Category: Cancer

Categories : Ageing Cancer Mental HealthTags :

Loneliness in Middle-aged Men Tied to Cancer Risk

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Older man sitting alone on beach. Photo by Engin Akyurt from Pexels

A recent study by the University of Eastern Finland shows that loneliness among middle-aged men is associated with an increased risk of cancer.

Cancer is the second leading cause of death around the world, and in high-income countries it has become the main cause. Recent scientific evidence demonstrates that stress plays a positive role in cancer initiation, progression and cancer metastasis, as well as a negative role for anti-tumor immune function and therapy response.

“It has been estimated, on the basis of studies carried out in recent years, that loneliness could be as significant a health risk as smoking or overweight. Our findings support the idea that attention should be paid to this issue,” said project researcher Siiri-Liisi Kraav from the University of Eastern Finland.

The study was launched in the 1980s with middle-aged men from eastern Finland participating. To avoid reverse causality, individuals who already had a cancer diagnosis or received a cancer diagnosis within two years after the baseline data collection were excluded from the analysis. The  2570 eligible participants had their health and mortality monitored on the basis of register data through to the present. Follow-up lasted an average of 20.44 years, and the average age of cancer diagnosis was 69.96 years.
Factors accounted for included age, socio-economic status, lifestyle, sleep quality, depression symptoms, body mass index, heart disease and other risk factors.

During the follow-up, 649 men (25% of participants) developed cancer, and 283 men (11%) died of cancer. Loneliness was associated with a roughlt 10% increased cancer risk. In addition, cancer mortality was higher in cancer patients who were unmarried, widowed or divorced at baseline.
Based on these results, the researchers recommended that consideration of loneliness and social relationships should be an important part of comprehensive health care and disease prevention. The findings were published in Psychiatry Research.

“Awareness of the health effects of loneliness is constantly increasing. Therefore, it is important to examine, in more detail, the mechanisms by which loneliness causes adverse health effects. This information would enable us to better alleviate loneliness and the harm caused by it, as well as to find optimal ways to target preventive measures,” concluded Kraav.

Source: University of Eastern Finland

Journal information: Kraav, S., Lehto, S.M., Kauhanen, J., Hantunen, S., Tolmunen, T., 2021. Loneliness and social isolation increase cancer incidence in a cohort of Finnish middle-aged men. A longitudinal study. Psychiatry Research: https://doi.org/10.1016/j.psychres.2021.113868

Categories : CancerTags :

Avocado Compound May Be Useful in Leukaemia Therapy

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Avocados may be good for more than just an expensive toast topping. According to a new study from the University of Guelph a compound in avocados offers a potential route to improved leukaemia therapy.

The compound in questions targets an enzyme that scientists have identified for the first time as being critical to cancer cell growth, explained Dr Paul Spagnuolo, at the Department of Food Science.

The study focus was on acute myeloid leukaemia (AML), which is the most severe form of leukaemia. Most cases occur in people over age 65, with fewer than 10% of patients surviving five years after diagnosis.

Leukaemia cells have elevated levels of an enzyme called VLCAD involved in their metabolism, said Dr Spagnuolo.

“The cell relies on that pathway to survive,” he said, explaining that the compound is a likely candidate for drug therapy. “This is the first time VLCAD has been identified as a target in any cancer.”

Dr Spagnuolo’s team screened nutraceutical compounds among a variety of compounds, searching for any substance that could inhibit the enzyme. “Lo and behold, the best one was derived from avocado,” said Dr Spagnuolo.

Avocados have already been shown to improve lipid profiles, as well as helping to control weight, likely through increased satiation. His lab previously examined avocatin B, a fat molecule found only in avocados, for potential application in diabetes prevention and obesity management. He’s now keen to see it put to use in leukaemia patients.

“VLCAD can be a good marker to identify patients suitable for this type of therapy. It can also be a marker to measure the activity of the drug,” said Dr Spagnuolo. “That sets the stage for eventual use of this molecule in human clinical trials.”

Around half of patients over 65 diagnosed with AML currently enter palliative care. Some may undergo chemotherapy, but these treatments are often toxic and result in patients dying.

“There’s been a drive to find less toxic drugs that can be used,” he noted.

