Scanning Electron Micrograph of a breast cancer cell. Credit: NIH
Breast cancer and diabetes have long been suspected to have some kind of relationship, but now new research in Nature Cell Biology reveals how breast cancer cells sabotage insulin production to fuel their own cravings for glucose.
Diabetes risk begins to increase two years after a breast cancer diagnosis, and by 10 years post-diagnosis, the risk is 20% higher in breast cancer survivors than in age-matched women without breast cancer.
But these epidemiological linkages are not clear-cut or definitive, and some studies have found no associations at all. In the paper, a research team describe a possible biological mechanism connecting the two diseases, in which breast cancer suppresses the production of insulin, resulting in diabetes, and the impairment of blood sugar control promotes tumour growth.
“No disease is an island because no cell lives alone,” said corresponding study author Shizhen Emily Wang, PhD, professor of pathology at UC San Diego School of Medicine. “In this study, we describe how breast cancer cells impair the function of pancreatic islets to make them produce less insulin than needed, leading to higher blood glucose levels in breast cancer patients compared to females without cancer.”
The researchers name the culprit as extracellular vesicles (EV), which carry DNA, RNA, proteins, fats and other materials between cells, a sort of cargo communication system.
The cancer cells were found to be secreting microRNA-122 into the vesicles. When vesicles reach the pancreas, Prof Wang said, they can enter the islet cells, offload their miR-122 cargo and damage the islets’ critical function in maintaining a normal blood glucose level.
“Cancer cells have a sweet tooth,” Prof Wang said. “They use more glucose than healthy cells in order to fuel tumor growth, and this has been the basis for PET scans in cancer detection. By increasing blood glucose that can be easily used by cancer cells, breast tumors make their own favorite food and, meanwhile, deprive this essential nutrient from normal cells.”
Feeding mice slow-releasing insulin pellets or an SGLT2 inhibitor restored normal control of glucose in the presence of a breast tumour, in turn suppressed the tumour’s growth.
“These findings support a greater need for diabetes screening and prevention among breast cancer patients and survivors,” remarked Prof Wang, noting that a miR-122 inhibitor is currently in clinical trial as a potential treatment for chronic hepatitis C. It has been found to be effective in restoring normal insulin production and suppressing tumour growth in mouse models of breast cancer.
“These miR-122 inhibitors, which happen to be the first miRNA-based drugs to enter clinical trials, might have a new use in breast cancer therapy,” Prof Wang posited.
Judge Edwin Cameron, Inspecting Judge of Correctional Services, writes about the need for healthcare professionals working in prisons should be shifted to the Department of Health.
Our country’s healthcare system is a cumbersome double-deckerbus: on top are those of us who have access of some kind to private healthcare (a high estimate is around 27% of the population). The great majority of necessity rely on public healthcare. But, within public healthcare, there is a further divide, an overlooked layer at the very lowermost – the healthcare afforded to people in prison.
During apartheid, healthcare for those inside prison and in police custody was used as a “tool of manipulation and coercion”. There was medical negligence, poor quality care, false medical and autopsy reports, and warped medical ethics. (Bram Fischer, in his dying days, received no treatment for his crippling cancer).
Some doctors and other medics were complicit in abuses, turning a blind eye to what was happening before them.
The Truth and Reconciliation Commission (TRC) Special Hearings on Prisons showed how basic access to medical treatment was used to punish. Henry Magkothi recounted how difficult it was to gain access on Robben Island to the hospital. “The doctor didn’t come often enough and even then there were so many obstacles they placed in your way.”
Not only did doctors have to have security clearance to work in prisons, but there were split institutional loyalties. Some health professionals were employed by the Department of Health and others by the Department of Prisons (now the Department of Correctional Services — DCS). This led to a dilemma of “dual obligations”, where the lines of authority for healthcare and custodial care were blurred. Health professionals owed loyalty to their patients (the inmates). But they had obligations to, and pressure from, their employers (the prison authorities).
Healthcare must be separated from prison administration
This blighted history led Dr Judith van Heerden, an expert in this area, to recommend to the TRC that prison healthcare “must be separated completely from custodial care”. All healthcare professionals in prisons “should be appointed, paid and responsible to the Department of Health” – and no longer to the prison authorities.
