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Drug delivery systems

Drug delivery refers to approaches, formulations, technologies, and systems for


transporting a pharmaceutical compound in the body as needed to safely achieve its desired
therapeutic effect.[1] It may involve scientific site-targeting within the body, or it might involve
facilitating systemic pharmacokinetics; in any case, it is typically concerned with both
quantity and duration of drug presence. Drug delivery is often approached via a drug's
chemical formulation, but it may also involve medical devices or drug-device combination
products. Drug delivery is a concept heavily integrated with dosage form and route of
administration, the latter sometimes even being considered part of the definition.[2]
Drug delivery technologies modify drug release profile, absorption, distribution and
elimination for the benefit of improving product efficacy and safety, as well as patient
convenience and compliance. Drug release is from: diffusion, degradation, swelling, and
affinity-based mechanisms.[3] Most common routes of administration include the preferred
non-invasive peroral (through the mouth), topical (skin), transmucosal (nasal,
buccal/sublingual, vaginal, ocular and rectal) and inhalation routes.[4][5] Many medications such
as peptide and protein, antibody, vaccine and gene based drugs, in general may not be
delivered using these routes because they might be susceptible to enzymatic degradation or
can not be absorbed into the systemic circulation efficiently due to molecular size and charge
issues to be therapeutically effective. For this reason many protein and peptide drugs have to
be delivered by injection or a nanoneedle array. For example, many immunizations are based
on the delivery of protein drugs and are often done by injection.
Current efforts in the area of drug delivery include the development of targeted delivery in
which the drug is only active in the target area of the body (for example, in cancerous tissues)
and sustained release formulations in which the drug is released over a period of time in a
controlled manner from a formulation. In order to achieve efficient targeted delivery, the
designed system must avoid the host's defense mechanisms and circulate to its intended site of
action.[6] Types of sustained release formulations include liposomes, drug loaded
biodegradable microspheres and drug polymer conjugates.
What are drug delivery systems?
Drug delivery systems are engineered technologies for the targeted delivery and/or controlled
release of therapeutic agents.
Drugs have long been used to improve health and extend lives. The practice of drug delivery
has changed dramatically in the last few decades and even greater changes are anticipated in
the near future. Biomedical engineers have not only contributed substantially to our
understanding of the physiological barriers to efficient drug deliverysuch as transport in the
circulatory system and drug movement through cells and tissuesthey have contributed to
the development of a number of new modes of drug delivery that have entered clinical
practice.

Yet, with all of this progress, many medications, even those discovered using the
most advanced molecular biology strategies, have unacceptable side effects due to
the drug interacting with parts of the body that are not the target of the drug. Side
effects limit our ability to design optimal medications for many diseases such as
cancer, neurodegenerative diseases, and infectious diseases.
Drug delivery systems control the rate at which a drug is released and the location in the body where it
is released. Some systems can control both.

How are drug delivery systems used in current medical practice?


Clinicians historically have attempted to direct their interventions to areas of disease or areas at risk
for disease. Depending on the medication, the way it is delivered, and how our bodies respond, side
effects sometimes occur. These side effects can vary greatly from person to person in type and
severity. For example, an oral drug for seasonal allergies may cause unwanted drowsiness or an
upset stomach.
Administering drugs locally rather than systemically (affecting the whole body) is a common way to
decrease side effects and drug toxicity while maximizing a treatments impact. A topical (used on the
skin) antibacterial ointment for a localized infection or a cortisone injection of a painful joint can avoid
some of the systemic side effects of these medications. There are other ways to achieve targeted drug
delivery, but some medications can only be given systemically.

What technologies are NIBIB-funded researchers developing for drug delivery?


Current research on drug delivery systems can be described in four broad categories: routes of
delivery, delivery vehicles, cargo, and targeting strategies.

Routes of Delivery
Medications can be taken in a variety of waysby mouth, by inhalation, by absorption through the
skin, or by intravenous injection. Each method has advantages and disadvantages, and not all
methods can be used for every medication. Improving current delivery methods or designing new ones
can enhance the use of existing medications.

Image of microneedle patch the size of a fingertip used to deliver influenza vaccines. Photo Credit: Dr.
Mark Prausnitz, Georgia Institute of Technology
Microneedle arrays are one example of a new method to deliver medications through the skin. In these
arrays, dozens of microscopic needles, each far thinner than a strand of hair, can be coated or filled
with a medicine. The needles are so small that, although they penetrate the skin, they dont reach
nerves in the skin, thus delivering medications painlessly.
NIBIB-funded scientists are developing a microneedle patch for vaccine delivery. These patches are
easy to use, do not need to be refrigerated, and dont require special disposal methods, so they could
be used by patients themselves at home. Such technology could be especially helpful in rural
communities that may not have many health care providers or adequate storage facilities for
traditional, refrigerated medicines.

