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Pancreatic cancer drug reaches Phase III status

A pancreatic cancer drug discovered in professors Paul Bingham and Zuzana Zachar’s lab in the Department of Biochemistry and Cell Biology at Stony Brook University has now entered Phase III, or multi-center testing stage.

During the multi-center testing stage, the drug will be tested among qualifying patients in clinical research centers nationwide, including Stony Brook Cancer Center. The trial will use a combination of FOLFIRINOX and CPI-613 — a partial inhibitor of the tricarboxylic acid (TCA) cycle, a pathway used in the mitochondria for glucose metabolism — in metastatic pancreatic cancer patients. Dr. Minsig Choi, an attending physician who specializes in gastrointestinal medical oncology, is the principal investigator of the trial.

FOLFIRINOX is a chemotherapy regimen that uses multiple drugs to kill cancer cells. The use of CPI-613, a lipoate analog — a chemically equivalent compound similar to one of the intermediates in the TCA cycle — may increase the vulnerability of cancer cells to traditional chemotherapy regimens by inhibiting cancer cells’ almost “addictive” use of the TCA cycle, Choi explained. Thus, combinational therapy may improve life expectancy for patients.

“While normal cells can use other pathways when the TCA cycle is inhibited, cancer cells are more sensitive to changes in the TCA cycle,” Choi said.

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European Society of Medical Oncology Congress Presentations Show B-Cell Vaccine Combinations

(ASX:IMU), a clinical stage immuno-oncology company, today announced two presentations by medical investigators at the European Society of Medical Oncology in Barcelona Spain showed combining its HER2 vaccines with PD1 vaccines reduced cancer growth in a number of standard preclinical models.

The findings were detailed in posters presented by Dr Tanios Bekaii-Saab from the Mayo Clinic Phoenix USA and Dr Joshua Tobias from the Medical University Vienna, Austria.

Dr Bekaii-Saab’s poster presentation was entitled ‘Antitumor activity and safety of a novel PD-1 vaccine (PD1-Vaxx) alone and in combination with two chimeric HER-2 peptide vaccine (B-Vaxx) in syngeneic Balb/c mice and canines.’

The presentation detailed how Imugene’s PD1-Vaxx combined with B-Vaxx was more effective in reducing tumour growth in a model of HER2 positive colon cancer compared to either the PD1-Vaxx vaccine alone, or the positive control standard anti-mouse PD-1 monoclonal antibody.

The vaccine combination was found to be safe and did not appear to exhibit toxicity or autoimmunity. Imugene is working to evaluate PD1-Vaxx and its potential efficacy in a range of human cancers.

Dr Joshua Tobias’ poster presentation was entitled ‘Active immunization with immune checkpoint inhibitors-mimotope elicits strong in vivo anti-tumor effect against Her-2/neu-expressing tumors.’

The presentation showed active immunization with a PD1-derived mimotope vaccine combined with Imugene’s HER-Vaxx increased the anti-tumour effect of the combination vaccine compared to each vaccine alone in a model of HER2 positive breast cancer.

Active immunisation with the PD1-derived mimotope vaccine increased cancer cell death and anti-proliferative effect of the HER2 positive cancer cells in breast cancer tumours.

Imugene will initiate a Phase 1 trial of PD1-Vaxx as a monotherapy in 2020. In addition to safety and efficacy, a focus will be to assess the vaccine when combined with Imugene’s immunotherapy pipeline and other immunotherapies on the market.

Imugene Managing Director and Chief Executive Officer Leslie Chong said, “The global medical community is actively seeking inmuno-oncology combination treatments which do not increase toxicity and demonstrate improved response rates and efficacy at minimal cost.”

“The promising new B-cell vaccine data presented at this year’s ESMO congress and other major cancer research conferences has helped raise the profile of our promising anti-cancer pipeline and its potential clinical value when used in combination with other immune-oncology therapies.”

“These latest presentations of comprehensive vaccine combination results help further demonstrate the significant value of Imugene’s B-cell vaccine strategy and the strength of our pipeline,” she said.

All the Imugene related research posters presented at ESMO are available on the company website.

Dr Bekaii-Saab’s poster presentation was entitled ‘Antitumor activity and safety of a novel PD-1 vaccine (PD1-Vaxx) alone and in combination with two chimeric HER-2 peptide vaccine (B-Vaxx) in syngeneic Balb/c mice and canines.’

Dr Joshua Tobias’ poster presentation was entitled ‘Active immunization with immune checkpoint inhibitors-mimotope elicits strong in vivo anti-tumor effect against Her-2/neu-expressing tumors.’

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Simple test produces a color change in urine to signal tumor growth in mice

A simple and sensitive urine test developed by Imperial and MIT engineers has produced a color change in urine to signal growing tumors in mice.

Tools that detect cancer in its early stages can increase patient survival and quality of life. However, cancer screening approaches often call for expensive equipment and trips to the clinic, which may not be feasible in rural or developing areas with little medical infrastructure. The emerging field of point-of-care diagnostics is therefore working on cheaper, faster, and easier-to-use tests.

