Continuing from my preceding para, I realised after some listening to the album this morning, that "Understand" contains two short musical phrases that connect directly with "Mr Raffles" and the preceding album. I guess this may have been in my unconscious, as I was writing the initial post.

Mr Raffles is the song I remember from my date with KT, either during late June or very early July, 1975. This was part of my own timeless flight and the album (which I hadn't heard at the time of its initial release, the following year). Everything changed (pardon the pun), as it had to...

"...Was in a frenzy from the midnight air when I saw the light
I realized only children can live upon a timeless flight..." (Harley, 1975/6)

Further to my recent post under the Lay Me Down thread (link below):

www.steveharley.com/forum/6-general-disc...e-down.html?start=12

Of course, some of Steve’s atoms from the lighter elements (hydrogen, oxygen, etc.) within his body will now be in the atmosphere above. This is in one way, an aspect of the late British scientist James Lovelock’s (1919-2022) Gaia hypothesis, when referring to the Earth functioning as one self-regulating system. Steve/Cockney Rebel and Bryan (Ferry)/Roxy Music, were/are important to me and so were Tim and Neil Finn/Split Enz. Tim and Neil wrote an album (2004) called 'Everyone Is Here'. I like to think that this too is a reflection of Gaia theory. This, to me, is appropriate on the first anniversary of Steve's death (today).

Steve’s nasty cancer (only his family and those closest to him are likely to know what type this was, and whether it metastasised – spread to other tissues - or otherwise) and his death and fellow fan Stella (Day)’s charitable thread about breast cancer – her and her family’s excellent efforts in that cause, my own part time studies in 2021, touching upon both breast cancer and (in more detail) prostate cancer, whilst working towards my DipHE (OU) health sciences (2022), as well as personal family experience from 2022 to the current time (latterly, one case of ‘active surveillance’, another case in healthy remission) leads me to suggest to the male part of the fan base over 50:

HAVE YOU EVER had a DRE (digital rectal examination) and a PSA (prostate specific antigen) blood test? I’d recommend both to those men over 50 that haven’t.

For men over 50, these short tests are readily available from (your) General Practice, by requested appointment.

Sir Chris Hoy the Olympian and multi gold medal winner, is an advocate, I believe, to have these tests more readily available at a younger age. Many of you will know he has Stage 4 cancer (metastasised to the bones). For many men, however, it can be a slow progressing cancer and in the early to intermediate classification, with the advances particularly since the 1990’s, it can now be very treatable – via a number of options - if caught early enough. One problem with the disease is that often there are no (or only mild) symptoms until it has progressed dangerously.

I’m not sure how far I’m going to develop this latest part of my thread here, but it won’t involve any charitable appeal, rather it will be informative for those that are interested, and from this point on, I’d only include any factual detail with adequate academic and peer reviewed references…in the meantime, take care and stay healthy for as long as you are able - all – men and women x I think Steve would have been OK with me posting this – otherwise I wouldn’t have done it (in any case I’d remove it if requested by the managers of his site). Stay your way x

I will develop this part of my thread using short bursts of energy! That way also, the reading won’t get too ‘heavy’. The average adult female has around a total of 28 trillion cells in her body and the average adult male has a total of around 36 trillion cells in his body (Source: New Scientist, 18 September 2023) i.e. 28,000,000,000,000 and 36,000,000,000,000, respectively.

In science, we would write these as 28 x 10 12 and 36 x 10 12.
NOTE: The script here doesn't seem to deal with scientific notation. PLEASE BEAR WITH ME - the 12's after the 10's above should be adjacent to the 10's and much smaller (to the above right of 10's - in other words, 10 to THE POWER 12).

Amongst these vast numbers, there are more than 200 different cell types (Source: Regenerative Medicine: Clinical Applications of Stem Cells (Mummery & Roelen, 2011), in Stem Cells: Scientific Facts and Fiction, 2011).

Within each cell there are a number of organelles, such as the nucleus (within this organelle are the chromosomes – these are storage devices for our DNA – our units of heredity from each parent as well as our own uniqueness), mitochondria (these also contain a small part of our DNA), ribosomes, the endoplasmic reticulum etc. It is mind blowing to think that something so small can be so complex, isn’t it? Oh, if you weren’t aware, DNA stands for Deoxyribonucleic acid.

Normal cells follow a typical cycle - they grow, divide and die (over varying durations within our lifetimes, depending on the type of cells and sometimes other factors. Cells obviously replicate in the early years as we grow and they also replicate to renew ourselves - for instance red blood cells (erythrocytes) have an average life cycle of about 120 days - sources both the OU and PubMed). I suppose some of the evidence we can appreciate here, is our natural ageing process over each decade or a little less.

