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Hypoxia – The Hallmarks of Cancer: Genome Instability and Immortality

 

Dr Burga Kalz Fuller continues to look at the way the iconic “Hallmarks of Cancer“, as first described by Douglas Hanahan and Robert Weinberg, are influenced by hypoxia in the tumour microenvironment.

Oxygen around and within the tumour cells is central to metabolism, immunology, epigenetics and therapy resistance of all the cancers; in the lab, oxygen levels during tumour cell culture exert effects on metabolism, maintenance, cell yield, and cell survival. That’s why the authentic physiological cell culture conditions in the Hypoxystation help advance research into tumour progression and other events which determine malignancy and outcome of cancer diseases. The Hypoxystation enables glove-less access to cultivate and manipulate cells under physiological conditions, in a HEPA-clean environment.

In this mini-review series, we take a closer look at the way Hypoxystation users worldwide are delineating Hypoxia and the Hallmarks of Cancer. Previously, we had showcased research by Hypoxystation users involved with Avoiding Immune Destruction and Tumour Promoting Inflammation. Next, we want to show the many ways in which Hypoxystation users are researching the Hallmarks Genome Instability and Mutation and Enabling Replicative Immortality. One of those researchers, Dr. David Ho of the University of Miami, presented his results at the Cell Symposium on Cancer, Inflammation and Immunity in San Diego in June.


Let us show you how Don Whitley Scientific can Define Your Environment.

David Ho

Dr. David Ho from the University of Miami with his poster presentation at the Cell Symposium on Cancer, Inflammation and Immunity

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1. Genome Instability and Mutation

Tumour hypoxia drives genomic instability both by increasing the volume of mutations (DNA strand breaks, base damage, and gene amplification) and by diminishing DNA repair efficiency. The low levels of oxygen typical of the tumor microenvironment decrease transcription of genes related to homologous repair and non-homologous end-joining, leading to the genetic instability observed in hypoxic tumour cells. Hypoxia induces production of reactive oxygen species ROS, which interact with nucleic acids, proteins and lipids, causing cellular damage and mutagenesis. Hypoxic activation of HIF-1 also upregulates expression of certain miRNA’s which suppress DNA repair pathways.

 

LITERATURE:

  • Jiang et al. (2016) “Hypoxia Potentiates the Radiation-Sensitizing Effect of Olaparib in Human Non-Small Cell Lung Cancer Xenografts by Contextual Synthetic Lethality” Int J Radiation Oncol Biol Phys, Vol. 95, No. 2, pp. 772 e781, 2016
    www.redjournal.org/article/S0360-3016(16)00056-0/abstract Hypoxystation user
  • Doherty et al. (2016) “Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand” Nature Scientific Reports 6:22668 (2016)
    www.ncbi.nlm.nih.gov/pmc/articles/PMC4778139/ Hypoxystation user
  • Hunter et al. (2016) “Hypoxia-activated prodrugs: paths forward in the era of personalised medicine” Br J Cancer. 2016 May 10; 114(10): 1071–1077
    www.ncbi.nlm.nih.gov/pmc/articles/PMC4865974/Hypoxystation user
  • Leszczynska et al. (2016) “Mechanisms and consequences of ATMIN repression in hypoxic conditions: roles for p53 and HIF-1” Scientific Reports 6:21698 (2016
    www.ncbi.nlm.nih.gov/pmc/articles/PMC4753685/ Hypoxystation user
  • Timpano and Uniacke (2016) “Human Cells Cultured Under Physiological Oxygen Utilize Two Cap-binding Proteins to Recruit Distinct mRNAs for Translation” Journal of Biological Chemistry 291(20):jbc.M116.717363
    www.jbc.org/content/291/20/10772.abstract Hypoxystation user
  • Haider et al. (2016) “Genomic alterations underlie a pan-cancer metabolic shift associated with tumour hypoxia“ Genome Biology (2016) 17:140
    www.ncbi.nlm.nih.gov/pubmed/27358048

