CHAPTER I:

1) What is the balneology and

physiotherapy?
BALNEOLOGY is a branch of science that studies the properties of
balneological factors (climate, mineral waters, medicinal sludge etc.), the processing methods
and their application to the body in the spa, as well as in sanatorium and physio-therapeutic
institutions with the purpose of treatment, recovery and prophylactically.
The balneology includes sections as follows:
Climato-therapy;
Balneo-therapy;
Balneo-tehnik;
Peloido-therapy.
Climato-therapy studies physical factors’ influence the external environment (air-therapy,
helio-therapy and hidro-therapy) on the human body and develops ways to use the curative
effect and prophylactic effect.
Balneo-therapy studies healing mineral waters in terms of their origin, and the physical and
chemical influence on the body in various diseases and how they are use (internal or external).
Balneo-tehnik develops technical and sanitary equipment to carry out accurately technical and
medical application of mineral waters and medicinal sludges.
Peloido-terapy studies the origin of medicinal sludges their physico-chemical properties and
the mechanisms of their action on the body in different conditions.

PHYSIOTHERAPY is the science that studies the action

mechanisms of physical enviroment factors, both natural as well as performance on the human
body and their using for treatment, recovery and prevention.
Physiotherapy includes the following sections:
general physiotherapy;
special and clinic physiotherapy.
General physiotherapy examines organizational and methodological bases to using accuretly
the physical factor, physiological and therapeutic mechanisms of action on the body and their
using in clinic.
Special (clinical) physiotherapy determines the particular use of physical curative factors and it
studies in the clinical specialties.

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 2) What is kineto - therapy?
The kinetotherapy notion has for some of us similar connotations to complementary
therapies such as: aroma-therapy; cromo-therapy; melo-therapy; reflexo-therapy even
bioenergy, etc. But I wish to clarify that it is the field of traditional medicine and its effects
may be replace successfully by complementary therapies to the extent that they understand and
accept them as a complement to classical treatments.
The most reactions of people who I talk about kineto-therapy are like: "O, kineto-therapy ... I
know ... massage, right?" Actually it is not so and I will explain why:
If for to do a massage, reflexo-therapy, bioenergy or anything like that it requires a
basic course by which they obtains a certificate. A kineto-terapeut must be licensed by the
kineto-therapy faculty either part of National Academy of Physical Education and Sport or part
of University of Medicine and Pharmacy.
So, the kineto-therapeut must think how to use therapeutics means and how to combine them
succesfully in the recovery programs.
Which are these means? It can be schedules of treatment based on a series of exercises results
of numerous studies and medical research, like the Bobath programe - used for the recovery of
children with poor motory; the Kabath programe - indicated in particular for those with
paralysis and paresis; the Williams programe – against, lumbar pain. Or exercises can be done
using mekano-therapy; the hidro-therapy and the list can be continue but the subject matter is
very complex. It would be like we are trying to explain the treatment prescribe by doctors.

The kinetotherapy to children:

Through specific exercises which we offer, kineto-therapy is a solution to the problems of
health of children, teaching them at the same time that the exercice is a healthy and
harmonious way of life. Kineto-therapy in the widest acceptance, is the sistematised exercice
principle in the form of physical exercises, aiming for a therapeutic purpose. Coverage of
medical specialties which profit by contribution of kineto-therapy is extremely broad and it
cover both prevention of diseases and especially the recovery of health. Contraindications
occur rarely, only disease in which the child is in a vital risk. In most of cases, motory
development of children who benefit from kineto-therapy is favorable. But there are situations
in which it appear motory difficulties and child’s motricity evolution is slow and problematic.
In these cases, kineto-therapy has specific means for intervention, maintaining the motory
mobility of child.

Principles and methods:

Apparently simple, kineto-therapy imposes strict rules for application which depend on child
and on kineto-therapeut. Respect the principle of “primum non nocere”, meaning in the first to
do nothing bad, is of paramount importance. The "non pain" rule beside the effort extenting are
basic principles in kineto-therapy. Treatment rooms arranged for kineto-therapy of children is

3
by creating environment properly for age, is a motivating principle for kids do not bore and
perceive the therapy as a game.
The kineto-therapeut’s skills are an essential factor in the treatment process. His
inventiveness and creativity can transform the kineto-therapeutic exercises in real hours of
play, and the children became motivated to return at treatment. From kineto-therapy view the
exercice is active or passive. In the active kineto-therapy, the child learns by motricity,
exercises which help to maintain the balance function and exercices to occur in the execution
of fine movements and complicated.
When the child has no got biological resources to execute and command the exercices, the
kineto-therapeut intervens through the passive therapy to reorganize "command center" which
is responsible for information needed for exercices initiation, but also for restoring the integrity
of the locomotory.

The effects of therapy:

The kineto-therapeutics intervention has strictly physiological effects - the formation of
new correct motor program, the maintain of joint mobility, the maintaining of troficitations
tissue around joints and normalizing the muscle tone. Aims to involve the whole body in
motion and to prepare the child’s body for effort, it formes habit of accurate and coordinated
movements. By kineto-therapy may be correct different deformation of the kids’ spine due to
an incorrect position on the bank or on the chair during the classes.
Kineto-therapy treats diseases of the spine, such as:
♦ cifosis;
♦ lordosis;
♦ scoliosis.
By kineto-therapy can treat diseases of the children’s locomotory:
congenital luxations of hips;
splay or of so-named "knee in X".
Children with neurological diseases like: hemiparisis, paraparisis, may benefit for a better
health by practice of kinetotherapeutic exercices. Rickets, obesity and other metabolic
disorders can be treated, also by kineto-therapy.

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 3)The aromatherapy:
It is used for various diseases and for preventing them, in body and spiritual
caring to each of us.

Reduction Anxiety:
According to research conducted in 2000 and systematized by B.Cooke, E.Ernest,
aromatherapy: “a systematic review”, which includes 6 clinical standardized studies from
United States, which totaled 456 participants, aromatherapy may have a benefical effect on
anxiety, but on short-time.
Three other studies conducted in the European Union, group 388 participants,
underlined a benefical effect of aroma-therapy for decrease of anxiety and improving state of
mind of hospitalized persons or who will make a surgical intervention. One of the studies focus
on patients who had to undergo a dental treatment. In the waiting room, they was put in
presence of an essential lavender or orange oil, or they listened a delicate music, or didn’t
have undergone any intervention - control group. The participants from the group that took part
of aromatherapy treatment had a lower level of anxiety and a better state of mind than others.
However, this study doesn’t allow the observation of the effect of specific essential oils,
compared with the inhalation of a delightful odors.
As specifies another study which included 66 women who expect to support an
abortion, the calming effect of inhalation of essential oils is egual with good smells of a
placebo.
Improving quality of life and physical symptoms of people affected by cancer was studied. In
the article "aromatherapy and massage for symptom relief in patients with cancer, D. Fellowes,
K. Barnes, S.Wilkinson concluded that massage combined with aromatherapy it could improve
physical condition of patients affected by cancer and, to a less extent, to reduce the anxiety and
some physical symptoms such as:
- Pain;
- Fatigue;
- Nauses;
- Vomiting;
- Constipation.
Others dotting about reducing crabs caused by haemolysis, improvement of living
conditions for children premature borned, or treatment of light sleeplessness or reduction of
menopausal symptoms.
Fairly recently, numerous studies have appeared in the medical literature regarding the
beneficial results of aromatherapy against certain diseases:
- Eczema;
- Infections;
- Respiratory diseases;
- Postoperative nauses;
- Arthritis;
- Multiple sclerosis;
- Reduction of birth process;
- Prenatal anxiety;

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- Epilepsy;
- Depression.
Some essential oils are irritable for skin and must be diluted with vegetal oils before the
application. Oils rich in ketones, may cause neurological problems. It seems that
rose-marine and camphor oil, can trigger attacks of epilepsy. Some oils may have a
fotosensibilised effect; can make the skin more vulnerable to sunlight.
Quite many specialists say that we must be careful in using the essentials oils during
pregnancy, birth or near the new borns.
Use the aromatherapy but respect strictly the indications the bottles with essential oil. Don’t
ignore the contraindications and inform as well before you use them. Your health depends on
these things.

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 4) Diseases in physio-kineto-therapy
With spas treatments, the modern man may treat his various diseases of the body,
which related to the locomotory, spinal column, the muscles, also through aromatherapy can
treat some mental illnessis such as depression and anxiety.
One of the most common diseases of spinal column which is treated by physio-therapy, is the
discopaty (lumbar, cervical, thoracic).
Spinal column is composed of vertebrae, intervertebral disk, ligaments and joint capsules.
Deterioration of intervertebral disk from the spine is known as discopaty. The discopaty known
as "intervertebaral disc disease" manifests by severe and pain, acute at the level of certain areas
of the spine (column cervical, thoracic or lumbar). The most frequently affected disks
arebetween vertebrae L4-L5 or L5-S1.
The supraponderability, repeated trauma, old age and maximum lumbar spine demands due to
rasing of some loads from incorrect positions (hiperextensif) are factors that predispose to the
occurrence of lumbar discopaty. Depending on the region in which it occurred the damage of
intervertebral disk, discophaty can be classified as follows:
- discophaty-cervical;
- discophaty-lumbar;
- discophaty-thoracic.