Delivery Vehicles
Just as its easier to carry a drink in a glass rather than on a plate, finding the right carrier for
medications helps to ensure they arrive at their destination intact.

Nanosponges, created by NIBIB-funded researchers, are a promising vehicle in treating cancer.


Comprising a scaffold of tiny, specialized polyester particles coated with disease-targeting compounds
and filled with an anticancer drug, the nanosponges home in on tumors after being injected into the
body. Once at their intended site, they safely and slowly degrade, releasing medication at the tumor
site at a steady, controlled rate. Early studies have also shown the nanosponges can be used to treat
glaucoma, the fourth leading cause of blindness.
By limiting the release of medications throughout the body, the nanosponge and related
biotechnologies may revive the use of drugs that were previously unsafe for disease treatment.
Beyond broadening treatment options, targeted vehicles for drug delivery may also help to address
multi-drug resistant diseases.

Cargo
Perhaps the most obvious route to improving disease treatment would be to focus on the medications
themselves. But there are also other treatment options. Drug delivery researchers are also exploring
the use of genes, proteins, and stem cells as treatments.

Tiny biodegradable particles for antigen coupling


Source: Lonnie Shea and Stephen Miller
One example of a protein treatment is being examined in an NIBIB-funded project to treat autoimmune
disorders, in which the bodys own defense system mistakenly attacks and destroys healthy tissue.
Current treatments generally involve drugs that reduce the overall activity of the immune system,
which also increases a persons risk of infections and other illnesses.
Taking cues from the bodys natural process for preventing the immune reaction, the researchers
developed microscopic, biodegradable particles that can selectively shut down immune cells
associated with the autoimmune disorder multiple sclerosis (MS). Bound with pieces of the protein
myelin, the insulating material covering nerve cells that is destroyed in MS, the microparticles were
effective at preventing the start of MS in mice and at stopping disease progression when injected after
the first sign of illness. The microparticle therapy may also be useful in treating other immune-related
conditions, including allergies, or to suppress organ rejection in transplant patients.

Targeting Strategies
Working backwards on a problem can sometimes reveal a solution. In drug delivery research, this
means starting with a delivery method that has a known target, which may be whole organs (heart,
lung, brain), tissue types (muscle, nerve), disease-specific structures (tumor cells), or structures inside
of cells.
NIBIB-funded researchers developed a plant virus nanoparticle that can target and attach itself to
prostate cancer cells. When labeled with fluorescent dyes, the viral nanoparticles can show
researchers whether cancer cells have spread into bone at earlier stages of the disease than with
traditional bone scans.
Made from modified viruses, viral nanoparticles take advantage of the natural ways that viruses have
developed to slip past immune defenses and enter cells. This means they do not need to be modified
as much as other types of nanoparticles to behave in desired ways, and their actions within the human
body are well understood. Plant-based viral nanoparticles are also biodegradable, harmless to
humans, easy to use, and cheap to produce.

Further research aims to develop viral nanoparticles that can deliver chemotherapy drugs directly to
tumors. Such an advance would reduce the severe side effects usually associated with cancer
treatment.

What are some important areas for future research in drug delivery systems?
As scientists study how diseases develop and progress, they are also learning more about the
different ways our bodies respond to illness and the influence of specific environmental or genetic
cues. Coupled with advances in technology, this increased understanding suggests new approaches
for drug delivery research. Key areas for future research include:

Crossing the Blood-Brain Barrier (BBB) in Brain Diseases and Disorders


When working properly, the various cells that comprise the BBB constantly regulate the transfer of
essential substances between the bloodstream and the central nervous system, as well as recognize
and block entry of substances that may harm the brain. Delivering drugs into the brain is critical to the
successful treatment of certain diseases such as brain tumors, Alzheimers disease, and Parkinsons
disease, but better methods are needed to cross or bypass the BBB. One method currently under
study uses advanced ultrasound techniques that disrupt the BBB briefly and safely so medications can
target brain tumors directly, with no surgery required.

Enhancing Targeted Intracellular Delivery


Just as our immune systems defend our bodies against disease, each of our cells also has internal
processes to recognize and get rid of potentially harmful substances and foreign objects, which may
include drugs enclosed in targeted delivery vehicles. So as researchers work to develop reliable
methods of delivering treatments to targeted cells, further engineering is still needed to ensure the
treatments reach the correct structures inside cells. Ideally, future health care will incorporate smart
delivery systems that can bypass cellular defenses, transport drugs to targeted intracellular sites, and
release the drugs in response to specific molecular signals.