ImmortalitySlice

2. Enabling Replicative Immortality

Cancer is characterized by a nearly unlimited capacity of the tumour cells to proliferate. Hypoxia in the rapidly growing tumour supports immortalisation of a subset of cancer cells, the “cancer stem cells”. Factors such as hypoxia in the tumour microenvironment derail signals indicating senescence and initiating apoptosis, enabling an immortal lifespan. Telomerase, Notch, c-Myc, and OCT4 mediate the acquisition of a stem cell-like phenotype through down-regulation of differentiation genes and activation of stem genes, generating CSC’s with aggressive properties. These cancer stem cells residing in an hypoxic tumour niche are uniquely resistant to many therapies, where low oxygen promotes stemness, maintenance, and self-renewal of the CSC’s. Metastasis and invasion by these CSC’s induce the formation of secondary tumours, which in most cases dramatically worsen the prognosis for cancer patients.

LITERATURE:

Sfam summer 2017

Successful SfAM Summer Meeting for DWS

Don Whitley Scientific exhibited at SfAM’s Conference last week, held in the BALTIC Arts Centre in Gateshead. SfAM (The Society for Applied Microbiology) offered an open invitation to all scientists with an interest in food microbiology to attend and participate in the event.

The event ran for four days, with Don Whitley Scientific setting up an exhibition stand on the Riverside Terrace of the BALTIC centre for day two. Our exhibition stand featured WASP Touch and ProtoCOL3, two products that are well suited to food microbiology applications. The WASP Touch is Don Whitley Scientific’s latest model of Whitley Automated Spiral Plater, which is extremely simple to use and provides real cost savings and process improvements. The ProtoCOL3 is a next generation instrument for colony counting and zone measuring, which works perfectly with the spiral plates that WASP Touch produces.

sfam prize winner

Olotu was very happy with her prize!

The meeting itself featured a packed schedule of lectures and poster sessions featuring topics from a range of international speakers that revolved around foodborne disease. There was also a social programme that included a barbecue on the Riverside Terrace, an interactive quiz and a conference meal in the restaurant located on the top floor of the conference centre. DWS also provided a prize for the exhibition competition, a picnic rucksack which was won by conference delegate Olotu Ifeoluwa, a food scientist from South Africa.

Social media is beginning to play a big role in how delegates and exhibitors can interact with events. SfAM set up a hashtag on Twitter at  which people could follow to keep up with what was happening at the exhibition. Don Whitley himself even featured on this hashtag as a delegate was keen to get a selfie with him!

This was a great exhibition for DWS to showcase products, with plenty of delegates showing interest in both WASP Touch and ProtoCOL3.

 

Biomedical Scientist_Clinical Microbiology of Anaerobes Course

Time to automate your media preparation?

 

Want the flexibility of making your own media?

Want to automate media production to save time?

Want consistently good quality plates?

 

 

Here’s what we can offer – faster, easier to clean systems that provide greater traceability.

Look no further than Masterclave Media Preparators

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Masterclave 10                                                                       This modern, colour touchscreen operated device can prepare from 1 to 10 litres of media. It is a benchtop media preparator but can be supplied with a trolley.

Masterclave 20 The Masterclave 20 can prepare from 1 to 20 litres of media. It comes complete with wheels and will fit perfectly under a laboratory bench when space is at a premium.

Masterclave 20
The Masterclave 20 can prepare from 1 to 20 litres of media. It comes complete with wheels and will fit perfectly under a laboratory bench when space is at a premium.

 

 

 

 

 

 

 

 

 

 

 


 

 

 

Use your Masterclave as part of a fully automated process for culture media preparation.

With a range of modern features plus options to tailor the Masterclave to your application, arrange your demonstration today.

