ANANT JAIN 11408008 SRM UNIVERSITY

WHAT IS PROSTATE GLAND???

Basically means "one who stands before", "protector", "guardian. is a compound tubulo alveolar exocrine gland of the male reproductive system in most mammals. Skene's gland is homologous to prostate in females. The prostate differs considerably among species anatomically, chemically, and physiologically.

FUNCTION OF PROSTATE GLAND

The function of the prostate is to store and secrete a slightly alkaline fluid, milky or white in appearance, that usually constitutes 2030% of the volume of the semen. The alkalinity of semen helps neutralize the acidity of the vaginal tract. The prostate also contains some smooth muscles that help expel semen during ejaculation.

Prostate histology

WHAT PROSTATIC SECRETION CONTAINS

In human prostatic secretions, the protein content is less than 1% and includes proteolytic enzymes, prostatic acid phosphatase, and prostate-specific antigen. The secretions also contain zinc with a concentration 500-1,000 times the concentration in blood.

REGULATION OF PROSTATE GLAND

To work properly, the prostate needs male hormones (androgens), which are responsible for male sex characteristics. The main male hormone is testosterone, which is produced mainly by the testicles. It is dihydrotestosterone that regulates the prostate.

STRUCTURE OF PROSTATE GLAND

A healthy human prostate is classically said to be slightly larger than a walnut. The mean weight of the "normal" prostate in adult males is about 11 grams. It surrounds the urethra just below the urinary bladder and can be felt during a rectal exam. Within the prostate, the urethra coming from the bladder is called the prostatic urethra and merges with the two ejaculatory ducts. The prostate is sheathed in the muscles of the pelvic floor, which contract during the ejaculatory process.

INTRODUCTION TO PROSTATE CANCER

Prostate cancer is classified as an adenocarcinoma, or glandular cancer, that begins when normal semen-secreting 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 prostatic intraepithelial neoplasia (PIN) Over time, these cancer cells begin to multiply and spread to the surrounding prostate tissue 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 bloodstream and lymphatic system

SOME MORE..
Prostate cancer is considered a malignant tumor because it is a mass of cells that can invade other parts of the body This invasion of other organs is called metastasis. Prostate cancer most commonly metastasizes to the bones, lymph nodes, rectum, and bladder RUNX2 (57kDa)is a transcription factor that prevents cancer cells from undergoing apoptosis thereby contributing to the development of prostate cancer The protein ZIP1(zinc transporter) is responsible for the active transport of zinc into prostate cells. One of zinc's important roles is to change the metabolism of the cell in order to produce citrate, an important component of semen The process of zinc accumulation, alteration of metabolism, and citrate production is energy inefficient, and prostate cells sacrifice enormous amounts of energy (ATP) in order to accomplish this task

AND SOME MORE.

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 produces the transporter protein ZIP1 Zinc inhibits NF-B pathways, is anti-proliferative, and induces apoptosis in abnormal cells

STAGES OF PROSTATE CANCER

Like other forms of cancer, the prognosis for prostate cancer depends on how far the cancer has spread at the time its diagnosed. Prostate Cancer Stage I In stage I, prostate cancer is found in the prostate only Stage I prostate cancer is microscopic, it cant be felt on a digital rectal exam (DRE), and it isnt seen on imaging of the prostate. Prostate Cancer Stage II In stage II, the tumor has grown inside the prostate but hasnt extended beyond it.

STAGES OF PROSTATE GLAND CONTD

Prostate Cancer Stage III Stage III prostate cancer has spread outside the prostate, but only barely Prostate cancer in stage III may involve nearby tissues, like the seminal vesicles. Prostate Cancer Stage IV In stage IV, the cancer has spread (metastasized) outside the prostate to other tissues Stage IV prostate cancer commonly spreads to lymph nodes, the bones, liver, or lungs.

Stages of Prostate Cancer

HISTORY OF PROSTATE CANCER

The history of prostate cancer began in 1536. It was not given official identification until the year 1853. In those days, prostate cancer was thought to be a rarity among diseases, because their life span was shorter and detection methods were poor. The first surgeries for prostate cancer were done in the 1890s, with mixed results. In 1904, the first surgery was done to remove the prostate gland. In the 1940s, a man named Charles Huggins began using the female hormone estrogen to combat the production of testosterone in men that had metastatic prostate cancer. This was the original chemical castration, and won the researcher the Nobel Prize for medicine in 1966.

