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Maitland                                                                                                                                                                           Prostate cancer: from bench to bedside

           composition could all be sorted out in the analysis   The perfect requirements for truly translational study
           - all that mattered was quantity. Of course we now   of prostate cancer:
           know that many of these early next-generation
           RNA/DNA  sequencing  projects  are  confounded  by   1. Provision of fresh human tissues. Most
           cellular heterogeneity or by the unexpectedly high   translational  projects  operate  by  “confirming”  cell
           error rate in the sequencing itself [28] . Sequences of   lines  studies  in  arrays  of  archival  and  fixed  human
           “model  systems”  reflect  the  enormous  genetic  drift   tissues.  Perhaps  a  better  model  for  study  should
           (and selection) imposed by decades in cell culture.   be  establishment  of  hypotheses  in  primary  human
           The quantities of nucleic acids required for the   tissues and subsequently confirming mechanisms in
           exercise are diminishing monthly: but there is still in   representative primary cells or cell lines.
           my  opinion  insufficient  control  of  homogeneity  and   Fresh human tissues impose a higher requirement
           quality.  At this level, minor populations would be   for clinical-science cooperation. In our laboratory we
           excluded and mutations in subpopulations perhaps   have observed that, for some purposes, tissue which
           missed  altogether.  Even  single  cell  sequencing   is more than 3 h from biopsy has significantly altered
           has the inherent bias introduced by comparison     properties, and that storage overnight destroys most
           to a canonical genome or cancer cell expression    of the infiltrating lymphocytes, for example.
           pattern [29] . The individual cells that fail to match this
           can be excluded as abnormal, unrepresentative      2.  Transportation of tissues, apart from rapidity,
           or even “normal”. Cell calling will improve, but at   requires a specialist medium. In some laboratories,
           present we are working with an imperfect resource,   an enriched cell culture medium containing high
           which I believe can only be solved by closer clinical-  calcium and fetal calf serum is used. In addition,
           scientific collaboration.                          prevention of opportunistic infections can be almost
                                                              eliminated by the presence of anti fungal and anti-
                                                              biotic agents. Transport medium should be relatively
                                                              neutral and isotonic such as RPMI: to eliminate false
                                                              growth and differentiation effects of calcium and calf
                                                              serum. Rapid chilling to 4 ˚C is advantageous, but not
                                                              always essential.

                                                              Personnel: key members of a clinical team for
                                                              translational research
                                                              When  establishing  such  a team I always  stress that
                                                              each member should do exactly what they are trained
                                                              to do best [Figure 3]. However, it is important that by
                                                              regular communication, the individual  specialities
                                                              should  understand  something  of the procedures
                                                              for obtaining  and the subsequent analysis of  tissue-
                                                              derived material. This feeds back to the key principle
                                                              of co-authorship in ultimate publications in addition to
                                                              obtaining ethical permission and design of the studies.

                                                              The urological surgeon
                                                              For benign, normal and organ confined or lymph node
                                                              biopsies of tissues, the cooperation of the surgeon
                                                              has  been  essential.  The  first  priority  should  be  to
                                                              ensure patient wellbeing, and the provision of fresh
                                                              tissues should not in any way compromise this. The
                                                              presence of a research nurse or a junior surgical team
                                                              member, who has been well briefed, is a major bonus
           Figure 3: Components of the team required for a clinic to   for this procedure (see below) and in fact this person
           laboratory collaboration. (A) For a Lab-Clinic collaboration to work,
           collaboration and communication between several willing parties   can act as the all-important bridge between the lab
           is required; (B) one key member of staff is a research nurse or   and the clinic.
           technician who can liaise between several different members of
           the team. Without this member, connection between the team
           members can be more challenging and there is more pressure on   We have also found it essential to plan ahead and to
           the urological surgeon                             receive  an  operation  list  1-2  weeks  before  surgery.
                           Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ November 17, 2017      267
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