In countries which allow the practice, assisted suicide would seem to be an alternative to conventional suicide – but new research shows that this is not a simple relationship. An analysis published in Cancer Medicine reveals the trends of self-initiated deaths – including assisted suicide (AS) and conventional suicide (CS) – in Switzerland over a 20-year period, focusing on people who suffered from cancer. While cancer-related AS rose, CS fell but then stabilised – suggesting that cancer-related CS has more complex reasons behind it.
Although supporters of assisted dying state that access to AS should lead to a reduction in violent CS, the study’s findings do not confirm this assumption. The situations and motivations for cancer-associated CS seem to be clearly different from those for cancer-related AS.
In Switzerland, assisting in a suicide is not punishable as long as it does not serve selfish motives. In this analysis of data from 1999–2018, investigators found that cancer was the most often listed principal disease for AS: 3580 people with cancer died by AS, representing 41.0% of AS cases. Cancer was listed in only a small minority of CS cases (832 people, representing 3.8% of CS cases).
There was approximately a doubling of AS cases among patients with cancer every 5 years. Also, the percentage of cancer-associated AS in relationship with all cancer-associated deaths increased over time to 2.3% in 2014–2018. The numbers of cancer-associated CS showed a downward trend in 1999–2003 and were stable through 2009–2018.
“Obviously, the situations and motivations for cancer-associated CS seem to be clearly different from those for cancer-related AS,” said corresponding author Uwe Güth, MD, of the University of Basel.
Depression and anxiety are thought to increase a person’s risk of developing cancer, but research results have been inconclusive. In an analysis of multiple studies from the Netherlands, the UK, Norway, and Canada, investigators found that depression and anxiety are not linked to higher risks for most types of cancer among this population. The analysis is published in the journal CANCER.
Experts have suspected that depression and anxiety may increase cancer risk by affecting a person’s health-related behaviours or by having biological effects on the body that support cancer development. Some research has supported an association between depression, anxiety, and cancer incidence, while other investigations have found no or negligible associations.
To provide additional insights, Lonneke A. van Tuijl, PhD, of the University Medical Center Groningen, and her colleagues examined data from the international Psychosocial Factors and Cancer Incidence consortium, which includes information from 18 prospective study groups with more than 300 000 adults from the Netherlands, the United Kingdom, Norway, and Canada.
The team found no associations between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers during a follow-up of up to 26 years. The presence of depression or anxiety was linked with a 6% higher risk of developing lung cancer and smoking-related cancers, but this risk was substantially reduced after adjusting for other cancer-related risk factors including smoking, alcohol use, and body mass index. Therefore, this analysis supports the importance of addressing tobacco smoking and other unhealthy behaviours including those that may develop as a result of anxiety or depression.
“Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” said Dr van Tuijl. “However, further research is needed to understand exactly how depression, anxiety, health behaviours, and lung cancer are related.”
B cells are thought to play a critical role in innate and adaptive immunity, but their exact role in anti-tumour immunity remains unknown. Looking at B cells with a technique called single-cell profiling, which looks at all the genes in the cell, researchers found a protein that – when deleted – reduced tumour growth. The researchers write in Nature that this regulator could be a target for new cancer treatments.
The team, consisting of immunologists at Brigham and Women’s Hospital and dermatologists from Massachusetts General Hospital, identified a subset of B cells that expands specifically in the draining lymph node over time in mice with melanoma tumours.
They found a cell surface receptor called TIM-1 expressed on these B cells during melanoma growth. They also characterised multiple accompanying cell surface proteins that were involved in the B cell’s immune function. Interestingly, they found that deleting a molecule TIM-1, but not any of the other accompanying proteins, dramatically decreased tumour growth. The researchers concluded that TIM-1 controls B cell activation and immune response that combats cancer, including activating another type of the killer tumour-specific T cells for inhibiting tumour growth.
“The collaboration across institutions was extremely fruitful as we combined our immunology expertise at the Brigham with work at David Fisher’s MGH laboratory where seminal discoveries in skin malignancies have been made,” said lead author Lloyd Bod, PhD, of the Department of Neurology at the Brigham, who conducted this work while completing his postdoctoral fellowship at the Brigham. “The collaboration allowed us to test and demonstrate the therapeutic potential of targeting TIM-1 in melanoma models.”