Cancer cells do not follow this cycle. Simplistically, the two factors or sources that encourage cancer to develop are (many) mutations in genetic code (a part of DNA) - these mutations accumulate over time and that's why generally/simplistically, cancer risk increases with age - and faulty synthesis of proteins during a process known as translation, starting with RNA and involving organelles like ribosomes (sometimes referred to as ‘protein factories’).

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5 February 2025 EDIT - there is a third factor or source - this involves long noncoding RNAs - and there is an example which has been linked to both breast cancer and prostate cancer. I will refer to more in that context the next time I make a full post here - the evidence linked with this has only been emerging over the last decade or two.

14 March 2025 EDIT - Up to now I've avoided reference to environmental factors and lifestyle choices, for the reason that the first three factors or sources are really describing the changes within the (individual) physiology i.e. the changes in cells - for me that is the main focus, here.

Over exposure to high doses of radiation, for instance, we know for certain, can trigger those changes in DNA and RNA of cells (the aftermath of Hiroshima and Nagasaki in 1945, should never be forgotten in this context).

Some of the lifestyle or 'intake' (what we eat, drink, breathe in, etc.) choices are more difficult to pin down as carcinogens (any agent that promotes the development of cancer) because sometimes, the scientific evidence can be somewhat contradictory. Anyway, I thought I should at least make some reference to these things.

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Later on, I’ll include reference to a relevant article about the regulation of protein translation and its implications for cancer. RNA stands for Ribonucleic acid.

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5 February 2025 EDIT - I'll also include reference to another article (2024) - this one is 'open access' - anyone in the public can view it - concerning noncoding RNAs .

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DNA provides the code for our cells activities. RNA converts that code into proteins to carry out cellular functions.

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EDIT 2 March 2025: As well as translation (in synthesising proteins) there is the fundamental process of transcription. This is where a segment of DNA is copied into RNA for the purpose of gene expression. This expression leads to observable traits (in the individual organism, for example, those observable traits in you, or me! - hair colour, for instance).

Reasonably early on in undergraduate health sciences study, it is appreciated how fundamental proteins are, to all life...and in the maintenance of all individuals... So we have proteins and we have replication of cells.

Replication is the copying of (our) pre-existing cells. This all starts, of course, with the mother's egg and the father's sperm making the original diploid cell, containing (usually) 23 chromosomes from the mother and 23 chromosomes from the father. The chromosome is made of protein and a single molecule of DNA. Replication precedes the dividing of cells and the copying is of (our) own existing genome. DNA and RNA are fundamental to both processes. In the creation and the maintenance, of the life and the death, of cells and the organism.

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Breast cancer is the most prevalent cancer in females. In the UK alone, between 2017 and 2019 inclusive, there were around 56,400 new cases every year (Source: Cancer Research UK). Breast cancer was the most common cancer in females in 157 countries out of 185, in 2022 (Source: World Health Organisation [WHO]).

Across the UK, prostate cancer is the most common cancer in males. More than 50,000 males are diagnosed with prostate cancer every year (Source: Prostate Cancer UK). Prostate cancer is the most commonly diagnosed cancer in males in 118 of 185 countries (Source: American Cancer Society, 2024).

[Close 2nd post of reference to subject matter, this part of my thread]

Just to support my earlier narrative, I said that ‘next time’, I’d include these as references:

A review article that is OPEN

“The Regulation of protein translation and its implications for cancer”

Authors: Ping Song, Fan Yang, Hongchuan Jin and Xian Wang
Signal Transduction and Targeted Therapy (2021) 6:68

“…the aberrant translation from mRNAs to proteins plays an important role in the pathogenesis of various cancers…”

(In the biological context) ‘Aberrant’ means, diverging from the normal type.
mRNAs are ‘messenger RNAs’ – the role of mRNA is to carry protein information from the DNA in a cell’s nucleus to the cell’s cytoplasm. Here, it floats around until it meets a ribosome (I’ve touched on these last time also). One other aspect of learning here is that ribosome to mRNA binding is facilitated by other proteins which in health sciences are known as ‘Initiation Factors (Ifs).

Cytoplasm – the gelatinous liquid that fills the inside of a cell. It is made up of water, salts and various organic molecules. It is bounded by the cell membrane. The organelles, which I have touched upon before, are contained also within this micro environment inside the cell.

Humans are about 60% water, by body mass. It is thought that salt is evolutionary evidence for the origin of life within the oceans – mind blowing!

‘Pathogenesis’ means the process by which disease develops. Pathos is from the Greek to suffer. Genesis is from the Greek for origin.

The other reference to a review article that is OPEN that I said I’d include as a reference is;

“Roles of long noncoding RNAs in human inflammatory diseases”

Authors: Yuliang Zhang; Hongliang Liu; Min Niu; Ying Wang; Rong Xu; Yujia Guo and Chunming Zhang

Cell Death Discovery (2024)10:235
CDDpress SpringerNature Published online: 15 May 2024

This is primarily about long noncoding RNAs in inflammatory disease per se, but there is also some reference to cancer, for e.g.