Referring to earlier work using avocatin B for diabetes, Spagnuolo said, “We completed a human study with this as an oral supplement and have been able to show that appreciable amounts are fairly well tolerated.”
The results of the study were published in the journal Blood.    

Source: Medical Xpress

Journal information: Matthew Tcheng et al, Very long chain fatty acid metabolism is required in acute myeloid leukemia, Blood (2021). DOI: 10.1182/blood.2020008551

Categories : CancerTags :

A Golden Opportunity for Metformin as a Cancer Drug

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In a new study from the National University of Singapore, a new approach to target highly resistant triple-negative breast cancers (TNBCs) has been developed using a gold-metformin prodrug.

Metformin, first approved by the FDA in 1994, is a widely prescribed “over-the-counter” medication for Type 2 diabetes. Some evidence shows that people taking metformin for an extended period have a significantly reduced cancer risk. In spite of evidence of its effects and its low cost, use of metformin as an anticancer agent has serious drawbacks, with poor uptake by cells necessitating repeated high doses to have a therapeutic effect.
A team of researchers led by Prof Ang Wee Han from the Department of Chemistry, National University of Singapore and Prof Maria Babak from City University of Hong Kong came up with a way of chemically conjugating metformin, as well as its analog phenformin. They accomplish this by using a gold-based active molecular fragment to increase bioavailability and achieve synergistic action of the two key components (metformin and gold molecules). 

The electrochemical activity of the gold-based molecule,enabled the team to successfully deliver metformin into cancer cells with high selectivity. The lead drug candidate, 3met, was found to have an anti-cancer activity over 6000 times higher than regular metformin.

Prof Ang said, “TNBCs represent an especially dangerous subset of breast cancers with the poorest prognosis and limited treatment options. However, this particular aggressiveness of TNBC cells is related to their increased dependence on glucose and lipids, which provide additional energy to sustain rapid cancer growth. Since our drug candidates interfered with energy production in the cancer cells, we hypothesized that TNBCs might be particularly responsive to such treatment.”

In tests with mice, the research team injected the drug candidate into breast tumours at their nipple region and monitored the growth of the tumours. They found that in a drug-treated group, tumour growth completely halted after three weeks, indicating the unique anticancer potential of the drug candidate. 

With an patent application filed for, the research team is actively working on the development of other efficient drugs for the treatment of chemo-resistant cancers.

Source: Medical Xpress

Journal information: Maria V. Babak et al. Interfering with Metabolic Profile of Triple‐Negative Breast Cancer using Rationally‐Designed Metformin Prodrugs, Angewandte Chemie International Edition (2021). DOI: 10.1002/anie.202102266

Categories : CancerTags :

Lipid-wrapped Peptide Sends Chemo Drugs Deep into Tumours

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A study has shown that a peptide wrapped in a fatty liposome capsule can deliver chemotherapy drugs deep into tumour sites.

University of Minnesota researcher Hongbo Pang led a cross-institutional study on improving the efficacy of nucleotide-based drugs against prostate cancer and bone metastasis.  

The researchers looked at whether liposomes (enclosures of fatty molecules), when integrated with the iRGD peptide (which binds strongly to tumour blood vessels), will help concentrate antisense oligonucleotides (ASOs, a type of nucleolytic drug) into primary prostate tumours and its bone metastases.

More importantly, they investigated whether this system helps more drugs across the vessel wall and deeply into the tumor tissue. This is critical because, although nucleotide drugs have unique advantages in treating tumours and other diseases, they often struggle to cross the blood vessels and penetrate the tumour tissue, where their targets reside. Their clinical applicability and efficacy is hampered as a result. Even typical chemotherapeutic agents only penetrate 3-5 cancer cell diameters deep.

“Our system demonstrates a good ability to deliver more ASOs into both primary tumor tissue and bone metastases — which is the primary site for prostate cancer metastasis. This further translates into a significant improvement of ASO efficacy to inhibit the growth of primary tumor and bone metastases,” said study leader Hongbo Pang, assistant professor at the College of Pharmacy, and member of the Masonic Cancer Center. “We expect this system to become a universal carrier system, to improve the clinical efficacy of ASOs and other nucleotide drugs.”