A new UK study has found that fatigue is the most significant symptom for long COVID patients, and can affect quality of life more than some cancers. The research, published in BMJ Open, examines the impact of long COVID on the lives of over 3750 patients who were referred to a long COVID clinic and used a digital app as part of their NHS treatment for the condition.
Patients were asked to complete questionnaires on the app about how long COVID was affecting them – considering the impact of long COVID on their day-to-day activities, levels of fatigue, depression, anxiety, breathlessness, brain fog, and their quality of life.
The researchers, from UCL and the University of Exeter, found that many long COVID patients were seriously ill and on average had fatigue scores worse or similar to people with cancer-related anaemia or severe kidney disease. Their health-related quality of life scores were also lower than those of people with advanced metastatic cancers, like stage IV lung cancer.
Overall, the team found that the impact of long COVID on the daily activities of patients was worse than that of stroke patients and was comparable to that of patients with Parkinson’s disease.
Dr Henry Goodfellow, who co-led the study alongside the late Professor Elizabeth Murray (both UCL Institute of Epidemiology & Health), said: “Up to around 17% of people who get COVID go on to develop long COVID *. However, the impact of the condition on patients’ day-to-day lives isn’t fully understood.
“Our results have found that long COVID can have a devastating effect on the lives of patients – with fatigue having the biggest impact on everything from social activities to work, chores and maintaining close relationships.”
Not only does long COVID negatively impact the lives of patients on an individual level, the researchers also believe that it could have a significant economic and social impact on the country.
In order to be referred to a long COVID clinic, a patient must have had symptoms in keeping with long COVID for at least 12 weeks after an acute infection.
Over 90% of long COVID patients using the app were of working age (18-65) and 51% said they had been unable to work for at least one day in the previous month, with 20% unable to work at all.
Meanwhile, 71% of patients were female. As working-age women make up a majority of the health and social care workforce, the impact of long COVID on their ability to function may add additional pressures to already stretched services.
Dr Goodfellow said: “We hope that a greater understanding of the symptoms and impact of long COVID in these patients will help the NHS and policymakers to target limited resources by adapting existing services and designing new ones to better meet the needs of patients with long COVID .”
Alongside fatigue, long COVID patients typically experience breathlessness, anxiety, depression and brain fog. This is the first study to report on the impact of the condition on day-to-day functioning and health-related quality of life in patients who have been referred for specialist rehabilitation in long COVID clinics across England.
Dr Goodfellow said: “Our findings show that fatigue should be an important focus for clinical care and the design of rehabilitation services.
“Post-COVID assessment services should consider focusing on assessing and treating fatigue to maximise the recovery and return to work for sufferers of long COVID .”
The year 2022 finally saw the COVID pandemic petering out, largely through the less-lethal but still highly contagious Omicron variant. Significant strides were made in cancer and Alzheimer’s research, although not without controversy. Amid growing public healthcare challenges in South Africa, the NHI Bill advanced closer to reality.
As Omicron displayed greatly reduced severity compared to prior strains, South African medical experts were some of the first to justify no longer being at ‘code red’. This brought an end to the cycles of lockdowns and travel restrictions characterised by the two previous years.
A number of key medical advances were made during the year for a variety of conditions. Studies showed that administering steroids after COVID hospitalisation with severe inflammation reduced mortality up to one year post-infection.
COVID was found to be linked to a spate of new-onset Type 1 diabetes, but this may just have been due to medical checkups as a result of developing COVID. The rheumatoid arthritis drug auranofin was found to relieve diabetes symptoms. And research suggested a possible way to deliver insulin and cancer drugs orally, by adding a ‘tag’ that lets them enter the bloodstream through the intestines.
The fields of cancer and Alzheimer’s research was rocked by findings of numerous red flags. This controversy did not stop real progress: the first new drug that had any real effectiveness against Alzheimer’s disease was confirmed in a historic trial. Fortunately, the flu jab also seems to protect against developing the disease. Indeed, serious infections appear to increase the risk of both Alzheimer’s and Parkinson’s.
In advanced ER-positive, HER-2 negative breast cancers, the new drug capivasertib halved the rate of progression.