Combining Diagnosis and Treatment


The full potential of drug delivery systems extends beyond treatment. By using advanced imaging
technologies with targeted delivery, doctors may someday be able to diagnose and treat diseases in
one step, a new strategy called theranostics

FLAVONOIDS: DEFINITION,
STRUCTURE AND CLASSIFICATION
What are flavonoids?
Flavonoids are the most abundant polyphenols in human diet, representing about 2/3 of all
those ones ingested. Like other phytochemicals, they are the products of secondary
metabolism of plants and, currently, it is not possible to determine precisely their number,
even if over 4000 have been identified.
In fruits and vegetables, they are usually found in the form of glycosides and sometimes as
acylglycosides, while acylated, methylated and sulfate molecules are less frequent and in
lower concentrations.
They are water-soluble and accumulate in cell vacuoles.

Chemical structure of flavonoids

Fig. 1 Skeleton of Diphenylpropane


Their basic structure is a skeleton of diphenylpropane, namely, two benzene rings (ring A
and B, see figure) linked by a three carbon chain that forms a closed pyran ring (heterocyclic
ring containing oxygen, the C ring) with benzenic A ring. Therefore, their structure is also
referred to as C6-C3-C6.
In most cases, B ring is attached to position 2 of C ring, but it can also bind in position 3 or 4;
this, together with the structural features of the ring B and the patterns of glycosylation and
hydroxylation of the three rings, makes the flavonoids one of the larger and more diversified
groups of phytochemicals, so not only of polyphenols, in nature.
Their biological activities, for example they are potent antioxidants, depend both on the
structural characteristics and the pattern of glycosylation.

Classification of flavonoids

Fig. 2 Flavonoid Subgroups


They can be subdivided into different subgroups depending on the carbon of the C ring on
which B ring is attached, and the degree of unsaturation and oxidation of the C ring.
Flavonoids in which B ring is linked in position 3 of the ring C are called isoflavones; those
in which B ring is linked in position 4, neoflavonoids, while those in which the B ring is
linked in position 2 can be further subdivided into several subgroups on the basis of the
structural features of the C ring. These subgroup are: flavones, flavonols, flavanones,
flavanonols, flavanols or catechins and anthocyanins.
Finally, flavonoids with open C ring are called chalcones.

Flavones

They have a double bond between positions 2 and 3 and a ketone in position 4 of the C ring.
Most flavones of vegetables and fruits has a hydroxyl group in position 5 of the A ring, while
the hydroxylation in other positions, for the most part in position 7 of the A ring or 3 and 4 of
the B ring may vary according to the taxonomic classification of the particular vegetable or
fruit.
Glycosylation occurs primarily on position 5 and 7, methylation and acylation on the
hydroxyl groups of the B ring.
Some flavones, such as nobiletin and tangeretin, are polymethoxylated.

Flavonols
Compared to flavones, they have a hydroxyl group in position 3 of the C ring, which may also
be glycosylated. Again, like flavones, flavonols are very diverse in methylation and
hydroxylation patterns as well, and, considering the different glycosylation patterns, they are
perhaps the most common and largest subgroup of flavonoids in fruits and vegetables. For
example, quercetin is present in many plant foods.
Flavanones
Flavanones, also called dihydroflavones, have the C ring saturated; therefore,
unlike flavones, the double bond between positions 2 and 3 is saturated and this
is the only structural difference between the two subgroups of flavonoids.
The flavanones can be multi-hydroxylated, and several hydroxyl groups can be
glycosylated and/or methylated.
Some have unique patterns of substitution, for example, furanoflavanones,
prenylated flavanones, pyranoflavanones or benzylated flavanones, giving a
great number of substituted derivatives.
Over the past 15 years, the number of flavanones discovered is significantly
increased.

Flavanonols
Flavanonols, also called dihydroflavonols, are the 3-hydroxy derivatives of flavanones;
they are an highly diversified and multisubstituted subgroup.

Isoflavones
As anticipated, isoflavones are a subgroup of flavonoids in which the B ring is attached to
position 3 of the C ring. They have structural similarities to estrogens, such as estradiol,
and for this reason they are also called phytoestrogens.

Neoflavonoids
They have the B ring attached to position 4 of the C ring.

