A combination of chemotherapy drugs during brain cancer surgery using a biodegradable paste, leads to long-term survival, researchers at the University of Nottingham have discovered.

In a new study published in Clinical Cancer Research, scientists found a significant survival benefit in rat models with brain tumours when a combination of two chemotherapy drugs, (etoposide and temozolomide), were delivered using a biodegradable polymer called PLGA/PEG.

The research was carried out by experts from the Children's Brain Tumour Research Centre (CBTRC) at the University of Nottingham, in partnership with researchers from Johns Hopkins University in the USA.
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Glioblastoma multiforme (GBM) is the most aggressive and common brain tumour with a dismal average survival of 15 months from diagnosis, killing 3500 UK people annually. This is despite treatment comprising surgery, radiotherapy and chemotherapy.
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The polymer formulation, which was originally designed to help mend broken bones, is made from two types of micro-particles called PLGA and PEG and has been developed and patented by leading tissue engineer Professor Kevin Shakesheff, based in the University's School of Pharmacy. A powder at room temperature, it can be mixed to a toothpaste-like consistency with the addition of water.

The paste can be applied to the brain cancer cavity created after removal of the bulk tumour during surgery. The paste then releases chemotherapy drugs into the brain, in so doing targeting the remaining cancer cells which cannot be safely removed by surgery and which cause the cancer to return.

More than 5 million cancer survivors in the United States experience chronic pain, almost twice the rate in the general population, according to a study published by Mount Sinai researchers in JAMA Oncology.

Researchers used the National Health Interview Survey, a large national representative dataset from the U.S. Centers for Disease Control and Prevention, to estimate the prevalence of chronic pain among cancer survivors. They found that about 35 percent of cancer survivors have chronic pain, representing 5.39 million patients in the United States.

"This study provided the first comprehensive estimate of chronic pain prevalence among cancer survivors," said corresponding author Changchuan Jiang, MD, MPH, a medical resident at Mount Sinai St. Luke's and Mount Sinai West. "These results highlight the important unmet needs of pain management in the large, and growing cancer survivorship community."

The researchers, including Susmita Bose, Herman and Brita Lindholm Endowed Chair Professor in the School of Mechanical and Materials Engineering, and graduate student Naboneeta Sarkar, report on their work in the journal, ACS Applied Materials and Interfaces.

Young patients with bone cancer are often treated with high doses of chemotherapy before and after surgery, many of which have harmful side effects. Researchers would like to develop gentler treatment options, especially after surgery when patients are trying to recover from bone damage at the same time that they are taking harsh drugs to suppress tumor growth.

Turmeric has been used in cooking and as medicine for centuries in Asian countries, and its active ingredient, curcumin has been shown to have anti-oxidant, anti-inflammatory and bone-building capabilities. It has also been shown to prevent various forms of cancers.

"I want people to know the beneficial effects of these natural compounds," said Bose. "Natural biomolecules derived from these plant-based products are inexpensive and a safer alternative to synthetic drugs."

Many physicians are not telling cancer patients about the cardiotoxicity risks of treatments and may not be fully aware of the dangers themselves. A new study reveals an urgent need to look after the hearts of these patients. 

"There was no mention that it could lead to heart disease. Would have been nice to know."

The growing number of cancer survivors and increasing number of over-65s needing chronic cancer therapy mean that the need for cardio-oncology services is rising. Heart failure caused by cancer therapy can occur up to 20 years after treatment. In 2012 over 32 million people worldwide were living with cancer.

"Depending on the type of chemotherapy and radiotherapy, between 1% and 25% cancer patients may develop heart failure due to cancer treatment," said study author Professor Robyn Clark, of Flinders University, Adelaide, Australia. "Risk also depends on cardiovascular risk factors such as smoking and obesity. Better monitoring of the heart and intervention before, during and after treatment can prevent or lessen the impact of this cardiotoxicity."

