Category Archives: Uncategorized

Inflammation and cancer

source link https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803035/

. Author manuscript; available in PMC 2010 Jan 7.
Published in final edited form as:
PMCID: PMC2803035
NIHMSID: NIHMS163568
PMID: 12490959

Inflammation and cancer

Lisa M. Coussens*§ and Zena Werb§

Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.

The functional relationship between inflammation and cancer is not new. In 1863, Virchow hypothesized that the origin of cancer was at sites of chronic inflammation, in part based on his hypothesis that some classes of irritants, together with the tissue injury and ensuing inflammation they cause, enhance cell proliferation. Although it is now clear that proliferation of cells alone does not cause cancer, sustained cell proliferation in an environment rich in inflammatory cells, growth factors, activated stroma, and DNA-damage-promoting agents, certainly potentiates and/or promotes neoplastic risk. During tissue injury associated with wounding, cell proliferation is enhanced while the tissue regenerates; proliferation and inflammation subside after the assaulting agent is removed or the repair completed. In contrast, proliferating cells that sustain DNA damage and/or mutagenic assault (for example, initiated cells) continue to proliferate in microenvironments rich in inflammatory cells and growth/survival factors that support their growth. In a sense, tumours act as wounds that fail to heal.

Today, the causal relationship between inflammation, innate immunity and cancer is more widely accepted; however, many of the molecular and cellular mechanisms mediating this relationship remain unresolved — these are the focus of this review. Furthermore, tumour cells may usurp key mechanisms by which inflammation interfaces with cancers, to further their colonization of the host. Although the acquired immune response to cancer is intimately related to the inflammatory response, this topic is beyond the scope of this article, but readers are referred to several excellent reviews,.

 

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Ionising Radiation, Inflammation and Autoimmune disease

source link: https://www.ncbi.nlm.nih.gov/pubmed/29554942

 2018 Mar 20;5(1):9. doi: 10.1186/s40779-018-0156-7.

Radiation-induced inflammation and autoimmune diseases.

Abstract

Currently, ionizing radiation (IR) plays a key role in the agricultural and medical industry, while accidental exposure resulting from leakage of radioactive sources or radiological terrorism is a serious concern. Exposure to IR has various detrimental effects on normal tissues. Although an increased risk of carcinogenesis is the best-known long-term consequence of IR, evidence has shown that other diseases, particularly diseases related to inflammation, are common disorders among irradiated people. Autoimmune disorders are among the various types of immune diseases that have been investigated among exposed people. Thyroid diseases and diabetes are two autoimmune diseases potentially induced by IR. However, the precise mechanisms of IR-induced thyroid diseases and diabetes remain to be elucidated, and several studies have shown that chronic increased levels of inflammatory cytokines after exposure play a pivotal role. Thus, cytokines, including interleukin-1(IL-1), tumor necrosis factor (TNF-α) and interferon gamma (IFN-γ), play a key role in chronic oxidative damage following exposure to IR. Additionally, these cytokines change the secretion of insulin and thyroid-stimulating hormone(TSH). It is likely that the management of inflammation and oxidative damage is one of the best strategies for the amelioration of these diseases after a radiological or nuclear disaster. In the present study, we reviewed the evidence of radiation-induced diabetes and thyroid diseases, as well as the potential roles of inflammatory responses. In addition, we proposed that the mitigation of inflammatory and oxidative damage markers after exposure to IR may reduce the incidence of these diseases among individuals exposed to radiation.

. Author manuscript; available in PMC 2016 Jan 1.
Published in final edited form as:
PMCID: PMC4378687
NIHMSID: NIHMS642044
PMID: 25481260

Radiation & Inflammation

Abstract

The immune system has the power to modulate the expression of radiation-induced normal and tumor tissue damage. On the one hand, it can contribute to cancer cure, on the other it can influence acute and late radiation side effects, which in many ways resemble acute and chronic inflammatory disease states. The way radiation-induced inflammation feeds into adaptive antigen-specific immune responses adds another dimension to the tumor-host crosstalk during radiation therapy and to possible radiation-driven autoimmune responses. Understanding how radiation impacts inflammation and immunity is therefore critical if we are to effectively manipulate these forces for benefit in radiation oncology treatments.

