Glial Tumor Stem Cells-Brain Tumor Stem Cells Tumor stem cells have been defined in pediatric as well as adult brain tumors. Studies have concentrated on the medullablastoma in the pediatric population and on the gliablastoma in the adult brain. The terms glial tumor stem cell, Glioma Stem Cell (GSC) and Brain Tumor Stem Cell (BTSC) are used interchangeably. Glioma stem cells may appear either by the transformation of normal embryonic stem cells or the transformation of progenitor cells back to the stem cell level in an abnormal manner. The reasons causing this are demonstrated as changes in pH, hypoxia, paracrine and autocrine cytokines and accumulation of genetic mutations formed by microglial response over time.

Brain Tumor Stem Cell and Treatment
Following radiotherapy, the percentage of CD133+ (Brain Tumor Stem Cell marker) cells within malign gliomas notably increases. This percentage depends on the elimination of tumor cells due to radiation or their survival depending on radiation resistance. The ability of BTSC’s to repair radiation related DNA damage is shown in glioma tumor cultures. Moreover, Conventional chemotherapeutic agents are produced out of studies performed on the final state of cancer cell clones.

Immunotherapy:
Immunotherapy for gliablastome include both signalling pathways and activities of niches ,activating stem cell’s autophagy, immun and viral theraphy based on stem cell. Immun system is excited toward stem cell or a small structure of stem cells plasma membrane. Two types of immunotherapies can use that active and passive immunotherapies. Both of them can either be non-specific or specific. Non-specific immunotherapies are induced a general immune response whereas specific immunotherapies are induced a particular immune response with a specific antigen. Active immunotherapy mean that activates the host’s immune system with part of tumor stem cell such as cancer vaccines, cellular immunotherapy. At the passive immunotherapy, the host immune’s response is initiated by external antibodies or other immune components such as monoclonal antibodies, Cytokines. These usually generate from laboratory.

Gene Therapy:
Another modality is gene therapy. The aim of gene therapy is to provoke an immune response to destroy tumor cells too . In the context of gene therapy, the antitumor response depends on the cell destruction from the virus and the induction of a systemic immune response from the local environment.

Non-viral Vectors and viral vectors can us efor this aim. Non-viral gene transfection and expression techniques applied to tumor stem cell may be generally categorized as physical (e.g., electroporation) and chemical (e.g., lipofection). Lot of size of genes are tried to transfer to tumor stem cell.

Nanotechnology:
The development of new technologies based on nanometersized particles (nanotechnology) for cancer treatment has been extensively investigated in the last decade and this approach shows potential benefit for glioma diagnosis and treatment. Few clinical trials using nanotherapies to target gliablastoma have been conducted. This section aim that focuses on nanometersized particles at gliablastoma , and the give brief information about nanotechnology.

An alternative approach for discovering proteins with specificity for GBM is offered by using nanobodies, which can use both stem cells fragments and transport equipment to target tissue.

Brain Tumor Treatment Options
Treatments for brain tumors include:
– Neuro – Surgery
– Gamma Knife® Radiosurgery
– Radiation therapy
– Chemotherapy

Surgery for Brain Tumors
The most common treatment for malignant brain tumors is surgery. The goal is to remove as much of the cancer as possible without causing damage to the healthy parts of the brain. While the location of some tumors allows for easy and safe removal, other tumors may be located in an area that limits how much of the tumor can be removed. Even partial removal of brain cancer can be beneficial. Brain surgery is typically used to remove the entire tumor, if possible. In the past, the surgeon would make large incisions to remove the tumor. Today, we’re often able to use more minimally invasive surgical techniques. Sophisticated tools enhance the precision and safety of brain cancer surgery. These tools allow the removal of tumors that may otherwise have been inoperable, while preserving neurological function:
Pre-operative evaluation that incluedes DTI-MRI, intellegent- learning software such as osirix does assist for succesfull surgery
Intraoperative neuronavigation uses an advanced MRI system to map areas of the brain responsible for important functions. The map then allows us to precisely plan surgery to avoid damage to those important areas.
Intraoperative electrophysiology “brain mapping” (also called motor mapping and language mapping) is like GPS for the brain. Small electrodes are placed on the outer layer of the brain to stimulate the brain and areas around the tumor. This helps locate regions of the brain to avoid, such as those responsible for speech or movement.

Risks of brain surgery include infection and bleeding. Clinically dangerous benign tumors are also surgically removed. Metastatic brain tumors are treated according to guidelines for the type of original cancer.

Surgery can be combined with other treatments, such as radiation therapy and chemotherapy.

Physical therapy, occupational therapy, and speech therapy can help you to recover after neurosurgery.

Gamma Knife® Radiosurgery
Gamma Knife radiosurgery is a painless procedure that uses hundreds of highly focused radiation beams to target tumors and lesions within the brain, without making a surgical incision.
Bezmialem University is the nation’s leading provider of Gamma Knife procedures. Approximately, its 10-years history at Gama Knife Unit , Gamma Knife stereotactic radiosurgery has been used to treat nearly 2,000 patients with benign or malignant brain tumors, vascular malformations, pain, and other functional problems.

Radiation Therapy
Also known as radiotherapy, radiation therapy uses a controlled dose of radiation to kill or damage cancer cells in the area being treated. We commonly use radiation to treat brain tumors as a complementary treatment with chemotherapy. Radiation therapy is usually combined with chemotherapy to treat glioblastomas (grade 4 tumours). This is called chemoradiation, and is better at treating brain tumours than radiation therapy alone after surgery.