The TRC embraced this sound advice in its recommendations. It suggested that: the Department of Health should assume control over prison healthcare; prison health responsibilities and obligations should be clearly defined with an independent line of authority.
These recommendations accord with international guidelines. The UN Mandela Rules entail a demarcation between healthcare and custodial care; there shall be “full clinical independence”. Healthcare professionals “shall not have any role in the imposition of disciplinary sanctions or other restrictive measures”. And clinical decisions may only be taken by healthcare professionals “and may not be overruled or ignored by non-medical prison staff”.
Experts have underscored the importance of providing health services in prison that are separate from the prison administration. The World Health Organisation and the United Nations Office on Drugs and Crime note that healthcare professionals should act “completely independent of prison authorities” and in “alignment with public health services.”
Furthermore, the Association for the Prevention of Torture advocates for the “integration of the prison health service into the national health service” to guard the “professional and ethical independence of the health staff” and “provide recourse to an independent body in case of conflicts.”
Did democratic South Africa heed this advice? No.
Medical ethicist Professor Solomon Benatar observes that the Department of Health “began to dismantle the District Surgeon Services” and “[i]t became possible for DCS to appoint nurses and other medical staff to deliver healthcare” in our prisons.
This is evident in the plain wording of the Correctional Services Act of 1998. Section 12(1) states that DCS “must provide, within its available resources, adequate health care services” and section 12(2)(b) outlines that medical treatment “must be provided by a correctional medical practitioner, medical practitioners or by a specialist or health care institution or person or institution identified by such correctional medical practitioner”. And according to section 12(3), if an inmate opts to be “visited and examined by a medical practitioner of [their] choice” it is “subject to the permission of the Head of Centre”.
Post-apartheid, healthcare in prisons is still not independent. Benatar slates this “retrogressive step”; “diverting some responsibilities for healthcare away from the Department of Health” and towards DCS, diminishes the “loyalty of some health professionals” as it ranks “allegiance to prison authorities higher than professional responsibility to patients.”
A special duty of care
In his book Health and Health Promotion in Prisons, Professor Michael Ross states that depriving inmates of liberty does not mean we may deprive them of access to healthcare. On the contrary, their deprivation of liberty means we owe them a “special duty of care”. Critically, Ross acknowledges that we provide “good care to bad people because we are professional, and because we, and they, are human” and if bad care is given “the humanity we degrade is also ours, not only theirs”.
Those in prison should have the same quality of healthcare as the public outside. This is the “equivalence of care” principle. It means that you don’t add poor healthcare treatment on top of imprisonment to punish. As I have written before, “prison health affects our health” and “equivalence of care” should be considered a minimum threshold. In light of the higher mortality rates in prisons; government may have to provide higher standards of healthcare in prisons.
We know that injuries and the use of anti-depressants are warning signs of trouble. Many cases of claimed abuse (especially sexual violations, assaults, use of force and torture) are reported to nurses and doctors. Later, investigators, both internal and external, rely on medical reports. Ross emphasises that one must ensure health assessments of inmates are based on medical criteria and inmates ought to trust their healthcare providers and feel safe to report and speak out about abuse.
In addition, nurses, psychologists and other medical practitioners play a role in how prisons are run. For example, they are expected to visit inmates in segregation (sometimes in solitary confinement). The Act provides that segregation “must be discontinued” if medical practitioners determine that “it poses a threat to the health of the inmate”.
Further, independent healthcare can provide another significant layer of independent monitoring over our closed-off prisons.
Two parallel healthcare systems are not advisable. Does DCS have adequate training facilities to ensure training and updates on clinical care for clinicians on its payroll? The Judicial Inspectorate for Correctional Services (JICS), which I head, believes not. DCS clinicians often miss out on training opportunities. Further, DCS’s data systems are standalone – they are not linked to the Department of Health’s facilities (connecting them would ensure continuity of care when inmates are released).
And a heartening thought – why not allocate community service doctors to prisons? This would alleviate costs and skills scarcity.
The state of healthcare in our prisons
Grievously, our prisons are a microcosm of all our country’s social ills. This is true of healthcare, but perhaps it is worse, since, notoriously, prisons are epidemiologic pumps for the spread of infectious viruses and diseases.