It should be noted that medical recovery of patients diagnosted with lumbar

discophaty so common, or cervical discophaty which is equally frequent, is not done at home
(at the patient's home), but in a kineto-therapy room (medical gymnastics) equipped with some
proper apparatus (espalier; pulley; ergonomic bicycle; walking sticks; weights and various
others).
Treatment of vertebral discopaty is for a long time and each patient must follow it with
earnestness and perseverance. In the first phase of recovery is treated symptoms (pain,
discomfort). This is possible only by carrying out some sessions of physiotherapy (ultrasound
and electrotherapy). For a more effective recovery is recommended physiotherapy sessions
associated with therapeutic massage (carefully!-Not relaxation massage). Therapeutic massage
and relaxation massage are different by maneuvers which are applied and by intensity with
appling them.
When the pain disappeared completely and the inflammation goes down it follows the
second phase of recovery - medical gymnastics (kinetotherapy). At this stage is treated the
cause of disease. In our country it used a program of medical recovery for lumbar discophaty
known as the Williams Program. The exercises which are part of the Williams Program help to
consolidation of abdominal muscles and strengthen of paravertebrale muscles brought the
spinal column in a position as physiological (normaly). Lumbar discopaty may worsen by
breaking of intervertebral disk producing the most serious form of discopaty - hernia disk.
Other forms of discopaty are lombosciatics and disk protrusia. Very serious cases of lumbar
disk hernia or rupture of cervical disk is treated only by surgery. Indication for surgery is given
by doctor specialist in
neuro-surgeon. Before appeal to the surgery the patient should make an investigation called
NMR (nuclear magnetic resonance).

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 The lumbar vertebral discophaty:
Is characterized by back pain located in lumbar region (classic pain of hips) and affects
on the average of 75-80% from active adults, regardless of sex or age, in some moment of their
lives.
Lumbar pain is also called lombalgy and may evolves towards lumbago crisis, being
accompanied by blockage of the area due the contraction of muscles that support the spinal
column.
Pain in lumbar region may radiate to the buttock or down to the knee or to the leg.
This situation is called lombosciatics and can be a sign of disk hernia if it associates a
degree of paresis, meaning affected limb moves difficultly or leg we "escape" to some
movements.
Lumbar discophaty is a deterioration of the intervertebral disk from the lumbar spine. Spinal
column consists of vertebrae (like nuts) put one over another. Between these vertebrae are
intervertebrale disk. Vertebral disks are made up of cartilages (like some gaskets between two
nuts).

Which are the parts spine?

- Cervical spinal column (the neck);
- Spinal column dorsal (thoracic);
- From the neck to where ends the ribs (in the lungs’ region);
- Lumbar spinal column;
- From the end of ribs to the pelvis;
Sacred spinal column;
Coccigian spinal column;

Vertebral’s holes placed one above the other forms a vertebral canal is passing the spinal
cord. Spinal cord is formed by a bundle of nerve fibers. These nerve fibers start from the
brain and transmitt controls from the brain to the entire body. Fibers start from the spinal
column through the spaces between the vertebrae (where there are intervertebrals disks). If
disks are not integral, then the vertebrae move closer one to another and pinch the nerve that
exits between them. Vertebral disk damage in the lumbar spine called lumbar discophaty. If the
intervertebral disk of lumbar vertebrae is deteriorated a lot and it breaks them it occur disk
hernia. The lumbar discophaty back pain. The pain can transmit in front the abdomen or on leg.
How is lumbar pain discopatia? The pain is appears on back (his pain). The pain is more
intense when the spine is moving or in some positions (sitting on chair, standing up,
trepidations).
The back can feel hurt also cough or sneeze. When pain from lumbar discophaty appear?
In lumbar discophaty case pain occurs when the spinal column is more solicitated:standing up
for a long time; split; bounce; lifting up driving car for a long time and especially at the big
trepidations.

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 Attention! Many people confuse this pain with kidney pain. In lumbar discophaty back
pain increases if spinal column is moving. It is not appropriate to make massages (especially
vigorous, energetical massages) because nerve irritation produced by massage adds to irritation
due to the vertebrae that are approaching (altered intervertebral disk) to nerves which are
irritated during the lumbar discophaty it produces some damage (ret nervous fiber) which can
not be fixed, whether it is made surgery later.
What lumbar discophaty to do to treat?Ask family doctor what to do to treat lumbar
discophaty! It may exacerbate by breaking of intervertebral disk and disk hernia when there is
no other solution than surgery. Surgery indication is made only practitioner of neuro-surgeon.
If it recommend surgery to this advice should be followed it means that is only solution to
treatment. Ask the doctor about your back pain, do not treat you as you heard from neighbors,
on radio or television.
Treatment of lumbar discophaty:
Disk hernia consists of:
- reducing the pain;
- promotting cure of invalid tissues;
- regional miorelaxing;
- return to the previous mobility;
- education to prevent installation of other episodes;
- return to its previous activities.

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 Cervical discophaty:
Due the weather from outside which is oscillating and also the temperature, which
goes up or falls, but standing in the current, or in a poor position – with shoulders set down and
head bent goes to appearing of neck discophaty, which represents those neck and shoulders
pain, which appear both to children and to adults. Cervical Discophaty is a deterioration of the
intervertebral disc from the cervical spine. For you have idea about the location of this disk,
you must know that a spinal column consists vertebrae positioned one above the other and
between these vertebrae are intervertebrale disk.
You can get rid of this discomfort or illness appealing the SPA on the wide burdock, known as
Lipan.
Spinal column occupies a central position in the locomotory apparatus. "Only one
who knows in what way is involved in the game column static and dynamic forces of the
human body, can properly integrate the importance of this organ central to thinking in
diagnosing and treatment" (Schmore-Iughanns).
Spinal column in the human body carries out the following functions:
- Office support (support an individual trunk posture printing feature)
- Function protection (protect spinal cord against mechanical aggression)
- Function of mobility (the complexity of the building gives the body its ability to move and to
move in space)
- Function morfogenetics (particularities spine mechanics turn the shape and placement
eviscerated thoraco-abdominal).
Vertebral spinal column consists of a sequence of 33-34 pieces bone called vertebra.
It is part of a very complex structures called axial organ. The axial complex is a structural and
functional which to participate:
- The last bone (vertebrae that make up the spinal column)
- Conjuctiva comprising the fibrous structure and the elastic connection between vertebrae
(intervertebrale discs, joint capsules, ligaments)
- The muscle (muscle spine)
- The neuro-vascular (spinal cord, nerve roots, blood vessels).
Altering any of these components reflect negatively on the whole organ function axial. Means
such as alarming disturbances may be caused by pathological changes of the vertebrae or discs
intervertebrale.
How to connect vertebrae between them? The vertebrals discs are linked by
intervertebrale the joints unsinovials while apofisis joints are linked by sinovials joints.
Between the vertebrae are found and ligaments along with the intervertebral disk and joint
capsules formed segment mobility.
The most important segment of mobility is the intervertebral disk.
What is the intervertebral disc? Intervertebral disc is located in the space between
vertebral corpii on that separate, but I solidarizeaza and at the same time. Intervertebal disc
cavity is devoid of joints, not possess any membrane Sinovial and liquid Sinovial. Therefore it
is included among articulations nesinoviale.
The disc consists of a peripheral portion, composed of fibrous tissue conjuncitv called fibrous
ring and a central portion of gelatinous matter, which is called core pulp.
Ring fiber is more resistant than in the previous posterior. In the ring fiber blades into fibrous

10
tissue, arranged concentrically around the core leg. These blades contain collagen fibers that
insert on the side of the body adjacent to the two neighboring vertebrae, which is located
between the intervertebral disk. Concentric ring of blades fiber are 15-20 in number of core
pulp before and after only 7-10, explaining low resistance requirements of the area.
Core leg traps water and develop an explosive force. Pulp core is a spherical gelatinous
nature situated central fast fiber ring at the periphery. It is very rich in water and avid in its
abstraction - hydrophilic. Exert compression on the formation of fibrous ring and nearby
vertebral body. Force explosive kernel the vertebrals corps back leg and put in a fiber ring
tension, which tends to approach him again. Through complex mechanisms, core and leg traps
normally attracts water and thus develop the high pressures inside the explosive shattering
force.
The vertebral discs with intervertebrals made a precomprimat.
Due to explosive force of leg core, the system developed by corpii vertebral discs and is
located under continuous pressure, even in a state of rest. Such a system is called technique
"precomprimat.
Precomprimarea substantially increases the strength and elasticity. Due to this property kernela
pulp disks intervertebrals increase elasticity of the spine and absorb mechanical shocks. When
hydrophilic decreases the core leg, reduce power and explosive installation disc degeneration.
Pressure from the pulp core at the same time increase the load.

