TORONTO – an antipsychotic drug used as a therapy for schizophrenia appears to have an unusual property — it can neutralize some cancer stem cells that allow tumours to come back after treatment.

In lab experiments, Canadian researchers found that thioridazine can alter cancer stem cells that give rise to a type of leukemia, as well as those that generate certain breast cancer cells, without harming normal stem cells.

The discovery, reported Thursday in the journal Cell, came after researchers screened about 3,000 compounds in search of those that would selectively inhibit human cancer stem cells.

Thioridazine is one of about 20 agents winnowed down through high-tech drug screening that appear to work against cancer stem cells, said principal investigator Mick Bhatia, scientific director of the Stem Cell and Cancer Research Institute at McMaster University.

“Cancer stem cells, what they do is they keep proliferating,” Bhatia said from Hamilton. “But they don’t do what normal stem cells do, which is make other cell types. and then those cells perform their function and then die. That’s the normal life cycle.

“Cancer stem cells refuse to go through that life cycle because they never differentiate. they just keep making copies of themselves.”

That’s why, even if a patient’s malignancy appears to have been eradicated with chemotherapy and radiation, the cancer can come back, Bhatia said.

“And the feeling there is that the drugs we’re using aren’t targeting the cancer stem cells, so you’re not getting to the root. You’re just picking the dandelion off the top.

“And it looks good for a while, the lawn looks fine, but if you don’t dig at it and get the root, it just comes back.”

Bhatia admits that thioridazine’s apparent power over cancer stem cells came as a bit of a surprise.

The drug works against schizophrenia, for example, by targeting dopamine receptors in the brain. Dopamine is a chemical messenger that plays a variety of roles in the brain, including helping to regulate attention, cognition and movement.

The drug is also used to treat the symptoms of Parkinson’s disease, which develop in response to declining dopamine levels caused by the death of brain cells that make the neurotransmitter.

Thioridazine doesn’t appear to kill cancer stem cells, but rather encourages them to differentiate, thus exhausting the pool of self-renewing cells.

The researchers showed that the drug affects leukemia stem cells without harming normal blood stem cells. It turns out that unlike normal blood stems cells, leukemia cells have a dopamine receptor on their surfaces — making them vulnerable to the drug.

Dopamine receptors also appear on some breast cancer stem cells, the researchers found.

“This gives us some explanation,” Bhatia said. It also suggests that dopamine receptors might serve as a biomarker for early detection of rare, tumour-initiating cells in patients.

Michael Rudnicki, CEO and scientific director of the Stem Cell Network of Canada, described the paper as a “beautiful study, a very nice piece of work.”

“I think this paper really exemplifies the Canadian leadership in cancer stem cell research,” Rudnicki said Thursday from Ottawa. “Cancer stem cells were really discovered here in Canada, and this work takes it to a new level.”

He said the researchers’ findings strongly support the notion that already-approved, “human-ready” drugs exist in the global pharmaceutical armamentarium that could bolster doctors’ ability to defeat some cancers.

“Everything that we can do to build up the toolbox for the clinicians treating cancer will help this,” said Rudnicki, who was not involved in the study.

The McMaster-led team, which includes physicians, is planning to test thioridazine in combination with standard anti-cancer drugs in a small group of adults with acute myeloid leukemia who have not responded to chemotherapy alone.

The researchers’ next step is to investigate the effectiveness of thioridazine in other types of cancer, as well as exploring the potential of the other compounds identified so far, Bhatia said.

“We really want these drugs to be something that we can target at a clinical level.”

In the future, thousands of other compounds will be analyzed with McMaster’s robotic stem cell screening system in collaboration with other academic groups and the pharmaceutical industry.

“The goal for all of the partners,” said Bhatia, “is the same — to find unique drugs to change the way we tackle and treat cancer.”

Causes ,effects symptoms and treatments of head and neck cancer

Head & Neck Cancer: Head and neck cancer occurs due to the spreading of cancer cells in the head and neck area. Generally, the cells grow and divide into multiple cells and they die when they grow old, and new cells take their place. But due to some causes these basic life cycle of the cells gets damage and began to grow rapidly without any controlling limit. These cells form a huge mass of tissue which is called as tumor.

Tumors are of two types they are: • Benign tumor: These tumors are not life threatening tumors. this cancer can be removed easily by surgery process. they don’t reoccur. These tumors grow in single site. they do not spread and invade other tissues around them. the benign tumor cells doesn’t contain metastatic characteristics( spreading nature to other parts of the body) • Malignant tumor: These tumors are cancerous tumors. they spread to other parts of the body. These tumors can be removed but sometimes they grow back. Malignant tumors invade nearby tissues and organs. These tumors contain metastatic characters. When the cancer cells spreads to the other parts will form a new tumor which has the same characteristic features of the primary tumor. for example, if the head and neck cancer cells spread to the lungs, the cancer cells in the lungs are actually belonging to the head and neck cancer cells. Then this cancer disease is called as metastatic head and neck cancer.

Head and cancer affects the following types:

Oral cavity: Oral cavity contains many parts like lips, tongue, tonsils, lining of the cheeks, salivary glands, hard palate (roof of the mouth), soft palate (back of the mouth), and floor of the mouth, gums and teeth.