                       Contact our sales office for more information on Tel: 01274 595728 or Email: sales@dwscientific.co.uk 

Please note that Don Whitley Scientific can only sell these products within the UK

 

 

 

 

 

bacr 2017 2

A Manic Month Continues for DWS

June continues to be busy for Don Whitley Scientific, with 6 exhibitions and events attended already. And we have two more to go!

In the month of June, we have attended several meetings and exhibitions that featured topics ranging from pathology, cancer research, LIMS systems and more. We helped to administer the 2017 Practical and Clinical Microbiology of Anaerobes Course, hosted by the UK Anaerobe Reference Unit, Cardiff. It was once again a fantastic success.

Next week (26th-28th June) DWS will be attending the Association for Radiation Research Annual Meeting, which this year focuses on the topic “Improving Radiotherapy Response through Radiation Research” featuring speakers from cancer research institutes from around the world. Don Whitley Scientific will have an exhibition stand at this meeting displaying the Whitley H45 Workstation. There will also be an interactive touchscreen presentation, which allows users to explore the full range of Whitley Workstations.

On 4th July we will also have an exhibition stand at the Society for Applied Microbiology Annual Applied Microbiology Conference at the BALTIC Centre in Gateshead. This meeting will focus on new insights into food safety. Here we will exhibit the ProtoCOL and WASP Touch, two products that provide real benefits in food microbiology applications.

 

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Don Whitley Scientific featured in Production Engineering Solutions

Don Whitley Scientific has featured in an article in the publication “Production Engineering Solutions”. The article focuses on the work that Hoffman Group did at the premises in Shipley to improve the efficiency of our production department.  Hoffman Group did a fantastic job in refurbishing our production department, installing equipment and furniture which will improve our levels of productivity and efficiency.

Read the article in full here – https://www.pesmedia.com/taking-efficiency-next-level/

 

Scientist Working in Whitley Workstation

Hypoxia in the Tumour Microenvironment

Hypoxia in the tumour microenvironment affects all the characteristic Hallmarks of Cancer, significantly impacting progression of the cancer and the patients’ prognosis. Inflammation and immunity are both acutely influenced by the low oxygen typical of the tumour microenvironment: hypoxia creates an immune-suppressive network supporting tumour growth and metastasis, and it induces sustained inflammation in a “wound that never heals”.

Cancer research depends on recreating a physiologically accurate environment for cell cultures in the lab, and hypoxia in a closed workstation format such as a Whitley Hypoxystation is the best way to do that. Incubate, image, manipulate and assay – all inside the continuous, reliably stable hypoxic environment. HEPA filtered air scrubbed to ISO 14644 class 3 standards, sterile humidity, and containment options make the Hypoxystation the safest, cleanest workstation available for hypoxic cell culture down to 0.1% O2.

Our Hypoxystation users are investigating all aspects of the Hallmarks of Cancer and how they are shaped by hypoxia. We review their recent research on Avoiding Immune Destruction and Tumour Promoting Inflammation here.

 

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Microbiology International at ASM Microbe 2017

Don Whitley Scientific’s US distributor, Microbiology International, will be exhibiting at the upcoming American Society for Microbiology annual conference. The event, known as ASM Microbe, will be held in New Orleans from June 1st to June 5th. Microbiology International will be showcasing Don Whitley Scientific products at Booth 2837.

The ASM continues to be the international leader in advancing microbial sciences across the globe, boasting more than 50,000 members. The annual ASM Microbe conference gives delegates and exhibitors the chance to experience everything that is happening in microbiology and connect with bright minds across the broad scope of the industry. The five day programme includes keynote speakers, poster sessions, workshops and also an optional city tour of New Orleans.

The Microbiology International stand will feature the Whitley A55 Anaerobic Workstation. Representatives will be available to explain why this is the best option when it comes to a range of microbiology applications. Two unique features of these workstations are the Instant Access Port System and Anaerobic Conditions Monitoring. The first ensures the workstation is easy and comfortable to work in whilst ACM ensures anaerobic conditions are monitored, providing consistently reliable results.