“…Moreover, IncRNAs are also involved in various cancer types. For example, PCA3 and PCGEM1 are highly specific to prostate cancer…HOTAIR, ANRIL, MALAT1 and LNP1 were positively associated with breast cancer…”

PCA3, PCGEM1, HOTAIR etc. are types of IncRNAs, which inhibit gene transcription. They also interact with proteins.

[Close of thread for this session, 3rd of this context]

Next time...I will focus more closely on prostate cancer (for the guys to be aware of).

4th post of this most recent context, within my thread.

PSA can be measured in nanograms per ml (ng/ml). Nano is a billionth, or 10 to the minus 9 - an extremely small quantity. A PSA measure exceeding 4 ng/ml certainly warrants further investigation. However a high PSA does not necessarily mean there is cancer present, it is a bio-marker though and a useful one. There is a really short scientific paper (only 3 pages including references) that can be downloaded, by WJ Catalona (2014/2015) cited by 60, titled;

'History of the discovery and clinical translation of prostate specific antigen', Asian Journal of Urology (2014) 1, 12-14, made available online by ScienceDirect.

In short, this measurement of PSA serum from blood, entered practice either in 1989 or the start of the 1990's, following the required approvals process.

The thing with PSA that doesn't make things straightforward, or clear - just as a single measurement, in the absence of other testing, or procedures - is that sometimes aggressive prostate cancers occur in the low PSA range of 4-10 ng ml (I should point out that untypically, cancer can also be present with PSA below 4ng ml). The intermediate range (not to be confused with intermediate risk grading) is over 10ng ml and under 20ng ml and the high range over 20ng ml. Metastases can occur within any range but they become more common with PSA over 40ng ml and become very likely over 100ng ml, so it's important to investigate all ranges as stated by NHS (UK). There are recorded cases of PSA reaching 5000ng ml (in advanced cases with bleak prognosis).

In a paper entitled "Outcomes of Men who Present with Elevated Serum PSA (>20ng/ml) to an Inner-City Hospital" by Satoshi Anai et al (2007 - Journal Of The National Medical Association, Vol 99, No. 8, August 2007), 7 from 65 men did not have cancer (11%) even with a PSA over 20ng ml. However, the study found a positive predictive value (PPV) of 72% for cancer, with PSA between 20 and 29.9ng ml. It found, at 30ng/ml, a PPV of 100%, however. We have to recognise a limitation of the study, in that, this comprised of only 65 men with the elevated PSA over 20ng ml.

In my own family I have known one case of locally advanced prostate cancer with PSA at just over 10ng/ml - (in his case, with a Gleason score 8) - and one case of early grade adenocarcinoma, attaching a low to intermediate risk (including a mix of clinically insignificant cancer, Gleason 6 and some Gleason 7 intermediate risk) with a PSA over 21ng/ml.

Adenocarcinoma forms in the glands - 'adeno' meaning, pertaining to a gland and 'carcinoma' meaning, pertaining to cancer.

The first thing with prostate cancer, is that the earliest focus is on how well the cells are DIFFERENTIATED. In essence, this is about GRADING of the cancer. The more differentiated the cells i.e. small and uniform glands with epithelial cells surrounding the lumen of the duct - which are all well defined - the better for the individual concerned.

Surprisingly, it is possible for some prostate cancer to be 'clinically insignificant' (I've now referred to this earlier too). This would be an early grade cancer, with a GLEASON score of 6 or below - a Gleason score of 6 is the lowest detectable score from biopsy. The cells are so well differentiated, they just look slightly different from normal. This would be a Group 1 cancer.

A Group 2 prostate cancer cells would still be well differentiated but there would be more stroma (connective tissue) between the cells/glands.

For those who aren't already aware, the function of the prostate organ is to contribute approximately 30% of the ejaculate.

Sources for the above (so far) The Open University's S290 module, Topic 2: Cancers: 1.6.3 Cancer grading (2021) AND familial experience of this disease, 2022-2025 AND as otherwise stated in this first main edit.

To lighten the mood : We're off to a Bowie tribute tonight. Whatever you're doing, have a good one! x -

- postscript 10/03/2025 (about Saturday Night) - We saw and heard - 'Bowie by Candlelight' at Oxford Town Hall - the very venue where, back in 1972, Mick Rock took the iconic photo of Bowie kneeling in front of Mick Ronson with face close to the guitar - you know the one - and the band that were performing were, DAVID LIVE.