The researchers reviewed medical records of 46 randomly selected cancer patients with cardiotoxicity who attended one of three hospitals between 1979 and 2015. Just 11% were referred to a cardiologist before chemotherapy and less than half (48%) were referred to a heart failure clinic after cancer treatment. Almost 40% were overweight or obese, 41% were current or ex-smokers, 24% were regular consumers of alcohol, 48% had hypertension, and 26% had diabetes.
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In a subset of patients, practice was compared before (1994-2011) and after (2012-2015) the 2012 European Society for Medical Oncology guidelines were published.3 Referral to a cardiologist before chemotherapy rose from 0 to 23% and conducting a baseline echocardiogram of the heart increased from 57% to 77%.

Researchers examined if a mouth rinse to detect human papillomavirus (HPV) DNA might be associated with helping to predict risk of recurrence of head and neck squamous cell cancer and death.

This study included 396 adults with head and neck squamous cell cancer of the mouth or throat, of which 202 patients had HPV-positive cancers. The adults were tested for the presence of HPV DNA with an oral rinse at various times. After completing cancer treatment, the repeated detection of HPV DNA identical to their tumor type in oral rinses was associated with a higher risk of cancer recurrence and death. The typical follow-up time of about two years in this study may have underestimated the associations between the persistence of HPV and cancer recurrence. More research is needed but these findings suggest HPV DNA may be a promising biomarker to understand cancer treatment response and future risk of progression.

Fakhry et al. Association of oral human papillomavirus DNA persistence with cancer progression after primary treatment for oral cavity and oropharyngeal squamous cell carcinoma. JAMA Oncol. 2019. doi:10.1001/jamaoncol.2019.0439  [Abstract]

Leukemia treatments often leave girls infertile, but a procedure developed by researchers at the University of Michigan working with mice is a step toward restoring their ability to be biological mothers.
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Ovarian follicles are the "nests" that carry eggs and support them to grow and become viable. The researchers demonstrated that they could dramatically improve the rate at which follicles develop mature eggs by surrounding the follicles with adipose-derived adult stem cells in a 3D scaffold that mimics the environment of the ovary.

Adipose-derived stem cells can be obtained from readily available fat tissue in adults.
The researchers point out that utilizing this approach in women is a ways off, but it could offer hope for many.

"Once a patient is cancer-free and they want biologically related children, we hope we'll be able to take their ovarian follicles, grow them in vitro and obtain healthy eggs for these young, otherwise healthy women," said Ariella Shikanov, U-M associate professor of biomedical engineering.

The described approach increased follicle survival from less than 5 percent to between 42 percent and 86 percent depending on the size of the follicle. The research was recently published in Stem Cell Research & Therapy Journal.

"This is a huge step toward being able to preserve the fertility of women and girls undergoing chemotherapy and radiation for cancer since those treatments are toxic to the follicles," said Claire Tomaszewski, a U-M doctoral student in biomedical engineering and member of the research team.
At this time, a young female leukemia patient's hope for carrying and delivering a biologically related child is freezing ovarian tissue prior to treatment, and hoping technology can eventually make follicle growth and maturation a viable procedure.
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And historically, attempts to grow human follicles into eggs in two-dimensional petri dishes have failed.
"A follicle is a three-dimensional structure, which becomes a pancake, not the spherical structure surrounded by supportive cells, when placed on a flat surface in a dish," Shikanov said. "As a result, it loses the contact between the supportive cells and the germs cells and then it fails to grow."

Denmark has one of highest incidences of cervical cancer in the Western world. But once a person has turned 65, they are no longer automatically screened - even though older women are in fact those who have the highest mortality. This is shown by new research from Aarhus University and Aarhus University Hospital.

"Cervical cancer has become known as 'a young women's disease'. But it's a myth that it only affects young people. In fact, the mortality rate among women above the age of 65 is 25-30 per cent higher than previously thought," says medical doctor and postdoc Anne Hammer from the Department of Clinical Medicine, Aarhus University and Aarhus University Hospital.

Anne Hammer is behind the new study which has just been published in the scientific journal Acta Obstetricia et Gynecologica Scandinavia. The researchers looked at cervical cancer mortality rates in Denmark between 2002-2015 and found that the over 65s stood out here. For example, the mortality rate was five times higher among woman aged 75-79 compared to those aged 40-45.

