NS 1150 Prelim 4

L21-L28, A4

How is Human Milk Produced

Produced in mammary glands through hormones through a process called lactation which begins during pregnancy and contiunes

Composition of Human Milk

Nourish, Communicate, and Protect

Carbohydrates(oligosaccharides & Lactose), Fat, Protein,

Benefits of Breastfeeding

Baby Benefits:

• Long-term protection from obesity, asthma, & diabetes

• Nutrient

• Provide protection

Mother Benefits:

• Reduce risk for breast & ovarian cancer

• Reduce risk of postpartum depression

• Reduce risk for type 2 diabetes

Recommended Breastfeeding Time legnth by AAP and WHO

6 months and then to 2 years (with complmentary food)

Contra-Indications of Breastfeeding

Untreated HIV

Human T Cell Leukemia-Lymphoma Virus Infection

Ongoing Drugs Use

Temporary stop breastfeeding while chemotherapy

Breastfeeding Pathology that affect breastmilk

First 14 days postpartum are important for lactation development

Pregnancy - Open paracellular pathway

Early Lactation - Closing paracellular pathyway

Established Lactation - Closed paracellular pathway

DNA is a made from

Polymers of Nucleotides

Nitrogenous bases consist of

Purine

• Adenine(A)

• Guanine(G)

Pyrimidine

• Cytosine(C)

• Thymine(T)

• Uracil(U)

Structure of DNA

Double Helix Structure

Sugar and phosphate of the nucleotides form backbone

Nitrogenous bases are stacked inside

Chargaff’s Rule

A%=T%

C%=G%

What is a Gene

A sequence of DNA that is transcribed to produce a functional RNA and/or Protein

Components of a Gene

Promotor Sequence - Binding sites for RNA transcription machinery

Exons - protein coding sequences

Introns - non-protein coding sequences

5’UTR/3’UTR - Untranslated region that contain non protein coding that transcribed into RNA and regulate protein translation

Enhancer/Silencer - regulate efficiency of gene transcription

Organization of Human Genome

46 Chromosomes:

• 22 pairs of autosomes

• 1 pair of sex chromosomes: XX(Female) & XY(Male)

Where does genetic diversity come from (3)

1) Genetic Mutations

2) Meiosis Cell Division

3) Sexual Reproduction by combining the genetic material from 2 individuals

Mechanism of Genetic Mutations

Exogenous Cause

• UV

• Irradiation

• Tabacoo

• Industrial pollutatns

Endogenous Cause

• Reactive Oxygen Species

• Errors in DNA replication

Consequences of DNA Mutation(4 types)

Silent Mutation - Doesn’t impact the encoded protein sequence

Missense Mutation - Changes the encoded amino acid(may or may not impact)

Nonsense Mutation - Changes amino acid to stop

Frameshift - insertion or deletion of a nucleotide will change the codon reading frame(significantly change amino acid)

Consequences of Chromosomal Mutation(4 types)

Duplication - increase the copy number of gene leading to increased expression

Deletion - loss of gene

Inversion - disrupt gene at border of the inversion

Translocation - fuse 2 different gene to create a fusion protein or bring a gene under control of a different promotor

What mechanism of Meiosis (Gametes) Cell Division gives genetic diversity

1) Crossing Overs

2) Independent Assortment

Sexual Reproduction:Mendelian Inheritance

Allele (y or Y)

• Dominant Allele: determines phenotype w/1 copy

• Recessive Allele: determines phenotype w/2 copies

Homozygous (yy or YY)

Heterozygous (Yy)

Monogenic Disorder(Mutation in single gene: autosomal recessive) in Human Nutrition (3 types) 

Absorption Disorder: Cystic fibrosis, Hereditary hemochromatosis

Metabolic Synthesis/Processing Disorder: Phenylketonuria

Energy Generation Disorder: Mitochondrial Defects

Cystic fibrosis

• Autosomal recessive genetic disorder by co-inheriting 2 mutatn allels of the CFTR gene on chromosome 7