Cervical spinal stenosis:

The term stenosis, a decrease pathological defines a permanent channel or hole (a
pinch of a channel or hole). Spinal stenosis cervical spinal canal is shrinking neck. Spinal canal
is the area bounded by the vertebrae that can be found in the spinal cord. Spinal cord is
composed of parts of nerves which cross the spinal canal to the brain to the lower lumbar area.
These nerves are responsible for the sensitivity and mobility of the territories which they
inerves. In cervical spinal stenosis, the spinal canal narrows and can compress nerve roots in
place leaving the spinal cord or irritate even the spinal cord. The first 7 vertebrae of the spine,
which stretch from the base of the skull to the upper thoracic area, forming the segment of the
cervical spine or cervical column. The compretion nerves and spinal cord in the cervical spinal
canal can cause functional disorders in the spinal cord, stiffness, pain and paraesthesia in the
neck, upper and lower limbs. Cervical spinal stenosis may be invalid if it is damaged spinal
cord.
Symptoms that may be occur if cervical stenosis:
Many people aged over 50 years with shrinking but the spinal canal, however, presents
no symptoms. Cervical spinal stenosis does not produce symptoms until the spinal cord or
nerves are compressed. Symptoms appear gradually in a long period of time and include:
- Stiffness, neck, shoulders, arms, hands or lower limbs pain;
- Balance disorder;
- Prevent or tarsirea legs during walking.

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Cervical stenosis can have causes the following:
Cervical spinal stenosis is often produced by changes in shape and spinal canal
typically occurs in people over 50 years. Due to age, producing thickening of the tissues that
make the connection between the bones (ligaments), distructions of the tissues that encase the
bones (cartilages) and excessive growth of bone at the extremity articulations. All these
changes can lead to shrinking spinal canal (spinal stenosis).

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 THE CANCER
In the eighteenth century, London physician Percival Pott made the first link between
cancer and environmental agents when he noted a high incidence of scrotal cancer among
chimney sweeps. He hypothesized that it was caused by exposure to coals and tars. Out of this
observation grew the two-stage model of cancer development by 1) initiators and 2) promoters.
In the years since Pott's observations a wide range of chemicals, radiation sources, viruses and
bacteria have been implicated in the development of cancer.
The initial experimental studies of carcinogenesis were conducted in animals. Chemicals able
to react with DNA and non-reactive compounds were both tested for their ability to cause
cancer. The model used was mouse skin carcinogenesis. In this system researchers painted test
chemicals on the skin and observed the growth of tumors. Researchers found that application
of a DNA reactive substance only resulted in tumor formation when the animals were further
treated with another non-reactive substance. A compound that reacts with DNA and somehow
changes the genetic makeup of the cell is called a mutagen. The mutagens that predispose cells
to develop tumors are called initiators and the non-reactive compounds that stimulate tumor
development are called promoters. Approximately 70% of known mutagens are also
carcinogens--cancer-causing compounds. A compound that acts as both an initiator and a
promoter is referred to as a 'complete carcinogen' because tumor development can occur
without the application of another compound.
Cancer (medical term: malignant neoplasm) is a class of diseases in which a group of
cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on
and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the
body via lymph or blood). These three malignant properties of cancers differentiate them from
benign tumors, which are self-limited, do not invade or metastasize. Most cancers form a
tumor but some, like leukemia, do not. The branch of medicine concerned with the study,
diagnosis, treatment, and prevention of cancer is oncology.
Cancer may affect people at all ages, even fetuses, but the risk for most varieties
increases with age. Cancer causes about 13% of all deaths. According to the American Cancer
Society, 7.6 million people died from cancer in the world during 2007. Cancers can affect all
animals.
Nearly all cancers are caused by abnormalities in the genetic material of the transformed
.
cells These abnormalities may be due to the effects of carcinogens, such as tobacco smoke,
radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may
be randomly acquired through errors in DNA replication, or are inherited, and thus present in
all cells from birth. The heritability of cancers are usually affected by complex interactions
between carcinogens and the host's genome. New aspects of the genetics of cancer
pathogenesis, such as DNA methylation, and microRNAs are increasingly recognized as
important.

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 Genetic abnormalities found in cancer typically affect two general classes of genes.
Cancer-promoting oncogenes are typically activated in cancer cells, giving those cells new
properties, such as hyperactive growth and division, protection against programmed cell death,
loss of respect for normal tissue boundaries, and the ability to become established in diverse
tissue environments. Tumor suppressor genes are then inactivated in cancer cells, resulting in
the loss of normal functions in those cells, such as accurate DNA replication, control over the
cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the
immune system.
Diagnosis usually requires the histological examination of a tissue biopsy specimen by a
pathologist, although the initial indication of malignancy can be symptoms or radiographic
imaging abnormalities. Most cancers can be treated and some cured, depending on the specific
type, location, and stage. Once diagnosed, cancer is usually treated with a combination of
surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more
specific for different varieties of cancer. There has been significant progress in the
development of targeted therapy drugs that act specifically on detectable molecular
abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of
cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the
disease. In addition, histological grading and the presence of specific molecular markers can
also be useful in establishing prognosis, as well as in determining individual treatments.
The Cancer Development section contains information on the following:
♦ Cancer Initiation
♦ Cancer Promotion
♦ Cancer Progression
♦ Carcinogens
♦ Environmental Agents
♦ Viruses and Bacteria
♦ Chronic Inflammation
♦ Carcinogens Table
♦ Cancer Development Summary Sheet
Initiation is the first step in the two-stage model of cancer development. Initiators, if
not already reactive with DNA, are altered (frequently they are made electrophilic) via drug-
metabolizing enzymes in the body and are then able to cause changes in DNA (mutations).
Since many initiators must be metabolized before becoming active, initiators are often specific
to particular tissue types or species. The effects of initiators are irreversible; once a particular
cell has been affected by an initiator it is susceptible to promotion until its death. Since
initiation is the result of permanent genetic change, any daughter cells produced from the
division of the mutated cell will also carry the mutation.
In studies of mouse skin carcinogenesis, a linear relationship has been observed between
the dose of initiator and the quantity of tumors that can be produced, thus any exposure to the
initiator increases risk and this risk increases indefinitely with higher levels of exposure.
Once a cell has been mutated by an initiator, it is susceptible to the effects of promoters. These
compounds promote the proliferation of the cell, giving rise to a large number of daughter cells

14
containing the mutation created by the initiator. Promoters have no effect when the organism in
question has not been previously treated with an initiator.
Unlike initiators, promoters do not covalently bind to DNA or macromolecules within
the cell. Many bind to receptors on the cell surface in order to affect intra-cellular pathways
that lead to increased cell proliferation. There are two general categories of promoters: specific
promoters that interact with receptors on or in target cells of defined tissues and nonspecific
promoters that alter gene expression without the presence of a known receptor. Promoters are
often specific for a particular tissue or species due to their interaction with receptors that are
present in different amounts in different tissue types.
While the risk of tumor growth with promoter application is dose-dependent, there is both a
threshold and a maximum effect of promoters. Very low doses of promoters will not lead to
tumor development and extremely high doses will not produce more risk than moderate levels
of exposure.
In mice, repeated promoter applications on initiator-exposed skin produces benign
papillomas. Most of these papillomas regress after treatment is stopped, but some progress to
cancer. The frequency of progression suggests that the papillomas that progress to cancer have
acquired an additional, spontaneous, mutation. The term progression, coined by Leslie Foulds,
refers to the stepwise transformation of a benign tumor to a neoplasm and to malignancy.
Progression is associated with a karyotypic change since virtually all tumors that advance are
aneuploid (have the wrong number of chromosomes). This karyotypic change is coupled with
an increased growth rate, invasiveness, metastasis and an alteration in biochemistry and
morphology.
Since the 1940s, scientists have isolated compounds and tested their ability to induce
cancer. Substances which can cause cancer are known as carcinogens. The process of cancer
development is called carcinogenesis. There had been a suspicion that carcinogens functioned
by causing DNA mutations. One observation supporting this was that x-rays, which damage
DNA, lead to an increased incidence of cancer.
Bacteria have proven to be good models for determining the mutagenic potential of
compounds. Bruce Ames, a biochemist, developed an assay to identify potential mutagens. The
Ames test works 'backwards' from what one might expect. The test starts with mutant bacteria
and looks for chemicals that can change them back into normal (wild type) bacteria. In the
Ames test, a potential mutagen is placed on a paper disc in the center of a petri dish on which
only bacterial cells that mutate are able to grow. The mutagenic potential of the compound in
question is determined by the amount of bacterial growth seen. Information obtained in this
way was shown to be comparable to results from tests in rodents. Researchers have also
manipulated mouse cells to make them potential targets for carcinogens and have transferred
genes from cancerous cells into healthy mice--all of which have led to the conclusion that
mutations in key genes can lead to the changes that result in cancer.

Classification
A large invasive ductal carcinoma in a mastectomy specimen.
Cancers are classified by the type of cell that resembles the tumor and, therefore, the
tissue presumed to be the origin of the tumor. These are the histology and the location,
respectively. Examples of general categories include:
Carcinoma: Malignant tumors derived from epithelial cells. This group represents the most
common cancers, including the common forms of breast, prostate, lung and colon cancer.
Sarcoma: Malignant tumors derived from connective tissue, or mesenchymal cells.
Lymphoma and leukemia: Malignancies derived from hematopoietic (blood-forming) cells.