Despite lessons learned in the COVID pandemic, South Africa saw the progression of systemic problems in healthcare such as a critical shortage of nurses. Dr Tim de Maayer’s open letter on appalling conditions at Rahima Moosa exposed deep-seated problems in Gauteng’s public healthcare system. This was followed by the shock resignation of top cancer surgeon Professor Carol-Ann Benn. The appointment of Nomantu Nkomo-Ralehoko as Gauteng Health MEC should hopefully change the province’s situation.
In a new Journal of the American Chemical Society paper, researchers describe how they are developing a new way for diabetes and cancer patients to manage their conditions by enabling drugs to be delivered in pill form instead of through injections.
Some drugs for these diseases are water soluble, so transporting them through the intestines, is not feasible and makes them impossible to administer orally. However, UCR scientists have created a chemical “tag” that can be added to these drugs, allowing them to enter blood circulation via the intestines.
This tag is composed of a small peptide. “Because they are relatively small molecules, you can chemically attach them to drugs, or other molecules of interest, and use them to deliver those drugs orally,” said research leader Min Xue, UC Riverside chemistry professor.
Xue’s laboratory was testing something unrelated when the researchers observed these peptides making their way into cells.
“We did not expect to find this peptide making its way into cells. It took us by surprise,” Xue said. “We always wanted to find this kind of chemical tag, and it finally happened serendipitously.”
This observation was unexpected, Xue said, because previously, the researchers believed that this type of delivery tag needed to carry positive charges to be accepted into the negatively charged cells. Their work with this neutral peptide tag, called EPP6, shows that belief was not accurate.
Testing the peptide’s ability to move through a body, the Xue group teamed up with Kai Chen’s group in the Keck School of Medicine at the University of Southern California and fed the peptide to mice. With PET scans, the team observed the peptide accumulating in the intestines, and documented its ultimate transfer into the animals’ organs via the blood.
Having proven the tag successfully navigated the circulatory systems through oral administration, the team now plans to demonstrate that the tag can do the same thing when attached to a selection of drugs. “Quite compelling preliminary results make us think we can push this further,” Xue said.
Many drugs, including insulin, must be injected. The researchers are hopeful their next set of experiments will change that, allowing them to add this tag to a wide variety of drugs and chemicals, changing the way those molecules move through the body.
“This discovery could lift a burden on people who are already burdened with illness,” Xue said.
A new study suggests the possibility that children born after use of a fertility procedure known as frozen-thawed embryo transfer may have a slightly higher risk of cancer than children born through other means. The researchers presented their findings in PLOS Medicine.
In assisted reproductive technology (ART) a doctor may immediately transfer a fertilised embryo to the uterus, or, in a practice that is increasing worldwide, the embryo might be frozen and later thawed before implantation. Prior research suggests that children born after frozen-thawed transfer may have higher short-term risk of certain medical issues than children born after fresh embryo transfer. However, potential long-term medical risks have been less clear.
To better understand these risks, Nona Sargisian of the University of Gothenburg, Sweden, and colleagues analysed medical data from nearly 8 million children in Denmark, Finland, Norway, and Sweden. Of these, 171 744 were born after the use of ART, and of these, 22 630 were born after frozen-thawed transfer.
Analysis showed that children born after frozen-thawed embryo transfer were at higher risk of cancer than children born after fresh embryo transfer and those without ART. When analysed as a single group (ie, those born after frozen-thawed transfer and fresh embryo transfer), however, the use of any type of ART did not have an increased risk of cancer. The most common types of cancer seen in this study were leukaemia and tumours of the central nervous system.
The researchers stress caution in interpreting the results due to the low number of cancer cases (48) in children born from frozen-thawed embryo transfer.
Nonetheless, the findings may raise concerns about frozen-thawed embryo transfer. Future research will be needed to confirm a possible link between the procedure and increased risk of cancer, as well as any biological mechanisms that may underlie such risk.
Coauthor Ulla-Britt Wennerholm added, “A higher risk of cancer in children born after frozen-thawed embryo transfer in assisted reproduction, a large study from the Nordic countries found. The individual risk was low, while at a population level it may have an impact due to the huge increase in frozen cycles after assisted reproduction. No increase in cancer was found among children born after assisted reproduction techniques overall.”
A new study published in Nature Biotechnology identifies risks in the use of CRISPR gene editing, which is employed in a number of therapies. Looking at its use in T cells, the researchers detected a loss of genetic material in a significant percentage – up to 10% of the treated cells. They explain that such loss can lead to destabilisation of the genome, which might cause cancer.