I hadn't realised that they've been around for a couple of decades - I think that is what their lead singer, CHARLIE FOWLER, said in a separate YouTube interview (just under an hour in length with an interviewer from New York). Anyway, Sasha and I met Charlie briefly after the show (he's charming and looks fantastic for his age).

Charlie's vocal was incredibly strong. In my view, there can't be a better tribute to David Bowie out there. Oxford loved them. I think the early Cockney Rebel took some influence from Bowie and The Spiders From Mars (we know that Steve held 'Ronno' in high regard from some of his actions, I think, in 2015?) I also think besides Steve's Dylan, T.S. Eliot and folk influences, in my view at least, early Cockney Rebel also took a little influence, from the 'For Your Pleasure' period Roxy Music.

Anyway, thinking back to DAVID LIVE and Charlie in particular, I think any tribute taking on Cockney Rebel, would hone in on the 1973 to 1976 period. David Live split the show into the Ziggy/Spiders period (predominantly) and the 80's/90's Bowie. Besides the quality of the vocals, the drumming, both guitarists and the keyboards man, what really made this work was Charlie's image (he changed for the second part of the show), his heart and effort and his age...he's old enough to have been a young fan right at the beginning. The whole thing left a considerable impression on us. Fantastic. This has also made me think again about two of my other threads, 'Suggestion to myself...' and 'Is Ian Nice still in music...', for (those who have read those threads) perhaps obvious reasons. Have a good week, tara. xx

5th post of this most recent context.

Incidentally, I've not included any illustrations of prostate cancer grading - only to ensure that I don't fall foul of copyright - these can easily be found by using your preferred search engine to find, say, 'Gleason grading of prostate cancer' and scroll down to 'Images'.

I've talked about Gleason 6 (3+3) and Gleason 7 (3+4), Groups 1 and 2 respectively, which are generally well differentiated cells. The former is clinically insignificant (it would probably be watched/monitored, rather than immediately treated) but the latter is (the first) of the clinically significant gradings, with more stroma/connective tissue, between the cells/glands.

I haven't referred to the numbers in brackets yet, but in essence these numbers reflect the smallness, uniformity, of the glands. Both of these, whilst positive for cancer, are relatively early grade (I may refer more to Staging at a later date, although if you look again to my first post in this context, where I've made reference to Sir Chris Hoy, you'll gather already that Stage 4 is when the primary cancer - in the prostate - has also spread to other tissues and become secondary cancer. Metastases to the bones is generally considered terminal).

If you do a search you'll pick up that a Gleason 7 (4+3 - NOTE it is still a Gleason 7 but the ordering has shifted from 3+4 to 4+3: the cancerous cells here are predominantly a higher Pattern 4 but there are also some lower Pattern 3's in the biopsy). This is a Group 3 cancer of the prostate. You'll see the uniformity of the cells is not so clear - there are in fact 'distinctly infiltrative margins' (this is how my OU module referred to it - the cells are predominantly undifferentiated).

There are three things then to think about with the classification of the grading of prostate cancer, the Gleason SCORE, the PATTERN of cells (from each core that is taken during the biopsy, a pattern is given, the first number represents the most frequently occurring pattern of cells in the core and to this is added the less frequently occurring pattern of cells - e.g.- (3 + 4)) and to this is added the GROUP (this is more up to date - but in my view it's unlikely that Gleason score will ever disappear from practice, it's too good). TOGETHER, these are all part of the GRADING.

On a Pathology report you might see the whole thing - GRADING - written like this: GROUP 2 GLEASON 7 (3+4), for example.

A Gleason 8 (4+4 or 3+5 or 5+3) are poorly differentiated with irregular masses of neoplastic glands. This is a Group 4 prostate cancer.

Neoplastic in the biological context: an abnormal mass of tissue. This came from the Greek for 'new formation'.

Gleason 9 and 10, each categorised as Group 5 prostate cancer, show only occasional gland formation. The cells are sometimes referred to as 'anaplastic'. These describe rapidly dividing cells with little or no resemblance to normal cells.

Next time: Evidence that supports the probability of at least some malignancy in the prostate by age range 70 to 80 (it's around 50%). This likelihood increases to approaching 70% at over 80 years of age - but many at that age will have had a less aggressive cancer, which may never need treatment. Another thing to bear in mind is that there are side effects to all treatments and whilst it is difficult to accept, one has to keep in mind average life expectancy (it can't last forever) and quality of life.

Many of us males (within the Harley fanbase) are in our 60's or even 70's now and that's why I've encouraged the male fanbase (those over 50 years of age - you see PSA tends to increase (slightly) naturally with age, even in the absence of disease and so even more reason to get tested) to seek a PSA serum blood test and a DRE. Each only take a few minutes...

Take care, stay your way,

It's coming up to the first anniversary of Steve's death and he (is) in my mind and I'm sure many of yours...

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