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Germ cell tumor: Tumors derived from totipotent cells. In adults most often found in the
testicle and ovary; in fetuses, babies, and young children most often found on the body
midline, particularly at the tip of the tailbone; in horses most often found at the poll (base of
the skull).
Blastic tumor or blastoma: A tumor (usually malignant) which resembles an immature or
embryonic tissue. Many of these tumors are most common in children.
Malignant tumors (cancers) are usually named using -carcinoma, -sarcoma or -blastoma as a
suffix, with the Latin or Greek word for the organ of origin as the root. For instance, a cancer
of the liver is called hepatocarcinoma; a cancer of the fat cells is called liposarcoma. For
common cancers, the English organ name is used. For instance, the most common type of
breast cancer is called ductal carcinoma of the breast or mammary ductal carcinoma. Here, the
adjective ductal refers to the appearance of the cancer under the microscope, resembling
normal breast ducts.
Benign tumors (which are not cancers) are named using -oma as a suffix with the organ name
as the root. For instance, a benign tumor of the smooth muscle of the uterus is called
leiomyoma (the common name of this frequent tumor is fibroid). Unfortunately, some cancers
also use the -oma suffix, examples being melanoma and seminoma.

Threatment of cancer:
Cancer can be threat through more medicals metods; like surgical oncology;
chemotherapy; acupuncture; radiation therapy; biotherapy or immunotherapy.
Certain types of cancer are treated most effectively by simply removing the tumor surgically.
Surgery is the oldest form of treating cancer and can also have an important role in
diagnosing and staging of cancer. The expert surgeons at Cancer Treatment Centers of
America are skilled in the most sophisticated surgical techniques. Surgery is done for many
reasons, often to accomplish one or more of these goals: preventative (or prophylactic) surgery,
diagnostic surgery, staging surgery, curative surgery, debulking (or cytoreductive) surgery,
palliative surgery, supportive surgery and restorative (or reconstructive) surgery.
Chemotherapy is the treatment of cancer with drugs that can destroy cancer cells by
impeding their growth and reproduction. These drugs often are called "anticancer" drugs.
Chemotherapy drugs are given intravenously, by injection or by mouth. Chemotherapy is often
used alone, or in conjunction with radiation therapy or surgery.
Chemotherapy can have many unpleasant side effects, such as nausea, vomiting, hair loss and

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mouth sores. New, and usually effective, approaches to prevent or moderate these side effects
will be utilized to help you through your chemotherapy treatment. The fractionated dose
approach may diminish the side effects, particularly nausea and vomiting.
In addition to offering many standard chemotherapy protocols, your care team at Cancer
Treatment Centers of America will continually revise our chemotherapy protocols to reflect
new treatments.
Chemoembolization is an innovative method used by the experts at Cancer Treatment
Centers of America to treat certain types of liver cancer, whether the tumor began in the liver
(liver cancer) or spread to it from another organ (metastasized to the liver). It involves injecting
chemotherapy directly into the blood vessels that feed the liver tumor. If you and your CTCA
care team determine that chemoembolization is the proper treatment for you, a small catheter
will be inserted through a needle (with X-ray guidance) into your femoral artery, located in
your groin. The radiologist will then thread the catheter up through your aorta (the largest
artery, located in your heart) and into the artery in your liver, which is the one that feeds the
tumor. Chemotherapy, mixed with a microsphere is injected directly through the catheter into
this artery and into the tumor. When blood flow in the artery stops due to the blockage from
the microsphere, the catheter is then removed. This procedure provides a high concentration of
chemotherapy into the tumor and provides, what is usually, a temporary cut off of the arterial
blood supply to the tumor.
There are many possible side effects from chemoembolization, since it involves both
chemotherapy and the possible destruction of normal liver tissue as well as tumor. Most people
experience some pain, fever, loss of appetite and fatigue. The overall risk of serious
complication is related to your general underlying health, as well as the overall function of
their liver.
Radiation therapy is one of the three traditional primary forms of medical treatment
used by the experts at Cancer Treatment Centers of America to treat your cancer, and for relief
of symptoms. It may be used alone or in combination with surgery or chemotherapy, almost
anywhere within your body. Innovative new techniques have evolved and are still evolving,
enabling delivery of higher radiation doses to cancer cells and limited doses to your normal
tissue.
Acupuncture is a form of ancient Chinese medicine in which fine, sterile needles are
applied to specific areas of the body, or acupoints, to stimulate energy flow (or “chi”). The
needles are usually left in place for a few minutes (skilled acupuncturists cause virtually no
pain). Energy is believed to circulate throughout the body along specific pathways called
meridians.
When energy is flowing freely through the meridians, the immune system is stimulated, which
is thought to bring on a healing response and balance. When the flow of energy is disturbed or
off-balance, pain or illness may occur. A goal of acupuncture is to restore balance and healthy
energy flow to the body to control pain and other symptoms. Worldwide, acupuncture is
sometimes used for conditions in which conventional approaches have failed, or as a
complement to traditional medicine.
In the United States and Europe, acupuncture is primarily used to control pain and relieve
symptoms of disease, but not to cure the disease itself. Some people find acupuncture useful
for helping to stop an addictive behavior, such as smoking or alcoholism. Others may find it
useful for relieving ailments such as headaches, low back pain, fibromyalgia, asthma, or carpal
tunnel syndrome.

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 Acupuncture in Cancer:
Acupuncture is not used by itself as a treatment for cancer. Rather, it is used in
combination with traditional cancer treatment options to help relieve symptoms related to
cancer and cancer treatment. In some cases, acupuncture may help to alleviate treatment-
related side effects, such as nausea and vomiting, as well as other common symptoms, such as
stress. Some individuals also find that acupuncture helps relieve fatigue, pain and neuropathy
associated with cancer and its treatment.
Biotherapy / Immunotherapy:
We at Cancer Treatment Centers of America believe that cancer treatment is
enhanced first by understanding, and then utilizing, your body's own power of protection,
known as the immune system. Immunotherapy (sometimes called biological therapy,
biotherapy, or biological response modifier therapy) uses your body’s immune system, either
directly or indirectly, to fight cancer or to lessen the side effects that may be caused by some
cancer treatments. Cancer may develop when the immune system breaks down or is not
functioning adequately. Biotherapy is designed to repair, stimulate, or enhance your body’s
own immune responses. Treatments such as interferon and colony stimulating factors are used
now at CTCA, either alone, or in conjunction with other modalities such as surgery, radiation
and chemotherapy.
Biotherapy may be used to:
• Stop, control, or suppress processes that permit cancer growth;
• Make cancer cells more recognizable, and therefore more susceptible, to destruction by
your immune system;
• Boost the killing power of your immune system cells, such as T-cells, NK-cells, and
macrophages;
• Alter cancer cells' growth patterns to promote behavior like that of healthy cells;
• Block or reverse the process that changes a normal cell or a pre-cancerous cell into a
cancerous cell;
• Enhance your body’s ability to repair or replace normal cells damaged or destroyed by
other forms of cancer treatment, such as chemotherapy or radiation;
• Prevent cancer cells from spreading to other parts of your body.

Melanoma is the most serious cancer of the skin. It begins in certain cells in the
skin called melanocytes. In some parts of the world, especially among Western countries, the
number of people who develop melanoma is increasing faster than any other cancer. In the
United States, for example, the number of new cases of melanoma has more than doubled in
the past 20 years.
Melanocytes are found throughout the lower part of the epidermis. They produce
melanin, the pigment that gives skin its natural color. When skin is exposed to the sun,
melanocytes produce more pigment, causing the skin to tan, or darken.
Sometimes, clusters of melanocytes and surrounding tissue form benign (noncancerous)
growths called moles. (Doctors also call a mole a nevus; the plural is nevi.) Moles are very
common. Most people have between 10 and 40 of these flesh-colored, pink, tan, or brown
areas on the skin. Moles can be flat or raised. They are usually round or oval and smaller than a

18
pencil eraser. They may be present at birth or may appear later on—usually before age 40.
Moles generally grow or change only slightly over a long period of time. They tend to fade
away in older people. When moles are surgically removed, they normally do not return.
Melanoma occurs when melanocytes (pigment cells) become malignant. Most pigment
cells are in the skin; when melanoma starts in the skin, the disease is called cutaneous
melanoma. Melanoma may also occur in the eye and is called ocular melanoma or intraocular
melanoma. Rarely, melanoma may arise in the meninges, the digestive tract, lymph nodes, or
other areas where melanocytes are found.
Melanoma can occur on any skin surface. In men, it is often found on the trunk (the area
from the shoulders to the hips) or the head and neck. In women, melanoma often develops on
the lower legs. Melanoma is rare in African Americans and others with dark skin. When it does
develop in dark-skinned people, it tends to occur under the fingernails or toenails, or on the
palms or soles. The chance of developing melanoma increases with age, but this disease affects
people of all age groups. Melanoma is one of the most common cancers in young adults.
When melanoma spreads, cancer cells are also found in the lymph nodes (also called lymph
glands). If the cancer has reached the lymph nodes, it may mean that cancer cells have spread
to other parts of the body, such as the liver, lungs, or brain. In such cases, the cancer cells in
the new tumor are still melanoma cells, and the disease is called metastatic melanoma rather
than liver, lung, or brain cancer.
At Cancer Treatment Centers of America (CTCA), we use many tools to help you fight
melanoma on all fronts. A powerful combination of traditional and new, innovative therapies
are provided by cancer experts who work with you to determine the appropriate combination of
therapies, which may include:
Surgery is often used as a treatment for melanoma. There are several types of surgery
depending on the stage and location of cancer.
Metronomic Chemotherapy divides a powerful dose of chemotherapy drugs into smaller doses,
given over several days. This approach exposes cancer cells to the drugs for a longer period of
time, while also seeking to reduce the unpleasant side effects often experienced with larger
doses.