• Cystic fibrosis transmembrane conductance regulator(CFTR) is an ion channel that transport Chloride ions into surface lumens in airways within lungs, pancreas, and GI

• Movement of Chloride into extracellular space creates an osmotic gradient to ensure mucus in lumen has adequate water content to reduce viscosity and improve mobility of mucus

• In Cystic fibrosis loss of CFTR ion channel lead to thickened mucus, leading to poor lung function due to mucus buildup, pancreatitis, and decreased absorption of fats, carbs, and protein

  • patients need extra pancreatic enzyme oral supplements(pancreases) with meals to aid digestion

Cystic Fibrosis in newborns/infants

Meconium ileus where thickened mucus accumulates in the ileum casuing abdominal distention and obstruction of GI tract 

• treated with an enema(lubricant) applied via rectum(then surgery if not sucessful)

What is one of the most common monogenic disorders in population of European descent

Cystic Fibrosis

• Carrier is 1/25

• Newborn 1/2500

Cystic fibrosis: Protection against cholera

Cholera is caused by the bacteria: Vibro cholerae which secretes toxin that causes overactivity in the CFTR ion channel, resulting in excessive water loss into the bowel lumen and diarrhoea

• CFTR mutation carriers do not suffer cystic fibrosis, but express reduced CFTR ion channels so are less susceptible to chlorea toxin

Absorption Disorder: Hereditary Hemochromatosis

• Iron is absorbed in SI, stored in liver & macrophages, & utilized for hemoglobin synthesis and as a metal co-factor for enzyme and redox reaction

• No physiological route to excrete iron from body, so iron is stored carefully maintained

• increased circulating iron level in the blood, liver protein HFE stimulate protein hepcidin which reduces iron absorption in bowel & reduce release of iron stored in macrophage

  • inherit 2 mutant alleles of HFE, the stimulation to release hepcidin is lost leading to increased absorption and release of iron into the body

Prominent feature of Hereditary Hemochromatosis

iron accumulation in the skin leading to the darker “bronze” apperance, permanent damage to the heart, liver, pancreas, and brain

Treatment of Hereditary Hemochromatosis

• Regular phlebotomy(removal of blood) as a method of removing excess iron: reliable blood donors

• Drugs that bind to iron(iron chelators), which the kidney can then excrete in the urine

• hypothesized that the HFE mutation evolved to minimize the impact of menstruation which cause iron deficiency

Metabolic synthesis/Processing Disorder: Phenylketonuria

• Rare autosomal recessive genetic disorder caused by co-inheriting 2 mutatn allels of the PAH gene on chromosome 12

• PAH gene encodes the phenylalanine hydroxylase enzyme that convert amino acid phenylalanine to tyrosine

• In phenylketonuria, the loss of PAH enzyme activity results in toxic accmulation of phenylalanine that interfere with newborn development of brain and nervous system

Phenylketonuria during pregnancy

Mother’s PAH enzyme activity can protect the developing fetus from phenylalanine accumulation

• All newborns are screened for phenylketonuria using a blood test to test for high levels of phenylalanine in the blood

Treatments for Phenylketonuria

Avoiding high protein diet including:

• meat and fish

• eggs and cheese

• nuts and seeds

• flour based food: bread, pasta, cakes, and biscuits

• soya, quorn, and tofu

Regular blood test are taken to check blood levels of phenylalanine

Energy Generation Disorder: Mitochondrial Defects

Mitchondria role in converting nutrients into ATP

Symptoms reflect insufficiency of ATP in muscles, nerves, and brain

• muscle weakness

• exercise intolerance

• seizures, headaches

• Ataxia

• Vision Defects

Inheritance of mitochondrial diorder

2 types of genes essential lfor mitchondria function

1. Gene encoded in the nuclear genome lead to autosomal dominant, autosomal recessive, & X-linked pattern

2. Mitochondrial genome inherited in a maternal pattern that is always from mother

   • During conception, when sperm fuses with egg, the sperms mitochondria do not contirbute to the fertilized egg, so all mitochondria come from mother

