yulius hermanto
Secret behind Malignant Gliomas
After about 4 years study at Gadjah Mada school of medicine, i think i have found my interest in medical field that is neurosurgery. Therefore, i hope i can continue my study in order to become neurosurgeon.
Here, i will discuss of one of malignant brain tumors that is gliomas. I hope i can share my knowledge about it.
Introduction
Actually primary malignant brain tumors is a rare case, and account for only 2% of all adult cancers, but these neoplasms give a disproportionate burden of cancer-related disability and death. The five-year survival rates for brain tumors are the third lowest among all types of cancer (pancreas and lung are first and second, respectively).
Malignant gliomas (glioblastoma multiforme [GBM] and anaplastic astrocytoma [AA]) are the most common types of primary central nervous system (CNS) tumors and have a combined incidence of 5-8/100,000 population or about 14.000 new cases is being diagnosed annually. The incidence of these brain tumors has increased slightly over the past two decades, especially in the elderly, primarily as a result of improved diagnostic imaging. The median age of patients at the time of diagnosis is 64 years in the case of glioblastomas and 45 years in the case of anaplastic gliomas.
Just like, most kind of cancers there no spesific underlying cause that has been identified for the majority of malignant gliomas. The only established risk factor is exposure to ionizing radiation. Evidence for an association with head injury, foods containing N-nitroso compounds, occupational risk factors, and exposure to electromagnetic fields is inconclusive. Although there has been some concern about an increased risk of gliomas in association with the use of cellular telephones, the largest studies have not demonstrated this.
Gliomas is more common to find in men than women, also it twice more common in whites than blacks.
A family history of brain tumor or gliomas, certainly raises the risk of having gliomas in lifetime compare to person without family history.
Pathogenesis of Gliomas
Recently, scientists have shown important progress in understanding of the pathogenesis of malignant gliomas, and especially the importance of cancer stem cells.
Basically, cancer is genetic disease result from malignant transformation of certain gene in regulation of cell growth and death. Malignant transformation in gliomas results from the sequential accumulation of genetic aberrations and the deregulation of growth-factor signaling pathways.
Deregulated Growth Factor Signaling
Growth factor–receptor signaling, through intermediate signal-transduction generators, results in the activation of transcriptional programs for survival, proliferation, invasion, and angiogenesis. Many of the pathways lead to the up-regulation of vascular endothelial growth factor (VEGF) and angiogenesis. EGFR, PDGFR, and VEGF-receptor (VEGFR) pathways also play an important role in the normal development of the nervous system by promoting the proliferation of multipotent stem cells.
Or in simple words, cancer cells can create their own growth factor or independent from our body regulation, thus makes them are uncontrolled in cell growth.
Role of Stem Cells in Pathogenesis and Resistance to Therapy
Although the genetic and signaling pathways involved in the development of malignant gliomas have been relatively well characterized, the cellular origins of these tumors are unknown. The adult nervous system harbors neural stem cells that are capable of self-renewal, proliferation, and differentiation into distinctive mature cell types. There is increasing evidence that neural stem cells, or related progenitor cells, can be transformed into cancer stem cells and give rise to malignant gliomas by escaping the mechanisms that control proliferation and programmed differentiation.
Resistance Mechanisms in Glioma Cells.
Although stem cells account for only a minority of the cells within malignant gliomas, they appear to be critical for generating these tumors.Recent studies suggest that glioma stem cells promote angiogenesis in the tumor microenvironment. In addition, tumor stem cells appear to require a vascular niche for optimal function. These observations raise the possibility that antiangiogenic therapy may inhibit the functioning of glioma stem cells. There is growing evidence that glioma stem cells may contribute to the resistance of malignant gliomas to standard treatments.
Radioresistance in stem cells generally results from the preferential activation of DNA-damage-response pathways, whereas chemoresistance results partly from the up-regulation of multidrug resistance genes, and the inhibition of apoptosis. Therapeutic strategies that effectively target stem cells and overcome their resistance to treatment will be necessary if malignant gliomas are to be completely eradicated.