FAMOUS PEOPLE WITH PROSTATE CANCER A. Those who chose surgery

Bob Dole U.S. Senator

Colin Powell Secretary of State

John Kerry U.S. Senator

Harry Belafonte Norman Schwarzkopf Musical artist, actor, Retired general entertainer

Richard S. Mueller III F.B.I. Director

B. Those who chose radiation therapy

Andy Grove President & CEO, Intel Corp.

Rudolph Giuliani NYC Mayor

Richard Riordan Former LA Mayor

Nelson Mandela Former President of South Africa

Chuck Tanner Former Pittsburgh Pirates Manager

C. Those who were diagnosed too late

Steve Ross Former Chairman Time-Warner Inc. 1927 - 1993

Telly Savalas Actor 1924 - 1994

Billy Bixby Actor 1934 1993

Linus Pauling, Ph.D. Scientist, Two-time Nobel Prize Winner 1901 - 1994

Frank Zappa Musician 1941 1993

Timothy Leary LSD Advocate Diagnosed: January, 1995 1920 - 1996

CAUSES OF PROSTATE CANCER

The specific causes of prostate cancer have yet to be explained. Studies have found the following risk factors for prostate cancer:

Age: Age is the main risk factor for prostate cancer. This disease is rare in men younger than 45. The chance of getting it goes up sharply as a man gets older. In the United States, most men with prostate cancer are older than 65.
Family history: A man's risk is higher if his father or brother has prostate cancer. Race: Prostate cancer is more common in African-American men than in white men, including Hispanic white men. It is less common in Asian and American Indian men. Certain prostate changes: Men with cells called high-grade prostatic intraepithelial neoplasia (PIN) may be at increased risk for prostate cancer. These prostate cells look abnormal under a microscope. Diet: Some studies suggest that men who eat a diet high in animal fat or meat may be at increased risk for prostate cancer. Men who eat a diet rich in fruits and vegetables may have a lower risk.

SYMPTOMS OF PROSTATE CANCER

Four primary urinary symptoms: Frequency - urinating much more often than normal. Urgency - having a sensation that you need to urinate immediately. Nocturia - getting up to urinate multiple times during the night. Hesitancy - difficulty starting the urine stream. All of these symptoms are a direct result of the urethra being pinched closed by the enlarged prostate.

Other less common symptoms include: Blood in the urine. Blood in the semen. New-onset erectile dysfunction (impotence). Bone pain (especially in the lower back, hips, or ribs). Loss of bladder control.

PREVALENCE
It is estimated that 217,730 men will be diagnosed with and 32,050 men will die of cancer of the prostate in 2010 SEER Incidence(Survelience epidemiology and end result)-National cancer institute From 2004-2008, the median age at diagnosis for cancer of the prostate was 67 years of age. Approximately 0.0% were diagnosed under age 20; 0.0% between 20 and 34; 0.6% between 35 and 44; 9.1% between 45 and 54; 30.7% between 55 and 64; 35.3% between 65 and 74; 19.9% between 75 and 84; and 4.4% 85+ years of age.

A. B.

PROSTATE CANCER INCIDENT RATE PROSTATE CANCER WITH MORTALITY RATE

Statistical comparison

GENETIC BASIS OF PROSTATE CANCER

Genetic background has been shown to contribute to prostate cancer risk. Men with one first-degree relatives with prostate cancer have a twofold higher risk Those with two first-degree relatives have a fivefold greater risk.

Many different genes have been implicated in prostate cancer: Mutations in BRCA1 and BRCA2 Hereditary Prostate cancer gene 1 (HPC1) 1. A possible susceptibility locus for hereditary prostate cancer 2. HPC1 on chromosome 1q24-q25 was first proposed in 1996. 3. Mutations in this locus are noted in some patients with hereditary (families with multiple cases of early-onset) prostate cancer.

GENETIC BASIS CONTD

4. Approximately 10% of prostate cancer cases are hereditary

5.

Research into HPC1 is ongoing

The androgen receptor:The AR gene for the androgen receptor is located on the X chromosome at Xq11-12 The primary mechanism of action for androgen receptors is direct regulation of gene transcription

The binding of an androgen to the androgen receptor results in a conformational change in the receptor which in turn causes dissociation of heat shock proteins, transport from the cytosol into the cell nucleus, and dimerization

GENETIC BASIS CONTD

The androgen receptor dimer binds to a specific sequence of DNA known as a hormone response element.