The study found that iRGD-liposomes can increase the tumor accumulation and vascular/tissue penetration of ASOs against the disease-driving gene of prostate cancer. It also found that the ability of ASOs to inhibit primary tumours and bone metastases growth was significantly improved with iRGD-liposomes. A long-term tumour inhibition study was also performed, which showed that iRGD-liposomes significantly extends the AR-ASO suppression of primary tumor growth.

Pang and his team concluded that iRGD-liposomes are proven as a desirable delivery system for ASOs, and could enhance the clinical efficacy of nucleotide drugs in cancer therapies.

Source: News-Medical.Net

Journal information: Guan, J., et al. (2021) iRGD‐Liposomes Enhance Tumor Delivery and Therapeutic Efficacy of Antisense Oligonucleotide Drugs against Primary Prostate Cancer and Bone Metastasis. Advanced Functional Materials. doi.org/10.1002/adfm.202100478.

Categories : CancerTags :

Glioblastoma Induces ‘Stockholm Syndrome’ to Subvert Body’s Defences

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Glioblastoma, an aggressive form of brain cancer, has been found to corrupt immune cells and make the tumour harder to treat.

Most people diagnosed with glioblastoma die in a short period of time after their diagnosis, but some glioblastoma patients see great benefits from chemotherapy and survive beyond expectations. Researchers at the University of Minnesota have revealed the reason for this in a new study published in the Proceedings of the National Academy of Sciences.

“Deciphering the molecular underpinning of these exceptional responses may hold the key to transforming the hope for miracles into the reality of an expected cure for glioblastoma patients,” said lead author Clark C Chen, MD, PhD, Lyle French Chair in Neurosurgery and head of the Department of Neurosurgery at the University of Minnesota Medical School.

Examining the gene expression profiles of glioblastoma samples from approximately 900 glioblastoma patients, the researchers sought to identify unique features associated with exceptional responders, defined as glioblastoma patients who survive more than two years after treatment.

“We utilized different state-of-the-art analytics to study these samples, including methods innovated by Dr. Aaron Sarver, a member of the University of Minnesota Institute of Health Informatics. Impressively, these analytics converged on a single observation, a paucity of microglia and macrophages,” Dr Chen said.

Specialised immune cells, microglia and macrophages act as scavengers, spotting and removing out-of-place cells in healthy brains. They travel to abnormal cancer cell sites to mount a defence, and can form over half the cells in a glioblastoma sample.

“If microglia and macrophages normally fend off cancer cells, more of them should allow the body to better fend off the tumor. So, we expected to see more of them in the exceptional responders; however, we found the contrary,” said Jun Ma, a researcher in the Department of Neurosurgery at the U of M Medical School and a co-first author of this study.

In order to resolve this paradox, the research team then demonstrated that glioblastoma cells can recondition the surrounding microglia and macrophages, corrupting their normal anticancer functions. Where they once fought off cancer growths, these immune cells are now re-programmed by glioblastoma cells to promote tumour growth.

“It is frightening to consider the possibility that cancer cells can ‘brainwash’ our own immune cells and convert them from cells that fight cancer to cells that promote cancer,” said Judith Varner, a co-senior author of the study and professor of pathology at the University of California, San Diego. “Fortunately, we have figured out how glioblastoma cells subvert our immune system and can now reverse this cellular version of the ‘Stockholm syndrome.'”

Stockholm syndrome is characterised as when a captive begins to identify closely with their captors, as well as with their agenda and demands, however there is little evidence for it being a true psychological phenomenon.

A protein known as phosphoinositide-3-kinase gamma isoform (PI3Kγ) could hold the key to cure this cellular “Stockholm syndrome” and possibly glioblastoma. This protein, when activated, is the switch that corrupts their anti-cancer role. Having studied this process for many years, Varner has pioneered drugs that restore the anti-tumour activities of microglia and macrophages.

“In our animal glioblastoma models, treatment with drugs targeting PI3Kγ consistently resulted in impressively durable responses to chemotherapy,” Chen said. “We are eager to translate these findings into a human trial, with the hope of transforming every glioblastoma patient into an exceptional responder.”

