SCIENTIFIC MANIA

Bacteria engineered to produce GASOLINE fuel

noreply@blogger.com (Gehad Youssef) — Sat, 16 Nov 2013 09:59:00 +0000

Modern civilisation depends on fossil fuel, we need them to provide energy to power our cars, heat our homes and even to make medicinal products. Simply put life as we know it today will be very different without fossil fuels.

The only problem is that fossil fuels will not last forever..so there is an intense race to find renewable sources of fuel.

One remarkable approach to this problem is to re-engineer bacteria to produce petrol (gasoline). Bacteria can be re-wired to do this by modifying their genes.

Two South Korean scientists reported in Nature a method for modifying E. coli bacteria to produce petrol and other hydrocarbons that can be used for fuel.

They interfered in the normal metabolism of E. coli by deleting certain genes and enhancing the activity of others to transform the E. coli bacteria into a mini gasoline production unit!

Here is the set up they used to ferment the bacteria and collect the gasoline

Machine that was used to ferment the engineered E. coli and to collect the gasoline. Source:
Nature 502, 571–574.

The engineered strains could produce roughly 589 mg of petrol per litre.

Imagine one day, we could generate petrol in the laboratory instead of relying on oil drilled from unstable Middle Eastern countries. Thus, would stablise fuel prices and even reduce unnecessary wars over oil!

The HIIT exercise protocol according to Little and co-workers (2009)

noreply@blogger.com (Gehad Youssef) — Sat, 16 Nov 2013 09:56:00 +0000

I have been interested in High Intensity Interval training (HIIT) ever since I have read the Tabata et al., 1996 paper on HIIT (Med Sci Sports Exerc. 1996 Oct;28(10):1327-30.)

I have summarised the protocol and results from the famous study performed by Little et al., 2009 (J Physiol. 2010 Mar 15;588(Pt 6):1011-22. Epub 2010 Jan 25. ).

This protocol is more practical than the original Tabata study as no specialised exercise equipment is needed.

Subjects underwent HIIT for 3 times a week (monday, wednesday, and friday).

Prior to training, each subject underwent 3 minutes cycling at medium intensity.

The subjects started off with 8 high intensity intervals for the first 2 weeks,

The next 2 weeks, the intervals was increased to 10, then the next 2 weeks they were increased to 12 intervals.

Each high intensity interval was for 60 seconds, followed by 75 second low intensity exercise.

The results were interesting:

Enzymes linked to improved muscle performance and increased metabolism and genes involved in glucose usage in the muscle were elevated significantly.

Non-Hodgkin's lymphoma: case studies with DCA

noreply@blogger.com (Gehad Youssef) — Fri, 19 Apr 2013 21:18:00 +0000

In the previous post, I briefly discussed the fact that tumours often have an altered metabolism and higher glucose uptake than normal cells - a phenomenon called the "Warburg effect" and that there are two case study reports in the scientific literature that describe complete remission with DCA in advanced non-Hodgkin's lymphoma.

Before I describe the case studies, it is important to point out as a way of a disclaimer that this blog does not in any way encourage or advise you to self medicate with DCA. To truly test the effectiveness of DCA against cancer, a clinical trial needs to take place so please do not take this post as medical advice. Instead, these case studies are highlighted because I want to encourage more research into the potential use of DCA as an anti-cancer drug.

The first case study was published in the Journal of Bioenergetics and Biomembranes and documented the full recovery and complete regression of stage IV non-Hodgkin's lymphoma in a 52 year old man who took DCA.

DCA case study 2. Source:

010;2010. pii: 414726. doi: 10.1155/2010/414726. Epub 2010 Sep 16.

The second paper was published in the Journal of Oncology reporting similar effects but this time in a 48 year old man.

DCA case study 1. Source: J Bioenerg Biomembr. 2012 Dec 20

First DCA case study

The patient is a 52-year old man who has had non-Hodgkin's lymphoma since the age of 46. When doctors performed a CT scan of his body, they discovered stage IV non-Hodgkin's lymphoma.

Stage IV non-Hodgkin's lymphoma detected in 52-year old man

Remember that cancer cells preferentially take up glucose at higher rates than normal cells. For this reason, the patient was given a FDG PET scan which basically detects glucose uptake by the tumours.

FDG-PET scan to show tumour areas that preferentially take up glucose

The patient was prescribed rituximab-CHOP, which is a monoclonal antibody and a combination of different chemotherapeutic agents. The patient initially responded well, however after 7 months, the cancer returned.

Tumour is back after chemotherapy

The patient was offered more R-CHOP, but he couldn't stand the horrible side effects of the chemotherapy and decided against the advice of the medical professionals to self-administer with DCA.

Every day he took 1000mg of DCA mixed with Mountain Dew (probably because the caffeine inside the drink is thought to help with the absorption of DCA into the body) and various supplements such as Vitamin B1.

71 days later....complete remission and the patient achieved a full recovery and has been tumour free for over 4 years.

Second DCA case study

In this report, the 48 year old man also took R-CHOP and after almost a year his tumour returned.

The patient took 900mg of DCA every day along with thiamine supplements (750mg/daily) to protect his nerves from any damage that DCA might cause.

4 months later....complete remission for over 18 months (the patient was tumour free in December 2008 and this report was published in July 2010).