Androgen receptors interact with other proteins in the nucleus resulting in up or down regulation of specific gene transcription Up-regulation or activation of transcription results in increased synthesis of messenger RNA which in turn is transcribed by ribosomes to produce specific proteins. Thus, changes in levels of specific proteins in cells is one way that androgen receptors control cell behaviour.

CONTD..
Loss of cancer suppressor genes, early in the prostatic carcinogenesis, have been localized to chromosomes 8p, 10q, 13q,and 16q. P53 mutations in the primary prostate cancer are relatively low and are more frequently seen in metastatic settings hence, p53 mutations are late event in pathology of prostate cancer.

DIAGNOSIS
Digital rectal examination Cystoscopy Transrectal ultrasonography Positron emission tomography

Prostate-Specific Antigen (PSA) Blood Test

Prostate-specific antigen (PSA) is a glycoprotein(34kDa) in the cytoplasm of prostatic epithelial cells produced by the prostate gland Elevated PSA levels may indicate prostate cancer or a noncancerous condition such as prostatitis or an enlarged prostate Most men have PSA levels under 4 (ng/mL) and this has traditionally been used as the cut-off for concern about risk of prostate cancer It is important to understand that the PSA test is not perfect Most men with elevated PSA levels have noncancerous prostate enlargement, which is a normal part of aging Conversely, low levels of PSA in the bloodstream do not rule out the possibility of prostate cancer

Diagnostic tools under investigation

Prostate mapping
Prostate mapping is a method of diagnosis that may be accurate in determining the precise location and aggressiveness of a tumor It uses a combination of multi-sequence MRI imaging techniques and involves taking multiple biopsies through the skin that lies in front of the rectum rather than through the rectum itself The procedure is carried out under general anesthetic

MOLECULAR DIAGNOSIS
Phase one: pre-clinical exploratory study The preclinical exploratory studies start with the identification of prostate cancer-specific genes. First generation research tests can be used for measurement of the putative biomarkers in tissue samples Phase two: development of a second generation research assay New biomarkers are revealed because of differences in expression patterns in malignant as well as non-malignant prostate tissues.

Phase three: retrospective analysis In this phase of biomarker development the second generation research assay developed in phase two is used on stored body fluid specimens that were collected from a cohort that reflects the target population for screening Phase 4: prospective analysis In this phase of biomarker development the biomarker-based research assay is applied in the screening of men for prostate cancer with the aim of early diagnosis and treatment of the disease

 Phase 5 and 6: marker commercialization and FDA approval When the biomarker-based research assay has passed all four phases it is commercialized and used for screening in the general population. These screening studies will be used to estimate the reduction in cancer mortality afforded by the new biomarker-based screening test. The next very important step will be clinical trials that lead to FDA approval (phase 6).

EXAMPLE OF BIOMARKERS
Phase one biomarkers BMP-6 Bone morphogenetic proteins (BMP) are involved in new bone formation and organ development. In prostate cancer tissue the expression of both BMP-6 mRNA and protein is up-regulated compared with adjacent normal prostate tissue PSCA Strong expression of prostate stem cell antigen (PSCA), a glycosylphosphatidylinositol-anchored cellsurface protein, was found in 72.7% of high-grade PIN, 83.4% of prostate cancers, 20% of BPH and 22.2% of low-grade PIN specimens

Phase two biomarkers 4.1. AMACR The diagnostic usefulness of -Methylacyl-CoA racemase (AMACR) was shown in prostate needle biopsies where AMACR protein expression had 97% sensitivity and 100% specificity for prostate cancer detection CRISP-3/SGP28 Specific granule protein of 28kDa (SGP28) was purified from human neutrophils and independently cloned from a human testis cDNA library. It is currently known as cysteine-rich secretory protein 3 (CRISP-3). EPCA The expression of early prostate cancer antigen (EPCA), a prostate cancer-associated nuclear structural protein, was found both in cancer areas and adjacent normal tissue areas of prostate cancer tissue specimen but was absent in normal prostate tissue sections obtained from healthy donors and BPH samples

Phase three biomarkers HK2 The potential of hK2 as a biomarker for prostate cancer has been discussed previously [15]. Highly sensitive hK2-specific immunoassays demonstrated the diagnostic applicability of the serum hK2 over free PSA ratio in the diagnostic gray-zone to distinguish prostate cancer patients from men with BPH

