The neural subtype was typified by the expression of neuron markers such as NEFL, GABRA1, SYT1, and SLC12A5, while often presenting themselves as normal cells upon pathological assessment.Many other genetic alterations have been described in glioblastoma, and the majority of them are clustered in two pathways, the RB and the PI3K/AKT. Glioblastomas have alterations in 68–78% and 88% of these pathways, respectively.Another important alteration is methylation of MGMT, a "suicide" DNA repair enzyme. Methylation impairs DNA transcription and expression of the MGMT gene. Since the MGMT enzyme can repair only one DNA alkylation due to its suicide repair mechanism, reserve capacity is low and methylation of the MGMT gene promoter greatly affects DNA-repair capacity. MGMT methylation is associated with an improved response to treatment with DNA-damaging chemotherapeutics, such as temozolomide. Cancer stem cells
Glioblastoma cells with properties similar to progenitor cells (glioblastoma cancer stem cells) have been found in glioblastomas. Their presence, coupled with the glioblastomas diffuse nature results in difficulty in removing them completely by surgery, and is therefore believed to be the possible cause behind resistance to conventional treatments, and the high recurrence rate. Glioblastoma cancer stem cells share some resemblance with neural progenitor cells, both expressing the surface receptor CD133. CD44 can also be used as a cancer stem cell marker in a subset of glioblastoma tumour cells. Glioblastoma cancer stem cells appear to exhibit enhanced resistance to radiotherapy and chemotherapy mediated, at least in part, by up-regulation of the DNA damage response.
Oldham Kelsey was given a Presidential award for distinguished service from the federal government for not allowing thalidomide to be approved for sale in the U.S.In Canada, the history of thalidomide dates back to April 1961. There were many different forms sold, with the most common variant being called Talimol. Two months after Talimol went on sale, pharmaceutical companies sent physicians letters warning about the risk of birth defects. It was not until March 1962, that both drugs were banned from the Canadian market by the FDD and, soon afterward, physicians were warned to destroy their supplies. Leprosy treatment
In 1964, Israeli physician Jacob Sheskin administered thalidomide to a patient critically ill with leprosy. The patient exhibited erythema nodosum leprosum (ENL), a painful skin condition, one of the complications of leprosy. The treatment was attempted despite the ban on thalidomides use, and results were favourable: the patient slept for hours and was able to get out of bed without aid upon awakening. A clinical trial studying the use of thalidomide in leprosy soon followed.Thalidomide has been used by Brazilian physicians as the drug of choice for the treatment of severe ENL since 1965, and by 1996, at least 33 cases of thalidomide embryopathy were recorded in people born in Brazil after 1965. Since 1994, the production, dispensing, and prescription of thalidomide have been strictly controlled, requiring women to use two forms of birth control and submit to regular pregnancy tests.