   • Egg will have hundreds of individul mitchondria, so severity of mitochondria disease reflects the number of mutated mitochondria in egg

Non-Mendelian Inheritance

• Physical characteristics and human diseaes are polygenic

  • phenotype is determined by combination of multiple genes

  • phenotype can also be influenced by environment and genetic factors

Polygenic Traits

• At least 8 genes determine the color of the human eye

  • a greater number of genes = increased complexity in inheritance pattern

How do we identify if specific genes play a role in the pathology of a trait or disease(4)

• Family History

• Twin Studies

• Adoption studies

• Genome wide association studies

Family History

• Collecting info on family members with and without the disease

• In Mendelian inheritance, this should lead to predictable pattern of inheritance

• Polygenic diseases do not exhibit Mendelian inheritance

  • Typically 1 or more first degree relative with the same disease will indicate heritable genetic factors that influence disease

• Interaction between specific genes and environment influence disease onset

• Incomplete info on family members beyond immediate family circle

Twin Studies

• Identical twins(monozygotic) form as a result of a single embryo dividing into two embryos and share 100% genetic identity

• Fraternal twins(dizygotic) form from fertilization of two separate eggs by 2 separate sperms, respectively, and share 50% genetic identity

  • If disease in monozygotic twin»dizygotic twin suggest a genetic factor play a role in disease development

Adoption Studies

• Studies compare groups of adoptees with their adopted families as well as their natural families

  • Adoptees typically share no genetic identity with their adopted family, & 50% genetic identity with their biological parents

  • If disease/trait in adoptees is strongly correlated w/the biologial parents, this indicates a genetic component that impacts the development of the disease

Genome Wide Association Studies(GWAS)

Powerful method to identify a statistically significant association between a genetic mutation and a polygenic disease

• An observational case-control study: collect info from cohorts of individuals with and without the disease: disease that are more frequently present in the disease population compared to control population

How do we find mutations in GWAS studies

• Whole genome sequencing to find mutations: expensive and not yet feasible to perform for every subject in large studies

• Single nucleotide polymorphism database use existing data with known locations of mutations present in the general population: cheaper and only part of gene

  • Single Nucleotide Polymorphism(SNP) are point mutations

What happens if a SNP is associated with a disease

SNP is the mutation in a gene that causes the disease but very rare as majority of SNP are non-gene coding regions

SNP are more like genetic “bookmarks” highlighting a region of the chromosome that could contain the real disease or mutation that impacts disease development

• More SNPs = more likely that we find a SNP that associates with the disease

• SNP databases will have SNPs that cover length of each chromosome: Human Genome Project 

Advantages of GWAS(Genome Wide Association Studies)

• Ability to use very large sample size to identify diverse number of genetic variation that contribute to the phenotype

• Rare genetic variants that only affect specific populations can be identified

Genetics of Obesity

• Enviornmental factor play a major role

• Twin Studies(meta analysis on 88 independent twin study)

  • existence of genetic factors that determine BMI and Obesity

• Family Study

  • Also agree twin studies showwing importance of genetic factor determining BMI

    • Heritability Index Range: 0-1

    • 0 = trait is not determined by genetics

    • 1 = trait is completely determined by genetics

2 Forms of Genetic Obesity

Monogenic(early onset, severe obesity)

• High Genetic contribution

• Single mutation in one gene

• Large genetic effect

• Rare

• High penetrance

• No environmental influence

Polygenic(Common obesity)

• Modest genetic contribution

• Hundreds of variants in or near many genes

• Each variant has a small effect

• Common

• Low penetrance

• Enviroment is a key determinant

Monogenetic Obesity: Leptin

Identified in mice or the (ob) mouse model

• ob mouse exhibit hyperphagia(excessive eating) leading to obesity

Performed a parabiosis experiemnt where blood vessel from a normal mouse was connected to the ob mouse