Biotherapy/Immunotherapy is a treatment that is sometimes used for melanoma.

Immunotherapy causes the body's own natural defenses (immune system) to attack the cancer.
In addition to the therapies described above, CTCA enriches your treatment by offering
complementary/alternative therapies such as naturopathic medicine, nutrition therapy, mind-
body medicine, image enhancement, and spiritual support. CTCA is with you every step of the
way in what truly is the fight of your life.
Cancer is a group of more than 100 different diseases that can occur within any part of the
body. Cancer occurs when cells become abnormal and keep dividing and forming more cells
without control or order. Normally, cells divide within the body to produce more cells only
when the body needs them. If cells keep dividing when new cells are not needed, a mass of
tissue forms. This mass of extra tissue, called a growth or tumor, can be benign (not cancerous)
or malignant (cancerous.)
According to the National Cancer Institute, This year, an estimated 1.2 million Americans
will be diagnosed with cancer. Avoiding tobacco use is the single most important step
Americans can take to reduce the cancer burden in this country. The NCI’s 2001 Cancer

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 Progress Report offers these suggestions for behavioral and exposure changes to prevent
cancer:
• Not using cigarettes or other tobacco products
• Not drinking too much alcohol
• Eating five or more daily servings of fruits and vegetables
• Eating a low-fat diet
• Maintaining or reaching a healthy weight
• Being physically active
• Protecting skin from sunlight
• Certain chemicals in the environment are known to cause cancer:
• Secondhand smoke (also known as environmental tobacco smoke)
• Radon in the home
• Benzene in the air
• Avoiding exposure to these substances will also greatly reduce the likelihood of
developing cancer.

There are a number of different methods used to treat cancer. Surgery, radiation and
chemotherapy are three common forms of treatment that have been used effectively for a
number of years. At Cancer Treatment Centers of America, we use many tools to help you
fight cancer on all fronts. Your type of cancer, the extent of your disease, and your general
state of health are all influential factors in determining the most appropriate treatment
combination. A powerful combination of proven traditional and new, innovative therapies are
provided by cancer experts who work with you to determine the most effective combination.
CTCA is with you every step of the way in what truly is the fight of your life.

Population (epidemiological) and laboratory studies have led to the discovery of many
potential environmental factors in the initiation, promotion and progression of cancer. Starting
with Pott's observations in the 18th century, certain occupations have been associated with an
increased risk of cancer development. The recognition of increased scrotal cancer in chimney
sweeps due to coal and tar exposure was followed by an observation in a British factory that all
men distilling 2-napthylamine developed bladder cancer. Nickel refining, leather working and
woodworking have also been associated with an increased risk of specific cancers due to
chronic exposure to carcinogenic chemicals. Exposure to mustard gas, used as a chemical
warfare agent in World War I has been associated with a higher risk of respiratory-tract and
lung cancers due to its mutagenic properties. Of interest, some chemotherapy drugs are
derivatives of mustad gas and are useful for the very same reason; they are highly mutagenic.
There have also been associations made between different geographical regions and particular
cancers. Stomach cancer is 5-6 times higher among Japanese men, attributed to the
consumption of fermented foods; breast cancer is 20 times higher among American women,
attributed to the high fat American diet; and liver cancer is 10 times higher in Africa, which
correlates with high rates of Hepatitis B infection. Liver cancer may also be caused by
aflatoxin, a food contaminant produced by fungi. This compound is prevalent in grain stores in
tropical and subtropical regions because the moist grain is a very good place for the fungi to
live.

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 The impact of many environmental factors can be reduced by making healthy lifestyle
choices. One of the most potent carcinogens in humans is benzo[a]-pyrene, a compound found
in cigarette smoke. In fact, the tar fraction of cigarette smoke includes both initiators and
promoters, making it especially dangerous. Alcohol is a promoter of carcinogenesis in humans,
as is asbestos. Additionally, UV radiation, from exposure to the sun or tanning beds, is a
powerful initiator in humans and is a cause of skin cancer.
Tamoxifen, a chemotherapeutic agent used to combat estrogen receptor positive (ER+) breast
cancer, increases the risk of endometrial cancer by increasing the rate of endometrial cell
proliferation. For this reason, long-term tamoxifen treatment is losing popularity in favor of
aromatase inhibitors. Estrogens themselves may also be important in the promotion of tumors,
particularly in post-menopausal women receiving exogenous estrogens, due to their ability to
increase mammary and endometrial cell division rates. This is an area of active research.
There are actually factors that can predispose an unborn to the development of cancer
later in life. These include exposure to radiation or the synthetic estrogen diethylstilbestrol.
These factors produce genetic damage in utero that can lead to cancer development upon
exposure to promoting factors after birth.
Certain viruses and bacteria have also been associated with the initiation and
promotion of tumor growth based on both epidemiological and experimental evidence. Some
DNA viruses contain genes whose products can take control of cell division in the host cell.
They promote the development of tumors by increasing proliferation rates and shutting down
the normal systems that prevent cells from dividing. These viruses include human
papillomavirus (HPV), the most significant risk factor for the development of cervical cancer.
Similarly, an RNA virus, human T-cell leukemia virus type 1 (HTLV-1) leads to adult T-cell
leukemia by stimulating the proliferation of infected T-cells. Epstein-Barr virus (EBV) is
another virus that increases cell proliferation. This virus also protects infected cells from death
(apoptosis). EBV infects more than 90% of the world's adult population and has been
implicated as a cause of Burkitt's lymphoma, nasopharyngeal carcinoma and gastric
lymphoma. Experimental evidence in rats and from human tumors, has implicated the JC virus
(a polyomavirus)in brain tumors, particularly medulloblastomas. Some viruses also have
indirect actions on tumor development. Hepatitis B causes damage that leads to increased cell
division and inflammation in the liver, potentially promoting the growth of tumors. The human
immunodeficiency virus (HIV) greatly reduces the function of the immune system and is the
cause of AIDS. HIV infection may also make patients susceptible to infection by a type of
human herpes virus 8 (HHV8), a risk factor for Kaposi's sarcoma.

In addition to chemicals and radiation, another source of mutation is viruses. Viruses

are very small 'organisms' that can infect the cells of other animals or plants. Humans are
susceptible to a large number of different viruses. Viruses are not the same as bacteria although
both can cause human disease. Treatments that cure bacterial infections are not useful in the
treatment of viral infection. Some examples of viruses include the agent that causes the flu
(influenza virus) and the causative agent of AIDS, the human immunodeficiency virus (HIV).
Viruses can disrupt cell behavior in several different ways.
They can directly cause DNA damage (mutations) by inserting their genomes into the DNA of
the host cell. The integration can disrupt important regulatory genes.

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 The viruses may contain their own genes that disrupt the regulation of the cell. This
process may be beneficial to the virus if it allows for rapid production of progeny but can be
seriously detrimental to the host.
Some viruses actually carry altered versions of genes that they have picked up from previous
host cells. These altered genes no longer function properly, and when they are inserted into a
new host cell, they cause disregulation and can lead to cancerous growth.
Through their mutagenic activity or their effects on cell behavior, viruses play a significant
role in the development of particular cancers in many different animals, including humans.
Viruses have also been a major target of scientific investigation with respect to cancer. Some
of the earliest work on the identification of oncogenes and tumor suppressors utilized viruses.
Viruses can be divided into two rough categories, those that have DNA as their genetic
material and those that have RNA as their genetic material. Both kinds of virus have been
found to be associated with cancers of different types. The cancers known to be associated with
a specific virus are:
• Epstein-Barr Virus (EBV) - Burkitt's Lymphoma
• Hepatitis B Virus (HBV) - Liver Cancer
• Hepatitis C Virus (HCV) - Liver Cancer
• Human Herpesvirus 8 (HH8) - Kaposi's Sarcoma
• Human Papillomavirus (HPV) - Cervical Cancer
may also cause head and neck, anal, and penile cancer
• Human T-cell Lymphotropic Virus 1 (HTLV) - Adult T-cell Leukemia
• Epstein-Barr Virus (EBV)

Associated Cancer: Lymphoproliferative disease, most commonly Burkitt's

Lymphoma. There is increasing evidence EBV is also associated with Hodgkin lymphoma.
Prevalence: It's estimated that more than 90% of the World population is infected with EBV.
EBV is responsible for infectious mononucleosis (the 'kissing disease')
Transmission: Mechanism of transmission generally unknown, possibly through saliva
Infection: EBV Infection usually begins in the epithelial cells of the oropharynx, posterior
nasopharynx and parathyroid glands. From there EBV infects B cells and persistent infection is
established. Almost all cases of EBV infection are controlled by the immune system and
infected individuals are asymptomatic (have no symptoms of infection).
Carcinogenic Potential: B cell Infection is necessary for EBV mediated carcinogenesis. Only a
small percentage of infections lead to cancer, most cases arising in immunocompromised or
transplanted individuals. These patients are especially susceptible because they lack sufficient
immune function to inhibit the growth of infected B cells. EBV-mediated carcinogenesis is
most likely caused by the actions of viral gene products. Two proteins in particular are thought
to play a major role in B cell immortalization; latent membrane proteins (LMP's) and EBV
nuclear antigen (EBNA's). LMP1 is inserted into the host cell membrane and acts as an
activated growth factor receptor, resulting in unregulated growth. EBNA's affect the cell in
many different ways; one pathway leads to altered activity of tumor suppressors including Rb,
p53, and Arf.

