Ovarian Cancer Growth Of Abnormal Malignant Cells Ovaries Biology Essay


Ovarian cancer, one of the most deadly cancers of female reproductive system, is a growth of abnormal malignant cells that begins in the ovaries. It is long thought to be a "silent" killer. These cancer cells are usually removed by surgical means or killed with chemical (chemotherapy) and radiation (radiotherapy). The growth of cancer cells can be inhibited or slowed down by blocking biochemical pathways that promote their growth (targeted therapy) and stimulate the immune system to attack them (immunotherapy). However, when it comes to advanced ovarian cancer -in stage 3 or 4, it has spread away from the ovary to other parts of the body. It is often diagnosed too late for treatment to be effective. Patients are usually told they have virtually no chance of recovery and only months to live. Hence, what are the experimental treatments that might be the solution in the future to treat this disease?

Figure 2.2 Ovarian cancer mortality trends over time [1]. It suggests that although the mortality rates of ovarian cancer has been decreasing over years, however, it is still considered as one of the top 15 cases of cancer that greatly affect people worldwide.

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Stages of Ovarian Cancer [2]

Stage I Stage II

Stage III Stage IV

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HITV Therapy

Also known as Human Initiated Therapeutic Vaccine therapy, which is developed by Dr. Kenichiro Hasumi, ICVS Tokyo Clinic, is an immunotherapy that combined with radiotherapy to treat advanced stage (also called metastatic) cancer. The therapy involves injecting a patient's immature dendritic cells (imDC) directly to his or her tumour before and after radiotherapy to reduce the number of cancer cells. This will generate an immune response to kill the cancer cells.

Whenever dendritic cells (DCs) detect an abnormal protein on surface of target cells, cytotoxic T-lymphocytes (CTLs) are ordered to attack and destroy the foreigners. Each day, about 5,000 cells in our body are cancerized, but we never develop cancer as long as DCs and CTLs destroy all the tumour cells. However, if our immune system becomes less effective due to stress, aging or other health problem, we are in a higher risk of getting cancer. So, gaining back the immune function that has weakened in a patient's body is considered the basis of dendritic cell vaccine therapy (DC therapy). By amplifying DCs and CTLs in-vitro, those immune cells are brought back to tumour site and replace weakened immune function.

Diagram 1.1 shows the roles of dendritic cells and T-lymphocytes in HITV therapy [3]

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"Over 350 patients have already been treated with the HITV therapy in Japan, including non-Japanese patients from oversea,"

(Dr. Hasumi, 18th of July 2010, The Star, Fit4Life SF2)

Dr. Hasumi also added that more than 70% of the advanced stage patients within the enclosure criteria responded with partial or complete regression. While he reassures the HITV therapy has been proved as a safe and established cancer immunotherapy to selected advanced stage cancer patients in Japan, the HITV therapy is in the process of getting ready for phase I and II clinical trials in the US.

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Combination of Cancer drugs

Carboplatin [4] Decitabine [5]

Carboplatin, which is administered intravenously, is a very common drug prescribed to ovarian cancer patients worldwide due to its effectiveness. It kills cancer cells by binding to the DNA and interfering with the cell's repair mechanism, which eventually leads to cell destruction. With its alkylation action property, the growth of tumour is hindered by stopping division of cancer cells. Although it is effective, patients with recurrent cancer eventually develop resistance to it.

"Carboplatin is the most efficient drug therapy to treat ovarian cancer. Unfortunately, patients with recurrent disease become resistant to the drug after one or two rounds."

(Dr. Daniela Matei, professor of medicine, Indiana University School of Medicine, 18th of July 2010, the Star, Fit4Life SF2)

Decitabine on the other hand, is used to treat myelodysplastic syndrome (a group of conditions in which the bone marrow produces blood cells that are misshapen and does not produce enough healthy blood cells). It is classified as a hypomethylation agent. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. However, it is claimed that it reactivates tumor suppression genes that are turned off in ovarian cancer cells.

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A phase I research done by the Indiana University reported that four out of 10 patients had no disease progression after six months of treatment, while one of them had complete resolution of tumour tissue. The clinical trial of combination of decitabine and carboplatin was designed to increase patients' sensitivity to the commonly prescribed drug, platinum-based carboplatin. This is because, women became resistant to carboplatin and they usually survive in less than a year when the cancer recurs. Since the results of phase I trial is encouraging, which determined the safety of using two different dosing regimens, a phase II trial which focused on assessing the effectiveness of a drug or treatment protocol is now under its way.

However, the reasons why trial patients were responsive to the combination of decitabine and carboplatin is not yet known, but based on the literature and an analysis of biopsy tissue and blood samples, scientists suspect that decitabine inhibits methylation, a process which prevents DNA from expressing genes.

"Our hypothesis is that decitabine isn't just targeting active ovarian cancer cells, but also cancer stem cells that seem to survive the first treatments,"

"By keeping tumor suppression genes from being methylated, carboplatin and other platinum-based treatments for ovarian cancer have a better chance of success in the late stages."