Advanced cancer
The research results support a study from November 2018 in which Anne Hammer and her research colleagues found that older women were very often diagnosed so late that the cancer was already too big to be surgically removed. In such cases patients are instead treated with radiotherapy and chemotherapy - a treatment that is associated with side effects such as pain and urination and defecation discomfort.
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More than half of the older women with cervical cancer who had followed the screening programme on a regular basis until it expired are diagnosed with cancer that is so advanced that surgery is no longer possible.

"When people are screened, the cancer can be discovered in its initial stages or at such an early stage that surgical treatment is still possible. This significantly reduces the risk of dying," says Anne Hammer.

When people with serious illness have conversations with their doctors and nurses about their personal values, goals, and what might be ahead with their illness, they are more likely to receive the care they want, feel less distress and report better quality of life. However, only a third of patients in their last year of life report having these conversations and, often, they happen too late in the course of illness to fulfill their most important wishes. Experts agree that all patients with serious illness should have these conversations; we need a new approach to assure that all patients are able to reap these benefits.

A new study shows that an innovative communication program developed by Ariadne Labs and tested at the Dana-Farber Cancer Institute resulted in more, earlier and better conversations between patients and their oncology clinicians, and led to significant reductions in emotional suffering for patients with advanced cancer. On average, patients and clinicians had a serious illness conversation 2.4 months earlier -- almost five months before death. The conversations were centered on what matters most to patients, with 90 percent of patients discussing goals and values.
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As a result of the intervention, the proportion of patients with moderate to severe anxiety and depression was reduced by half, and the anxiety improvements were sustained for at least 24 weeks. The study was unable to demonstrate whether the conversations resulted in care that aligned with patient goals, or brought about greater peacefulness at the end of life. The intervention did not impact survival rates.

It has long been thought that stress contributes to cancer progression. Scientists from the University of Basel and the University Hospital of Basel have deciphered the molecular mechanisms linking breast cancer metastasis with increased stress hormones. In addition, they found that synthetic derivatives of stress hormones, which are frequently used as anti-inflammatory in cancer therapy, decrease the efficacy of chemotherapy. These results come from patient-derived models of breast cancer in mice and may have implications for the treatment of patients with breast cancer, as the researchers report in the scientific journal Nature.

One major obstacle in the treatment of metastatic breast cancer is the phenomenon of tumor heterogeneity. As the disease progresses, the tumor becomes more diverse, and the difference between the cancer cells may lead to inadequate treatment.

Because the underlying mechanisms of this phenomenon remain unclear, the research group of Prof. Mohamed Bentires-Alj from the Department of Biomedicine at the University of Basel and University Hospital of Basel has been studying the cells of a highly metastatic form of cancer known as triple-negative breast cancer. This cancer type is resistant to standard therapies leaving patients with fewer treatment options.

One major obstacle in the treatment of metastatic breast cancer is the phenomenon of tumor heterogeneity. As the disease progresses, the tumor becomes more diverse, and the difference between the cancer cells may lead to inadequate treatment.
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Because the underlying mechanisms of this phenomenon remain unclear, the research group of Prof. Mohamed Bentires-Alj from the Department of Biomedicine at the University of Basel and University Hospital of Basel has been studying the cells of a highly metastatic form of cancer known as triple-negative breast cancer. This cancer type is resistant to standard therapies leaving patients with fewer treatment options.

"At the clinical level, we've known for some time that heart dysfunction from chemotherapy is a major issue, but at the scientific level, we've only recently begun to look at signalling pathways that may be implicated in this condition," said Gopi Sutendra, Alberta Innovates Translational Health Chair in Cardio-Oncology at the U of A.
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"This is the first targeted therapy at the preclinical level to actually prevent the side-effects of chemotherapy on the heart and simultaneously enhance tumour regression."

​The heart resides in an oxygen-rich environment, compared to a tumour which resides in an oxygen-poor environment.

The team found that the oxidation of proteins--a process that requires oxygen--was preferentially increased in the heart. By stabilizing a specific metabolic protein called pyruvate kinase M2 (PKM2)--also preferentially oxidized in the heart--with a drug compound, the researchers completely prevented heart damage from the chemotherapy, and enhanced the potency of the chemotherapy against lung tumours in preclinical mouse models.