An international pair of engineering labs have now developed a tool that changes the color of mouse urine when colon cancer is present. The findings from testing the fast, non-invasive cancer test are published today in Nature Nanotechnology.

The early-stage technology, developed by teams led by Imperial's Professor Molly Stevens and MIT professor and Howard Hughes Medical Institute investigator Sangeeta Bhatia, works by injecting nanosensors into mice, which are cut up by enzymes released by the tumor, known as proteases.
When the nanosensors are broken up by proteases, they pass through the kidney, and can be seen with the naked eye after a urine test that produces a blue color change.

The researchers applied this technology to mice with colon cancer, and found that urine from tumor-bearing mice becomes bright blue, relative to test samples taken from healthy mice.

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Gene Linked to CRC in Younger Patients Identified Interview with:

Valentine N. Nfonsam, MD, MS, FACS
Associate Professor of Surgery
Program Director, General Surgery Residency
Colon and Rectal Surgery
Division of Surgical Oncology
University of Arizona, Tucson What is the background for this study? What are the main findings?

Response: The overall incidence of colon cancer in the United states has gone down in the last few decades. However, there has been a significant increase in the incidence of sporadic colon cancer is young patients (
These young patients do present with more advanced disease and with aggressive features. We demonstrated in our study that the colon cancer tumor biology was different between young and older patients. We also singled out a particular gene, Cartilage oligomeric Matrix Protein (COMP) which was significantly over-expressed in young patients and demonstrated its role in cancer proliferation and metastasis and also its potential as a prognostic biomarker since we were able to detect it in plasma. What should readers take away from your report?

Response: There is increasing incidence of colon cancer in young patients and the reason is likely multi-factorial. The biology of the tumors in younger patients is different and specific genes like COMP plays a role in carcinogenesis. What recommendations do you have for future research as a result of this work?

Response: We will like to further evaluate the role of COMP as a prognostic biomarker and also further elucidate its role in carcinogenesis.

Study was funded by SAGES grant.


Increasing Incidence of Colon Cancer in the Young: Assessing the Tumor Biology
Nfonsam, Valentine N. et al.
Journal of the American College of Surgeons , Volume 0 , Issue 0

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Scientists connect dots between colitis and colon cancer

Lingering inflammation in the colon is a known risk factor for colorectal cancer and now scientists report one way it resets the stage to enable this common and often deadly cancer.

Inflammation is supposed to be a short-term response to an infection or other irritant in the body that is essential to eliminating it. But when inflammation persists, it can contribute to a myriad of common conditions, from cancer to cardiovascular disease.

In their quest to determine just how chronic inflammation of our large intestines, or colon, enables cancer, a scientific team led by Dr. Kebin Liu at the Medical College of Georgia and Georgia Cancer Center at Augusta University has found it turns one more protective mechanism against us and silences another.

The pathway to cancer they delineated in the journal Cell Reports goes like this: The chronic inflammation of ulcerative colitis prompts high levels of myeloid-derived suppressor cells, or MDSCs, to accumulate in the colon. High levels of MDSCs, in turn, produce higher levels of IL-10, a cytokine known to suppress inflammation. But at this high level, the function of IL-10, like the environment in the colon, changes. IL-10 instead activates STAT3, a protein that works as a gene regulator, which in turn increases expression of two genes—DNMT1 and DNMT3b—in the colon. These genes alter the DNA of and ultimately silence a tumor suppressor called interferon regulator factor 8, or IRF8.

Liu notes that the pathway they found that ends with silencing IRF8, likely is not a factor for non-colitis associated colon cancer.

Next steps include finding ways to inhibit high expression of IL-10 in the colon.

"IL-10 has a dual function. It can either be promoting or interfering with an immune response," says Liu. "What we found here is IL-10 promotes colon cancer."

In a healthy state, IL-10 and IRF8 have no known interaction but both work in different ways to protect against invaders, says Liu, a cancer immunologist in the MCG Department of Biochemistry and Molecular Biology.

The scientists set out to look at whether and how the two are connected in a chronically inflamed colon and test the hypothesis that IRF8 functions as a colorectal cancer suppressor.

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UN Scientist Stands Behind Bacon Research

Christopher Wild, the outgoing director for the UN’s International Agency for Research on Cancer (IARC) has spoken in defense of research that links the consumption of processed meats like bacon to cancer.

The Guardian reports that the original research, which was released by the World Health Organization (WHO) in October 2015, caused an outcry when it concluded that processed meat is carcinogenic, like smoking and asbestos. Just over three years later, Wild still stands by the study’s findings, which sparked headlines such as “save our bacon.”

“The science was crystal clear,” Wild said. “We placed quite a bit of emphasis on the dose-response, if you like – the relationship between quantities eaten and effect.”

Wild further explained the original research, stating that although tobacco, ultraviolet radiation, alcohol, and processed meat are all “grade 1 carcinogens,” this does not mean that they are all equally hazardous. Rather, risk factor depends on how much, and how often processed meat is eaten.

