Tag: cancer

Categories : CancerTags :

Electromagnetic Fields Could Inhibit Breast Cancer Cell Spread

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A new study has shown that electrical fields can slow, and in some cases halt, the spread of breast cancer cells through the body.

The research also found how electromagnetic fields (EMFs) have the ability to hinder the number of cancer cells that can spread. Pulsed EMFs have also been shown to have some effectiveness in pain management, and low level EMFs were shown also to reduce blood glucose in animal models, a possible first step to treating diabetes.

“We think we can hinder metastasis by applying these fields, but we also think it may be possible to even destroy tumours using this approach,” said senior author Vish Subramaniam, former professor of mechanical and aerospace engineering at The Ohio State University. Subramaniam retired from Ohio State in December.

“That is unclear at this stage, but we are working on understanding that – how big should the electromagnetic field be, how close should it be to the tumour? Those are the next questions we hope to answer,” he said.
Subramaniam said that this had the effect of the EMF is to slow down some of the cancer cells. “It makes some of them stop for a little while before they start to move, slowly, again. As a group, they appear to have split up. So how quickly the whole group is moving and for how long they are moving becomes affected.”

The effect was applied to human cancer cells in vitro and has not been applied in humans.

The EMFs seem to selectively slow down the cancer cells’ metabolism by affecting the electrical fields inside the individual cells—completely noninvasively and without side effects like ionising radiation, which would mean a revolutionary form of cancer treatment if it could be made to work in practice. This ability to access a cell’s internal workings is new to the study of how cancer metastasises, said Prof  Subramaniam.

“Now that we know this, we can start to answer other questions, too,” Subramaniam said. “How do we affect the metabolism to the point that we not only make it not move but we choke it, we completely starve it. Or can we slow it down to the point where it will always remain weak?”

Source: News-Medical.Net

Journal information: Jones, T.H., et al. (2021) Directional Migration of Breast Cancer Cells Hindered by Induced Electric Fields May Be Due to Accompanying Alteration of Metabolic Activity. Bioelectricity. doi.org/10.1089/bioe.2020.0048.

Categories : Cancer PaediatricsTags :

Delaying Lumbar Puncture Cuts Relapse in Childhood Leukaemia

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Commencing chemotherapy several days before the first lumbar puncture for diagnosis and treatment of acute lymphoblastic leukaemia (ALL) may lower the risk of central nervous system (CNS) relapse in children, according to a study from St Jude Children’s Research Hospital and collaborators in China. 

“This study identified factors to help us predict and better manage the risk of CNS relapse that will be useful for treating ALL patients worldwide, in both resource-rich and resource-limited countries,” said corresponding author Ching-Hon Pui, MD, chair of the St. Jude Department of Oncology. Dr Pui pioneered paediatric ALL treatment that has achieved 94% long-term survival for St. Jude patients that did not receive brain irradiation.

Using an adapted paediatric protocol from St Jude Hospital, 7640 children and adolescents across 20 Chinese hospitals were enrolled in the trial. However, there was a great disparity across the hospital settings. For example, just three of the hospitals offered total intravenous anaesthesia for children undergoing spinal taps, while only two had flow cytometry for the diagnosis of leukaemia cells in cerebrospinal fluid.

The five-year overall survival rate was 91% for study patients, and the cancer-free survival rate was 80%, which is a dramatic improvement over previous clinical trials in China. But 1.9% of patients relapsed in the CNS alone, and in another 2.7% of patients the relapse involved the CNS. In comparison, a Canadian study reported a 6.6% rate for CNS-involved relapse in paediatric ALL patients followed over 10 years.

According to Dr Piu, in order to increase the survival rate of paediatric ALL patients requires identifying those at risk for CNS relapse, along with increasing their quality of life. Three factors reduced the risk of CNS relapse. First, commencing dexamethasone a few days before the spinal tap, prevents leukaemia cells entering the cerebrospinal fluid (CSF). Second, intravenous anaesthesia reduced bleeding risk during lumbar punctures, and improved  intrathecal therapy. Third, flow cytometry enables more accurate diagnosis of leukaemia cells in CSF, and reduced CNS relapse.

Source: Medical Xpress

Journal information: Jingyan Tang et al. Prognostic Factors for CNS Control in Children with Acute Lymphoblastic Leukemia Treated Without Cranial Irradiation, Blood (2021). DOI: 10.1182/blood.2020010438

Categories : CancerTags :

Natural ‘Brake’ Keeps Neuroblastomas Benign

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Researchers have found that a signal molecule produced by Schwann cells found in benign neuroblastomas acts as a natural ‘brake’ keeping them benign and preventing their uncontrolled growth. This also works on malignant neuroblastoma cultures. 