Diagnosis
Person who is having malignant gliomas may present with a variety of symptoms, including headaches, seizures, focal neurologic deficits, confusion, memory loss, and personality changes. Although the classic headaches that are suggestive of increased intracranial pressure are most severe in the morning and may wake the patient from sleep, many patients experience headaches that are indistinguishable from tension headaches.
In order to get the definite diagnosis, the person may undergo imaging diagnostic of the brain such as MRI and CT-Scan to visualize brain condition whether there is a tumor or not.
Treatment
In treatment of gliomas, we can divide into two: general and specific.
General medical therapy is aimed to correct general medical condition that usually accompanies patients with gliomas such as seizure, peritumoral edema, venous thromboembolism, and fatique.
With treatment of general medical condition, we can improve quality of life and performance status thus decrease treatment related morbidity.
Spesific medical therapy of gliomas, consist of Surgery if feasible, radiotherapy and chemotherapy. The doctor will decide what kind of therapy that someone will gonna take.
Radiotherapy is the mainstay of treatment for malignant gliomas. The addition of radiotherapy to surgery increases survival among patients with glioblastomas from a range of 3 to 4 months to a range of 7 to 12 months. Conventional radiotherapy consists of 60 Gy of partial-field external-beam irradiation delivered 5 days per week in fractions of 1.8 to 2.0 Gy. After standard radiotherapy, 90% of the tumors recur at the original site.65 Strategies to increase the radiation dose to the tumor with the use of brachytherapy and stereotactic radiosurgery have failed to improve survival. Newer chemotherapeutic agents, targeted molecular agents, and antiangiogenic agents70 may enhance the effectiveness of radiotherapy.
Take Home Message
Our Knowledges and technologies still in progress of development, we hope that we can achieve better outcome in cancer treatment.
Regardless of today technologies, our hope must not be gone, We keep our spirit to live and to fight the cancer itself.
Because The God will appreciate our efforts.
Don't give up to cancer, my friends.
Here, i will discuss of one of malignant brain tumors that is gliomas. I hope i can share my knowledge about it.
Introduction
Actually primary malignant brain tumors is a rare case, and account for only 2% of all adult cancers, but these neoplasms give a disproportionate burden of cancer-related disability and death. The five-year survival rates for brain tumors are the third lowest among all types of cancer (pancreas and lung are first and second, respectively).
Malignant gliomas (glioblastoma multiforme [GBM] and anaplastic astrocytoma [AA]) are the most common types of primary central nervous system (CNS) tumors and have a combined incidence of 5-8/100,000 population or about 14.000 new cases is being diagnosed annually. The incidence of these brain tumors has increased slightly over the past two decades, especially in the elderly, primarily as a result of improved diagnostic imaging. The median age of patients at the time of diagnosis is 64 years in the case of glioblastomas and 45 years in the case of anaplastic gliomas.
Just like, most kind of cancers there no spesific underlying cause that has been identified for the majority of malignant gliomas. The only established risk factor is exposure to ionizing radiation. Evidence for an association with head injury, foods containing N-nitroso compounds, occupational risk factors, and exposure to electromagnetic fields is inconclusive. Although there has been some concern about an increased risk of gliomas in association with the use of cellular telephones, the largest studies have not demonstrated this.
A family history of brain tumor or gliomas, certainly raises the risk of having gliomas in lifetime compare to person without family history.
Pathogenesis of Gliomas
Recently, scientists have shown important progress in understanding of the pathogenesis of malignant gliomas, and especially the importance of cancer stem cells.
Basically, cancer is genetic disease result from malignant transformation of certain gene in regulation of cell growth and death. Malignant transformation in gliomas results from the sequential accumulation of genetic aberrations and the deregulation of growth-factor signaling pathways.