Phase 5 biomarkers Osteoprotegerin The most common site for prostate cancer metastases is the bone. In normal bone, the regulation of bone forming osteoblasts and bone degrading osteoclasts is balanced through osteoclastogenesis, which is regulated by the proteins, RANK, RANKL and osteoprotegerin (OPG). Telomerase The diagnostic applicability of telomerase has been described previously . High telomerase activity has been found in 90% of prostate cancers and was shown to be absent from normal prostate tissues

TREATMENT OPTIONS AVAILABLE

Surgery
Patients in good health are usually offered surgery as treatment for prostate cancer. The following types of surgery are used: Pelvic lymphadenectomy: A surgical procedure to remove the lymph nodes in the pelvis. Radical prostatectomy: A surgical procedure to remove the prostate, surrounding tissue, and seminal vesicles. There are 2 types of radical prostatectomy:
Retropubic prostatectomy: A surgical procedure to remove the prostate through an incision(cut) in the abdominal wall. Removal of nearby lymph nodes may be done at the same time. Perineal prostatectomy: A surgical procedure to remove the prostate through an incision (cut) made in the perineum . Nearby lymph nodes may also be removed through a separate incision in the abdomen.

 Transurethral resection of the prostate (TURP): A surgical procedure to remove tissue from the prostate using a resectoscope (a thin, lighted tube with a cutting tool) inserted through the urethra. Transurethral resection of the prostate may also be done in men who cannot have a radical prostatectomy because of age or illness.

Transurethral resection of the prostate

Radiation therapy
Radiation therapy is a cancer treatment that uses highenergy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. There is an increased risk of bladder cancer and/or rectal cancer in men treated with radiation therapy.

Hormone therapy
Hormone therapy is a cancer treatment that removes hormones or blocks their action and stops cancer cells from growing. Hormone therapy used in the treatment of prostate cancer may include the following: Luteinizing hormone-releasing hormone agonists can prevent the testicles from producing testosterone. Examples are leuprolide, goserelin, and buserelin. Antiandrogens can block the action of androgens (hormones that promote male sex characteristics). Two examples are flutamide and nilutamide. Orchiectomy is a surgical procedure to remove one or both testicles, the main source of male hormones, to decrease hormone production. Estrogens (hormones that promote female sex characteristics) can prevent the testicles from producing testosterone. However, estrogens are seldom used today in the treatment of prostate cancer because of the risk of serious side effects.

New types of treatment are being tested in clinical trials.

Cryosurgery Cryosurgery is a treatment that uses an instrument to freeze and destroy prostate cancer cells. This type of treatment is also called cryotherapy. Impotence and leakage of urine from the bladder or stool from the rectum may occur in men treated with cryosurgery. Chemotherapy Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy).

Biologic therapy Biologic therapy is a treatment that uses the patients immune system to fight cancer High-intensity focused ultrasound High-intensity focused ultrasound is a treatment that uses ultrasound (high-energy sound waves) to destroy cancer cells. To treat prostate cancer, an endorectal probe is used to make the sound waves. Proton beam radiation therapy Proton beam radiation therapy is a type of high-energy, external radiation therapy that targets tumors with streams of protons (small, positively charged particles).

PREVENTION
A balanced diet rich in fruits and vegetables!

Lower your intake of red meat, processed and fried foods. Eat more plantbased food like soy protein
Eat foods with lycopene (tomatoes, watermelon and red grapefruit) which may be associated with a decreased risk of prostate cancer Lycopene is a bright red carotene and carotenoid pigment It is an Antioxidant which help in stimulating the immune system and has been shown to cause cancer cells to die on their own. Selenium supplements in the organic form grown in yeast. (200 mcg) Natural vitamin E (50 IU) Daily use of anti-inflammatory medicines such as aspirin, ibuprofen, or naproxen may decrease prostate cancer risk

Hospitals for prostate cancer treatment in India

Apollo hospital, Hyderabad Artemis Health Institute, Gurgaon St. johns Medical College Hospital, Bangalore Sant Parmanand Hospital, Delhi Subodh Mitra Cancer Hospital And Research Centre, Kolkata Tata Memorial hospital, Mumbai Manipal Hospital, Bangalore Lilavati hospital, Mumbai Ruby General Hospital, Kolkata Cancer centre Welfare Home and Research Institute, Kolkata

REFERNCES
WIKKIPEDIA http://www.cancer.gov/cancertopics/pdq/treatm ent/prostate National institute of health Pubmed,NCBI National cancer institute (william dahut presentations) Rosaland T. Skeen presentations Random sites in google

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