While energising a tumour with a growth factor to halt it does not sound logical, with neuroblastomas the Schwann cells trigger the maturation of nerve cells and bring the growth to a halt.

Schwann cells produce a signalling molecule called epidermal growth factor like 8 (EGFL8). The researchers showed that EGFL8 stimulates the differentiation, or maturation, of neuroblastoma cells. “Until recently, we only knew that this protein existed, but its function was not known. We now for the first time know where EGFL8 is produced and how it acts,” explained study author Sabine Taschner-Mandl, PhD, head of the Tumor Biology Group at St. Anna Children’s Cancer Research Institute. The study results also showed that high levels of EGFL8 were linked to improved survival rates in neuroblastoma patients.

“In cell cultures, we have demonstrated that Schwann cells as well as their secreted signaling molecules exert anti-tumour effects, even in aggressive neuroblastoma cells. Thus, we are able to exploit a process that occurs naturally in benign neuroblastomas to stop the malignant ones,” Sabine Taschner-Mandl and her colleague Tamara Weiss, PhD, from the Medical University of Vienna, explained. 

However, there is still much to be discovered about how the interplay of Schwann cells with the rest of the body; currently the researchers are examining how they interact with immune cells.

The study also uncovered a significant finding: that Schwann cells in benign neuroblastomas have a similar cellular status to those that support healing in injured peripheral nerves. Schwann cells in the tumour were found to express repair-associated genes and demonstrated repair functions. “It is amazing that we have discovered a signalling molecule that plays a role in both tumour development of benign neuroblastomas and regeneration of injured nerves. Since EGFL8 stimulates the formation of nerve cell extensions, it could be of great importance for the treatment of injured nerve fibers”, said Tamara Weiss.

Source: Medical Xpress

Journal information: Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor like protein 8, Nature Communications (2021). DOI: 10.1038/s41467-021-21859-0

Categories : Cancer Environmental EffectsTags :

Brominated Flame Retardants May Raise Breast Cancer Risk

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Brominated flame retardants (BFRs) are present in a wide variety of household fixtures and furniture, and particles of this may increase the risk of breast cancer through prolonged exposure at critical times in a woman’s life.

BFRs are endocrine disruptors, and since they are not tightly bound to the substances they are included into, they are able to escape into the household environment. Endocrine disruptors can be problematic to protect against since they can exert harmful effects even at low doses. Exposure to endocrine disruptors is most disruptive in the foetal stage and during infancy; these compounds also easily cross the placental boundary and are found in breast milk. At high exposures, cells have a toxic response, but at a low dose, similar to the levels of naturally occurring hormones, endocrine dysregulation is the outcome.

Exposure to these compounds can cause problems for organs such as mammary glands, which are sensitive to hormones, which BFRs can mimic. “BFRs pose a significant risk, particularly during sensitive periods, from intrauterine life to puberty and during pregnancy,” said Professor Plante, co-director of the Intersectoral Centre for Endocrine Disruptor Analysis and environmental toxicologist.

The researchers exposed female rodents to a mixture of BFRs, similar to that found in house dust, prior to mating, during gestation and during lactation. Biologists were able to observe the effects on the offspring at two stages of development and on the mothers.

Early development of mammary glands was seen in prepubertal rats. For pubescent rats, the results, published in 2019, showed a deregulation of intercellular communication. Similar effects were observed in female genitors in a 2017 study. All of these effects are associated with an increased risk of breast cancer.

In the early 2000s, observation showed that human exposure to BFRs peaked, Professor Isabelle Plante pointed out. “Young women exposed to BFRs in utero and through breastfeeding are now in the early stages of fertility. Their mothers are in their fifties, a period of increased risk for breast cancer,” said Prof Plante. This is why the team is currently studying endocrine disruptors related to a predisposition to breast cancer, funded by the Breast Cancer Foundation and the Cancer Research Society.

In all three studies, most of the effects were observed at a low dose, raising questions about the current legislation for endocrine disruptors. “To evaluate the ‘safe’ dose, experts give an increasing dose and then, when they observe an effect, identify it as the maximum dose. With endocrine disruptors, the long-term consequences would be caused by lower doses,” reported Prof Plante.