Deregulated Growth Factor Signaling
Growth factor–receptor signaling, through intermediate signal-transduction generators, results in the activation of transcriptional programs for survival, proliferation, invasion, and angiogenesis. Many of the pathways lead to the up-regulation of vascular endothelial growth factor (VEGF) and angiogenesis. EGFR, PDGFR, and VEGF-receptor (VEGFR) pathways also play an important role in the normal development of the nervous system by promoting the proliferation of multipotent stem cells.
Or in simple words, cancer cells can create their own growth factor or independent from our body regulation, thus makes them are uncontrolled in cell growth.
Role of Stem Cells in Pathogenesis and Resistance to Therapy
Although the genetic and signaling pathways involved in the development of malignant gliomas have been relatively well characterized, the cellular origins of these tumors are unknown. The adult nervous system harbors neural stem cells that are capable of self-renewal, proliferation, and differentiation into distinctive mature cell types. There is increasing evidence that neural stem cells, or related progenitor cells, can be transformed into cancer stem cells and give rise to malignant gliomas by escaping the mechanisms that control proliferation and programmed differentiation.
Resistance Mechanisms in Glioma Cells.
Although stem cells account for only a minority of the cells within malignant gliomas, they appear to be critical for generating these tumors.Recent studies suggest that glioma stem cells promote angiogenesis in the tumor microenvironment. In addition, tumor stem cells appear to require a vascular niche for optimal function. These observations raise the possibility that antiangiogenic therapy may inhibit the functioning of glioma stem cells. There is growing evidence that glioma stem cells may contribute to the resistance of malignant gliomas to standard treatments.
Radioresistance in stem cells generally results from the preferential activation of DNA-damage-response pathways, whereas chemoresistance results partly from the up-regulation of multidrug resistance genes, and the inhibition of apoptosis. Therapeutic strategies that effectively target stem cells and overcome their resistance to treatment will be necessary if malignant gliomas are to be completely eradicated.
Diagnosis
Person who is having malignant gliomas may present with a variety of symptoms, including headaches, seizures, focal neurologic deficits, confusion, memory loss, and personality changes. Although the classic headaches that are suggestive of increased intracranial pressure are most severe in the morning and may wake the patient from sleep, many patients experience headaches that are indistinguishable from tension headaches.
In order to get the definite diagnosis, the person may undergo imaging diagnostic of the brain such as MRI and CT-Scan to visualize brain condition whether there is a tumor or not.
Treatment
In treatment of gliomas, we can divide into two: general and specific.
General medical therapy is aimed to correct general medical condition that usually accompanies patients with gliomas such as seizure, peritumoral edema, venous thromboembolism, and fatique.
With treatment of general medical condition, we can improve quality of life and performance status thus decrease treatment related morbidity.
Spesific medical therapy of gliomas, consist of Surgery if feasible, radiotherapy and chemotherapy. The doctor will decide what kind of therapy that someone will gonna take.
Radiotherapy is the mainstay of treatment for malignant gliomas. The addition of radiotherapy to surgery increases survival among patients with glioblastomas from a range of 3 to 4 months to a range of 7 to 12 months. Conventional radiotherapy consists of 60 Gy of partial-field external-beam irradiation delivered 5 days per week in fractions of 1.8 to 2.0 Gy. After standard radiotherapy, 90% of the tumors recur at the original site.65 Strategies to increase the radiation dose to the tumor with the use of brachytherapy and stereotactic radiosurgery have failed to improve survival. Newer chemotherapeutic agents, targeted molecular agents, and antiangiogenic agents70 may enhance the effectiveness of radiotherapy.
Take Home Message
Our Knowledges and technologies still in progress of development, we hope that we can achieve better outcome in cancer treatment.
Regardless of today technologies, our hope must not be gone, We keep our spirit to live and to fight the cancer itself.
Because The God will appreciate our efforts.
Don't give up to cancer, my friends.