The 2020-2021 annual report of the Judicial Inspectorate for Correctional Services paints an agonising picture of the state of prison healthcare.
Inmates do not get regular access to nurses and doctors, clinics in prisons are cramped and there is limited privacy for consultations, correctional officials are not always available to escort inmates to healthcare facilities, medications are not always dispensed on time, some medications have expired, health check-ups and screenings upon admission are not always conducted and medical files are not always updated.
Healthcare professionals in prisons, especially psychologists and social workers, are working with a desperate population. In the single year covered in the report, JICS reported 86 hunger strikes, 66 attempted suicides and 27 suicides. According to DCS’s annual report “suicide is the leading cause of [unnatural] deaths in correctional facilities”.
JICS’s recent quarterly report lists 40 unnatural deaths. We don’t know the cause of most; seemingly healthy inmates died. This requires JICS’s close investigative scrutiny of the post-mortem and medico-legal documents, which are in the hands of DCS and sometimes mysteriously go missing.
Further, there were 113 deaths as a result of natural causes, including pneumonia, cancer, meningitis, septicaemia and asthma. Could some of these deaths have been avoided with early detection, close monitoring and regular access to medical assistance? JICS thinks so.
JICS is also alarmed by the 116 declared state patients in prison; these are individuals whom the courts have found are suffering from mental unwellness challenges. As they wait indefinite periods for a transfer to a psychiatric hospital, they are wrongly housed in correctional facilities. State patients should not be a DCS responsibility. JICS has raised its voice on this: correctional facilities are not conducive for state patients, and correctional officials and fellow inmates are not trained to properly accommodate them.
To end off
While inspecting prisons, I have met passionate nurses and committed doctors. Prisons are tough, dangerous and complicated places. I acknowledge that DCS has worked hard to progress in dealing with Covid, HIV and TB behind bars. But we have to do better.
We need institutional reform. Healthcare professionals working in prisons ought to be independent of DCS. This means shifting all healthcare professionals to the Department of Health and ensuring proper channels of authority and oversight within prisons. In addition, healthcare professionals need specific and ongoing training for the prison environment. We also need more healthcare professionals working in prisons – and they must be accessible, proactive and willing to speak out.
That takes us back to where we started. Our Department of Health must be well-resourced, well-capacitated and well-run – and healthcare professionals must be trained and supported and have job security. And this goes to the heart of whether we have a capable state, strong institutions and a culture of accountability.
Judge Cameron is Inspecting Judge of Correctional Services.
Views expressed are not necessarily those of GroundUp.
Scanning Electron Micrograph image of a human T cell. Credit: NIH/NIAID
While T cells are the body’s warriors against infection, without rest and maintenance T cells can die, leaving their hosts more susceptible to pathogens, researchers reported in the journal Science.
“We may have to change how we teach T cell biology,” said Professor Lieping Chen, who is the senior author of the study.
T cells remain in a quiescent state until pathogens are detected, but the molecular mechanisms of this state were previously unknown.
In the new study, researchers showed that a protein known as CD8a – which is found in a subset of T cells called CD8 cells – is crucial to keeping the cells in this dormant state. When scientists deleted this protein in mice, the protective CD8 cells were unable to enter a quiescent state and died, leaving the host vulnerable to infections.
Further, they identified another protein, PILRa, that provides a biochemical signal to CD8a. By disrupting this protein pair, both “memory” CD8 cells – previously been exposed to pathogens – and naïve cells died because they lacked the ability to stay in a quiescent state.
The researchers hope that understanding why this resting state is crucial to maintenance and survival of T cells can lead to improved immune system function.
Chen noted that as people age they tend to lose both naïve and memory T cells, making older individuals more susceptible to infections. It is possible that the inability of T cells to remain in a quiescent state could lead to people becoming more susceptible to infections and cancer, the authors suggest.
An Australian study published in Allergy, has identified the key immunological changes that support the remission of peanut allergy in children, a discovery that could pave the way to new, more targeted treatments.
The research showed, for the first-time, that specific gene networks are rewired to drive the transition from peanut allergy to clinical remission following a combination treatment of a probiotic and peanut oral immunotherapy.
The study found that this network reprogramming essentially shuts down the allergic immune response that was responsible for causing a food allergy.