• Surgically connected ob mouse showed decrease food intake leading to weight loss

• By sharing a blood supply, normal mouse must be sharing its satiety factor with the ob

• Protein hormone called leptin

Congenital Leptin Deficiency

A family with congenital leptin deficiency was reported in 1997

• Affected individuals were homozygous for a single nucleotide deletion in their leptin gene causing a frameshift mutation

Leptin-Melanocortin pathway

Leptins action is in the CNS, where it activates the hypothalamic leptin-melanocortin pathway

In the hypothalamus, leptin acts on leptin receptors on neurons that produce the protein proopiomelanocortin(POMC)

POMC undergoes proteolytic cleavage to produce a number of neuroactive pepide like MSH

MSH peptides act on melanocortin receptor 4(MC4R) expressed on neurons in the paraventricular nucleus(PVN) within the hypothalamus resulting in reduction of food intake and modified energy metabolism

Polygenic Obesity(Common Obesity)

Caused by additive effect of hundreds/thousands of common genetic variants

GWAS have identified more than 1100 independent loci associated with a range of obesity traits(3-5%)

Polygenic Obesity: Fat mass - and obesity- associated (FTO) gene

GWAS identified several SNPs in the intron of FTO that was associated with obesity and type 2 diabetes

FTO encodes for alpha-ketogultarate-dependent dioxygenase enzyme that removes methyl groups from RNA

FTO in obesity remains unclear, but later transpired that obesity association for this locus is at least in large part due to altered regulation of a neighboring gene, iroquois homeobox 3(IRX3) which has an impact on peripheral adipocyte metabolism

Nutritional Genomics & Nutrigenetics

Nutrigenomics - the study of the effects of nutrients on the expression of an individuals genetic makeup

Nutrigenetics - the study of how genotype determines metabolism of food components, nutrient requirements, and dietary tolerance

Examples of Nutrigenetic 

Hereditary hemochromatosis

Phenylketonuria

Lactose intolerance - genetic deficiency of lactase enzyme

Alchol flushing syndrome - genetic mutation in acetaldehyde dehydrogenase 2 enzyme

Examples of Nutrigenomics

Influence of bioactive components in food on gene expression and phenotype

Impact gene expression at any point in the process(Transcription, translocation, post translational modification)

S-Adenosyl-Methionine Deficiency

• Folate provides the methyl group that is added onto homocysteine to make methionine & vitamin B12 is the cofactor for the enzyme methionine synthase

• Methionine is subsequently converted to S-Adenosyl-Methionine(SAM) which is utilized by DNA methyltransferase enzyme to methylate DNA

  • DNA methylation is an important mechanism of silencing gene expression by shutting down transcription of genes

• Folate Deficiency limits SAM synthesis leading to hypomethylation of DNA which lead to inappropriate expression of gene

What is Cancer

Abnormal growth and spread of cells that arise from failure to control cell growth and migration

Cancer is a genetic disease

Genetic info encoded in our genome provides the instruction for growth and development

Changes in this genetic codde can lead to aberrant instructions that causes cancer

Terminology: Tumor, Benign, Malignant, & Metastasis

Tumor = Describes an abnormal growth of cells which can be benign or malignant (cancerous)

Benign = A tumor that is not capable of spreading to other tissues, locally or to distant organs(metastasis)

• A benign tumor is not a cancer, but a benign tumor can acquire further genetic mutations to become a malignant tumor

Malignant = A tumor with the ability and potential to spread and form metastasis.

• A malignant tumor = cancer(interchangeably).

• Describes a functional property of the tumor, and tumor doesn’t have to form any metastases to be classified as malignant.