Source: Medical Xpress

Journal information: Rita-Josiane Gouesse et al, In Utero and Lactational Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants Induces a Premature Development of the Mammary Glands, Toxicological Sciences (2020). DOI: 10.1093/toxsci/kfaa176

Categories : Cancer New Compounds and TreatmentsTags :

Novel Glioblastoma Drug Can Cross The Blood-brain Barrier

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An experimental spherical nucleic acid (SNA) drug was able to penetrate the blood-brain barrier and trigger glioblastoma tumour cell death in an early clinical trial.

Glioblastoma is the most common and aggressive brain tumour, accounting for 16% of cases. It affects 3.2 per 100 000 people, at an average age of 64 years although it can appear at any time.

The new drug, NU-0129, is the first SNA drug developed for systemic use. The SNA groups RNA or DNA around a nanoparticle. A revolutionary new class of drugs, it can be adapted to a number of neurological diseases such as Parkinson’s.

“We showed the drug, NU-0129, even at very small doses, causes tumour cells to undergo what’s called apoptosis or programmed cell death,” said lead investigator Dr Priya Kumthekar, associate professor of neurology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. “It’s a remarkable finding in humans that confirms what we had previously seen in our animal studies.”

The study participants received the drug intravenously prior to surgery to remove the tumour. The researchers team studied the tumours to determine how well the drug crossed the blood-brain barrier and its effect on their cells.

“This unique 3D design has the ability to infiltrate tumor cells to correct the genes inside and make them susceptible for therapy-induced killing,” said senior author Alexander Stegh, an associate professor of neurology at Northwestern.

Unusually, the drug was developed entirely within the university without involving pharmaceutical licensing.
“We want to move the technology forward as quickly as possible because there are patients with a disease with no current cure,” Kumthekar said.

Dr Leon Platanias, director of the Lurie Cancer Center, said, “These exciting findings for the first time support the potential of spherical nucleic acids for drug delivery to brain tumors. They may prove to have important long-term translational implications for the treatment of these tumours.”

Source: Medical Xpress

Journal information: P. Kumthekar el al., “A first-in-human phase 0 clinical study of RNA interference–based spherical nucleic acids in patients with recurrent glioblastoma,” Science Translational Medicine (2021). stm.sciencemag.org/lookup/doi/ … scitranslmed.abb3945

Categories : CancerTags :

No Survival Benefit Seen for PD-1 Inhibitor in Triple-negative Breast Cancer

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Results of a large randomised trial showed no survival improvement in previously treated metastatic triple-negative breast cancer (TNBC) with single-agent pembrolizumab versus chemotherapy.

Eric Winer, MD, of Dana-Farber Cancer Institute in Boston, presented findings from his team’s randomised trial KEYNOTE-119, which compared pembrolizumab monotherapy versus single-agent chemotherapy as second or third-line therapy for metastatic TNBC. Investigators randomised 622 patients to the two treatment arms. The primary analysis in patients with a PD-L1 combined positive score (CPS) ≥10 showed a median overall survival (OS) of 12.7 months with pembrolizumab and 11.6 months with investigator’s choice of chemotherapy. No significant advantage for pembrolizumab was seen in analyses of patients with CPS ≥1 and the overall population. 

Pembrolizumab led to fewer grade 3/4 treatment-related adverse events (TRAEs). The most common grade 3/4 TRAEs all  more often with chemotherapy, with serious AEs occurring in 20% of each group.
After a median follow-up of 31 months, analysis of the CPS ≥10 subgroup showed the pembrolizumab arm had a non-significant 22% reduction in the survival hazard. The CPS ≥1 analysis yielded median OS values of 10.7 months for the pembrolizumab arm and 10.2 months for the chemotherapy arm. Analysis of the overall population showed a median OS of 9.9 months with pembrolizumab and 10.8 months with chemotherapy. There was some evidence from a post hoc exploratory analysis that pembrolizumab activity might increase with higher CPS values.

“These findings might inform future research of pembrolizumab monotherapy for selected subpopulations of patients, especially those with PD-L1-enriched tumours, and inform a combinatorial approach for the treatment of patients with metastatic triple-negative breast cancer,” the researchers concluded.

The findings are consistent with the history of single-arm anti-PD-1/L1 therapy for breast cancer, said Eitan Amir, MD, and David W Cescon, MD, PhD, both of Princess Margaret Cancer Center in Toronto. In all types of breast cancer, checkpoint inhibitors have produced low response rates, but this has been consistent.