Lead researcher, Professor Mimi Tang of Murdoch Children’s Research Institute, said this was the first study to map the complex gene to gene communication and connectivity underlying clinical remission of peanut allergy.
“The immunological changes leading to remission of peanut allergy were largely unknown,” she said. Previous studies had mostly focused on examining the levels of gene expression, without also exploring how genes interact with each other. But genes don’t work in isolation; instead, biological responses are controlled by large numbers of genes communicating with each other, so it made sense to look at these interactions more closely.
“What we found was profound differences in network connectivity patterns between children who were allergic and those who were in remission. These same changes were also seen when we compared gene networks before and after immunotherapy in the children who achieved remission following immunotherapy.”
The randomised controlled trial involved 62 peanut allergic children, ages 1–10, who received a combination treatment of a probiotic and oral immunotherapy (gradual introduction of the allergen) or a placebo. Following 18 months of treatment, 74% taking the combination treatment achieved remission compared with 4% in the placebo group.
The peanut oral immunotherapy that was used in combination with the probiotic in the trial was PRT120, a lead candidate from biotech company Prota Therapeutics.
The team led by Professor Tang also recently showed in a separate trial that two treatments — the combination probiotic and peanut oral immunotherapy treatment and the peanut oral immunotherapy alone — were highly effective at inducing remission and desensitisation. About half of the treated children achieved remission, which allowed them to stop treatment and safely eat peanut freely.
Murdoch Children’s Dr Sarah Ashley said while oral immunotherapy could successfully induce desensitisation and remission, desensitisation often waned after treatment ended or even during ongoing maintenance dosing.
“Certain changes in the allergen-specific immune cells, called Th2 cells, are critical to achieving lasting remission,” she said. Th2 cells are essential for generating allergen-specific antibodies and the development of food allergy. We found that the Th2 signalling that drives allergy is ‘turned off’ in children in remission.”
Food allergy is a global public health concern, affecting 10% of infants and 5–8% of children.
South Africa’s medicines regulator has officially terminated the special dispensation to use Ivermectin as a treatment for COVID, stating that “there is currently no credible evidence to support a therapeutic role for Ivermectin” in the treatment of the disease.
On Monday 30 May, the South African Health Products Regulatory Authority (SAHPRA) officially withdrew its authorisation [PDF], bringing to end something of a saga which saw vocal proponents pitched against the scientific and regulatory establishment.
The antiparasitic Ivermectin gained considerable notoriety as the COVID pandemic went on, based on preliminary studies that seemed to demonstrate its effectiveness. Pressure born out of desperation for some kind of treatment led to SAHPRA – amidst its own apparent misgivings – granting compassionate use authorisation under strict guidelines in January 2021. Use was allowed under Section 21 guidelines without having to wait for Section 21 authorisation, which was misinterpreted as full authorisation by some media sources.
The social media furore and misinformation surrounding Ivermectin led to dangerous instances of COVID self-treatment, with hospitalisations and even deaths reported.
In its terribly botched response to COVID, Brazil adopted Ivermectin on a mass scale, and essentially became a living laboratory for its effectiveness. Despite even administering Ivermectin as prophylaxis, Brazil’s health system was overwhelmed with COVID patients during the surge caused by the Gamma variant.
Studies turned up scant evidence in favour of Ivermectin’s effectiveness, with serious flaws and even outright data fabrication were picked up in a number of studies that seemed to show a significant benefit – even flying right through the peer review process only to be picked up at a later stage. This lead to a major meta-analysis by Hill et al. showing a effectiveness instead being retracted, which SAHPRA noted in its decision.
Finally, the I-TECH and the Together randomised clinical trials of 2021 showed no effect. Like hydroxychloroquine before it, Ivermectin prescribing was found to be driven by political interests. Thus, Ivermectin quietly disappeared from the media as viable antivirals such as Paxlovid came into the market.
The termination comes after a distinct decline in demand for Ivermectin use in South Africa, with no new applications for importation of unregistered Ivermectin products place since August 2021. SAHPRA also noted a marked decline in the number of health facilities applying for permission to hold bulk stock after August 2021.
Furthermore, no individual named patient applications have been approved since December 2021. Finally, there was little in the way of reporting of outcomes achieved by the treating healthcare providers.
