Meeting report: November 2017
The second meeting of the 2017/ 2018 session was held in Lecture Theatre 2 of GDH on Tuesday 21st November 2017 commencing at 7pm.
There were 72 members and guests in attendance. Apologies were received from 4 members. The minutes of the previous meeting, published online were approved.
The President, Professor Jeremy Bagg, welcomed the members and guests to the meeting.
The President introduced the speaker Professor Keith Hunter and invited him to give his address to the society entitled “Who wants to live forever? – investigating cellular immortalization in oral cancer”. Professor Hunter started by paying tribute to his mentor Professor Gordon MacDonald.
He explained that he was going to discuss the molecular processes underlying the immortalisation of epithelial cells and how this knowledge will affect the diagnosis of carcinoma and the provision of new therapies. He then discussed that from a molecular point of view to understand how cells become immortal we need to understand the molecular basis of aging. He then went onto discuss the molecular basis of aging. He discussed the Hayflick limit (cells grown in cell culture grow exponentially and after a period of time stop growing. The cells have stopped growing but are still viable – replicative senescence) He explained that short telomeres (region at the end of the chromosome which shortens every time the cell divides) correlate with replicative senescence and young cells have long telomeres, old cells have short ones. This doesn’t occur in stem cells. They have an enzyme called telomerase. He then described the evidence that telomeres are involved with aging and that telomerase slows down the loss of telomere DNA and by implication aging.
He then described the processes occurring in senescence and how the body would usually deal with senescent cells. Problems arise when the clearance of senescent cells is not efficient. Chronic inflammatory cells, fibrosis, tissue dysfunction all lay an effective bed for the emergence of carcinoma. If senescent proteins are not removed in a timely fashion circumstances occur which promote aging and tumour progression. If it was possible to stop the accumulation of senescent cells or drive the immune system to clear them then it may be possible to prolong life / prevent aging.
There are a number of drugs being trialled to intervene in this process.
He then discussed Henrietta Lacks and her contribution to the understanding and investigation of cancers. Her cervical carcinoma cells were the source of the HeLa cell line, the first immortalised cell line. He then discussed how oral cancers arise and described the Califano model which describes the progression from normal mucosa to invasive carcinoma. This may not be a linear progression (Normal – Hyperplasia – Dysplasia – Carcinoma in situ – Carcinoma) it is more likely that it involves an unrecognised precursor lesion. There is an underlying genetic progression and there is increasing understanding of the molecular changes underlying the genetic changes.
The molecular markers (ploidy e.g. aneuploidy, gene copy number alterations, individual markers e.g. p53 mutations, early loss p16, DNA damage) are known and the changes may be related to cells escaping the growth controls in which cells continue to grow and get to the stage where chromosomal ends become so short they stick to each other and the cell goes into ‘crisis’. Most cells die but some are able to activate telomerase and become functionally immortal. Professor Hunter then described a study involving senescence in oral premalignancy. He then described the importance of immortality in the development of SCC. Patients whose tumours derived an immortal cell line had a poorer prognosis at 2 years.
Professor Hunter described the science involved in the development of biomarkers and described how there is a list of approximately 200 consistent changes between normal and Head and Neck SCC cells both in vitro and in vivo. The changes seen are good candidates for functional investigations and possible therapeutics. He then described the science of the hox gene and angiomotin expression and how this can be used in the research of H&N SCC. He then described hox genes and H&N SCC survival and described the work on hox inhibitors. Clinical trial are about to start in 2018.
He finished by describing the work of his BMSI and PhD students and acknowledged their help and the help of his sponsors.
Professor Hunter was happy to answer questions.
The Vote of Thanks was proposed by Professor Vince Bissell who thanked the speaker for his very relevant research into a disease where the pressure for understanding the disease is urgent and the pace of advance is slower than we would expect due to the complexity of the subject. The audience was fortunate to listen to the lecture and most importantly the benefits to the patient, which he wished Professor Hunter well with. He then asked the audience to thank the speaker in the usual manner. The President then presented the speaker with an Odontological Society paperweight.
Under AOCB the President then asked that any member wishing to propose another member for Honorary Membership status contact the Secretary with their nominee.
He informed the audience that booking tickets for the Dinner is now open and your ticket can be booked on the website. It is in the RCPS Glasgow on Saturday 24/02/18. The cost of a ticket is £65. There is a proposal for a post Dinner Reception in the Dakota Hotel and a reduced rate for overnight accommodation that evening. Details will be available on the website.
The next meeting is on Tuesday 5th December 2017 in the Lecture Theatre, Anatomy Department, University of Glasgow. The speaker is Dr A Ross and he will give his lecture entitled “Complexity, flexibility and simplicity: the role of human factors in dentistry”. Guests are welcome at this meeting and there will be refreshments after the meeting in the Anatomy Museum.