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 Cell Division and Mitosis:
During a lifetime, many of the cells that make up the body age and die. These cells
must be replaced so that the body can continue functioning optimally. Reasons that cells are
lost and must be replaced include the following:
Sloughing off of epithelial cells such as those lining the skin and intestines. The old, worn out
cells on the surface of the tissues are constantly replaced. A special case of this is the monthly
replacement of the cells lining the uterus in pre-menopausal women.
Wound healing requires that cells in the area of the damage multiply to replace those lost. Viral
diseases such as hepatitis may also cause damage to organs that then need to replace lost cells.
Replacement of the cells that make up blood. Red blood cells carry oxygen to tissues. White
blood cells such as B and T lymphocytes are part of the body's immune system and help to
ward off infections. Most of these cells have very short lifespans and must be constantly
replaced. The precursors of these cells are located in bone marrow. These precursors, or
stem cells, must reproduce at a very high rate to maintain adequate amounts of the blood cells.
The process by which a cell reproduces to create two identical copies of itself is
known as mitosis. The goal of mitosis is the formation of two identical cells from a single
parent cell. The cells formed are known as daughter cells. In order for this to happen, the
following must occur:
• The genetic material, the DNA in chromosomes, must be faithfully copied. This occurs
via a process known as replication.
• The organelles, such as mitochondria, must be distributed so that each daughter cell
receives an adequate amount to function.
• The cytoplasm of the cell must be physically separated into two different cells.
• As we will see, many of the features of cancer cells are due to defects in the genes that
control cell division. The cell division process occurs as an orderly progression through four
different stages. These four stages are collectively known as the cell cycle. The following
pages describe the cell cycle in detail.

Cancer Cell Division:

When it comes to cell division, cancer cells break just about all the rules!
Cancer cells can divide without appropriate external signals.
This is analogous to a car moving without having pressure applied to the gas pedal. An
example would be the growth of a breast cancer cell without the need for estrogen, a normal
growth factor. Some breast cancer cells actually lose the ability to respond to estrogen by
turning off expression of the receptor for estrogen within the cell. These cells can still
reproduce by bypassing the need for the external growth signal.
Cancer cells do not exhibit contact inhibition.
While most cells can tell if they are being 'crowded' by nearby cells, cancer cells no longer
respond to this stop signal. The continued growth leads to the piling up of the cells and the
formation of a tumor mass.
Cancer cells can divide without receiving the 'all clear' signal.
While normal cells will stop division in the presence of genetic (DNA) damage, cancer cells
will continue to divide. The results of this are 'daughter' cells that contain abnormal DNA or

23
even abnormal numbers of chromosomes. These mutant cells are even more abnormal than the
'parent' cell. In this manner, cancer cells can evolve to become progressively more abnormal.
Continued cell division leads to the formation of tumors. The genetic instability that results
from aberrant division contributes to the drug resistance seen in many cancers. Mutations in
specific genes can alter the behavior of cells in a manner that leads to increased tumor growth
or development. The next chapter will examine a few of the best-studied examples of these
genes. More information on this topic may be found in Chapter 8 of The Biology of Cancer by
Robert A. Weinberg.

Cell Division Control Introduction:

Cell division is a normal process. Mechanisms exist to ensure DNA replication occurs
correctly and the environmental conditions are favorable for cell division. Replication errors
may also be corrected after they occur.
Normal cells stop dividing when there is genetic damage or conditions are not favorable.
Cancer cells continue to divide even when conditions are not appropriate.

Cell Division Signaling:

Most cells in the body are not actively dividing, but are carrying out their normal
functions.
Cells divide in response to external signals in the form of protein or steroid growth factors.
Cells stop dividing for several reasons, including:
A lack of positive external signals
The cell senses that it is surrounded on all sides by other cells-contact dependent (density
dependent) inhibition
Most cells seem to have a pre-programmed limit of the number of times they can divide
Cell Division in Cancer Cells
Cancer cells can divide without appropriate external signals.
Cancer cells do no exhibit contact inhibition.
Cancer cells continue dividing in the presence of genetic damage.
The uninhibited, continued division of genetically damaged cells can lead to tumor formation.

Mutation and Cancer:

The abnormal behaviors demonstrated by cancer cells are the result of a series of
mutations in key regulatory genes. The cells become progressively more abnormal as more
genes become damaged. Often, the genes that are in control of DNA repair become damaged
themselves, rendering the cells even more susceptible to ever-increasing levels of genetic
mayhem.
Most cancers are thought to arise from a single mutant precursor cell. As that cell divides,
the resulting 'daughter' cells may acquire different mutations and different behaviors over a
period of time. Those cells that gain an advantage in division or resistance to cell death will
tend to take over the population. In this way, the tumor cells are able to gain a wide range of
capabilities that are not normally seen in the healthy version of the cell type represented. The
changes in behavior seen in cancer cells are the focus of the Tumor Biology chapter of the site.

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Since genetic changes and the resulting changes in cell behavior are at the heart of cancer
biology, we will now take a look at some of the different kinds of genetic changes (mutations)
seen in cancer and then examine the causes of these changes.

Cancer Detection and Diagnosis

One of the key problems in the treatment of cancer is the early detection of the disease.
Often, cancer is detected in its later stages, when it has compromised the function of one or
more vital organ systems and is widespread throughout the body. Methods for the early
detection of cancer are of utmost importance and are an active area of current research.
After the initial detection of a cancerous growth, accurate diagnosis and staging of the disease
are essential for the design of a treatment plan. This process is dependent on clinical testing
and the observations of physicians. It is important for cancer patients and their families to
understand the results given to them so that they can take an active role in the planning of the
treatment protocol to be used.
This chapter discusses some of the detection methods currently in use for several
different cancer types. Also discussed are some possible tests that are still under investigation.
There is a section dedicated to describing the results presented in pathology (path.) reports and
a section that describes the process of cancer staging.
Detecting cancers early is an important step in preventing significant health problems.
Almost universally, cancers are easier to treat when detected early. Because early-stage cancers
are small and often have no symptoms, researchers have been trying to develop simple,
inexpensive screening procedures that are sensitive enough to detect these cancers. Such tests
must be inexpensive and easy because performing invasive, expensive procedures on otherwise
healthy people would be unethical and would be inefficient at the population level. Blood tests
are a common and straightforward means of screening people for cancer in its early stages. If a
chemical in the blood that signals the presence of even a small tumor can be detected, the
cancer could be treated sooner and would be more likely to be cured.
When a test is performed to detect a disease, there are four possible outcomes.
If a test indicates that a patient has a disease that the patient does indeed have, this is
called a true positive. However, if the test indicates that a patient has a disease when she does
not, it is called a false positive. If the test indicates the patient is disease-free, and this is indeed
the case, it is called a true negative. Finally, if the test indicates the patient is healthy when in
fact the patient has the disease

Frequently Asked Questions: False Positives and Negatives

What is a false positive test result?

A false positive test result is one that leads a physician to suspect a disease or condition is
present when one is NOT really there.
What is a false positive test result?
A false negative test result is one that leads a physician to think a patient does not have a
particular disease or condition when they actually DO have it.
What causes false-positive test results?
There are many reasons why a test result may indicate the presence of a condition that is not
really there. These include human error and the limits of the techniques used.
Example 1 (imaging): Many different types of imaging techniques are now used to diagnose
disease. These include mamography, CT, PET, MRI, ultrasound and combinations of these.