The study was led by Drs Adi Barzel, Dr Asaf Madi and Dr Uri Ben-David at Tel Aviv University.
Developed about a decade ago, CRISPR cleaves DNA sequences at certain locations in order to delete unwanted segments, or alternately repair or insert beneficial segments. It has already proved impressively effective in treating a range of diseases – cancer, liver diseases, genetic syndromes, and more. In 2020 at the University of Pennsylvania, the first approved clinical trial ever to use CRISPR took T cells from a donor, and expressed an engineered receptor targeting cancer cells, while using CRISPR to destroy genes coding for the original receptor – which otherwise might have caused the T cells to attack cells in the recipient’s body.
In the present study, the researchers sought to examine whether the potential benefits of CRISPR therapeutics might be offset by risks resulting from the cleavage itself, assuming that broken DNA is not always able to recover.
Dr Ben-David and his research associate Eli Reuveni explained: “The genome in our cells often breaks due to natural causes, but usually it is able to repair itself, with no harm done. Still, sometimes a certain chromosome is unable to bounce back, and large sections, or even the entire chromosome, are lost. Such chromosomal disruptions can destabilise the genome, and we often see this in cancer cells. Thus, CRISPR therapeutics, in which DNA is cleaved intentionally as a means for treating cancer, might, in extreme scenarios, actually promote malignancies.”
To examine the extent of potential damage, the researchers repeated the 2020 Pennsylvania experiment, cleaving the T cells’ genome in exactly the same locations – chromosomes 2, 7, and 14. Using single-cell RNA sequencing, they analysed each cell separately and measured the expression levels of each chromosome in every cell.
They detected a significant loss of genetic material in some of the cells. For example, when chromosome 14 had been cleaved, about 5% of the cells showed little or no expression of this chromosome. When all chromosomes were cleaved simultaneously, the damage increased, with 9%, 10%, and 3% of the cells unable to repair the break in chromosomes 14, 7, and 2 respectively. The three chromosomes did differ, however, in the extent of the damage they sustained.
Dr Madi and his student Ella Goldschmidt explained: “Single-cell RNA sequencing and computational analyses enabled us to obtain very precise results. We found that the cause for the difference in damage was the exact place of the cleaving on each of the three chromosomes. Altogether, our findings indicate that over 9% of the T-cells genetically edited with the CRISPR technique had lost a significant amount of genetic material. Such loss can lead to destabilisation of the genome, which might promote cancer.”
Based on their findings, the researchers caution that extra care should be taken when using CRISPR therapeutics. They also propose alternative, less risky, methods, for specific medical procedures, and recommend further research into two kinds of potential solutions: reducing the production of damaged cells or identifying damaged cells and removing them before the material is administered to the patient.
Dr Barzel and his PhD student Alessio Nahmad conclude: “Our intention in this study was to shed light on potential risks in the use of CRISPR therapeutics,” adding that as scientists, they “examine all aspects of an issue, both positive and negative, and look for answers.”
A study published in the JAMA Oncology looking at the correlation between daily insulin dose and cancer incidence among patients with type 1 diabetes has found that higher insulin dose is positively associated with cancer incidence and that the association is stronger among those with insulin resistance.
“In patients with type 1 diabetes, our results show that traditional metabolic factors such as obesity (represented by body mass index), sugar control (by Haemoglobin A1c), and blood pressure control do not associate with cancer incidence,” study leader Dr Yuanjie Mao Mao said. “However, cancer incidence was higher for those who took larger dose of insulin. Our results implied that clinicians might need to balance the potential cancer risk when treating patients with type 1 diabetes on a high daily insulin dose or that improving insulin sensitivity may be preferred than simply increasing the insulin dose.”
To conduct the study, Dr Mao collaborated with Wenjun Zhong, PhD, an epidemiologist of Merck Research Labs, to analyse the associations of more than 50 common risk factors in 1303 patients with type 1 diabetes whose data were collected over 28 years. A variety of databases were drawn upon and analysed, including he Diabetes Control and Complications Trial (DCCT.) which was was a controlled clinical trial originating with 1441 patients with type 1 diabetes who were randomised into conventional diabetes therapy or intensive therapy to assess whether reducing hyperglycaemia would decrease the risk of complications of type 1 diabetes.