Salivary glands: These glands are useful in producing the fluid (saliva) in the throat moist and mouth. These glands are located in the jawbone and in the floor of the month.

Paranasal sinuses and nasal cavity: the Paranasal sinuses consist of small hollow spaces in the head bones surrounding the nose and the nasal cavity is located in the hollow space inside the nose.

Larynx: It is also called as voice box. It is located just below the neck. Larynx contains vocal chord. There is small tissue called epiglottis in the larynx which helps in preventing the entry of food from entering the air passage.

Lymph nodes in the upper part of neck: Squamous cancer cells are present in the lower part of the neck. These cancer cells contain metastatic characteristics.

Pharynx: it is a hollow tube which is located behind the nose and leads to esophagus. Pharynx consists of three parts.

Hypopharynx: It is the lower part of the pharynx. Neasophayrnx: It is located in the upper part of pharynx. Oropharynx: Oropharynx is the middle part of the pharynx. It is the    base part of the tonsils and tongue.

Causes of head and neck cancers: the main causes for breast cancer are not identified but the risk factors for the breast cancer are identified and here is the list.

Risk factors for breast cancer:

These are the two main risk factors for causing head and neck cancers.

Chewing of tobacco: Tobacco chewing increases the risk factor for causing head and neck cancers. this activity has more adverse effects. Tobacco plays vital role for many cancer related disease. Tobacco smoking also leads to head and neck cancers. In which 87 percent of the cases are related to death cases due to its effect. Head and neck is the leading cancer in both men and women. Smoking also causes pancreatic, stomach, kidney, colon and leukemia cancer.

Alcohol: Taking of alcohols will reduce the performance of body immune system which causes the chances of many cancer diseases.

Other risk factors for head and neck cancers:

Oral cavity: Oral cavity contains many parts like lips, tongue, tonsils, lining of the cheeks, salivary glands, hard palate (roof of the mouth), soft palate (back of the mouth), and floor of the mouth, gums and teeth .due to the exposure to severe sun blistering of this oral cavity the risk factors increases.

Salivary glands: Severe exposure to harmful radiations can increase the risk for head and neck cancers

Paranasal sinuses and nasal cavity: severe exposure of this Paranasal sinuses and nasal cavity to industrial effects can increase the cancer effects.

Larynx: Due to exposure of larynx part to air borne particles will increase the risk factors.

Pharynx: Due to HPV infection of this part there is a chance for increase in risk factors.

Types of head and neck cancers: Hypopharyngeal Cancer, Laryngeal Cancer, Lip and Oral Cavity Cancer, Nasopharyngeal Cancer, Oropharyngeal Cancer, Paranasal Sinus and Nasal, Cavity Cancer and Salivary Gland Cancer are the following head and neck cancers.

Symptoms of head and neck cancer:

• Sore throat stays for longer time. • Hoarseness • Occurrence of Lump or sore that doesn’t heal. • Pain during swallowing • Pain in throat • Ear pain • trouble speaking • trouble breathing • Chin swelling • Pain in the neck • Paralysis of face muscles. • Loss of hearing • headaches

Treatment procedure for head and neck cancers: the treatment procedure of head and neck cancers include surgery, radiation therapy and chemotherapy.

Surgery: Surgery is the main therapy for the curing of head and neck cancer in the early stage. this surgery process is carried by identifying the staging of the head and neck cancer. Surgery is carried to remove the tumor part in the mouth and neck area. during the surgery process the damaged lymph nodes and nearby tissues in the neck are also removed. during some cases, the major portion of other infected organs will be removed for avoiding the spreading of the disease throughout the body. most of the time, patients will be given radiation therapy along with surgery treatment for complete removal of the tumor.

Radiation therapy: this treatment is based on the extent of the disease. Radiotherapy is a process of removing cancer cells by using high intensity x-rays. These high energy x-rays are aimed at the affected part to destroy the cancer cells.

There are two types of radiotherapy treatments they are.

• External radiations: External radiation process is carried out from outside the body. the powerful x-ray beams are aimed at the effected area from outside the body and destroys the cancer causing cells permanently

• Internal radiations: X-ray beams are passed into the body by making some small incisions in the head and neck area. this treatment gives better results than the external radiation therapy.

Chemotherapy: Chemotherapy is one of the treatments useful in killing head and neck cancer causing cells by the usage of drugs. this treatment process is carried by either pills or through intravascular injections. the anti-cancer drug enters into the bloodstream and travels towards the damaged tissues and destroys the cancer cells. Chemotherapeutic drugs attack the head and neck cancer cells by stopping their unusual growth. the nature of this head and neck cancer cells were brought to the normal condition by controlling the divisibility of the cells. the chemotherapy drugs are given in the following form:

In tablet or pill form(head and neck) by taking injection(Intravenous or intramuscular) Injection taking in the (Intrathecal)

This cancer chemotherapy drug can be given at either clinic or at home. the usage of this drug can be daily, weekly or monthly depending on the stage of the cancer and body immune system. Chemotherapy treatment is given by considering the following basis like age, gender, drug toxicity and body weight. the dosage and usability should be carried under proper supervision.

Head and neck cancer occurs due to unusual growth of cancer cells in the head and neck region. this cancer is referred as metastatic cancer for its effects and causes. this cancer can be cured only in the early stage of its occurrence. this cancer has many risk factors.

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