University of Nottingham | December 2018 | From eye drops to potential leukaemia treatment
Scientists at the University of Nottingham have found eye drops have the potential to be used in treatment for an aggressive form of blood cancer: acute myeloid leukaemia (AML). Nottingham staff collaborated on research led by experts at the Wellcome Sanger Institute, University of Cambridge, and other scientists which led to the discovery that a compound identified in eye drops, being developed to treat a form of eye disease, has shown promise for treating AML.The active ingredient in eye drops has the potential to treat AML, as it targets leukaemic blood cells without harming non-leukemic blood cells.
Full details of the research are available from:
University of Nottingham [press release]
Wellcome Sanger Institute [press release]
We recently identified the splicing kinase gene SRPK1 as a genetic vulnerability of acute myeloid leukemia (AML). Here, we show that genetic or pharmacological inhibition of SRPK1 leads to cell cycle arrest, leukemic cell differentiation and prolonged survival of mice transplanted with MLL-rearranged AML. RNA-seq analysis demonstrates that SRPK1 inhibition leads to altered isoform levels of many genes including several with established roles in leukemogenesis such as MYB, BRD4 and MED24. We focus on BRD4 as its main isoforms have distinct molecular properties and find that SRPK1 inhibition produces a significant switch from the short to the long isoform at the mRNA and protein levels. This was associated with BRD4 eviction from genomic loci involved in leukemogenesis including BCL2 and MYC. We go on to show that this switch mediates at least part of the anti-leukemic effects of SRPK1 inhibition. Our findings reveal that SRPK1 represents a plausible new therapeutic target against AML.
The full article is available to read from Nature Communications
The findings of a cluster randomized (1:1) trial have been published in the Journal of Clinical Oncology’s website. The researchers leading the trial sought to compare the effect of a policy adding a clinician- delivered bedside pain assessment and management tool (Edinburgh Pain Assessment and management Tool [EPAT]) to usual care (UC) versus UC alone on pain outcomes.
Employing a two-arm, parallel group, cluster randomized (1:1) trial, the scientists observed pain outcomes in 19 cancer centres in the UK, these centres were randomly assigned to implement EPAT or to continue UC. As part of the trial they enrolled 1,921 patients, with a mean age of 60; 49% of whom were female with a variety of cancer types.
The findings of this multicentre, cluster randomized trial indicate that a policy of integrating systematic pain assessment and management into routine cancer centre care using a simple tool (EPAT) improves pain outcomes for patients with moderate or severe cancer-related pain.
The scientists conclude that the centres employing EPAT had greater improvements in prescribing practice and in the Brief Pain Inventory Short Form pain subscale score. Other pain and distress outcomes and opioid adverse effects did not differ between EPAT and UC.
Pain is suboptimally managed in patients with cancer. We aimed to compare the effect of a policy of adding a clinician-delivered bedside pain assessment and management tool (Edinburgh Pain Assessment and management Tool [EPAT]) to usual care (UC) versus UC alone on pain outcomes.
Patients and Methods
In a two-arm, parallel group, cluster randomized (1:1) trial, we observed pain outcomes in 19 cancer centers in the United Kingdom and then randomly assigned the centers to either implement EPAT or to continue UC. The primary outcome was change in the percentage of study participants in each center with a clinically significant (equal to 2 point) improvement in worst pain (using the Brief Pain Inventory Short Form) from admission to 3 to 5 days after admission. Secondary outcomes included quality of analgesic prescribing and opioid-related adverse effects.
Ten centers were randomly assigned to EPAT, and nine were assigned to UC. We enrolled 1,921 patients and obtained outcome data from 93% (n = 1,795). Participants (mean age, 60 years; 49% women) had a variety of cancer types. For centers randomly assigned to EPAT, the percentage of participants with a clinically significant improvement in worst pain increased from 47.7% to 54.1%, and for those randomly assigned to continue UC, this percentage decreased from 50.6% to 46.4%. The absolute difference was 10.7% (95% CI, 0.2% to 21.1%; P = .046) and it increased to 15.4% (95% CI, 5.8% to 25.0%; P = .004) when two centers that failed to implement EPAT were excluded. EPAT centers had greater improvements in prescribing practice and in the Brief Pain Inventory Short Form pain subscale score. Other pain and distress outcomes and opioid adverse effects did not differ between EPAT and UC.
A systematic integrated approach improves pain outcomes for inpatients in cancer centers without increasing opioid adverse effects.
The full article can be read at Journal of Clinical Oncology, where it has been published online
Reference: DOI: 10.1200/JCO.2017.76.1825 Journal of Clinical Oncology – published online before print March 15, 2018
ScienceDaily reports the following Cancer related research:
Zinc can halt the growth of cancer cells, study says
Zinc supplements can significantly inhibit the proliferation of esophageal cancer cells, according to a new study.
Tracking the body’s mini-shuttles
The development of a new technique for labelling the body’s own transporters — exosomes — could have long term benefits in the treatment of life-threatening medical conditions, including cancer.
Scientists create endocytosis on demand by ‘hotwiring’ cells
A solution to the problem of creating endocytosis on demand is being compared to ‘hotwiring’ a car. A team has managed to trigger clathrin-mediated endocytosis in the lab.
Medication that treats parasite infection also has anti-cancer effect
Scientists report a new gene target, KPNB1, for treatment against epithelial ovarian cancer (EOC). EOC is the fifth leading cause of cancer-related deaths in women and has a particularly grim outlook upon diagnosis. They also find that ivermectin exerts an anti-tumor effect on EOC cells by interacting with the KPNB1 gene. Because ivermectin is already approved to treat parasitic infections in patients, experiments for its effectiveness in an anti-cancer regimen is expected to significantly lower costs compared to untested drug compounds.