Flavanols or flavan-3-ols or catechins


Flavanols are also referred to flavan-3-ols as the hydroxyl group is almost always bound to
position 3 of C ring; they are called catechins as well

Unlike many flavonoids, there is no double bond between positions 2 and


3. Another distinctive features, e.g. compared to flavanonols, with which they
share a hydroxyl group in position 3, is the lack of a carbonyl group, that is, a
keto group, in position 4. This particular chemical structure allows flavanols to
have two chiral centers in the molecule, on positions 2 and 3, then four
possible diastereoisomers. Epicatechin is the isomer with the cis configuration
and catechin is the one with the trans configuration. Each of these
configurations has two stereoisomers, namely, (+)-epicatechin and (-)epicatechin, (+)-catechin and (-)-catechin.
(+)-Catechin and (-)-epicatechin are the two isomers most often present in
edible plants.

Another important feature of flavanols, particularly of catechin and epicatechin, is the


ability to form polymers, called proanthocyanidins or condensed tannins. The name
proanthocyanidins is due to the fact that an acid-catalyzed cleavage produces
anthocyanidins.
Proanthocyanidins typically contain 2 to 60 monomers of flavanols.
Monomeric and oligomeric flavanols (containing 2 to 7 monomers) are strong
antioxidants.

Anthocyanidins
Chemically, anthocyanidins are flavylium cations and are generally present as chloride
salts.
They are the only group of flavonoids that gives plants colors (all other flavonoids are
colorless).
Anthocyanins are glycosides of anthocyanidins. Sugar units are bound mostly to position 3
of the C ring and they are often conjugated with phenolic acids, such as ferulic acid.
The color of the anthocyanins depends on the pH and also by methylation or acylation at
the hydroxyl groups on the A and B rings.

Chalcones
Chalcones and dihydrochalcones are flavonoids with open structure; they are
classified as flavonoids because they have similar synthetic pathways

LIPIDS: DEFINITION, CLASSIFICATION AND


FUNCTIONS
What are lipids?

High Fat/Oil Foods


Lipids, together with carbohydrates, proteins and nucleic acids, are one of the four major
classes of biologically essential organic molecules found in all living organisms; their
amounts and quality in diet are able to influence cell, tissue and body physiology.
Unlike carbohydrates, proteins and nucleic acids they arent polymers but small molecules,
with a molecular weights that range between 100 and 5000, and also vary considerably in
polarity, including hydrophobic molecules, like triglycerides or sterol esters, and others more
water-soluble like phospholipids or very short-chain fatty acids, the latter completely miscible
with water and insoluble in non polar solvents.

The little or absent water-solubility of many of them means that they are subject to special
treatments at all stages of their utilization, that is in the course of digestion, absorption,
transport, storage and use.

Chimical structure of lipids


There are eight general categories of lipids, but I will only go into seven(fatty
acids, waxes, triacylglycerides, phospholipids, prostaglandins, steroids,
and lipophilic vitamins)

Classification of lipids
They may be classified based on their physical properties at room temperature (solid or liquid,
respectively fats and oils), on polarity, or on their essentiality for humans, but the preferable
classification is based on their structure.
Based on structure, they can be classified in three major groups.

Simple lipids
They consist of two types of structural moieties.
They include:

glyceryl esters that is esters of glycerol and fatty acids: e.g. triacylglycerols, mono- and
diacylglycerols;
cholesteryl esters that is esters of cholesterol and fatty acids;
waxes which are esters of long-chain alcohols and fatty acids, so including esters of vitamins
A and D;
ceramides that is amides of fatty acids with long-chain di- or trihydroxy bases containing 12
22 carbon atoms in the carbon chain: e.g. sphingosine.
carbon chain: e.g. sphingosine.

Complex lipids
They consist of more than two types of structural moieties.
They include:

phospholipids that is glycerol esters of fatty acids;


phosphoric acid, and other groups containing nitrogen;
phosphatidic acid that is diacylglycerol esterified to phosphoric acid;

phosphatidylcholine that is phosphatidic acid linked to choline, also called lecithin;


phosphatidylethanolamine;
phosphatidylserine;
posphatidylinositol;
phosphatidyl acylglycerol in which more than one glycerol molecule is esterified to
phosphoric acid: e.g. cardiolipin and diphosphatidyl acylglycerol;
glycoglycerolipids that is 1,2-diacylglycerol joined by a glycosidic linkage through position
sn-3 with a carbohydrate moiety;
gangliosides that is glycolipids that are structurally similar to ceramide polyhexoside and also
contain 1-3 sialic acid residues; most contain an amino sugar in addition to the other sugars;
sphingolipids, derivatives of ceramides;
sphingomyelin that is ceramide phosphorylcholine;
cerebroside: they are ceramide monohexoside that is ceramide linked to a single sugar moiety
at the terminal hydroxyl group of the base)
ceramide di- and polyhexoside that is linked respectively to a disaccharide or a tri- or
oligosaccharide;
cerebroside sulfate that is ceramide monohexoside esterified to a sulfate group.