The IARC study is not alone in linking eating bacon and other processed meats to health issues. According to the WHO, diets high in red meat cause up to 50,000 deaths a year while processed meat is responsible for 34,000.

Last May, a study released by the World Cancer Research Fund (WCRF) revealed that ditching processed meat, adopting a regular exercise regime, and avoiding alcohol and sugary drinks can reduce the risk of cancer by 40 percent.

Researchers noted that while processed meat raises the risk of cancer, a plant-based diet rich in whole foods like beans, grains, nuts and seeds, vegetables, and fruits can protect against it. The WCRF advises that people should “consume very little, if any, processed meat.”

Adding to the growing body of medical research on the health benefits of a vegan diet, a study published in the JAMA Internal Medicine revealed that a plant-based diet may lower the risk of colon cancer by as much as 16 percent and rectal cancer by 29 percent. Meat-heavy diets such as keto and paleo, meanwhile, do not lower one’s risk of cancer. Additionally, a study published in The Lancet Public Health, which analyzed the diets of more than 16,000 adults, found that low-carb, high-meat diets could reduce life expectancy...

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Kat Smith
News Editor
January 2019

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Smile please, Dr AI will see you now

By Will Peakin/ December 15, 2018

A trial is underway in the Highlands and Islands of a potentially transformative procedure that will use artificial intelligence to detect bowel cancer.

A capsule containing a tiny camera is swallowed by a patient and passes through their gastrointestinal tract, capturing up to 400,000 images which are then transmitted for analysis.

The procedure is accurate, cost effective, and significantly less disruptive to patients than existing methods. The new funding will support the development of artificial intelligence in analysing the images.

Bowel cancer is the third most commonly diagnosed cancer in both men and women in Scotland, and the second most deadly with around 1,600dying from the disease every year.

Currently, invasive, time-consuming and expensive optical endoscopes are used to investigate bowel cancers and gastrointestinal diseases; 30 million in the world, 1m in the UK and 100,000 in Scotland.

Using the minimally invasive colon capsule endoscopy (CCE),a gastrointestinal investigation can be initiated by a GP, undertaken in the patient’s home, and overseen by a consultant remotely.

The pioneering programme involves a partnership comprising NHS Highland, the Digital Health and Care Institute (DHI), the web services provider OpenBrolly, and Danish firm CorporateHealth International (CHI), which has established a base in Inverness.

Feasibility studies have already been conducted at primary care sites in Skye and Ullapool.

Now, from their base in Aurora House on Inverness Campus, CHI and its partners are developing a new ‘patient pathway’ that is locally-based and delivers fast results in a cost-effective way.

“By enabling what are currently complex hospital investigations to be done easily at home,” explained Hagen Wenzek, CorporateHealth’s chief innovation officer, “and by allowing a patient’s medical team to quickly see very accurate results, we’re delivering benefits for clinicians, for public spending and, importantly, for patients. The potential is huge.”

CHI’s founders, Hamburg- based Dr Cornelius Glismann and New York-based Dr Wenzek had been looking around the world for the right partners to develop their diagnostic pathway.

An existing collaboration between the University of Southern Denmark and Scotland’s Digital Health and Care Institute led to Wenzek and Glismann sharing their proposals with DHI’s chief executive George Crooks.

Professor Crooks introduced them to Professor Angus Watson at NHS Highland and James Cameron, Head of Life Sciences at Highlands and Islands Enterprise (HIE). Professor Watson was already exploring this type of approach but lacked the resources to scale it up, which is CHI’s speciality.

Watson had also been working with Elgin-based IT specialists OpenBrolly on projects such as MyCancerPortal. OpenBrolly were experienced in pulling information across NHS firewalls and had learnt effective ways to anonymise patient information and then re-attach it to individual patient records.

Facilitated by DHI and HIE, the partners discovered that they shared the same commitment and confidence in the benefits the project promises. “I didn’t think a government agency could be so flexible and proactive,” added Wenzek. “The collaborative support we’ve had from HIE has been outstanding.”

CHI was one of the first companies to open a base at Inverness Campus,a 215-acre enterprise park with a particular focus on Life Sciences which is becoming a significant economic driver for the Highlands and Islands.

Thirty jobs, including AI and data specialists, are to be created at Inverness Campus over three years and, as demand rises, medical analysts based in Hamburg will be augmented by additional analysts in Inverness who will be reviewing images submitted from capsules across the UK.

Inverness will be CHI’s global research and development centre and, through its collaboration with HIE, the company has already won a contract with Addenbrooke’s Hospital in Cambridge to research ways that the analytical process can be undertaken by artificial intelligence.

“This exciting initiative is leading the way toward scalable, community-based bowel cancer screening in a way that can address the substantive backlogs we currently face,” commented Adrian Smith, head of digital transformation at NHS Arden & GEM CSU.

“This is an exceptional and highly creative programme driven by a passionately committed and knowledgeable set of partners that will underpin significant patient, clinician and system-wide benefits.”

Click here to read the full article sourced by Future Scot.

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