(Kenneth Nephew, geneticist in the IU Medical Sciences Program-Bloomington, 18th of July 2010, the Star, Fit4Life SF2)

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Social Issues

I believe that awareness of ovarian cancer is inadequate even among those who are educated. The symptoms of ovarian cancer are frequently confused with less serious and a more common conditions such as irritable bowel syndrome or urinary tract infection. Many women with symptoms such as constipation, indigestion, fatigue, back pain or frequent urge to urinate do not seek medical help. When medical treatment is ignored, ovarian cancer symptoms are very much misdiagnosed as there is no reliable test that can absolutely identify the disease initially. Here, I would suggest patients to undergo a less conclusive procedure to confirm diagnosis. This includes pelvic exam, a blood test and imaging test. An exploratory surgery, on the other hand is a more conclusive method to diagnose ovarian cancer.

Knowing that an end-stage disease has strike our body is rather miserable as only time that will decide how long more we can live. Patients are more depressed and would have emotional distractions as they will grieve over the unfortunate happenings. I am sure that patients who cannot cope will not be able to manage their diseases properly as they are lacking in support especially from friends and family. Since there are staging in cancers, it is rather challenging as it involves decision-making for treatments. It is advisable for patients to reach out for supports and not feel embarrassed by their diseases because there are survivors of ovarian cancer out there.

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HITV Therapy

HITV therapy which is already practiced by the Japanese shows promise to cancer treatment. The protocol uses the body's innate immune system to fight cancer; it is therefore not harmful to the body.

"Dendritic cells are harvested from the patient and cultured in a laboratory, then they are introduced back into the patient's body. "

(Prof Dr Cheong Soon Keng, president of the College of Pathologists, Academy of Medicine of Malaysia, The Star, Fit4Life, SF2)

This therapy can be used to treat other types of advanced cancers and it is found to be effective in patients with any type of solid tumour (less than 3cm in diameter) that can be reached with a needle. Though, the procedure is inappropriate for cancers of blood (leukemia), brain tumours, and those with fluid accumulation (pleural effusion) or abdominal cavity (ascetic effusion). Limitations here include to those whose cancer has spread to more than five locations in the body. Patients may also experience mild fever or flu-like symptoms after the treatment.

Combinations of Cancer Drugs

This treatment seems rather convincing as the outcome for phase I trial conducted are encouraging. However, there are several adverse reactions from the trial which include nausea, fatigue, and neutropenia (reduced white blood cell count). Some cases also showed that decitabine appears to have caused six of the 10 patients to become hypersensitive to carboplatin (a mild allergic reaction, treatable with steroids). Although the side effects are not obvious in a larger population, I believe that scientists are trying to resolve the problem. Since the two-drug treatment is still on its way for further confirmations, it is not yet approved for general use. The IU Simon Cancer Center is the only site for this clinical study.

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Ovarian cancer and its treatment can deplete the body's nutrients, suppress appetite, and even affect the digestive system. Improving diet by increasing intake of food that contains antioxidants such as fruits and vegetables promote cancer-fighting. When the cells are in contact with oxygen molecules, the cells are weakened and are more likely to mutate. Therefore, antioxidants are essential to prevent oxidation. Although there is no evidence of studies that eating a diet rich in antioxidant properties can help to fight cancer, it does improve health overall. Scientists therefore hypothesized that this may reduce the risk of developing cancer, and also help to counter side effects of chemotherapy.

Oncology Rehabilitation

Staying fit and healthy is an important way to help strengthen the body in the fight against ovarian cancer. It is crucial that patients of ovarian cancer to maintain some level of physical activity. Regular exercise increases heart rate and muscle flexion, helping to strengthen and boost the body's tolerance to chemotherapy and radiation treatments. Participating in daily exercise programs not only will gain a sense of physical control over the condition, it will also provide an outlet for stress and anxiety. This is because; stress reaction can interfere with the healing process and may worsen the patient's condition. So, it is also advised that patients to undergo massage therapy and also meditations.

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Source 1

The Indiana University Melvin and Bren Simon Cancer Center is a patient care, research, and educational organization within the Indiana University School of Medicine. The benefits of their website, IU Simon Cancer Center, are very clear as they provide a wide range of innovative and advanced treatment options. Expert teams of diverse professionals who focused on their specific cancer type also include representatives from the schools of nursing and dentistry as well as the Purdue University School of Science. I believe that their research is vigorous, innovative and devoted to taking an improved cancer care into the future as they are constantly seeking out promising treatments. This is further proven by a cancer program in Indiana which has been ranked by the U.S. News & World Report in its 2010 publication as the "America's Best Hospitals." Their rankings are also supported by detailed and meaningful data such as death rates, procedure volume, and balance of nurses and patients. What makes the IU Simon Cancer Center a very dependable and trustworthy source is that their scientific excellence is well recognized and supported by the National Cancer Institute.

Source 2

In this website, http://immgen.jp/hitv.php, ImmGen of Japan provide aim to provide a borderless delivery of innovative cancer vaccine treatment to the world. They provide a good source of HITV therapy, explaining how the therapy works in many cases to treat late-stage cancer patients. They also discuss about the disadvantages of other DC therapy and how immune cells are not strong enough to eliminate tumour cells. Even if they are very convinced with the efficacy of HITV therapy, they do not reveal any of the treatment results to the public, unless with specific purpose known. Even though the article is published in The Star, I think they should disclose some data to gain more support to the treatment.

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