Radiation therapy uses high-energy rays to treat cancer. It works by damaging the cancer cells and making it hard for them to reproduce. The body then is naturally able to get rid of these damaged cancer cells. Radiation therapy also affects normal cells. However, normal cells are able to repair themselves in a way that cancer cells cannot. Radiation can be given to treat primary tumors in brain or tumors that have spread to brain from another part of body (metastasized).The patient will have either external beam radiation therapy or stereotactic radiosurgery depending on your treatment plan.

During external beam radiation, a treatment machine will aim beams of radiation directly to the tumor. The beam passes through your body and destroys cancer cells in its path. Patient do not see or feel the radiation.

Stereotactic radiosurgery can be used in some tumors and is even more precise. It targets a small area in your brain with high doses of radiation and delivers lower doses of radiation to the normal tissue around it. You are able to receive higher doses to the tumor at each treatment session, which shortens the overall course of treatment.

Radiation therapy takes time to work. It takes days or weeks of treatment before cancer cells start to die, and they keep dying for weeks or months after radiation therapy.

Side Effects and Complications of Radiation Therapy for Brain Tumors
Radiation therapy is commonly associated with some side effects. However, patients experience side effects at different rates and to different degrees. A dose that causes some discomfort in one patient may cause no side effects in another, and may be disabling to a third. Side effects of radiation therapy can be grouped into general and those pertaining to neurological, or brain function. General side effects may include:
– Skin irritation
– Hearing problems
– Nausea/Vomiting
– Appetite changes
– Fatigue

Chemotherapy
Chemotherapy uses drugs to stop the growth of cancer cells. Systemic chemotherapy for brain cancer

These types of chemotherapy drugs enter the bloodstream and reach areas throughout the body. A challenge with brain cancer chemotherapy is finding drugs that can cross the blood-brain barrier (the natural barrier that protects the brain) to reach tumor cells in the brain.

Chemotherapy drugs may be administered orally in pill form or injected into the vein. For some types of brain cancer, chemotherapy drugs may be given directly into the cerebrospinal fluid (CSF), either in the brain or spinal column. To help with this, a special reservoir under the scalp may be surgically implanted. The reservoir is attached to a tube that leads into a ventricle of the brain where the CSF circulates.

Local Chemotherapy for Brain Cancer
These chemotherapy drugs go directly to the area of the brain tumor at the time of surgical resection. As all or part of the brain tumor is removed, a biodegradable wafer containing the chemotherapy drug is placed in the space left by the tumor or near parts of the tumor that can’t be removed. The wafer slowly releases the chemotherapy over several days.

This technique increases the drug concentration at the tumor site while reducing the side effects typically associated with systemic chemotherapy.

Targeted Therapy
Targeted therapies for brain cancer target specific pathways or abnormalities in brain tumor cells involved in tumor growth. Targeted therapy is often combined with other brain cancer treatments, such as chemotherapy. This treatment is often an option for patients who have a tumor recurrence after previous brain cancer treatments

We use combination of surgical and non-surgical approaches to maximize the benefits of surgery while minimizing risks.

1- Primary Brain Tumors
Primary brain tumors originate in your brain. They can develop from your:
– Brain cells
– The membranes that surround your brain, which are called meninges
– Nerve cells
– Glands
Primary tumors can be benign or cancerous. In adults, the most common types of brain tumors are gliomas and meningiomas.

GLIOMAS
Gliomas are tumors that develop from glial cells. These cells normally:
– Support the structure of your central nervous system
– Provide nutrition to your central nervous system
– Clean cellular waste
– Break down dead neurons
Gliomas can develop from different types of glial cells.

THE TYPES OF TUMORS THAT BEGIN IN GLIAL CELLS ARE:
– Astrocytic tumors such as astrocytomas, which originate in the cerebrum
– Oligodendroglial tumors, which are often found in the frontal temporal lobes
– Glioblastomas, which originate in the supportive brain tissue and are the most aggressive type
– Other primary brain tumors
OTHER PRIMARY BRAIN TOMORS INCLUDE:
– Pituitary tumors, which are usually benign
– Pineal gland tumors, which can be benign or malignant
– Ependymomas, which are usually benign
– Craniopharyngiomas, which occur mostly in children and are benign but can have clinical symptoms like changes in vision and premature puberty
– Primary central nervous system (CNS) lymphomas, which are malignant
– Primary germ cell tumors of the brain, which can be benign or malignant
– Meningiomas, which originate in the meninges
– Schwannomas, which originate in cells that produce the protective cover of your nerves (myelin sheath) called Schwann cells
Most meningiomas and schwannomas occur in people between the ages of 40 and 70. Meningiomas are more common in women than men. Schwannomas occur equally in both men and women. These tumors are usually benign, but they can cause complications because of their size and location. Cancerous meningiomas and schwannomas are rare but can be very aggressive.

2- Secondary Brain Tumors
Secondary brain tumors make up the majority of brain cancers. They start in one part of the body and spread, or metastasize, to the brain. The following can metastasize to the brain:
– Lung cancer
– Breast cancer
– Kidney cancer
– Skin cancer
Secondary brain tumors are always malignant. Benign tumors don’t spread from one part of your body to another.