuring the availability of SAM, which is critical for DNA methylation, gene expression, and other cellular functions.

how are single nucleotide polymorphism associated with cancer risks?

Single nucleotide polymorphisms (SNPs) can be associated with cancer risks through genome-wide association studies (GWAS) and other genetic analyses. In a GWAS, researchers analyze the DNA of individuals with and without a particular type of cancer to identify SNPs that are more common in one group than the other. These SNPs are potential genetic markers associated with cancer risk. GWAS involves large-scale statistical analysis to determine whether the presence of specific SNPs is statistically associated with an increased or decreased risk of cancer. This analysis considers the frequency of SNPs in cases (individuals with cancer) compared to controls (healthy individuals).

How is telomerase related to cancer?

Telomerase is an enzyme that plays a key role in maintaining the length of telomeres, which are the protective caps at the ends of chromosomes. It consists of two main components: telomerase reverse transcriptase (TERT) and telomerase RNA (hTR or hTERC), which serves as a template for the addition of new telomeric DNA repeats. In many cancer cells, telomerase is upregulated or overexpressed, leading to the maintenance or even lengthening of telomeres. This is a crucial step in the development of many tumors because it allows cancer cells to divide continuously and avoid the normal process of senescence or apoptosis that occurs when telomeres become critically short. Upregulation of Telomerase: Approximately 90% of human tumors have been found to upregulate telomerase activity. This upregulation is often associated with the uncontrolled growth and immortality of cancer cells. TERT and hTR Components: Telomerase consists of two main components. TERT, or telomerase reverse transcriptase, is the catalytic subunit responsible for adding new telomeric DNA repeats. hTR, or telomerase RNA, serves as a template for the synthesis of telomeric DNA. Somatic Mutations in TERT Promoter: In some cancers, somatic mutations occur in the promoter region of the TERT gene. These mutations can lead to increased transcriptional activity of TERT, resulting in higher levels of TERT protein. Mutations such as C->T or CC->TT in specific regions of the TERT promoter have been associated with TERT upregulation. These mutations can create new binding sites for transcription factors, leading to increased TERT expression. Role in Immortality: Telomerase upregulation is critical for the immortality of cancer cells. By maintaining or lengthening telomeres, cancer cells can continue to divide unchecked. This ability to bypass the normal limits of cell division is a hallmark of cancer. Therapeutic Target: Telomerase has been explored as a potential therapeutic target in cancer treatment. Inhibiting telomerase activity could potentially limit the ability of cancer cells to divide continuously, leading to cell senescence or apoptosis. Understanding the role of telomerase in cancer is important for developing strategies to target this enzy

how does differentiation affect the net number of cells?

The cells are neither dividing to increase number drastically nor are they dying. They are just there so just add.

Mismatch repair

The cellular process that uses specific enzymes to remove and replace incorrectly paired nucleotides. Corrects replication errors escaped editing by polymerases MutS Homolog 2 (MSH2) recognizes and binds to mismatches or small insertions/deletions in DNA while MutL Homolog 1 (MLH1) helps coordinate the repair process.

How do transcription factors regulate gene expression?

They bind to specific DNA sequences and either activate or repress the transcription of nearby genes. TFs are composed of several structural domains that enable them to carry out their functions: 1. DNA Binding Domain: Helix-Turn-Helix: This domain consists of two alpha helices separated by a short turn. It is a common DNA-binding motif found in many TFs. One of the alpha helices fits into the DNA's major groove to make sequence-specific contacts. Leucine Zipper: Leucine zippers are dimerization motifs. TFs with leucine zipper domains often work in pairs, with each monomer contributing a helical structure. These TFs can form coiled-coil structures that facilitate DNA binding. Helix-Loop-Helix: Similar to the leucine zipper, TFs with helix-loop-helix domains also function as dimers. This domain consists of two alpha helices separated by a loop region. It allows for protein-protein interactions and DNA binding. Zinc Finger: Zinc finger domains are small protein motifs that often contain a zinc ion coordinated by specific cysteine and histidine residues. They can form structures that bind to DNA sequences with high specificity. 2. Transactivation Domain: Transactivation domains are responsible for activating gene expression. They interact with other components of the transcriptional machinery, such as RNA polymerase and coactivators, to initiate transcription of the target gene. 3. Other Domains: Dimerization Domain: As mentioned earlier, some TFs work as dimers. The dimerization domain facilitates the formation of protein complexes, which can enhance their DNA-binding specificity and regulatory functions. Ligand Binding Domain: In some TFs, ligand binding domains allow them to respond to specific signaling molecules or ligands. Upon binding to their ligands, these TFs undergo conformational changes that affect their activity.

how do you use FISH to detect chromothripis

To detect chromothripsis using FISH (Fluorescence In Situ Hybridization): Design fluorescent probes targeting specific chromosomal regions. Apply probes to the sample, allowing them to bind to their complementary sequences on chromosomes. Wash away unbound probes. Visualize and analyze the sample under a fluorescence microscope. Look for complex chromosomal rearrangements indicative of chromothripsis.