Derived lipidsThey occur as such or are released from the other two major groups
because of hydrolysis that is are the building blocks for simple and complex lipids.
They include:

fatty acids and alcohols;


fat soluble vitamins A, D, E and K;
hydrocarbons;
sterols.
Classification adapted from: Bloor W.R. Proc Soc Exp Biol Med, 17, 138, 1920; Christie
W.W. in Lipid Analysis Pergamon Press, Oxford, 1982; Pomeranz Y. and Meloan C.L. in
Food Analysis; Theory and Practice 4th ed., AVI, Westport, Connecticut, 1994; Akoh C.C.
and Min D.B. Food lipids: chemistry, nutrition, and biotechnology 3th ed. 2008.

Functions of lipids

They are stored in adipose tissue (triglycerides) and are one of the major energy
source. Lipids are the best energy source for humans since at a parity of weight they
provide the major part of calories: if carbohydrates, on average, gives 4 kcal/g, as proteins,
lipids provide, on average, 9 kcal/g. Moreover, they can be present in foods without there
are also fiber or water (for polysaccharides 2 g water/g) allowing to contain a great
quantity of energy in a little weight.
Mostly of Nutrition Organizations recommend that lipids must contribute up to 30% (with
saturated fatty acids only less than 10%) of the total daily energy intake.

Some lipids are essential nutrients like fat-soluble vitamins A, (necessary for vision)
and D (necessary for calcium metabolism), present in some fats and oils of animal origin,
vitamin E (prevention of autoxidation of unsaturated lipids), present in vegetable oils, and

vitamin K (normal clotting of blood) present in green leaves, essential fatty acids, in
particular linoleic and -linolenic acids, founders of the family of omega-6 and omega3 fatty acids respectively.

During growth they are utilized as bricks for construction of biological membranes
(phospholipids, cholesterol and glycolipids together with proteins), so contributing to
construction of that barrier that separates intracellular environment from extracellular
one and, inside cell, circumscribes organelles like mitochondria, Golgi apparatus or
nucleus, and whose integrity is the basis of life itself; moreover they are also important
for maintenance, physiochemical properties and repairing of cell membranes
themselves.

Many hormones are lipids: steroid hormones, like estrogens, androgens and cortisol,
are formed from cholesterol (essential also during embryogenesis), prostaglandins,
prostacyclin, leukotrienes, thromboxanes, and other compounds (all eicosanids)
from omega-3 and omega-6 polyunsaturated fatty acids with 20 carbon atoms.

On plasmatic cell membranes they can act as receptors, antigens and membrane
anchors for proteins and can modify the structure, and therefore the functionality, of
membrane enzymes.

Many lipids, like diacylglycerol, ceramides, sphingosine and platelet-activating factor


act as regulators of intracellular processes.

There are fat deposits not accessed during a fast, classified as structural fat, the
function of which is to hold organs and nerves in the right position protecting

them against traumatic injuries and shock; fat pads on the palms and buttocks protect
the bones from mechanical pressure.

A subcutaneous layer of fat is present in humans: it insulates the body reducing the
loss of body heat and contributing to maintain body temperature.

On epidermis they are involved in maintaining water barrier.

They are electrical insulator of axon of neurons that are covered over and over again
by plasmatic membranes of Swann cells, in peripheral nervous system, and of
oligodendrocytes in central nervous system; these plasmatic membranes have a lipid
content greater than that of the other cells. This lipoprotein coating is

On digestive tract they facilitate the digestive process depressing gastric secretion,
slowing gastric emptying and stimulating biliary and pancreatic flow.

Bile salts (by-products of cholesterol) are natural detergents synthesized in the liver
and secreted into bile. They solubilize phospholipids and cholesterol in the bile,
permitting the secretion of cholesterol into the intestine (the excretion of both
cholesterol and bile acids is the major way by which cholesterol is removed from the
body). Bile salts also aid in the digestion and absorption of fat and soluble-fat vitamins
in gut.

In many animals, some lipids are secreted into external environment and act as
pheromones that attract or repel other organisms.

They affect the texture and flavor of food and so its palatability.

Food manufacturers use fat for its textural properties, e.g. in baked goods fat increase the
tenderness of the product. Chefs know that fat addiction add to the palatability of meal and
increase satiety after a meal.

