Applying Autophagy and Apoptosis for Strategies to improve treatment of Glioblastoma

When cancer forms, your body has ways of trying to stop it from further developing. The four regulators are known as proto-oncogenes (which when mutated are known as oncogenes), tumor suppressor genes, apoptosis, and telomerase genes. When there is a mutation in each of the genes, cancer can develop. Once cancer develops it continues to grow and divide and turn into a tumor. For a tumor to develop it essentially needs something supplying it with blood and nutrients so that it can continue to grow. One player in the game of supplying the tumor with blood is a protein kinase known as Protein kinase C. A protein kinase is simply a molecule that regulates numerous cellular responses including gene expression, protein secretion, cell proliferation, and the inflammatory response. According to researchers at Harvard University, EBC-46 has the ability to target protein kinase C and inhibit it, which in turn causes the tumor to die because it is no longer has the ability to synthesize proteins it needs to survive. According to the Queensland Institute, the inhibition of  protein kinase C helps destroy the blood vessels that supply the tumor with the oxygen and the nutrients it would need for survival. Pretty exciting stuff

Glioblastoma (pronounced like gleO blastoma) is an incurable brain cancer,Survival rate is usually measured in months.This became a word that was instantly defined, researched, dissected, feared, and tried to comprehend and understand by family,friends and acquaintances of Larry McKee (McKee)who was personally affected from this single word, it was quickly added to their vocabulary, because of the of the events that transpired on October 22, 2011 that forever changed lives “Glioblastomas are tumors that arise from the astrocytes- the star-shaped cells that make up the “glue-like,” or supportive tissue of the brain. These tumors are usually highly malignant (cancerous) because the cells reproduce quickly and they are supported by a large network of blood vessels.”(A.B.T A..) He was diagnosed with stage four.

Glioblastoma is the most common and aggressive form of malignant brain cancer in adults. On average, 8 of every 100,000 people in the U.S. are diagnosed with glioblastoma every year – representing approximately 2% of all cancers diagnosed [1]. Glioblastoma tumors form when astrocytes, star-shaped cells which support and protect the brain, re-enter the cell cycle and start to rapidly divide. Because the brain is supported by a large network of blood vessels, tumors grow quickly and are difficult to remove surgically. Present treatments for glioblastoma are limited to surgery, radiation therapy, and chemotherapy; however, despite these interventions tumors are likely to regrow. Consequently, typical survival time following glioblastoma diagnosis is less than 2 years.

Therefore, the most notable P53-induced mechanisms in mediating this response are cell cycle arrest and apoptosis [18], which activation depends on the cellular context and the extent of damage [20].

DIPG (Diffuse Intrinsic Pontine Glioma) is a disease which strikes at the heart of childhood. At the base of the brain, just above the spinal cord is the brainstem. The tumor affects the pons area of the brainstem, supplying the nervous system function unattainable. ‘“There’s not a single drug approved”’ (Mukhopadhyay). Due to the location of the tumor, it cannot be surgically removed. Unfortunately, the only option available is Radiation that is considered temporary, with no benefits. “Chemotherapy is frequently ineffective, since anti-cancer drugs cannot cross the blood-brain barrier and reach the tumor” (Zhiping 2). In the end, leaves the patient and parents hopeless for fighting this

For years people have been looking for a cure for the devastating disease of cancer. Cancer is the third highest killer in the US with over 2,500,000 victims per year. Oncologists and scientists around the country are researching all forms of cancer in an effort to understand, treat, and ultimately defeat this disease. Already there have been numerous advances in the field, such as chemotherapy and gene therapy. One advance has been the use of a cell process known as apoptosis. By harnessing this normal cell process, scientists hope to have found an effective way to combat cancer.