• Histological appearance of the primary malignant tumor often correlated with its potential to metastasize

Metastasis = process of forming new colonies of tumor in distant organs/tissues

Histological apperance under the microscope of Benign Tumor

Benign tumor

• Confined to original site of the body

• Clearly defined and intact boundaries

• Often physically separated from surrounding tissue by a capsule of connective tissue

• Cells often resemble the apperance of normal cells

Histological apperance under the microscope of Malignant Tumor

Malignant Tumor

• Poorly defined boundaries that can exhibit disruption with infiltration of cells into surrounding tissue

• exhibit more abnormal apperances including large nucleus, loss of normal cellular structures, and loss of normal organization with neighboring cells

Causes of Cancer

Mutations in genes cause cancer

• Understand origins of DNA mutations

Different Types of DNA Damage

DNA breaks

Base modification

Crosslinks

Challenges in discovering the cause of cancer (3)

1) Heterogeneous disease: cause of one type of cancer does not necessarily cause other type of cancer

2) Cancer usually takes several years/decades to develop, so challenging to track down the initiating cause of cancer

3) Cancer develops from a multi-step process; therefore a normal may require multiple insults from different causes to turn into a cancer

Methods used to discover casues of Cancer

Epidemiology Method

• Observational studies that identify an association between enviromental factor and specific cancer

  • lung cancer and tobacco smoking

  • DOESN’T ESTABLISH CAUSATION

Experimental Method

• Bacterial & Cell line model to test if specific chemicals cause DNA mutation

• Animal models to test if specific chemicals lead to cancer formation

• DOESNT NOT ALWAYS MODEL HUMAN CANCER

How Does Nutrition Contribute to Causes of Cancer (5)

1) Direct voluntary consumption of carcinogen: alcohol

2) Contamination of cosumed food: aflatoxin

3) Food Borne infectious pathogen can cause cancer

4) Deficiency in specific nutrient can increase DNA damage

5) Clear epidemiology association between obesity and cancer but mechanism currently not well understand

Alcohol & Cancer

All alcoholic drinks are associated with increased risk of cancer

• Cancer related to alcohol reflects epithelial cells of the GI tract

Mechanism of Alcohol carcinogenicity

Ethanol is metabolized to acetaldehyde which damages DNA to cause mutations

Mammals have evolved acetaldehyde detoxification enzyme ALDH1A1 & ALDH2 to prevent toxic accumulation of acetaldehyde

What region is ALDH2 polymorphism common

EAST Asia

Cancer risk between ALDH2 polymorphism and alcohol intake

Aldehyde Dehydrogenase 2 and Head and Neck Cancer

• Meta-analysis of multiple observational studies shows the odds ratio(OR) of developing head and neck cancer in individuals with ALDH2 polymorphism vs general

  • OR = 1 means equal likelihood of developing cancer compared to general population

  • OR = 2, twice as likely to develop cancer compared to general population

• People with Alcohol flushing syndrome shouldn’t drink alcohol

Aflatoxin & Cancer

Aflatoxin B1 is a potent toxin produced by the fungus Aspergillus flavus

• can contminate many agricultural crops like peanuts, corn, cereal grains

• aflatoxin B1 remain stable during drying, storage, and processing of crops

• ingestion of food with aflatoxin B1 is associated with increased DNA dmage & hepatocellular carcinoma

Heliobacter Pylori & Cancer

H-Pylori is a sprial shaped bacterium that infects the stomach lining

• transmitted via contaminated food and water

• In stomach, H-pylori survive the acid environment in stomach by neutralizing the surrounding acid, and burrowing into the mucus layer of the stomach

• H-Pylori infection causes injury to the gastric epithelium, leading gastritis, & gastric ulcers

  • Untreated leads to ROS = DNA damage & cell proliferation = high chance of mutation

Folate Deficiency & Cancer

Folate Deficiency has been implicated in development of cancers of colon, breast, ovary, pancreas, brain, lung, and cervix

Individuals with high dietary folate intake exhibit reduced risk of colon cancer compared to low intake

