CHAPTER TWO

LITERATURE REVIEW

2.0 PROSTRATE CANCER

Prostate cancer is one of the malignancies that affects men and significantly
contributes to increased mortality rates in men globally.prostrate cancer which is also
called prostatic carcinoma is the type of cancer that forms in the tissues of the
prostrate which is a gland in the male reproductive system found below the bladder
and in front of the rectum .
Prostate cancer is the most common cancer and the second leading cause

of cancer death among men in the world . (Prostate Cancer.National Cancer

Institute.)

2.1 PHYSIOLOGY OF THE PROSTRATE GLAND

The prostate gland is a complex organ found within the male

reproductive system that creates and secretes semen, which is

one half of the reproduction equation .The prostate relies on

male hormones, namely testosterone produced in the testicles,

for normal growth and function. Testosterone also attributes to

male sex characteristics, such as low vocal tones and facial and
body hair. Located adjacent to the bladder and the urethra, the

prostate can also affect the overall function and health of the

urinary system.Found below the bladder, midway between the

rectum and the base of the penis, the prostate gland is

approximately the size of a walnut (4 cm by 3 cm by2cm) (

https://www.hifuprostateservices.com/prostate-gland) .A healthy prostate gland

weighs twenty grams and contains fifteen to twenty branched

glands which in turn form the four prostate lobes: anterior,

posterior, lateral and median. Although the prostate is divided

into lobes, doctors typically utilize three zones to identify the area

in which they are referring , the prostrate zones are- The first

zone, known as the peripheral zone, is where most prostate

cancers begin and is best identified as the zone doctors can locate

with a digital rectal exam. The second zone, known as the

transition zone, makes up less than 5 percent of the total prostate

volume. However, the transition zone is where patients suffering

an enlarged prostate will see that total volume percentage

increase because this is where the majority of enlarged prostates

see the most growth. Lastly, the third zone, known as the central

zone, is rarely discussed as it is not linked to most prostate health

problems.
 .

The main function of the prostate is to produce a thick white fluid that creates semen when
mixed with the sperm produced by the testicles.it’s primary functions is to create fluids in the
semen and force semen through the urethra when it’s time for ejaculation.

2.2 PATHOPHYSIOLOGY OF PROSTRATE CANCER

In prostate cancer, the cells of these prostate glands mutate into cancer cells.The prostate glands
require male hormones, known as androgens,to work properly.Androgens include testosterone,
which is made in the testes, dehydroepiandrosterone,made in the adrenal glands; and
dihydrotestosterone,which is converted from testosterone within the prostate itself. Androgens
are also responsible for secondary sex characteristics such as facial hair and increased muscle
mass.Prostate cancer is classified as an adenocarcinoma, or glandular cancer, that begins when
normal semen- screening prostate gland cells mutate into cancer cells. The region of prostate
gland where the adenocarcinoma is most common is the peripheral zone. Initially, small clumps
of cancer cells remain confined to otherwise normal prostate glands, a condition known as
carcinoma in situ or prostate intraepithelial neoplasia(PIN).Overtime, these cancer cells begin to
multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor. Eventually,
the tumor may grow large enough to invade nearby organs such as the seminal vesicles, or the
rectum, or the tumor cells may develop the ability to travel in the blood stream and lymphatic
system. The invasion of other organs is called metastasis. Prostate cancer most commonly
metastasizes to the bones, lymph nodes, and may invade rectum, bladder and lower ureters after
local progression. The route of metastasis to bone is thought to be venous as the prostatic
venous plexus draining the prostate connects with the vertebral veins.(Males Genitalis-Prostate
Neoplasms university of Virginia school of medicine).
The prostate is a zinc-accumulating, citrate-producing organ.Prostate cancer cells are generally
devoid of zinc. This allows prostate cancer cells to save energy not making citrate, and utilize the
new abundance of energy to grow and spread. The absence of zinc is thought to occur via a
silencing of the gene that producing the transporter proteinZIP1.ZIP 1 is called a tumor
suppressor gene product and is responsible for the active transport of gene into the prostrate cell
.

2.3 CLASSIFICATION OF PROSTRATE CANCER

prostrate cancer is classified using the TNM staging system where
T- size of tumor with numbers 1-4 ( where 1 for small -4 for large )
N-lymph nodal involvement with numbers 0-3 ( 0 for no lymph nodes and 3 for nodal
involvement)
M - metastasis with number 0-1 ( 0 - cancer has not spread and 1 cancer has spread )
In the TNM system, clinical T1 and T2 cancers are found only in the prostate, while T3 an d T4
cancers are have spread elsewhere.(American Society of Clinical 0ncology.).

2.4 TYPES OF PROSTRATE CANCER

Almost all prostate cancers are adenocarcinomas. These cancers develop from the gland cells in
the prostate (the cells that make the prostate fluid that is added to the semen).
Other types of cancer that can start in the prostate include:
* Small cell carcinoma (small cell neuroendocrine carcinoma)
* Other neuroendocrine tumors (including large cell carcinoma)
* Transitional cell carcinoma
* Sarcomas

Some prostate cancers can grow and spread quickly, but most tend to grow slowly.(World Cancer
Report)

2.5 RISK FACTORS FOR PROSTRATE CANCER

the following risk factors may make it more likely:

 Age: The risk of prostate cancer increases after the age of 50, but it is rare
before 45.
 Race or ethnicity: The condition is more common in Black people than in
white people. Asian and Hispanic people have a lower risk than Black or white
people.
 Family history: A person with a close relative with a history of prostate
cancer has a higher chance of developing it.
 Genetic factors: Inherited features, including changes to
the BRCA1 and BRCA2 genes, may increase the risk. Mutations in these genes
also increase the chance of breast cancer. Men born with Lynch syndrome also
have a higher risk of prostate and other cancers.
 Diet: Some evidenceTrusted Source suggests that high fat diets may
increase the risk of prostate cancer .
2.6 SIGNS AND SYMPTOMS OF PROSTRATE CANCER
males who experience symptoms may notice :

 difficulty starting and maintaining urination

 a frequent urge to urinate, especially at night
 a weak urine stream
 blood in the urine or semen
 painful urination or ejaculation
 pain in the back, hips, or pelvis
advanced prostate cancer can involve the following symptoms:

 bone pain
 unexplained weight loss
 tiredness

2.7. DIAGNOSIS OF PROSTRATE CANCER

Starting at age 50(45 if African American or brother or father suffered from condition before age
65) then are advised to go for screening as early detection is the key to treating prostrate cancer.
They are several test used in the diagnosis of prostrate cancer and it includes ;

• Digital Rectal Examination andProstate Imaging:

Digital rectal examination (DRE) may detect the prostate abnormalities. Cystoscopy shows the
urinary tract from inside the bladder, using a thin, flexible camera tube inserted down the
urethra.Transrectal ultrasonography creates a picture of the prostate using sound waves from a
probe in the rectum.Prostate MRI has better soft tissue resolution than ultrasounds.(Bonekamp
et Al) currently(2011) MRI is used to identify targets for prostate biopsy using fusion MRI with
ultrasound(US) or MRI-guidance alone. In men who are candidates for active surveillance, fusion
MR/US guided prostate biopsy detected 33% of the cancers compared to 7% with standard
ultrasound guided biopsy (NatarjanS,MarksLS,MargolisDJ,etal.)

•. Biopsy,GleasonScore And Staging;

During a biopsy a urologist or a radiologist obtains tissue samples from the prostate via the
rectum. Biopsy gun inserts and removes special hollow-core needles (usually three to six on each
side of the prostate) in less than a second. Antibiotics should be used to prevent complications
like fever, urinary tract infections and sepsis.Fifty-five percent of men feel discomfort during
prostate biopsy.(Essnik-Bot ML,deKoningHJ,etal.).Tissue samples are then examined to determine
whether cancer cells are present, and to evaluate the microscopic features(Gleason score) of any
cancer found. Prostate specific membrane antigen is over- expressed in prostate cancer tissues
and is associated with a higher Gleason score. The Gleason system is used to grade prostate
tumors from 2 to 10,and Gleason score of 10 indicates most abnormalities.
Prostate cancer screening options include the digital rectal examination(DRE) and the prostate
specific antigen(PSA) blood test.

2.71. PROSTRATE SPECIFIC ANTIGEN (PSA) TESTING

Prostate specific membrane antigen is a transmembranecarboxypeptidase and exhibits folate
hydrolase activity.The blood test, called a prostate-specific antigen (PSA) test, measures the level
of PSA and may help detect early prostate cancer.
If you are over 50, you can ask a GP for a PSA test.
PSA tests are not routinely used to screen for prostate cancer, as results can be unreliable.
Your PSA level can also be raised by other, non-cancerous conditions.
Raised PSA levels also cannot tell a doctor whether you have life-threatening prostate cancer or
not.
If you have a raised PSA level, you may be offered an MRI scan of the prostate to help doctors
decide if you need further tests and treatment.

2.8. COMPUTER AIDED DRUG DESIGN

Computer-aided drug design (CADD) is essentially using computer modeling and simulations to
accelerate the drug discovery process. It's a multifaceted approach that utilizes various tools to
achieve this goal.
CADD helps researchers identify promising drug candidates, optimize their properties, and
predict how they might interact with biological targets. This can lead to the development of more
effective drugs with fewer side effects. There are two main approaches: structure-based, which
analyzes the 3D structure of a target molecule, and ligand-based, which uses information about
existing drugs to find similar ones.

2.81. NIGERIAN PLANTS WITH ANTIPROSTRATE CANCER ACTIVITY

Panax ginseng,Arum palaestinum,Melissa officimalis, Ganoderma lucidum,Psidiumguajava

Artemisia,Prunus africana"Hook.f),Kaliman (Pygeum africanur),Pseudocedrela kotschyi,
Asparagus africanus Lam.,Bulbinella toraunda (Thunb.),Kigelia-africana (Lam.) Benth.
Hypoxis hemerocallideaFisch,,Aloe ferox Mill ,catharanthus roseus (L.) ,
Ximenia caffra Sond.,Aloe volkensii Engl.,Opuntia sp ,Steganotaenia araliacea Hochst ,
Euclea natalensis A.DC.,Moringa oleifera Lam.,Capsicum frutescens L.,Byophyllum pinnatum
(Lam),Burkea africanaHook.,Alstonia congensis Engl.,Chenopodium ambrosioides L.,
Pseudolachnostylismaprouneifolia Pax.,Nymphaea lotus L.,Petiveria alliacea L,Sutherlandia
frutescens L.,Xylopia aethiopica (Dunnal),Plumbago zeylanicaL,Duranta erecta L,Gongronema
latifolium Benth.,Hibiscus sabdariffaL.,Musa sapientum L,Kigelia africana Lam. Benth.,Ocimum
basilicum ,Vernonia amygdalina Delile,Momordica charantia L,Heliotropium indicum L.,
Naudea latifolia Sm,Momordica cubruei (Cogn.),.Euphorbia lurta L,Mangifera indica La,Cannabis
sativa L,Heteromorpha trifoliata Wend.,Raphia mambillensis/Vernonia guincensis
Benth,,Circurma longa ,Solanum .( PHARMACOGNOSY.journal)