If you are at this event make sure you visit Booth 2837 to discuss how our product range could help you in your work.

WASP Touch Spiral Plater

New WASP Touch Spiral Plater Video

Don Whitley Scientific is pleased to announce a new video featuring WASP Touch, the spiral plater designed for the needs of modern microbiology laboratories. The video outlines the way in which spiral plating brings several cost and time savings to the laboratory, as well as discussing the options and accessories that are available to help tailor the system to your particular application.

If you haven’t already seen WASP Touch, here’s some background information on the product. If you need any further information, please see our website or contact us at sales@dwscientific.co.uk.

Read more

Clostridium difficile studies can be done in a Whitley Workstation

New Whitley Workstation Videos

 

Not convinced you need an anaerobic workstation?

Still juggling jars to grow your anaerobes?

Need the perfect atmosphere for your microaerophiles?

 

These new videos from Don Whitley Scientific will make you think again and realise that you can do so much more with a workstation:

An Introduction to Whitley Anaerobic Workstations

An Introduction to Whitley Microaerobic Workstations

As well as introducing the range of workstations available, the videos give an insight into the options and accessories that can tailor your anaerobic or microaerobic cabinet to your particular application or study.

You may work in a busy clinical or contract laboratory with a high throughput of samples to process. You could be a researcher performing a range of experiments, restricted by the limitations of the equipment available to you. Whatever your discipline, let us show you how you can benefit from a Whitley Workstation.

For further information, please contact our UK sales team on 01274 595728. For visitors from other countries, please contact your local distributor from the list on our website.

 

Samantha Fryer being presented with her award

Leeds University Poster Prizes 2017

Frank Charlton - 2nd Prize - Lab based projects

Frank Charlton – 2nd Prize – Lab based projects

Andrew Pridmore, Head of Microbiology, visited the University of Leeds Faculty of Biological Sciences on 4th May 2017 to present prizes to undergraduate students on the Microbiology, Medical Microbiology and Microbiology in relation to Medicine BSc degree courses.

These prizes, sponsored by Don Whitley Scientific, are awarded each year for poster presentations of the students’ final year research projects.  These are divided into two categories – laboratory research and literature review.  The winners this year were:

Laboratory-based projects:

1st   –    Samantha Fryer: “Lifestyle Choices of Dietary Supplement Users” (Samantha is pictured top left with Dr Pridmore)

2nd  –    Frank Charlton: “A Pharmacological Approach to Identifying BUNV Entry Mechanisms”

3rd   –    Danielle Beeson: “Mutant calreticulin requires Tyr-626 of the thrombopoietin receptor for oncogenic transformation”

Literature reviews:

Prize winner Katherine Kelleher with Dr Andrew Pridmore

Prize winner Katherine Kelleher with Dr Andrew Pridmore

1st   –    Katherine Kelleher: “How to create a successful oncolytic agent”

2nd  –    Kurt Rushworth: “Brain Metastases: Mechanisms and Therapeutics”

3rd   –    Hope Denyer: “Old Drugs, New Wheels: reinvigorating natural products against cancer”

All posters were of a very high standard, but Andrew was especially pleased to find several research projects on the subject of antibiotic susceptibility / resistance and some interesting concepts for novel antibacterial therapies.  A selection of these is provided below:

  • Adhiron and the antibiotic resistance crisis: a change in direction (Edward Davies)
  • Can understanding bacterial immune evasion strategies help to generate novel antivirulence therapeutics? (Rebecca Golenya)
  • Immune evasion strategies employed by Pseudomonas aeruginosa as potential drug targets (Marie Horsler)
  • BAM: A solution to the antibiotic resistance crisis in Gram-negative bacteria? (Charles Kelleher)
  • The emerging role of anti-virulence therapies within antimicrobial resistance (Scarlet-Daisy Prior)

We wish the very best of luck to all of the final year students who are now immersed in their examinations!

To download copies of any of the above papers, please go to this page on our website.