“Given the low response rates observed in the overall population with pretreated triple-negative breast cancer in previous studies of anti-PD-1 or anti-PD-L1 monotherapy, the primary results of KEYNOTE-119 are unsurprising,” they wrote. “Since KEYNOTE-119 was launched, clinical development has focused principally on combinations of chemotherapy and immunotherapy in the first-line setting.”

Drs Amir and Ceson cautioned that the results of the post hoc analysis are intriguing but must be treated with caution.

“The finding that this higher PD-L1 expression threshold might be a predictor of pembrolizumab monotherapy benefit adds to previously observed associations with single-drug immunotherapy benefit, including de novo metastatic disease, absence of previous chemotherapy, normal lactate dehydrogenase, lung or nodal involvement, and absence of liver metastases […] . It would be intriguing to see if similar results can be validated in triple-negative breast cancer,” Amir and Cescon added.

Source: MedPage Today

Categories : Cancer General InterestTags :

Impact of French Nuclear Testing Underestimated

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A new report has found that the extent of radiation exposure to people involved in nuclear testing in French Polynesia has been significantly underestimated.

Over 1966 to 1996 at Moruroa and Fangataufa atolls in French Polynesia, France conducted An unofficial report has gone through thousands of recently declassified documents, focusing on the impact of three key nuclear tests: Aldébaran, Encelade and Centaure in 1966, 1971 and 1974.
The report suggests that the French government has underestimated fallout by as much as 40%, opening the door for tens of thousands more to claim compensation.

One millisievert (mSv) per annum is the maximum allowable public exposure. There is clear evidence for radiation effects at doses over 100mSv, while doses less than 10mSv are undetectable even in very large epidemiological studies and such low dose effects on human health are controversial. According to the linear-no dose-threshold (LNT) theory, all radiation exposure carries some level of harm.

Last February, a report was sent from Paris to French Polynesia on a cluster of cancers uncovered there, believed to be linked to radiation exposure . Email evidence suggests that at least 2000 of the 6000 military personnel involved in the tests had contracted at least one form of cancer.
It was only in 2010 that France established a compensation claims board for people with one of 23 cancers associated with radiation and who lived in French Polynesia at the time of the tests. However, many claimants do not have the means to access these claims, such as those who live on remote islands.

Faulty and imprecise monitoring equipment impacted the results, which were used to calculate the original dose calculations. The researchers recalculated the estimated doses absorbed by the population based on samples taken by the military at the time, and also using new methods involving meteorological data to plot the spread of radioactive fallout. Some recalculations did not show much change, but a 1966 test produced a level three times higher than the official estimate. Some 11 000 people exposed to the nuclear testing received a dose higher than 5mSv, the researchers found.

Source: The Guardian

Categories : Cancer Metabolic DisordersTags :

‘Obesity Paradox’ in Kidney Cancer Continues to Mystify

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Obese patients with metastatic renal cell carcinoma (RCC) were more likely to survive compared to their normal weight counterparts when receiving immune checkpoint inhibitors (ICI), a study has shown.

RCC is the most deadly of the urogenital cancers, and its incidence is increasing. Males are twice as likely as females to develop it.
A team of researchers including Toni Choueiri, MD, of Dana-Farber Cancer Institute in Boston, conducted an analysis of 735 metastatic RCC patients who received PD-1/L1 immunotherapies. 

Those with a BMI of 25 or greater had significantly longer overall survival (OS), with 1-year rates of 79% versus 66% for those with a BMI below that cutoff. This relationship was observed across tumour categories.

“These findings are consistent with the obesity paradox that was previously seen during the VEGF-targeted therapy era,” the team noted.

“Several hypotheses have attempted to explain this clinical observation in RCC,” Choueiri’s team wrote. “Low fatty acid synthase gene expression, which is inversely correlated with BMI, was associated with longer OS in VEGF-treated patients. Transcriptomic analysis suggests that patients with obesity have tumors with increased angiogenesis gene signatures and peritumoral adipose tissues with increased hypoxia, inflammation, and immune cell infiltration signatures.”

In 319 patients with next-generation sequencing technology, there was no difference between groups for tumour mutation burden, at an average 6.8 mutations per megabase for the low and high BMI groups. Genomic alteration frequency analysis also picked up no differences.

Limitations of the study authors included its retrospective nature, incomplete gene-expression profiling, and between-group imbalances. Patients with higher BMI had greater odds of having better performance status and being in more favourable risk groups, had greater odds of having clear cell histology, having had prior nephrectomy, and having received a checkpoint inhibitor as first-line therapy.