What is a secondary tumor?

Tumor forms in another site but spreads to the brain (lung, skin or breast cancers) [Tumor travels there]

Describe the tumor microenvironment

Tumors consist of many cell types, including cancer cells, mast cells, endothelial cells, macrophages pericytes, fibroblasts and inflammatory white blood cells...endothelial cells..capillaries eventually feed it Communication between these different cells plays a role in development

Why is UVC sunlight less dangerous to humans than UVB even if the energy of UVC radiation is higher?

UVC sunlight is less dangerous to humans than UVB despite having higher energy because UVC radiation is largely absorbed by the Earth's atmosphere and does not reach the surface in significant amounts. In contrast, UVB radiation, although of lower energy, penetrates the atmosphere and can reach the Earth's surface. This is why UVB is more relevant and poses a greater risk to human health, as it can cause skin damage, sunburn, and an increased risk of skin cancer when we are exposed to it through direct sunlight. UVC, on the other hand, is largely filtered out by the atmosphere, so it doesn't have the same impact on human health.

How does a tumor form?

When cells grow and divide rapidly and they have nowhere to go so they pile on top of each other Normal development [gene regulation] go awry Gained access to genomic information that is normally denied to them Corruption in genomic sequence Altered structure and information content (mutation)

what are the risk factors associated with breast cancer?

alcohol late pregnancy (>30) early period late menopause obesity after menopause hormone replacement therapy oral contraception increase estrogen concentration

Why is plasticity important for development?

allows organisms to adapt to changing environments, ensuring better survival and reproduction. It enables them to adjust their growth and behavior in response to varying conditions. Cells acquire new fates and activate new genes

What was the oldest recorded case of cancer found in Egypt in 1600BC?

breast cancer

What are the goals of cancer therapy?

cytotoxic - kill cancer cells cytostatic - prevent cancer proliferation increase therapeutic index because its safer

Where are carcinomas found?

epithelial tissue

Where are adenocarcinomas found?

glandular cells

how does an oncogene lead to abnormal growth?

if it is a growth inducer, it just goes dominantly without regulation

how do Drugs target estrogen action?

in breast cancer and hormone replacement therapy in post-menopausal women: 1. Blocking Estrogen Receptors: Drugs in this category are known as Selective Estrogen Receptor Modulators (SERMs) and Selective Estrogen Receptor Degraders (SERDs). They work by either blocking the estrogen receptor or by degrading it, preventing estrogen from binding to the receptor and exerting its effects. Examples of SERMs include tamoxifen and raloxifene. Tamoxifen is used in the treatment of hormone receptor-positive breast cancer and for reducing the risk of breast cancer recurrence. Raloxifene is used to prevent and treat osteoporosis in post-menopausal women. Fulvestrant is an example of a SERD used in the treatment of hormone receptor-positive breast cancer. It works by binding to the estrogen receptor and causing its degradation. 2. Blocking Estrogen Synthesis: Aromatase inhibitors are drugs that inhibit the enzyme aromatase, which is responsible for converting androgens (male hormones) into estrogen. By blocking this enzyme, aromatase inhibitors reduce the production of estrogen in the body. Examples of aromatase inhibitors include anastrozole, letrozole, and exemestane. These drugs are commonly used in post-menopausal women with hormone receptor-positive breast cancer to reduce estrogen levels in the body.

What is chemotherapy?

inducing cytotoxic agents that kills neoplastic cells preferentially by sparing normal tissues, or at least by inflicting only tolerable side effects on the patients.

How do we study the interactions between DNA and proteins using an EMSA?

investigate the binding of proteins, such as transcription factors, to specific DNA sequences. 1. Protein-DNA Complex Formation: - target DNA fragment containing DNA sequence of interest, "probe," is labeled w/ fluorescent tag. The protein of interest, like transcription factor AP-1 (Activator Protein 1), is added to labeled DNA probe. If the TF has a binding site within the probe, it will bind to it, forming a protein-DNA complex. 2. Electrophoresis: The next step involves running the protein-DNA mixture through a polyacrylamide gel in an electric field, separating molecules based on their size and charge. -protein-DNA complex is larger and differently charged than the free DNA probe 3. Visualization: After electrophoresis, gel is stained and separated DNA fragments are visualized as bands on the gel. 4. Interpretation: -if the TF (in this case, AP-1) binds to the DNA probe, it will form a slower-moving complex that will appear as a shifted or "retarded" band on the gel compared to the free DNA probe. The intensity of the shifted band can provide information about the strength of the protein-DNA interaction. Stronger binding results in a more intense shifted band.