Cancer
What is cancer?
Cancer is a term used for diseases in which abnormal cells divide without control and are
able to invade other tissues. Cancer cells can spread to other parts of the body through the
blood and lymph systems.
Cancer is not just one disease but many diseases. There are more than 100 different types of
cancer. Most cancers are named for the organ or type of cell in which they start - for example,
cancer that begins in the colon is called colon cancer; cancer that begins in melanocytes of the
skin is called melanoma

Origins of Cancer
All cancers begin in cells, the body's basic unit of life. To understand cancer, it's helpful to
know what happens when normal cells become cancer cells.
The body is made up of many types of cells. These cells grow and divide in a controlled way
to produce more cells as they are needed to keep the body healthy. When cells become old or
damaged, they die and are replaced with new cells.
However, sometimes this orderly process goes wrong. The genetic material (DNA) of a cell
can become damaged or changed, producing mutations that affect normal cell growth and
division. When this happens, cells do not die when they should and new cells form when the
body does not need them. The extra cells may form a mass of tissue called a tumor.

Cancer is not one disease. It is a group of more than 100 different and distinctive diseases.
Cancer can involve any tissue of the body and have many different forms in each body area.
Most cancers are named for the type of cell or organ in which they start. If a cancer spreads
(metastasizes), the new tumor bears the same name as the original (primary) tumor.

Symptoms
Signs and symptoms caused by cancer will vary depending on what part of the body
is affected. Some general signs and symptoms associated with, but not specific to,
cancer include:

Fatigue

Lump or area of thickening that can be felt under the skin

Weight changes, including unintended loss or gain

Skin changes, such as yellowing, darkening or redness of the skin, sores that
won't heal, or changes to existing moles

Changes in bowel or bladder habits

Persistent cough

Difficulty swallowing

Hoarseness

Persistent indigestion or discomfort after eating

Persistent, unexplained muscle or joint pain

Persistent, unexplained fevers or night sweats

How Cancer is Treated


The cancer treatment options your doctor recommends depends on the type and stage of cancer,
possible side effects, and the patient's preferences and overall health. In cancer care, different
types of doctors often work together to create a patient's overall treatment plan that combines
different types of treatments.

all the main cancer treatments:

surgery,
radiotherapy,
chemotherapy,
hormone therapy
biological therapies,
bisphosphonates
bone marrow and stem cell transplants.
There is also information about complementary and alternative therapies.

Tumor
Definition of tumor: An abnormal mass of tissue. Tumors are a classic sign of inflammation,
and can be benign or malignant (cancerous). There are dozens of different types of tumors. Their
names usually reflect the kind of tissue they arise in, and may also tell you something about their
shape or how they grow. For example, a medulloblastoma is a tumor that arises from embryonic
cells (a blastoma) in the inner part of the brain (the medulla). Diagnosis depends on the type and

location of the tumor. Tumor marker tests and imaging may be used; some tumors can be seen
(for example, tumors on the exterior of the skin) or felt (palpated with the hands).
Cancer stem cells may play a major role in tumor growth, three studies published in the journals
Nature and Science revealed in August 2012. Scientists believe cancer might have its own stem cells
that impact on the regrowth of tumors. They added that if further studies confirm their findings, the way
we treat cancerous tumors may change dramatically.

What is a benign tumor?


A benign tumor (benign neoplasm) cannot metastasize - it cannot spread. Examples include
uterine fibroids and moles. "Benign" means it is non-progressive, it remains as it is.
Most benign tumors are not harmful to human health. Even though they are not cancerous,
some may press against nerves or blood vessels and cause pain or other negative effects. Benign
tumors of endocrine tissues may result in the excessive production of some hormones.
Examples of benign tumors include:
Adenomas - tumors that arise from glandular epithelial tissue - epithelial tissue is the

thin membrane that covers glands, organs and other structures in the body. A polyp in the
colon is a type of adenoma. Other examples include pituitary adenoma, adrenocortical
adenoma, basal cell adenoma, bile duct adenoma, chromophobe adenoma, follicular
adenoma, hepatocellular adenoma, and nipple adenoma (there are many more).
Although adenomas are not cancerous, they can change and become so; then they are called
adenocarcinomas.

Fibroids (fibromas) - benign tumors that grow on fibrous or connective tissue of any

organ in the body. Uterine fibroids are common. Uterine fibroids can cause vaginal bleeding,
pelvic pain or discomfort, and urinary incontinence.
The fibroma durum (hard fibroma) is made up of many fibers and few cells. The fibroma
molle (soft fibroma) is made up of several loosely connected cells and less fibroid tissue. Soft
fibroma is usually found in the armpits, groin, neck and eyelids.