Mao also found that age and sex are associated with cancer incidence when evaluated separately and that a daily insulin dose posed a higher risk of cancer than age, especially a higher insulin dose. According to the paper, when the daily insulin dose is classified into three groups, low: less than 0.5; medium: greater than or equal to 0.5 or lower than 0.8; and high: greater than or equal to 0.8 units/kg per day, the hazard ratios were significantly higher in the high dose versus the low dose group. Cancer incidence was 2.11, 2.87, and 2.91 per 1000 persons in the low, medium, and high insulin dose groups, respectively.
He went on to explain that specifically, women carry a higher risk than men; however, it was unclear what risk factors may contribute to the higher cancer incidence in type 1 diabetes.
“We know that people with type 1 diabetes have a higher incidence of cancer compared to people without diabetes,” Liz Beverly, Ph.D. co-director of the diabetes institute and professor in the Heritage College, said. “Dr. Mao’s research identifies a potential mechanism to explain this association. His findings will lead to continued research in this area and potential policy changes in cancer screening and insulin dosing recommendations.”
Although previous studies have concluded that patients with diabetes have a higher risk of cancer in general, this is the first study to explore the associated cancer incidence factors in type 1 diabetes.
“Type 1 diabetes accounts for an estimated five to 10 percent of all diabetes cases, and recent studies in type 1 diabetes also found a higher incidence of certain cancers such as stomach, liver, pancreas, endometrium and kidney cancers in the population compared with the general population,” Mao explained. “Whereas, in type 2 diabetes, increased risk is attributed to metabolic factors such as obesity, chronic inflammation status, and insulin resistance.”
Although the results of the study suggest that the higher the dose of insulin, the higher the cancer incidence, Dr Mao says further investigation is still necessary.
Researchers have identified a key signalling molecule for cancer metastasis. one which is already known for its involvement in atherosclerosis, suggesting a possible treatment approach for both diseases simultaneously. The discovery was published in the International Journal of Cancer.
In order to become malignant, metastasising cancer, tumour cells undergo a series of transformations involving interactions with the immune system. Growing evidence exists that in tumour progression to metastasis, inflammation of blood vessel-lining endothelial cells is a key process.
A team of researchers led by Professor Kyoko Hida at Hokkaido University have discovered that, in malignant tumours, endothelial cells accumulate low-density lipoprotein (LDL) and neutrophils. Neutrophils are immune suppressor cells which are known to contribute to tumour progression.
Previous work by the team had revealed that blood vessels in malignant tumorus expressed a high level of proteoglycans, and it is known that cancerous tissue is inflamed – similar to what is seen in atherosclerosis.
The research team showed that metastasising tumors, in contrast to non-metastasising ones, accumulate proteoglycan molecules; these, in turn, attach to and accumulate LDL to the walls of blood vessels, where it becomes oxidised. There are also high levels of its receptor, LOX-1, in the blood vessel-lining endothelial cells of metastasising tumours. This, they found, causes these cells to produce inflammation signals that attract neutrophils. Using a mouse model, they proved that the suppression of LOX-1 can significantly reduce tumour malignancy, and also that LOX-1 overexpression caused an increase in signalling molecules attracting neutrophils.
This sequence of interactions observed in malignant tumours is not novel: it occurs in atherosclerosis. “Atherosclerosis and cancer appear to be completely different diseases, but they share several common pathophysiological features in the blood vessels,” said Prof Hida.
Though some questions remain, especially on the mechanism of how neutrophils contribute to cancer malignancy, this study is the first to explicitly prove the mechanistic commonalities between cardiovascular disease and cancer progression and trace the mechanism involving LDL accumulation and LOX-1 expression in in vivo tumour tissue.
“Our present study focused on the importance of LOX-1 in endothelial cells as a common factor between cancer and atherosclerosis,” Prof Hida explained. “The presence of neutrophils in tumours is a telltale sign of tumor progression.”
The study also points to a promising approach for treating and preventing malignant cancer (and cardiovascular disease) by targeting neutrophil recruitment to endothelial cells. Prof Hida concluded: “The number of patients with cancer who die not of cancer, but of cardiovascular events, is increasing. Targeting the LOX-1/oxidised LDL axis might be a promising strategy for the treatment of the two diseases concomitantly.”