How is plasticity is required for adult tissue repair?

it allows cells and tissues to adapt and regenerate in response to injury or damage. This adaptability enables the body to heal and replace damaged tissue, restoring normal function.

how can non-coding RNAs and epigenetic changes, such as DNA methylation patterns, be harnessed as diagnostic and screening tools for various cancers?

lncRNA PCA3 in Prostate Cancer: Long non-coding RNA (lncRNA) PCA3 is known to be overexpressed in approximately 95% of primary prostate cancer samples. PCA3 is used as a biomarker for prostate cancer detection and can be assessed through a non-invasive RNA-based urine test. This urine test, often referred to as the PCA3 test or Progensa PCA3 test, measures the levels of PCA3 in a patient's urine sample. Elevated levels of PCA3 in the urine can indicate the presence of prostate cancer, and this test can help in the diagnosis and monitoring of the disease. BMP3 and NDRG4 in Colon Cancer: In colon cancer, there are specific DNA methylation changes that occur in the promoters of certain genes. Two such genes are BMP3 (Bone Morphogenetic Protein 3) and NDRG4 (N-Myc Downstream-Regulated Gene 4). Aberrant DNA methylation in the promoters of these genes is associated with colon cancer. This DNA methylation pattern can be detected in stool samples, and it serves as a non-invasive method for colon cancer screening. Stool DNA tests, such as the Cologuard test, look for these methylation changes along with other genetic markers and blood in the stool to identify individuals at risk for colon cancer or with early-stage disease.

Chemotherapy: Antimetabolites

mimic natural metabolites, disrupting vital cellular processes like DNA and RNA synthesis. They interfere by competitive inhibition or incorporating into genetic material, leading to chain termination. Examples include compounds resembling folic acid, pyrimidines, and purines, hindering cancer cell growth.

how is DNA methylation linked to gene repression?

occurs primarily in CpG islands, represses gene expression. It blocks transcription factor binding, recruits repressive proteins, condenses chromatin, and interferes with enhancer-promoter interactions. This epigenetic modification, mediated by enzymes like DNMT1, DNMT3a, and DNMT3b, plays a vital role in regulating gene activity.

caveats to cancer surgery treatment?

people do not like scars - can be traumatizing Lymphedema - the flow of lymphatic fluid through lymph vessels or nodes becomes impaired. The fluid can back up and enter the nearby soft tissue, causing the characteristic swelling

Why does cancer decrease with age?

rate of senescence increases with age so although cancer rates increase, senescence overpowers cancer

what are Telomeres and telomerase?

telomeres shorten with each round of DNA replication because DNA replication machinery cannot fully replicate ends of linear chromosomes. When critically short due to repeated cell divisions, they signal cell to enter a state of senescence or apoptosis, serving as a protective mechanism to prevent cells with damaged or unstable genomes from continuing to divide, potentially becoming cancerous. Telomerase: enzyme that adds new telomeric DNA repeats to ends of chromosomes by using its RNA component as a template to synthesize new telomeric DNA. It is typically active in certain stem cells, germ cells, and immune cells, allowing these cells to maintain their telomere length despite repeated divisions. Crisis After Senescence: After a certain number of cell divisions, most normal somatic cells reach a state of senescence due to telomere shortening. At this point, the cells no longer divide. If telomeres continue to shorten beyond senescence, cells can enter a crisis stage, which often leads to cell death or genomic instability. However, some cells, particularly cancer cells, can bypass this crisis stage through telomerase reactivation or alternative lengthening of telomeres (ALT) mechanisms, one of the ways in which cancer cells can achieve immortality and continuous proliferation. Role in Aging and Disease: Telomere shortening is associated with the aging process, and it has been linked to age-related diseases. The loss of regenerative capacity in tissues as a result of telomere shortening is thought to contribute to the aging phenotype. Telomere dysfunction is also implicated in a variety of diseases, including cancer, cardiovascular diseases, and certain genetic disorders.

Where are sarcomas derived from?

the mesoderm ie bone , muscle

what is the difference between transition vs. transversion mutations?

transition - purine for a purine transversion - pyrimidine for purine or vice versa

How do we identify oncogenes, tumor suppressors, and other factors?

• Correlative. • Loss-of-function • Gain-of-function

DNA repair ----5 types

• One-step repair • Base excision repair (BER) • Nucleotide excision repair (NER) • Mismatch repair • Recombinational repair