Source: Medical Xpress

Journal information: Jie Li et al, PI3Kγ inhibition suppresses microglia/TAM accumulation in glioblastoma microenvironment to promote exceptional temozolomide response, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2009290118

Categories : CancerTags :

Wrapping up Tumours With Micromesh Nets

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An innovative new nanomedicine has been developed that wraps up tumours in a micromesh net, conforming to the surface of tumor masses and efficiently delivering drugs.

The scientists at the IIT (Istituto Italiano di Tecnologia (Italian Institute of Technology) who developed the mesh described it in the journal Nature Nanotechnology.

Brain tumors are rare but they are some of the most aggressive and difficult to treat. In particular, glioblastoma multiforme (GBM), which is a grade 4 glioblastoma has the most severe prognosis: the average survival is just over 12 months and only 5% of the patients survive beyond 5 years.

GBM typically affects men and women between 45 and 75 years of age. Furthermore, unlike other malignancies, there has been no significant diagnostic and therapeutic improvements for this malignancy over the past 30 years. In fact, both the incidence of new cases and the number of deaths has remained practically unchanged. The only therapeutic strategy currently used is based on surgery, which consists of removing a part of the tumor mass and reducing intracranial pressure, followed by radiotherapy and/or chemotherapy.

The biomedical system developed by IIT and its collaborators can play a very important role in the fight against the disease, representing a possible effective alternative to the few pharmacological treatments used to date.

The microMESH is a micrometric-scale polymeric net, made from biodegradable materials and wraps around the tumour mass, enclosing it. In fact, the micrometric thick polymeric fibers are very flexible and are arranged to form regular openings, which are also on the same scale as cancer cells. This unique feature allows the microMESH to achieve a closer interaction with the tumor mass, increasing the therapeutic efficacy.

Its structure consists of two separate compartments in which different drugs can be loaded which are released towards the tumor mass in an independent, precise, and prolonged fashion. Combining different therapies: chemotherapy, nanomedicine, and immunotherapy enables the microMESH to ‘attack’ glioblastoma.

This work has been carried out by a team led by Prof Paolo Decuzzi, head of the IIT Laboratory of Nanotechnology for Precision Medicine, in collaboration with the Neural Stem Cell Biology Laboratory of Dr Rossella Galli at the San Raffaele Hospital in Milan and a team led by Prof Gerald Grant at the Lucile Packard Children’s Hospital of Stanford University.

The group will continue to develop the microMESH by integrating different types of drugs and therapies to tackle other types of tumors. In the short term, their major objective will be to validate the technology on glioblastoma patients.

Source: News-Medical.Net

Journal information: Mascolo, D. D., et al. (2021) Conformable hierarchically engineered polymeric micromeshes enabling combinatorial therapies in brain tumours. Nature Nanotechnology. doi.org/10.1038/s41565-021-00879-3.

Categories : Cancer General Interest PaediatricsTags :

Donated Afro Hair Wigs Now Possible Thanks to UK Girl

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A silhouetted woman with afro hair reading a book by a window. Photo by Thought Catalog from Pexels

A British girl who was told her afro hair was too delicate to donate for wig-making prompted a new wig-making approach to use it, BBC News reports.

When eleven year old Carly Gorton wanted to donate her afro hair to the Little Princess Trust charity, which makes natural hair wigs for children who have lost theirs from cancer treatment and other causes, she was initially frustrated as the charity said the hair was too delicate. Undeterred, Carly had urged the charity to rethink, which it did.

Following research and a trial to make them possible, the charity described the new wigs as a “historic breakthrough”.

“It’s really beautiful,” said Carly, of one of the new wigs.

A BMJ study showed that wigs positively impact psychological wellbeing for people with alopecia, attributed to increasing their confidence of going out in public and the perception of fewer comments about hair loss.

At a special school assembly, Carly’s mother Anna Mudeka then cut her daughter’s hair and it was donated for use in the first new wigs to be worn by other children.

Phil Brace, The Little Princess Trust’s chief executive, said Carly’s “determination” to donate her hair had pushed them to find a solution.

The charity worked with the 120-year-old London company Raoul to develop a wefting method to weave and tie the donated locks.

Carly’s mother, Anna Mudeka, said: “History has been made and we are so proud of Carly.