Type, size, grade of glioma, location of glioma, age, and overall health of a patient helps to determine a treatment. Surgery to remove the glioma is commonly the first step in treatment. Sometimes, the tumor is small and surrounded by healthy tissue and can be surgically removed. Other times, gliomas are not easily separated from healthy tissue and are located in or around areas that cannot be surgically removed. Radiation therapy sometimes follows surgery. Chemotherapy is another treatment used for gliomas. Chemotherapy is often used with radiation therapy. Chemotherapy is a type of medication used to kill tumor cells. Targeted drug therapy is also sometimes used as a treatment of gliomas. Some people also like to use alternative medicine including, hypnosis, acupuncture, meditation and music therapy.

Glioblastoma(GB) is the most common primary malignant solid brain tumor in adults1. Known for its aggressive characteristics and poor prognosis, the median survival rates of GB patients remain less than 18 months2,3. Tumor relapse owing to chemotherapeutic resistance is almost universal and GB is no exception, thus reflecting in high mortality and morbidity rates4. The WHO 2016 classification of brain tumors identifies GB tumors based on histology, molecular and genetic characterization into defined transcription profiles such as classical, neural, pro-neural and mesenchymal types5. Additionally, the commonly occurring genetic aberrations of primary GB are amplifications/mutations of EGFR, PDGFRA, PTEN, and of secondary GB are IDH1, MDM2

Gliomas are the most common type of primary brain tumor, accounting for 10-20% of its total. (5,19–21). Histopathology pattern is the most important feature in glioma classification. (22) The 2007 WHO classification of tumors of the central nervous system divides gliomas into four main types, with increasing degree of malignancy (from I-IV). Low-grade gliomas are defined a grade I and grade II, in opposition to the “high-grade gliomas”, WHO grade III and IV. The so-called “diffuse low-grade gliomas” integrate 2007 WHO II class, and include diffuse astrocytomas, oligodendroglioma and oligoastrocytoma (mixed glioma) (19). There are some pertinent critics to this grading system, such as the great inter-variability among neuropathologist experts. More importantly, 2007 WHO grading doesn’t contemplate the continuum between grade II and III. In fact, many DLGG has an “intermediate” behavior, with some more aggressive microfoci lodged in the core of the neoplasm (19,23,24). Hence, the term diffuse low-grade glioma is preferred in this article.

B. Studies reveal that when brain tumor cells have access to glucose and glutamine, the disease will progress because gliomas cells depend on glucose for growth and

Traditionally, the sole job given to p16 has been regulating the cell cycle and this role occurs in the nucleus. Astonishingly, there is significant support that numerous neoplasms display noteworthy levels of p16 in the cytoplasm (16). Furthermore, p16

Another major breakthrough that occurred in the early 1970’s was the discovery of the first promising chemotherapy for glioma. A glioma is a malignant tumor that begins in the glial cells which surround the nervous system. Gliomas can be found in the brain and spinal cord. Researchers studied a chemotherapy drug called carmustine (BCNU) and

Brain is one of the vital organ in human body, it has an extensive capillary network which is highly vascularized. The brain capillary endothelial cells (BCECs), astrocytes, pericytes and neuron forms the blood brain barrier (BBB) [1]. There are several types of tumor affects the brain, one such type of tumor is Glioblastoma multiforme (GBM). GBM is the most frequent and aggressive form of primary tumor found in central nervous system, the world health organization (WHO) defined GBM as grade IV astrocytoma [2]. Therefore, this urge us to propose a novel technique to treat GBM.

According to world health organization (WHO), malignant tumors figure among the leading causes of morbidity and mortality worldwide 1. For instance, One of the most challenging type of tumors that have extracted a lot of attention in the field of cancer study is glioma which represents 30% of all brain tumors and 80% of

Normally in healthy cells, the protein kinases (PK) may act as proto-oncogenes or tumour suppressor. However, alteration in PKs may lead to development of cancer by several mechanisms, including the activation of cell multiply pathways, genomic instability, diminish of apoptotic pathways, the endorsement of angiogenesis and cell motility. Receptor and non receptor TKs are mostly deregulated in several types of cancer. EGFR is a transmembrane receptor kinase that is overexpressed or aberrantly activated in NSLC.