Source: MedPage Today

Journal information: AKA Lalani, et al “Assessment of immune checkpoint inhibitors and genomic alterations by body mass index in advanced renal cell carcinoma” JAMA Oncol 2021; DOI: 10.1001/jamaoncol.2021.0019.

Categories : CancerTags :

Lower Mobility Linked to Increased Cancer Mortality

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A retrospective study examining the difference in physical mobility between cancer survivors and those never diagnosed with cancer shows that poor mobility is strongly associated with mortality.

The beneficial role of physical activity in preventing cancer is well known, effects of exercise during and after cancer treatment are less well explored.  Common cancers diagnosis and treatment has been shown to be linked to poor functional health, but association for other cancers is less well understood.

“Given that cancer survivors are living longer than ever, understanding how the diagnosis and treatment of a broad range of cancers may affect ambulatory function–a potentially modifiable risk factor–could lead to new treatment and rehabilitation strategies to improve the health of these patients,” explained Elizabeth Salerno, PhD, MPH, assistant professor of surgery at Washington University School of Medicine.

Using data from self-reported questionnaires from the National Institutes of Health American Association of Retired Persons (AARP) Diet and Health Study, Dr Salerno and her team compared 30 403 cancer survivors to 202 732 individuals with no cancer diagnosis.

They found that cancer survivors were 42% more likely to walk at a slower pace than those without cancer diagnosis, and 24% more likely to have mobility disability after adjusting for factors such as weight. Those with slower walking or mobility disability were at greater risk for cancer-specific and all-cause mortality. The strongest association was seen for oral and respiratory cancers. Cancer survivors also had a stronger association with mortality and slower walking speeds than those without cancer diagnosis.

“Our findings suggest that functional health may be adversely affected by a broad range of cancer diagnoses and may be an important determinant for survival,” said Dr Salerno. “There is still much to be learned about these complex relationships, but our results highlight the potential importance of monitoring, and even targeting, ambulatory function after cancer for survival benefits, particularly in older cancer survivors.”

Salerno’s team will try to determine why some cancers were more associated with reduced mobility and mortality. “More information about behavioral, biological, and cancer-specific factors from before, during, and after diagnosis and treatment will be important to better characterize these associations in specific cancer types,” she said.

Source: Eureka Alert

Categories : Cancer Immune SystemTags :

New Biomarker Can Predict Response to Checkpoint Inhibitor Therapy

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A team of researchers at Roswell Park Comprehensive Cancer Center have identified a biomarker that could be used to predict how well immune checkpoint inhibitors will be tolerated.

Immune checkpoint inhibitors (ICI) activate anti-tumour defences either through the disruption of inhibitory interactions between antigen-presenting cells and T cells at so-called checkpoints or else through the stimulation of activating checkpoints. Not all patients can tolerate ICI well; side effects can be severe, including colitis, which is one of the most common.

Pre-treatment biomarkers are of limited value in predicting response to ICI. Tumour biopsy shortly after ICI therapy is started can provide helpful information, but is invasive and difficult to do in some certain cancers.
Uncovering blood-based biomarkers that reflect the change of the tumour microenvironment and can predict a patient’s response to ICIs could improve current treatment regimens significantly, Dr. Ito notes. The team’s previous research indicates that T cells with varying levels of the chemokine receptor CX3CR1 responded differently to ICI therapy.

Based on those findings, the researchers sought to test CX3CR1 as a T cell biomarker in ICI therapy. They found that ICI therapy is linked to increased frequency and clonality of some CX3CR1-positive T cells; that the frequency of these CD8+ T cells stays high during ICI therapy; and that there are many genomic similarities between CD8+ tumour-infiltrating lymphocytes and this subset of CX3CR1-positive T cells.

Fumito Ito, MD, PhD, FACS, explained: “Although ICIs revolutionized the cancer treatment for significant numbers of people, many cancer patients do not respond to them, and some develop severe toxicity.”

“Currently, we are in need of a better biomarker to predict the response to immunotherapy, which is part of standard treatment in advanced and metastatic lung cancer,” said Hongbin Chen, MD, PhD. “This study sheds light on a promising blood-based biomarker that is potentially very useful in identifying which patients with lung cancer are most likely to benefit from immunotherapy. We look forward to investigating its utility in further clinical research.”

Source: News-Medical.Net

Journal information: Yamauchi, T., et al. (2021) T-cell CX3CR1 expression as a dynamic blood-based biomarker of response to immune checkpoint inhibitors. Nature Communications.doi.org/10.1038/s41467-021-21619-0.