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All of these techniques produce images that are then interpreted by physicians or trained
technicians. Because image quality and experience factor into every test, there is always the
chance that a result will be misreported. This will typically result in additional tests to confirm
the result.
Example 2 (blood tests): A blood test commonly used to detect prostate cancer measures
amounts of prostate specific antigen (PSA), a protein. This test is used because many prostate
cancers over produce this protein. However, there are other reasons that a man's PSA levels
can go up. These include inflammation and infection. In these cases, it is possible that a PSA
test would come back positive, potentially leading to unnecessary additional procedures.
What causes false-negative test results?
Example 1 (imaging): Because young women have dense breast tissue, it may be difficult to
identify a small cancerous growth on a mammogram, especially if it is the first exam because
there is nothing with which to compare the results.
Example 2 (blood tests): As described in the previous question, the PSA test is used to detect
prostate cancers. Because not all prostate cancers increased amounts of PSA, it is possible for a
screening exam to miss a case of prostate cancer.
Is there anything I can do to reduce the chance of a false-positive or false-negative
test result?
While there is nothing that a patient can do about the limitations of any particular test, there are
things that you can do to reduce your chances of obtaining an incorrect result.
Make sure you follow all the pre-test instructions. As an example, before a colonoscopy, it is
important to make sure that you clear out your digestive system so that no small polyps or
other abnormalities will be blocked from view.
Make sure that the individual/facility performing the test is fully accredited with the
appropriate organization. This can usually be done online.
Write down any questions you have about the test beforehand and bring them with you to ask.
Dont hesitate to seek additional testing from a different provider.

Sensitivity and Specificity of Medical Tests

When referring to the accuracy of a medical test, statisticians use the words
sensitivity and specificity. Sensitivity refers to the proportion of the times that a test yields true
positives. The closer the sensitivity is to 100%, the more likely a positive result actually means
that the patient has a disease. Specificity refers to the proportion of the time that a test yields
true negatives. The closer the specificity is to 100%, the more likely a negative result means
that the patient is truly disease-free.
A perfect test gives only true positives and true negatives, and the worst possible test would be
the same as guessing. While many medical tests are highly accurate, all tests used in medicine
fall somewhere in between these two extremes. This uncertainty raises some difficult issues. A
test that yields a positive result will usually lead to the performance of a second, more accurate
test. If the second test used is still simple and non-invasive, then a preliminary test that yields a
high number of false positives may be acceptable. If the second test is difficult to perform or
risky, the initial blood test may lead many people to have unnecessary medical procedures.
If the first test is imperfect it may incorrectly indicate that patients are healthy, when in fact
they are not. If the disease is mild and will probably not hurt the patient's health, then the blood

26
test does little harm when it is wrong. If the disease is serious, the blood test may prevent
patients from obtaining necessary treatments. The value of any blood test is a balance between
the sensitivity and specificity of the test, and the severity of the disease detected. It is important
that patients discuss the sensitivity and specificity of tests given with their physician.

What does 'sensitivity' mean when used to describe medical tests?

No medical test is perfect. It is important to know the limitations of any test so you can judge
how to factor in the test results to your treatment decisions. The sensitivity of a medical test is
a measure of how well the test identifies people who have a particular disease. Example:
Suppose there is a group of ten women and three of them have breast cancer. If all of the
women are given a test to detect the cancer and it finds two of the three, the test has only 66%
(2/3) sensitivity.
What does 'specificity' mean when used to describe medical tests?
No medical test is perfect. It is important to know the limitations of any test so you can judge
how to factor in the test results to your treatment decisions. The specificity of a medical test is
a measure of how well the test identifies people who do not have a particular disease. In other
words, specificity is a way of measuring whether or not the test inaccurately flags normal
people as having a condition. Example: We will use the same sample as above; 10 women, 3 of
who have cancer. If the test identifies all three cancer patients but flags any normal women as
having the disease, it would have 100% sensitivity but reduced specificity. The more normal
women the test identifies as having cancer, the lower the specificity of the test.
Why would a medical test have reduced specificity or sensitivity?
No medical test is perfect. Tests can give false positive or false negative results because of
the limits of technology, human error or machine error. Any of these can lead to reduced
specificity and/or sensitivity for a test.
Is there anything I can do to reduce the chances that my test result will be incorrect?
While there is nothing that a patient can do about the limitations of any particular test, there
are things that you can do to reduce your chances of obtaining an incorrect result.
Make sure that you follow all the pre-test instructions. As an example, before a colonoscopy, it
is important to make sure that you clear out your digestive system so that no small polyps or
other abnormalities will be blocked from view.
Make sure that the individual/facility performing the test is fully accredited with the
appropriate organization. This can usually be done online.
Write down any questions you have about the test beforehand and bring them with you to ask.
Don't hesitate to seek additional testing from a different provider.

The Role of Mutation in Cancer

Mutations in key regulatory genes ( tumor suppressors and proto-oncogenes ) alter the
behavior of cells and can potentially lead to the unregulated growth seen in cancer.
For almost all types of cancer studied to date, it seems as if the transition from a normal,
healthy cell to a cancer cell is step-wise progression that requires genetic changes in several
different oncogenes and tumor suppressors. This is one reason why cancer is much more
prevalent in older individuals. In order to generate a cancer cell, a series of mutations must
occur in the same cell. Since the likelihood of any gene becoming mutated is very low, it
stands to reason that the chance of several different mutations occuring in the same cell is truly

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very unlikely. For this reason, the cells in a 70 year old body have had more time to
accumulate the changes needed to form cancer cells but those in a child are much less likely to
have acquired the requisite genetic changes. Of course, some children do get cancer but it is

much more common in older individuals. The graph below shows colon cancer rates in the
United States as a function of age. The graph was obtained from the National Cancer Institute.

By looking at the shape of curves like the ones shown above, it has been concluded that
several independent genetic changes are required to create cells that become cancerous.
In the laboratory, researchers have been attempting to create tumor cells by altering or
introducing key regulatory proteins. Several studies have attempted to define the minimal
number of genetic changes needed to create a cancer cell, with intriguing results.
To complicate matters, it is clear that the changes needed to create a cancer cell can be
accomplished in many different ways. Although all cancers have to overcome the same
spectrum of regulatory functions in order to grow and progress, the genes involved may differ.
In addition, the order in which the genes become de-regulated or lost may also vary. As an
example, colon cancer tumors from two different individuals may involve very different sets of
tumor suppressors and oncogenes, even though the outcome (cancer)is the same.
The great heterogeneity seen in cancer, even those of the same organ, means that diagnosis and
treatment are complicated. Current advances in the molecular classification of tumors should
allow the rational design of treatment protocols based on the actual genes involved in any
given case. New diagnostic tests may involve the screening of hundreds or thousands of genes
to create a personalized profile of the tumor in an individual. This information should allow for
the tailoring of cancer treatments geared to the individual. For more information on this see the
Genomics/Proteomics subsection.
The genetic changes that lead to unregulated cell growth may be acquired in two different
ways. It is possible that the mutation can occur gradually over a number of years, leading to the

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development of a 'sporadic' case of cancer. Alternatively, it is possible to inherit dysfunctional
genes leading to the development of a familial form of a particular cancer type. Some examples
of cancers with known hereditary components include:
Breast cancer- Inheritance of mutant versions of the BRCA1 and BRCA2 genes are known risk
factors. Although many, if not most, individuals with breast cancer do not have detectable
alterations in these genes, having a mutant form increases the likelihood of developing breast
cancer.
Colon cancer- Defects in DNA repair genes such as MSH2 are known to predispose
individuals to hereditary non-polyposis colorectal cancer (HNPCC).
Retinoblastoma- Defects in the Rb tumor suppressor gene are known to cause this eye cancer
and several other types of cancers. More on this particular disease can be found in the chapter
on Rb
This is an incomplete list of the known inherited cancer types, and it is certain that more
inherited forms of cancer will identified as the genetics of various types of cancer are clarified.
More information on this topic may be found in Chapters 2 and 4 of The Biology of Cancer by
Robert A. Weinberg.

Lymphoma: Introduction
Cancer arising in the lymphatic system, called lymphoma, is the most commonly
occuring blood cancer. Approximately 1,000 people worlwide are diagnosed with lymphoma
every day. The cells affected by this disease are part of the body's immune system. In 2008, the
American Cancer Society estimates that 74,340 new lymphoma cases would be diagnosed and
20,510 cancer deaths due to lymphoma would occur in the United States.
The lymphatic system is composed of a vast network of tubes (vessels) and grapelike clusters
called lymph nodes. The vessels transport colorless fluid called lymph and cells of the immune
system (lymphocytes) throughout the body. The lymphatic system resembles a river system.
Small capillaries carry lymph into larger vessels which eventually drain into two large lymph
vessels that empty into blood vessels at the base of the neck.
The lymphatic system serves many purposes including: filtration, transport of fluid and
initiation of immune responses. The vessels of the lymphatic system are responsible for
absorbing and filtering the fluid which surrounds the cells and tissues of the body.
Lymph nodes are small sac-like structures located along the lymph vessels. They are home to
lymphocytes, a type of white blood cell. Lymph nodes store lymphocytes and help control the
immune response by allowing lymphocytes to come into contact with foreign materials
(antigens) in a manner that stimulates their activity.
All lymphocytes originate from stem cells in the bone marrow but they are not all the same.
The two main categories of lymphocytes are B cells and T cells. B cells fully develop in the
bone marrow. T cells leave the bone marrow in an immature state and continue to develop in
the thymus and other organs. T cells and B cells play different roles in the immune system and
their functions are described more fully in the Vaccine section.
The extensive nature of the lymphatic network allows it to serve as a way for cancer cells to
spread throughout the body. Cancer metastasis frequently occurs via migration of cancer cells
through the lymphatic system.
Cancer cells of these patients are usually abnormal B-cells referred to as a Reed-Sternberg
(R-S) cells. Although less commonly observed, R-S cells may also develop from T-cells. R-S
cells most often develop in lymph nodes located in the upper body regions and spread to
neighboring lymph nodes via lymphatic vessels. There are two distinct types of Hodgkin's
lymphoma: classical and non-classical Hodgkin's lymphoma.