There are many types of fibromas, such as angiofibroma, cystic fibroma (fibroma
cysticum), myxofibroma (fibroma myxomatodes), nonossifying fibroma, ossifying
fibroma, cemento-ossifying fibroma, pleomorphic fibroma, fibroma of tendon sheath
nuchal fibroma, chondromyxoid fibroma, desmoplasmic fibroma, collagenous fibroma,
and perifollicular fibroma.

Some fibromas can cause symptoms and may require surgical removal. Rarely, fibroids
can change and eventually become cancerous, they are then called fibrosarcomas.

Hemangiomas - benign tumors which consists of a collection of too many blood cells.
They can sometimes be seen on the surface of the skin and are colloquially called
strawberry marks. The majority of hemangiomas appear at birth and gradually go away
after some months or years.
Hemangiomas do not usually require any treatment. If they affect the patient's ability to
eat, hear or see, the doctor may recommend treatment with corticosteroids. If the patient
is over 10 years of age, they are more commonly removed today using laser surgery.

Lipomas - the most common form of soft-tissue tumor. Lipomas consist of adipose tissue
(fat cells). Most of them are very small, painless, soft to the touch, and generally movable. They
are more common among people aged 40+ years. Experts disagree on whether lipomas can
change and become cancerous (malignant).
There are many kinds of lipomas, such as angiolipoleiomyoma, angiolipoma, chondroid
lipoma, corpus callosum lipoma, hibernoma, intradermal spindle cell lipoma, neural
fibrolipoma, pleomorphic lipomas, and superficial subcutaneous lipoma (the most common
type, found just below the skin's surface).

What is a premalignant tumor?


A premalignant or precancerous tumor is one that is not yet malignant, but is about to become
so.
Examples of premalignant growths include:

Actinic keratosis - also known as senile keratosis or solar keratosis is a premalignant


growth consisting of crusty, scaly and thick patches of skin. Fair-skinned people are more
susceptible to these types of growths, especially those who are exposed to sunlight (it is linked
to solar damage).
Actinic keratoses are seen as potentially premalignant because a number of them progress to
squamous cell carcinoma. Doctors usually recommend treating them because of this. There is
a 20% risk that untreated lesions eventually become cancerous. Continuous sun exposure
increases the risk of malignancy.

Dysplasia of the cervix - the normal cells lining the cervix of the uterus change. The
growth can be premalignant, a prelude to cervical cancer. Cervical dysplasia is diagnosed with
a PAP smear. According to the National Institutes of Health, USA, about 5% of PAP smears

detect the presence of cervical dysplasia. They are more common in women aged 25 to 35.
They may be removed with Cryotherapy (freezing), or conization (the cone of tissue from the
cervix is removed).

Metaplasia of the lung - the growths occur in the bronchi, tubes that carry air from the
windpipe into the lung. The bronchi are lined with glandular cells, which can change and
become squamous cells. Metaplasia of the lung is most commonly caused by smoking.

Leukoplakia - thick, white patches form on the gums, bottom of the mouth, insides of
the cheeks, and less commonly on the tongue. They cannot be scraped off easily. Experts
believe tobacco smoking and/or chewing is the main cause. Although Leukoplakia is rarely
dangerous, a small percentage are premalignant and can eventually become cancerous. Many
mouth cancers occur next to areas of leukoplakia.
If smokers quit, the condition usually clears up. Quitting both alcohol and tobacco together
has better results. The patches can be removed using laser, a scalpel or a cold probe that
freezes the cancer cells (cryoprobe).

What is a malignant tumor?


Malignant tumors are cancerous tumors, they tend to become progressively worse, and can
potentially result in death. Unlike benign tumors, malignant ones grow fast, they are ambitious,
they seek out new territory, and they spread (metastasize).
The abnormal cells that form a malignant tumor multiply at a faster rate. Experts say that there is
no clear dividing line between cancerous, precancerous and non-cancerous tumors - sometimes
determining which is which may be arbitrary, especially if the tumor is in the middle of the
spectrum. Some benign tumors eventually become premalignant, and then malignant.
Metastasis - malignant tumors invade nearby cells, and then the cells near those, and spread.
Some cells can break off from the tumor and spread to various parts of the body through the
bloodstream or the lymphatic system, and establish themselves anywhere in the body, and form
new malignant tumors. Metastasis is the process by which cancer cells spread from their primary
site to distant locations in the human body. For example, a patient may have started off with
melanoma (skin cancer) which metastasized in their brain.
The cancer cells that metastasize are the same as the original ones. If a lung cancer spreads to
the liver, those cancer cells that grow in the liver are lung cancer cells which have acquired the
ability to invade other organs.
There are different types of tumors, which are made up of specific types of cancer cells:

Carcinoma - these tumors are derived from the skin or tissues that line body organs
(epithelial cells). Carcinomas can be, for example, of the stomach, prostate, pancreas, lung,
liver, colon or breast. Many of the most common tumors are of this type, especially among
older patients.