Mechanism of Carcinogenesis from Folate Deficiency: Uracil Misincorporation

Uracil Misincorporation

• Folate is required for the conversion of deoxyuridine(dU) to deoxythymidine(dT), an essential nucleotide required for DNA replication and DNA repair

• Folate deficiency limits dT synthesis & elevates dU

• As dT and dU are structurally similar, dU is incorporated into DNA

• dU in DNA is unstable(break DNAstrand) and excised by DNA repair enzyme

Mechanism of Carcinogenesis from Folate Deficiency: S-Adenosyl-Methionine Deficiency

S-Adenosyl-Methionine Deficiency

• Folate provides the methyl group that is added onto homocysteine to make methionine & vitamin B12 is the cofactor for the enzyme methionine synthase

• Methionine is subsequently converted to S-Adenosyl-Methionine(SAM), which is utilized by DNA methyltransferase enzyme to methylate DNA

• DNA methylation is an important mechanism of silencing gene expression by shutting down transcription of genes

• Folate Deficiency limits SAM synthesis leading to hypomethylation of DNA which lead to inappropriate expression of gene

Obesity & Cancer

Nearly all of the evidence linking obesity to cancer risk comes from large cohort observational studies

More than 1000 observational studies on cancer risk and excess body fatness have been conducted

Significant associations between BMI and Cancer risk were reported

Mechanisms of Obesity and Cancer(not fully understood yet)

Obesity leads to mechanisms like

• Chronic inflammation

• Increased circulating a lipids as nutrient for cancer cells

• increased insulin and insulin growth factor 1 (IGF-1) are utilized by cancer cells as growth factors

• Fat cells(Adipocytes) secrete adipokines, hormones that play roles in cancer development

  • leptin is an adipokine that regulate appetite but can also stimulate growth of cancer cells

Cancer impact diet and Nutrition: Obstruction

• Airway causing hypoxia - reduced energy for eating, discomfort can reduce appetite

• Oral-pharynx/esophagus - dysphagia(difficult swallowing)

• Lower GI obstruction - nausea, vomiting, and abdominal pain reduces appetite and reduce GI absorption

• Urinary Tract - discomfort can reduce appetite, acute kidney failure lead to vomitting

Cancer impact diet and Nutrition: Compression

Compression of GI tract can lead to obstruction

Compression of brain and nerves can impact muscles involved in eating and swallowing

Cancer impact diet and Nutrition: Pain

Compression/infilration of nerves

Ulceration

Bone fracture

Pain Reduces appetite

Cancer impact diet and Nutrition: Bleeding

Chronic Gastrointestinal Bleeding can lead to iron deficiency

Cancer impact diet and Nutrition: Inappropriate Secretion of Hormone

Insulin secreted by pancreatic beta cell tumor - cause persisent hypoglycemia

PTHrp secreted by lung cancer - cause hypercalcemia

ADH secreted by lung cancer - cause hyponatremia from excess water reabsorption in kidney (Syndrome of Inappropriate ADH secretion SIADH)

Cancer impact diet and Nutrition: Cachexia

Cachexia - metabolic wasting syndrome commonly in people with advanced cancer

• involuntary weight loss, including loss of fat and muscle, loss of appetite, weakness and fatigue

• Not reversed by increase dietary intake

• complex metablic state that involves increased breakdown of protein

Cancer impact diet and Nutrition: Cancer Treatment

Nausea and Votmiting caused by systemic chemotherapy - Reduce oral intake

Mucositis - inflammation of GI lining from chemotherapy and radiotherapy

Causing SIADH

6 Hallmark of Cancer

Specific biological capabilites of cancer

• Sustain proliferative signaling

• Evade growth suppressor

• Metastasis

• Imortatlity

• Induce Angiogensis

• Resist Cell Death

Emerging Hallmarks of Cacner

Avoid Immume Destruction

Tumor Promoing inflammation

Genome instability/mutation

Deregulating cellular energetics

How does Cancer Hijack and Rewire Metabolism: Growth Factors

Hijack growth promoting signaling pathways to sustain growth

• Cancer mutate gene in growth factor signaling pathways to grow in absence of signals