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Classical Hodgkin's Lymphoma: This lymphoma features R-S cells with a classical
appearance. It may be diagnosed as Nodular Sclerosis Hodgkin Disease, Mixed Cellularity
Hodgkin's Disease, Lymphocyte-Rich Hodgkin Disease or Lymphocyte-Depleted Hodgkin
Disease.
Non-classical Hodgkin's Lymphoma: This lymphoma features larger cancer cells that
are variants of R-S cells and is most often found in the nodes of the upper body, arms and
neck.
The cancerous cells of non-Hodgkin lymphoma patients may be either T or B cells. In the
United States, approximately 15% of cases of non-Hodgkin lymphoma cases develop from T
lymphocytes and 85% develop from B lymphocytes.
Normal white blood cells may develop into over thirty different variations of abnormal cells,
each classified as a distinct type of non-Hodgkin lymphoma.
The American Cancer Society estimates approximately 66,120 (89%) of the 74,340 lymphoma
cases diagnosed in the United States in 2008 will be classified as non-Hodgkin lymphoma.
Burkitt’s lymphoma is an aggressive form of non-Hodgkin lymphoma involving B cells. It
occurs as the result of chromosome translocation involving the Myc gene. Translocation
disrupts Myc expression leading to abnormal cell growth and proliferation. The rate of cell
division in Burkitt’s lymphoma is one of the highest among human tumors. It was first
described by Dr. Denis Burkitt in 1958 while he was working in Uganda. Burkitt’s lymphoma
was later discovered to be highly associated with the Epstein-Barr virus; this was the first time
a virus was linked to a form of cancer.
The WHO describes three clinical variants of Burkitt’s lymphoma: endemic, sporadic, and
immunodeficiency-associated.
Endemic Burkitt’s lymphoma primarily refers to cases occurring in African children. This type
usually involves the facial bones, especially the jaw, maxilla, and orbit. The Epstein-Barr virus
(EBV) is associated with over 90% of endemic Burkitt’s lymphoma.
Sporadic Burkitt’s lymphoma refers to cases occurring in no specific geographic or climatic
region. This type usually involves the abdomen. Unlike endemic lymphoma, infection with
EBV is found in only about 20% of sporadic lymphoma. It accounts for 40-50% of childhood
non-Hodgkin’s lymphoma, but only 1-2% of adult lymphomas in Western Europe and the
United States.
Immunodeficiency-associated Burkitts lymphoma refers to cases occurring in patients infected
with HIV, transplant patients (most often solid organ), or individuals with other immune
system disorders. BL accounts for 30-40% of non-Hodgkin’s lymphomas diagnosed in HIV
infected individuals. However, HIV is not directly related to cancer formation. EBV is found in
30-40% of these cases of Burkitt’s lymphoma.

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Risck Factors:

The cause of the majority of lymphoma cases is unknown. However, several factors may
influence one's risk of developing lymphoma. The relative effects of these factors in any given
case of cancer is variable and very difficult to determine with accuracy at this time. Some of
these risk factors are discussed below.

Sex:
Specific subtypes of non-Hodgkin lymphoma, such as follicular lymphoma, are predominant in
women; however, non-Hodgkin lymphoma is overall more common in men. Mantle cell
lymphoma shows the highest predisposition in males (70% of cases are men).

Geography:
Non-Hodgkin lymphoma is most common in developed regions of the world, specifically the
United Sates, Australia, New Zealand and Europe.
Epstein Barr virus (EBV), a type of herpes virus that infects B lymphocytes, increases a
person's risk of developing fast growing lymphomas. In Africa and Southeast Asia, EBV is
related to the development of Burkitt lymphoma and Hodgkin's lymphoma.

Genetics:
As discussed in the Genetic Change section DNA mutations can cause cancer by enhancing
cell division and/or reducing tumor suppressor mechanisms. Lymphoma is rarely caused by
inherited mutations in the DNA sequence and there is no increased risk of lymphoma in
children of lymphoma patients.

Age:
The incidence of lymphoma peaks in individuals over 70 years of age. Non-Hodgkin
lymphoma is rarely observed in children and most commonly develops in older adults. Less
than 1% of non-Hodgkin lymphoma diagnoses reported in 2001 occurred in children under the
age of 15 years.
The age groups most frequently affected by Hodgkin's lymphoma are early adults (age 15-40)
and late adults (above 55).

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 CHAPTER II:
150 of those terms medicinals:
1. allergies = alergii
2. anthropology = antropologie
3. anxiety = anxietate
4. acupuncture = acupunctura
5. acute = acut
6. anesthesy = anestezie
7. analgesy = analgezie
8. blood = sange
9. cancer = cancer
10. cardiovascular = cardiovascular
11. cadaver = cadavru
12. clinical = clinic
13. diseases = boli
14. diagnosis = diagnostic
15. depression = depresie
16. hyperthyroidism = hipertiroidism
17. heart = inima
18. osteoporosis = osteopareza
19. treatment = tratament
20. neoplasm = neplasm
21. infections = infectii
22. therapeutics = terapeutic
23. organisms = organisme
24. digestive system = sistem digestiv
25. cells = celule
26. endocrine system = sistem endocrin
27. immune system = sistem imunitar

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28. nervous system = sistem nervos
29. organs = organe
30. erythrocytes = eritrocite
31. therapy = terapie
32. lymphocyte = limfocite
33. biopsy = biopsie
34. symptoms = simptome
35. cytoplasm = citoplasma
36. brain = creier
37. chemotherapy = chimioterapie
38. cholesterol = cholesterol
39. chronic = cronic
40. hepatitis = hepatita
41. cirrhosis = ciroza
42. heme = hem
43. hemoglobine = hemoglobina
44. hemorrhage = hemoragie
45. methabolism = metabolism
46. myalgy = durere musculara
47. pathogen = patogen
48. vaccine = vaccin
49. vein = vena
50. varices = varice
51. viral hepatitis = hepatita virala
52. eczema = eczema
53. pain = durere
54. vomiting = voma
55. discopathy = discopatie
56. hygiene = igiena
57. to sterilize = a steriliza
58. thermometer = termometru
59. disinfectant = dezinfectant
60. prophylactic = profilactic

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61. paralysis = paralizie
62. paresis = pareza
63. muscle = muschi
64. lordosis = lordoza
65. scoliosis = scolioza
66. luxation = luxatie
67. congenital = congenital
68. hips = solduri
69. vertebral column = coloana vertebrala
70. artrology = artrologie
71. motricity = motricitate
72. joint = jonctiuni
73. to splay = a disloca
74. tissue = tesut
75. rickets = rahitism
76. obesity = obezitate
77. nausea = greata
78. epilepsy = epilepsie
79. sclerosis = scleroza
80. arthritis = artrita
81. infection = infectie
82. constipation = constipatie
83. fatique = oboseala
84. patients = pacienti
85. neurological = neuro-chirurgical
86. neuron-surgeon = neuro-chirurg
87. skin = fata
88. ligaments = ligamente
89. cervical = cervical
90. thoracic = tiracic
91. lumbar = lombar
92. recovery = recuperare
93. ribs = coaste

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 94. nerves = nervi
95. fibers = fibre
96. vertebrals = vertebre
97. pelvis = pelvis
98. abdominal = abdominal
99. to prescribe = a prescrie
100. disk hernia = hernie de disc
101. lancet = bisturiu
102. syringe = seringa
103. dressing = pansament
104. splint = atela
105. recipe = reteta
106. abortion = avort
107. invalid = bolnav; invalid
108. intestine = intestin
109. intestinal = intestinal
110. to intern = a interna
111. insulin = insulina
112. spine = coloana vertebrala
113. spleen = splina
114. diabetes = diabet
115. doctor = doctor
116. surgeory = chirurgie
117. surgeon = chirurg
118. surgical = chirurgical
119. syphilis = sifilis
120. sword-cut = rana; cicatrice
121. symptom = symptom
122. neurotik = bolnav cu nervii
123. neuroastheny = neuro astenie
124. thrombophlebite = tromboflebita
125. tuberculosis = tuberculoza
126. tubercular = tuberculos

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127. abortive = premature
128. acne = acnee
129. affection = afectiune; boala
130. authopsy = autopsie
131. arm = brat
132. hand = mana
133. appendicitis = apendicita
134. appendix = apendice
135. analysis = analiza
136. ambulance = ambulanta
137. antidote = antidote
138. bones = oase
139. prostate = prostata
140. infertility = infertilitate
141. abdominal pain = durere abdominala
142. abscess = abces
143. electrocardiogram = electrocardiograma
144. trauma = trauma
145. meningitis = meningita
146. testicle = testicul
147. testosterone = testosteron
148. tumor = tumoare
149. enterocolysis = enterocolita
150. ventricular tachycardia = tahicardie ventriculara

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