Windscale/Sellafield Pt. 10. Full text of Report on the Investigation of the Possible Increased Incidence of Cancer in West Cumbria 1986, COMARE. HMSO.

https://www.academia.edu/38201320/Report_on_the_Investigation_of_the_Possible_Increased_Incidence_of_Cancer_in_West_Cumbria_a.pdf

“Report on the Investigation of the Possible Increased Incidence of Cancer in West Cumbria : Committee on Medical Aspects of Radiation in the Environment (COMARE), first report HMSO 1986.”
This report is the first such report published as a result of British media reports in 1984. These media reports uncovered an apparent excess of childhood cancers in populations living in the vicinity of the Windscale/Sellafield nuclear facility.
Comare continues to publish reports on this matter. These are easily obtained from the UK national archives and from Comare. However, the first such Comare report is harder to obtain. It was published in 1986, coincident with the Chernobyl disaster, timing which the British government of the time considered “unfortunate” (National Archives). Few copies of the Comare 1 report were printed.
Hence I am placing the report online. It was obtained by requesting it from Comare UK. It is an open unclassified document.
Paul Langley

Windscale/Sellafield Pt. 9 “Cancer in Cumbria and in the vicinity of the Sellafield nuclear installation, 1963-90” Draper et all 1993

https://www.bmj.com/content/bmj/306/6870/89.full.pdf

Cancer in Cumbria and in the vicinity ofthe Sellafield nuclear
installation, 1963-90

G J Draper, C A Stiller, R A Cartwright, A W Craft, T J Vincent

BMJ 1993; 306 doi: https://doi.org/10.1136/bmj.306.6870.89 (Published 09 January 1993)
Cite this as: BMJ 1993;306:89

Full text at link above.

Conclusion from Abstract: “Conclusions-During 1963-83 and 1984-90 the
incidence of malignant disease, particularly lymphoid
leukaemia and non-Hodgkin lymphomas, in
young people aged 0-24 in Seascale was higher than
would be expected on the basis of either national
rates or those for the surrounding areas. Although
this increased risk is unlikely to be due to chance, the
reasons for it are still unknown.” end quote. source as above.

Windscale/Sellafield Pt. 8. Comare Reports 1 – 6. Summary only available

Link to UK Archive: https://webarchive.nationalarchives.gov.uk/20140507011723/http://www.comare.org.uk/comare_docs.htm

Preamble at the UK archive site:https://webarchive.nationalarchives.gov.uk/20140507011723/http://www.comare.org.uk/comare_docs.htm “Summary of the First Six COMARE Reports
COMARE Reports 1-6 are not available in PDF. The PDF document below summarises the conclusions and recommendations of these six reports.” UK National Archives.

Summary document text:

Summary of the work of COMARE as published in its first six reports
The Committee on Medical Aspects of Radiation in the Environment (COMARE) was established in November 1985 in response to the final recommendation of the report of the Independent Advisory Group chaired by Sir Douglas Black (Black, 1984). Our terms of reference are to “assess and advise Government and the Devolved Authorities on the health effects of natural and man-made radiation in the environment and to assess the adequacy of the available data and the need for further research”.
The Black Advisory Group had been commissioned by the Minister of Health in 1983 to investigate reports of a high incidence of leukaemia occurring in young people living in the village of Seascale, 3 km from the Sellafield nuclear site and the suggestion that there might be an association between the leukaemia incidence and the radioactive discharges from Sellafield. The Advisory Group confirmed that there was a higher incidence of leukaemia in young people resident in the area but also concluded that the estimated radiation dose from the Sellafield discharges and other sources, received by the local population, could not account for the observed leukaemia incidence on the basis of knowledge available at that time. The uncertainties in the available data led the Advisory Group to make recommendations for further research and investigation.
Our First Report (COMARE, 1986), examined the implications of some further information concerning discharges of uranium oxide particles from Sellafield in the 1950s, which had not been available to the Black Advisory Group. The Committee concluded that this additional information did not change the essential conclusions of the Black report.
Our Second Report investigated the incidence of leukaemia in young people living near to the Dounreay Nuclear Establishment in Caithness, Scotland (COMARE, 1988). We found evidence of an increased incidence of leukaemia in young people in the area and although the conventional dose and risk estimates suggested that radioactive discharges could not be responsible, we noted that the raised incidence of leukaemia at both Sellafield and Dounreay tended to support the hypothesis that some feature of these two plants led to an increased risk of leukaemia in young people living in the surrounding area. The report also considered other possible explanations and recommended further investigations.
Our Third Report considered suggestions of an increased incidence of childhood cancer near the Atomic Weapons Research Establishment at Aldermaston and the Royal Ordnance Factory at Burghfield (COMARE, 1989) We found a small but statistically significant increase in registration rates of childhood leukaemia and other childhood cancers in children in the vicinity of the two sites. However, we judged that the doses from the radioactive discharges were far too low to account for the observed increase in the incidence of childhood cancer. We considered a number of possible explanations for the findings including other mechanisms by which radiation could be involved, but there was insufficient evidence to point to any one explanation, although the possibility remained that a combination of factors might be involved. Further investigations were recommended. Our Third Report concluded by saying that the distribution of cases of childhood leukaemia or other childhood cancers around nuclear installations could not be seen in proper context in the absence of comparable information about the pattern throughout the UK. We recommended, therefore, that further work be carried out to determine the national
1

geographical pattern of distribution of childhood cancer and that this work should be given high priority.
Our Fourth Report was the result of the Committee’s review of the dosimetric, epidemiological and other scientific data relating to the Sellafield Site and the village of Seascale, together with other relevant advances in scientific knowledge, that had become available since the publication of the report of the Black Advisory Group in 1984. In the report we concluded that there was good evidence for a continuing, significantly elevated level of all malignancies in young people (0-24) in Seascale throughout the period considered by the Black report (1963-83) and our subsequent analysis (1984-92), covering a total period of three decades. We considered the current estimate of the radiation doses to the Seascale population, from both routine and accidental discharges from Sellafield, to be too small to account for the observed excess of cases of leukaemia and NHL on the basis of current knowledge. We considered a number of other hypotheses involving radiation exposure and also those involving exposures to chemicals and infectious agents, either singly or in combination. We concluded that no single factor could account for the excess of leukaemia and NHL but that a mechanism involving infection may be a significant factor affecting the risk of leukaemia and NHL in young people in Seascale. We made five recommendations for further research, all of which were accepted by Government.
Our Fifth Report examined whether there is, or has been any unusual incidence of cancer in the vicinity of the former Greenham Common Airbase and whether there is or has been any association with local levels of radioactivity in the area. With regard to childhood cancer we have examined the local incidence of these diseases in the context of the geographical distribution of these malignancies nationwide. We have found nothing to suggest that a nuclear weapon was involved in the accident or subsequent fire that took place on 28 February 1958. In overall terms the environmental monitoring data, indicated that the levels of man-made and natural radionuclides in this area are low when compared with many other areas of the UK. We also concluded that the environmental monitoring undertaken in the past and currently is consistent with Aldermaston discharges. The finding of an excess of leukaemia in children aged 0-4 in the West Berkshire area in the current study confirms the excess observed in the studies described in our Third report. We also noted the excess of leukaemia in young people aged 0-24 in ward 2 in Newbury, but there was no significant increases of cancer in this age group in the other wards in and around Newbury. We have concluded that the levels of radiation in the local area are so low that they could not be responsible for the local incidence of childhood leukaemia. We have pointed out other factors which might explain the noted excess of childhood leukaemia, particularly those which may be associated with the social class structure of the local area. We hope to examine this further when the results of the geographical studies recommended in our Third report are complete. Part of the reason for undertaking the work in our Fifth Report was to examine the possibility that the environmental monitoring data in previously classified reports, might have had some effect on the conclusions of our Third Report. These data were not made available to us at the time. In the event, this has not altered the overall conclusions of our Third report. Nevertheless, we have expressed our concern that the failure of organisations to make available information about relevant activities constrains our ability to comply with our remit. As a result of this particular incident mechanisms have been developed whereby, should issues arise in the future where a high security classification is deemed still to be appropriate, classified information may be made available to appropriate committee members.
2