Ancient ink for cancer treatment
For hundreds of years, Chinese calligraphers have used a plant-based ink to create beautiful messages and art. Now, one group reports that this ink could noninvasively and effectively treat cancer cells that spread, or metastasize, to lymph nodes.
First-in-human testing of new cancer drug reported
The first clinical trials of a new drug that targets solid cancer tumors has now been tested. The Phase 1A clinical trials mark the first time ever the drug, called BXQ-350, was used in people. BXQ-350 is comprised of a human protein called SapC and a human lipid called DOPS.
, Issue 7, pages 1557–1562, 1 April 2016
- Towards personalized screening: Cumulative risk of breast cancer screening outcomes in women with and without a first-degree relative with a history of breast cancer (pages 1619–1625)Theodora Maria Ripping, Rebecca A. Hubbard, Johannes D.M. Otten, Gerard J. den Heeten, André L.M. Verbeek and Mireille J.M. Broeders
Breast cancer screening is shifting away from a one-size-fits-all approach, where age determines mammography frequency, to personalized approaches, which balance the benefits and harms of mammographic screening. This study shows that women with a first-degree family history of breast cancer are more likely to have favorable and unfavorable screening outcomes than women without a family history of the disease. Women with a family history had a higher chance of small invasive cancers being detected but also were at increased risk of interval cancers and false-positives. The findings emphasize the need for careful benefit-harm assessment in mammographic screening.
- Clinicopathological and molecular alterations in early gastric cancers with the microsatellite instability-high phenotype (pages 1689–1697)Ryo Sugimoto, Tamotsu Sugai, Wataru Habano, Masaki Endoh, Makoto Eizuka, Eiichiro Yamamoto, Noriyuki Uesugi, Kazuyuki Ishida, Tomonori Kawasaki, Takayuki Matsumoto and Hiromu Suzuki
The relevance of the clinicopathological and molecular features of early gastric cancers with the microsatellite instability (MSI)-high phenotype remains to be clarified in sporadic gastric carcinogenesis. This study shows that early gastric cancers with the MSI-high phenotype exhibit distinct histological features and accumulation of both genomic damage and MSI within the same tumors. In regions with genomic damage, the frequencies of 3p and 22q AI were significantly higher in the MSI-high phenotype than in the microsatellite stable phenotype. The treatment strategies for patients with gastric cancers having the MSI-high phenotype may thus need to differ from patients with colorectal cancer.
- High hemoglobin A1c levels within the non-diabetic range are associated with the risk of all cancers (pages 1741–1753)Atsushi Goto, Mitsuhiko Noda, Norie Sawada, Masayuki Kato, Akihisa Hidaka, Tetsuya Mizoue, Taichi Shimazu, Taiki Yamaji, Motoki Iwasaki, Shizuka Sasazuki, Manami Inoue, Takashi Kadowaki, Shoichiro Tsugane and for the JPHC Study Group
Diabetes and cancer share a positive association, yet the relationship between cancer risk and the most reliable blood glucose marker, hemoglobin A1c (HbA1c), remains unclear. This large-scale prospective study with strictly standardized HbA1c values in a Japanese population, which was cancer-free at baseline, shows that elevated HbA1c levels are significantly associated with risk for all reported cancer sites in both sexes, independent of potential confounding factors. The findings support the idea that glycemic control is key to cancer prevention in both diabetic and nondiabetic individuals with high HbA1c levels.
Rethinking Cancer, a new report by the International Longevity Centre- UK (ILC-UK) quantifies the cost of cancer to the UK economy, its families and its communities. The independent report presents research on the economic and societal impact of cancer.
The report considers the wider cost of cancer alongside the 160,000 deaths it causes each year in the UK.
- In a single year over 50,000 people of working age lose their lives to the disease and in 2014 these people could have contributed £585 million to the UK economy.
- The 1.8 million people living with and beyond cancer in the UK contribute approximately £6.9 billion to the UK economy each year through paid employment.
- The wider societal contributions of cancer survivors are significant and have been valued at £15.2 billion per year. This includes providing hours of informal care to others, along with voluntary and domestic work.
‘Rethinking Cancer’ outlines the changes required to increase survivorship and better support those living with and beyond cancer, their employers, families, friends and relatives.
Increase survival rates
The report reveals that the gap in cancer survival rates between England and the European average has remained at around 10% for the last two decades. ILC-UK calculate that closing the gap would contribute £117 million to the UK economy.
Support Cancer Survivors
Rethinking Cancer finds that if employment rates for cancer survivors were the same as for the rest of the population cancer survivors would contribute an additional £4 billion to the UK economy each year.
Even light and moderate drinking (up to one drink a day for women and up to two drinks a day for men) is associated with an increased risk of certain alcohol related cancers in women and male smokers, suggests a large study published by The BMJ today.
The study, which involved almost 136,000 people, found women who drank the equivalent of a glass of wine a day over a 30-year period were 13% more likely to develop one of the alcohol-related cancers (breast cancer being the most common) than women who didn’t drink at all.
The study found low to moderate drinking increased the risk of certain types of cancers already thought to be linked to alcohol, but only among women or people who smoked. Men who didn’t smoke and drank moderately had no increased risk of any type of cancer.
Full reference: Yin Cao et al. Light to moderate intake of alcohol, drinking patterns, and risk of cancer: results from two prospective US cohort studies. The BMJ, August 2015.