“Through her sheer determination and everyone pulling together to hear her voice, children of black and mixed heritage can now donate their hair to the Little Princess Trust.”

Ms Mudeka, of Southburgh, added that children needing wigs through illness could now receive a wig “true to their heritage”.

Carly and her mother’s campaign had created a “fundamental change in wig manufacturing”, said Mr Brace. “The commitment and work that has gone on has shown just what is possible when groups of people get together and bring different skills to find a solution.”

Source: BBC News

Categories : CancerTags :

CD40 Agonists Before Therapy Kick Off T Cell Response

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Giving a CD40 immune-stimulating drug to early-stage pancreatic cancer patients helped kick off a T cell attack on the tumour’s stubborn microenvironment before surgery and other treatments, according to a new study.

Altering the tumour microenvironment to host more T cells using a CD40 agonist earlier could help slow cancer progression and prevent metastasis.

The data was presented by Katelyn T Byrne, PhD, an instructor of Medicine in the division of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania, during a plenary session at the American Association for Cancer Research annual meeting.

“Many patients with early-stage disease undergo surgery and adjuvant chemotherapy. But it’s often not enough to slow or stop the cancer,” Dr Byrne said. “Our data supports the idea that you can do interventions up front to activate a targeted immune response at the tumor site–which was unheard of five years ago for pancreatic cancer–even before you take it out.”

CD40 is a tumour necrosis factor receptor superfamily member expressed broadly on antigen-presenting cells (APC) such as dendritic cells, B cells, and monocytes as well as many non-immune cells and a range of tumours.

CD40 agonists serve to accelerate the immune system by activating antigen-presenting cells, such as dendritic cells, to “prime” T cells and also through enhancement of destruction of the tumour site through non-immune system means. This has been investigated mostly in combination with other therapies for pancreatic cancer patients. This is the first study showing the drug drove immune response in early-stage patients both at the tumour site and systemically, mirroring mouse study findings.

Prior to surgery, 16 patients were treated with selicrelumab. Of those, 15 underwent surgery and received adjuvant chemotherapy and a CD40 agonist. Data collected from those patients’ tumours and responses were compared to data from controls (CD40 not received before surgery) treated at Oregon Health and Science University and Dana Farber Cancer Institute.

Multiplex imaging of immune responses revealed that in patients who received the CD40 agonist before surgery, 82% of tumours were T cell enriched, compared to 37% of untreated tumors and 23% chemotherapy or chemoradiation-treated tumours.

Selicrelumab tumours also had less tumour-associated fibrosis, which are tissue bundles inhibiting T cell and drug entry, and antigen-presenting cells known as dendritic cells were more mature.

Disease-free survival was 13.8 months in the treatment group, and median overall survival was 23.4 months, with eight patients alive at a median of 20 months after surgery.

“This is a first step in building a backbone for immunotherapy interventions in pancreatic cancer,” Dr Byrne said.

On the strength of these findings, researchers are pursuing combining CD40 with other therapies to help further boost immune response in pre-surgery pancreatic cancer patients.

“We’re starting to turn the tide. This latest study adds to growing evidence that therapies such as CD40 before surgery can trigger an immune response in patients, which is the biggest hurdle we’ve faced,” said senior author Robert H Vonderheide, MD, DPhil, and Director, Abramson Cancer Center (ACC), University of Pennsylvania. “We’re excited to see how the next-generation of CD40 trials will take us even closer to better treatments.”

Source: News-Medical.Net

Categories : CancerTags :

Study Discovers How Melanoma Cells Hide From Immune System

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Melanomas in some patients do not respond well to immunotherapy treatments, and now researchers have discovered that a defect in STING gene expression in melanoma cells helps them escape immune cell surveillance.

Cancer cells use a variety of recently discovered mechanisms to avoid detection and destruction by immune cells, including defective detection and destruction of T cells, losses in expression of critical proteins on tumour cells and defective cell signaling in both immune and tumor cells.

The interferon signaling pathway is an important signaling pathway in interactions between tumour and immune cells. This pathway increases expression of molecules allowing tumour cells to be targeted by immune cells. One of the interferon signaling pathway’s key molecules is STING, which is activated by the protein cGAS.