In our Sixth Report we summarised the work undertaken since 1995 and up until October 1998, to locate the source of the radioactive particles found in the general environment around the Dounreay Nuclear Establishment and reconsider the possible health implications of encountering these particles. We have also considered whether ingestion of these particles could be associated with the previously reported excess of leukaemia and NHL in young people living in Thurso. We noted that if individuals were to ingest particles with activities at the top of the range of those particles already found on the Dounreay foreshore, very serious acute radiation effects would occur. However, at that time very few particles had been found on the publicly accessible beach at Sandside Bay and all were of them were of low activity. We concluded that an implausibly large number of these particles would have needed to be ingested to have given rise to the known level of childhood leukaemia in the area around Dounreay. We recommended increased and regular and improved beach monitoring in the area to ensure any particles coming ashore could be found and removed.
3

end quote.

These people do not know the importance of the concept of adding up. To appreciate this concept of adding up radiological insults, one has to understand the role of normal background radiation exposure has in the genesis of the types of cancers being investigated by Comare from 1984 on to the present time. What a junket!

Windscale/Sellafield Pt. 7. Research for a book length study

reply from Ian Fairlie regarding where abouts of the full text of the first COMARE report of 1986:
1. “Sent: Mon, 21 Jan 2019 11:34
Subject: Re: Website: “The first COMARE report (1986)”

Hi Paul
I do not have a link to the first COMARE report. Interesting that theyseem to have withdrawn it. Or was it published on paper in pre web days?
I have asked a friend Pete Roche if he has a link.
Best
IAN ”

2. ” There only seems to be a summary of the first six reports.

https://webarchive.nationalarchives.gov.uk/20140507011723/http://www.comare.org.uk/comare_docs.htm
Report on the Investigation of the Possible Increased Incidence of Cancer in West Cumbria

Pete Roche
http://www.no2nuclearpower.org.uk
http://www.nuclearwasteadvisory.co.uk/
http://www.cumbrianenergyrevolution.org.uk/
http://www.microgenscotland.org.uk

down the rabbit hole I guess.

link to Summary of the first six Comare reports:

https://webarchive.nationalarchives.gov.uk/20140507011723/http://www.comare.org.uk/comare_docs.htm

Windscale/Sellafield Pt. 6. Research for a book length study

I am now searching for the full text of Comare report number 1 of 1986. Two years after the Black report and the TV program which highlighted the leukemia cluster around Sellafield (1984). These occurred prior to Chernobyl.

In my search I found the following archive record of the government response to the first comare report: http://www.nationalarchives.gov.uk/about/news/newly-released-files-1985-1986/prime-ministers-files-prem-1986/ which if you scroll down the page records this:

Report on leak at Windscale: policy towards Sellafield; environmental pollution; report on incidence of cancer in west Cumbria; report of the Committee on Medical Aspects of Radiation in the Environment; part 1
Catalogue reference: PREM 19/1741
Date range: 28 July 1980 – 22 July 1986

Patrick Jenkin suggests a ‘Sellafield dimension’ to Government policies where financial compensation would be given to areas near nuclear plants, such as the Workington Enterprise Zone. This is rejected by David Pascall of the Policy Unit (1 June 1984). The Black Report published in July 1984 causes concern as it looks at leukaemia among young people in Seascale, near Sellafield (17 July 1984). Correspondence between Thatcher and the Taoiseach, Garret Fitzgerald in March 1986 demonstrates Irish concerns over the safety of Sellafield. Advisor Michael Addison describes the Committee on Medical Aspects of Radiation in the Environment (COMARE) report as having come at ‘an unfortunate time, after Chernobyl.” end quote. Source: UK National Archives, Prime Minister’s files (PREM) 1986. No surprises there. Unfortunate given the number of afflicted children, Thatcher you old demented dead devil.

Oops.