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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