  • i.e insulin signaling pathway where receptor is overexpressed in cancer leading to more proliferation

How does Cancer Hijack and Rewire Metabolism: Induce Angiogensis

Induce angiogenesis to increase blood supply to cancer

• Angiogenesis = process of sprouting new blood vessel from existing vessel

• Cancer turn on proaniogenic factor to secure blood supply, but new vessel are fragile and prone to bleeding which can help cancer spread

How does Cancer Hijack and Rewire Metabolism: Dysregulating cellular energetics(4 types)

increased nutrient utilization

alternative nutrient utilization

altered tumor microenvironment

metabolic toxin

Increased Nutrient Utilization

Ccancer cells exhibit increased glucose uptake and utilization: Warburg effect

Increased Nutrient Utilization: Altered Bioenergetics

• Altered Bioenergetics: increased glucose use is for synthesis of other essential macromolecules

Increased Nutrient Utilization: FDG-PET Imaging

18F Fluorodeoxyglucose is an analogue taken up by cells and can be detected by positron emission tomography

Alternative nutrient utilization

Cancer can use other nutrients 

• Pancreatic cancer uses uridine(ribionucleotide where sugar feed into glycolysis

Altered tumor microenvironment

Cancer can modulate neighboring stromal cells like fibroblast and adipoicyte

• secretion of lactate,glutamine, and glutathione to help growth of cancer

Metabolic Toxin

Increased production of ROS, but cancer protect themselves by increasing expressing of ROS detoxification gene like superoxide dismutase and catalse

Cancer Therapy Terminiology: Cure, Remission, Relapse

Cure = complete eradication of cancer cell from body

• rarely acheived

Remission = no longer detect the cancer after treatment

Relapse = subsequently growth of cancer after remission

Surgery Treatment & Side Effects

Best method to achieve cure if tumor is localized

Side Effects

• Lymphoedema: after breast surgery where excision of lymphatic vessel in axilla lead to accumlation of lymph in arm

• Stoma: after bowel surgery where end of resected bowel is externalized at abdomen to allow drainage of fecal content into a stoma bag

Radiotherapy & Side effects

Targeted Delivery of ionizing radiation to Cancer leading to DNA damage

Side Effect:

• Bone marrow suppression

• Nausea vomit

• Hair loss

• Fatigue

• Secondary Cancer

  • To minimize damage try to use smaller dose

Chemotherapy & Side effects

Delivery of cytotoxic agent systemically into body to target cancer(multiple routes)

Side effect:

• DNA damage (cisplatin)

• inhibit synthesis of DNA nucleotide (methotrextate)

• Disrupt mitosis (taxol)

Targeting cancer metabolism: Anti-folates

Aminopterin and methotrexate are drugs that inhibit enzyme dihydrofolate reductase (role in folate cycle) thus reducing synthesis of nucleotides since no THF

Targeting cancer metabolism: Asparaginase

Asparagine is non essential amino acid synthesized by asparagine synthetase enzyme

• acute lymphoid leukemia cell do not express asaragine synthetase therefore they rely on external asparagine

• Asaparaginase depletes asparagines from blood starving ALL cells: normal cell can produce their own but not cancer

Nutrition During Cancer Treatment

1) Maintain General Health to protect agaisnt treatment related side effect

2) Avoid certain food/drink that could interact with bioactivity of cancer drug

3) Avoid food that increase risk of food borne infection

Immunotherapy

Immume checkpoint inhibitors - reawaken anti cancer immume response countering cancer cells immunosuppressent factors

Cell Based Thearpy - extract lymphocytes from cancer patient, reprogram their surface receptor to target cancer cells “chimeric antigen receptor T cells(CAR-T)

Mediterranean Diet vs Ketogenic Diet

Mediterranean - Healthy Fats (fish and meat)

Ketogenic - Low Carb, Medium Protein, High Fat