Previously Moffitt researchers showed that STING activity is suppressed and altered in a subset of melanomas, rendering tumour cells invisible to the immune system.

Using a process called epigenetic modification to turn genes on or off with methylation groups, the researchers sought to improve the understanding of alterations in STING signaling in melanoma and find out how STING expression is suppressed. 

The researchers performed a series of laboratory experiments and discovered that the DNA regulatory region of the STING gene is highly modified by methylation groups resulting in loss of STING gene expression in certain melanoma cell lines. Importantly, they confirmed these findings in patient clinical samples of early and late-stage melanomas and showed similar methylation events and loss of expression of the upstream STING regulator cGAS.

The researchers demonstrated the possibility of reactivating STING and/or cGAS expression with a demethylating drug or genetic approaches. These successfully reactivated STING activity, resulting in increased interferon levels when triggered by STING agonist drugs that enabled the melanoma cells to now be recognised and targeted by immune cells.

“These studies show the critical importance of an intact STING pathway in melanomas for optimal T cell immunotherapy success, and how to overcome a notable STING defect in melanoma cases of gene hypermethylation by a combination therapy,” said senior author James J. Mulé, PhD, and Associate Center Director, Translational Science, H. Lee Moffitt Cancer Center & Research Institute.”Unless patients’ melanomas are pre-screened for intact versus defective STING, it is not at all surprising that clinical trials of STING agonists have, to date, uniformly failed.”

Source: News-Medical.Net

Journal information: Falahat, R., et al. (2021) Epigenetic reprogramming of tumor cell–intrinsic STING function sculpts antigenicity and T cell recognition of melanoma. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2013598118.

Categories : CancerTags :

High Melanoma Rates Reported in Sunny US State

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A study reports that melanoma mortality among people in Utah, a sunny, high-altitude state, outpaced that of the rest of the country over 1975 to 2013.

This runs counter to the falling melanoma death rates in recent years in both Utah and the United States, a trend likely due to improved treatments such as immunotherapy. It is still the deadliest skin cancer type, with melanoma diagnosis rate in Utah the highest in the US.

Motivation for the research was recent evidence showing that for most of the 1990s and 2000s, even as melanoma mortality in the United States remained constant, incidence increased six-fold. This increasing incidence without accompanying mortality rise indicates overdiagnosis, ie false cancer diagnoses. 

In the case of melanoma, overdiagnosis may result from increased scrutiny, where increasing numbers of biopsies may find a benign lesion that would have gone undetected.

Since Utah has the highest melanoma incidence, a team from Huntsman Cancer Institute (HCI) at the University of Utah set out to evaluate the state’s melanoma diagnosis and death rate data. Biostatistician Kim Herget analysed data from the Utah Cancer Registry, a National Cancer Institute Survival, Epidemiology, and End Results (SEER) database, and the researchers found that in contrast to the rest of the country, melanoma mortality in Utah rose 0.8% per year from 1975 to 2013. Even though Utah’s melanoma death rates have been falling in recent years, they are still higher than the rest of the country.

“Although we agree that overdiagnosis of melanoma is a growing problem, the sustained increase in melanoma mortality in Utah suggests that at least some fraction of the increasing incidence is real and cannot be attributed solely to overdiagnosis,” said Doug Grossman, MD, PhD, who co-leads the HCI melanoma and skin cancer centre at HCI and serves as professor of dermatology at the University of Utah. “Our research underscores an increased risk for Utahns, and so we must remain vigilant about melanoma. For doctors, this means regular conversations with patients about their skin health and family history. For patients, this means practicing sun-safe behaviors like diligent sunscreen use, wearing sun-protective clothing, and monitoring their skin at home on a monthly basis to reduce risk of skin cancer and optimize early detection.”

Future studies should determine whether this trend in people living in Utah results from increased ultraviolet exposure in a mostly fair-skinned population living in a sunny, high-altitude climate or if it is associated with other factors such as environment or genetics. Melanomas are also found at higher rates in immune compromised patients.

Source: Medical Xpress

Journal information: Doug Grossman et al, The Rapid Rise in Cutaneous Melanoma Diagnoses N Engl J Med 2021; 384:e54 DOI: 10.1056/NEJMc2101980