Sarcoma - these are tumors that start off in connective tissue, such as cartilage, bones,
fat and nerves. They originate in the mesenchymal cells outside the bone marrow. The
majority of sarcoma tumors are malignant. They are called after the cell, tissue or structure
they arise from, for example fibrosarcoma, liposarcoma, angiosarcoma, chondrosarcoma, and
osteosarcoma.

Lymphoma/Leukemia - cancer arises from the blood forming (hematopoietic) cells that
originate in the marrow and generally mature in the blood or lymph nodes. Leukemia
accounts for 30% of childhood cancers. Leukemia is thought to be the only cancer where
tumors are not formed.

Germ cell tumor - these are tumors that arise from a germ cell, pluripotent cells (cells
than can turn into any kind of cell). Germ cell tumors most commonly present in the ovary
(dysgerminoma) or testicle (seminoma). The majority of testicular tumors are germ cell ones.
Less commonly, germ cell tumors may also appear in the brain, abdomen or chest.

Blastoma - tumors derived from embryonic tissue or immature "precursor" cells. These
types of tumors are more common in children than adults. "Blastoma" is often the root word
used in longer ones that describe tumors, for example, medulloblastoma and glioblastoma
are kinds of brain tumors, retinoblastoma is a tumor in the retina of the eye, osteoblastoma is
a type of bone tumor, while a neuroblastoma is a tumor found in children of neural origin.

What is a biopsy?
To decide whether a tumor is malignant or not, a sample must be taken by a surgeon or an
interventional radiologist and sent to the laboratory and examined under a microscope by a
pathologist - the sample is called a biopsy. There are three different types of biopsies:

Excisional biopsy - the entire lump or suspicious area is surgically removed.


When the specimen plus some surrounding uninvolved tissue is sent to the lab, the
pathologist determines the extent of surgical margins around it to see whether the cancer
spread beyond the area biopsied. Clear margins, also known as negative margins means that
none of the tumor has spread beyond the edges of the biopsied specimen. Positive margins
means the tumor has grown beyond the biopsied specimen. Sometimes a wider excision may
be needed if the diagnosis is uncertain.

Incisional (core) biopsy - a sample is surgically removed from the tumor

Needle aspiration biopsy - fluid or a sample of tissue is removed with a needle.

CELL:

Definition: is the basic structural, functional, and biological unit of all known living
organisms. Cells are the smallest unit of life that can replicate independently, and are often
called the "building blocks of life". The study of cells is called cell biology.
Cells consist of a protoplasm enclosed within a membrane, which contains many
biomolecules such as proteins and nucleic acids. Organisms can be classified as unicellular
(consisting of a single cell; including most bacteria) or multicellular (including plants and
animals). While the number of cells in plants and animals varies from species to species,
humans contain about 100 trillion (1014) cells.] Most plant and animal cells are visible only
under the microscope, with dimensions between 1 and 100 micrometres
The cell was discovered by Robert Hooke in 1665. The cell theory, first developed in 1839 by
Matthias Jakob Schleiden and Theodor Schwann, states that all organisms are composed of
one or more cells, that all cells come from preexisting cells, that vital functions of an
organism occur within cells, and that all cells contain the hereditary information necessary for
regulating cell functions and for transmitting information to the next generation of cells.

Healty cell
A healthy cell does not turn into a cancer cell overnight. Its behaviour gradually
changes, a result of damage to between three and seven of the hundreds of
genes that control cell growth, division and life span. First, the cell starts to grow
and multiply. Over time, more changes may take place. The cell and its
descendants may eventually become immortal, escape destruction by the body's
defences, develop their own blood supply and invade the rest of body.

Unhealty cell:

Shapes of Healthy and Unhealthy


Cells
What is the basic difference between a healthy cell and an
unhealthy cell? A healthy cell has a clean surface and innards. It
produces clean energy for its functions and efficiently cleanses
itself of waste. An unhealthy cell is swollen and its surface and
innards are smeared with toxic materials. It cannot breathe well,
produce clean energy, or rid itself of toxins. Near their death,
diseased cells somtimes shrink. A healthy cell has a sharp outline
(cell membrane) and its internal structures can be seen clearly
with a microscope. An unhealthy cell has a fuzzy cell membrane
and its innards are swollen and irregularly shaped.