First image shows clearly the tumour and the bottom image shows the tumour has gone when the patient took DCA.

It is important to realise, we are only talking here about 2 individual case studies and which only dealt with one type of cancer (non-Hodgkin's lymphoma). It is unclear whether other all patients with non-Hodgkin's will also respond just as well or whether other types of tumours (breast, prostate, lung etc...) will be sensitive.

However, these reports are interesting and this blog will definitely keep an eye on new reports about DCA in the scientific literature.

Male with cancer mixes DCA drug with Mountain Dew....and achieves FULL remission!

noreply@blogger.com (Gehad Youssef) — Tue, 09 Apr 2013 17:07:00 +0000

Cancer cells change their metabolism in such a way that it allows them to preferentially uptake and utilise glucose as their primary energy source. This phenomenon is called the "Warburg Effect", named after Otto Warburg, who was awarded the 1931 Noble Prize in Medicine.

Otto Warburg, 1931 Nobel Prize winner. Source: http://www.nobelprize.org/nobel_prizes/medicine/laureates/1931/warburg-bio.html

Normal cells do take up glucose, but the way they metabolise or process glucose is different. Normal cells utilise oxygen in the mitochondria (the powerhouse of the cell) to make use of the full potential of glucose. Cancer cells often switch off this oxygen requiring part of glucose metabolism and instead uptake much more glucose so that they can survive in the absence of oxygen. This has two advantages:

1) Since they are no longer dependent on oxygen, cancer cells can divide quickly with an adequate energy source despite the lack of oxygen.

2) The mitochondria where oxygen is normally utilised also happens to be the site which can instruct the type of cells that don't behave (such as cancer cells) to commit suicide in a process called apoptosis. By switching off the mitochondria, you prevent apoptosis!

Back in 2007, a group led by Dr Evangelos Michelakis in Alberta, Canada caused widespread excitement by reporting that a drug called dichloroacetate (DCA) which is already available for patient with inherited mitochondrial disorders, can reverse the Warberg effect in cancer cells.

In the next two posts which I will post soon, I am going to present to you two case studies of patients who had stage 4 non-Hodgkin's lymphoma and their tumour relapsed and returned with a vengeance after chemotherapy treatment. These two patients refused any further treatment and started to self-administrate with DCA.

The first case study involves a male patient who mixed DCA with Mountain Dew (yes the softdrink) and the second patient took DCA with thiamine (protects nerves).

Follow this blog and please do return back soon for more updates!

EphA3 a New potential target in high risk Gliobastoma

noreply@blogger.com (Gehad Youssef) — Mon, 25 Mar 2013 01:47:00 +0000

In the February issue of Cancer Cell, an Australian team (Dr Bryan Day and his colleagues) published findings implicating the Eph receptor, EphA3 in high risk Gliobastoma, which they highlight is the most commonly occurring brain cancer and has median survival rates of less than 15 months.

Source: Cancer Cell 23, 238-248

Eph receptors normally help neurons during embroyonic development, but is not expressed at high levels later in development. However, these receptors are re-expressed in some cancers.

This research paper focused on one such receptor in particular called EphA3. This study analysed the expression EphA3 in 80 patient biopsies and in cells derived from patients. They also explored the effect of knocking out the expression of EphA3 using shRNA technology (remember that term from the previous post!). Mice were also transplanted with cancer cells under the skin in one set of experiments and directly into the skull in the second set of experiments and then EphA3 was knocked down to try to rescue them.

Below are some of their key findings:

EphA3 is highly expressed in gliobastoma especially in the most severe type called mesenchymal glioblastoma

When EphA3 expression was knocked down in patient cancer cells, these cells could no longer form tumours

Of the mice that had cancer cells transplanted under their skin, all mice receiving EphA3 knockdown survived for more than 100 days without tumour formation whereas all mice not receiving EphA3 had tumours of 1cm diameter (at this point they had to be sacrificed). One one mice (there was six in total for each group) that recieved the EphA3 knockdown had a small tumour when the experiment ended at day 140 when the experiment ended.

Of the mice that had cancer cells transplanted into their skull, all mice receiving EphA3 knockdown treatment survived and had no tumours at day 145 when the experiment ended.

Below is a biopsy of the mice brain, where you can see that on the left side, there is a clear and large tumour. This is because this side did not receive any EphA3 knockdown. The right side on the other hand did receive EphA3 and as you can see it appears normal with no tumour formation.

Source: Cancer Cell 23, 238-248

They then went on to target the receptor usign radioactive EphA3 monoclonal antibody which targets the EphA3 receptor without having to knockdown the EphA3 gene expression. This treatment destroyed the tumours in mice and prevented them from regrowing. Importantly, targeted the cells that initiated the tumour.

This finding is exciting because EphA3 would make an ideal therapeutic target against Glioblastoma. Dr Day and his collegues ended the paper by saying: "What might then be the benefits of therapeutic targeting of this cell-surface receptor? EphA3 is expressed at low targets in adult tissues, making it relatively tumor specific. More importantly, our results suggest that such therapy can eliminate the tumor-initiating cells, thereby stopping the tumour at its source."

Targeting TGF-beta 1 signalling in Pancreatic Cancer

noreply@blogger.com (Gehad Youssef) — Thu, 21 Mar 2013 23:32:00 +0000

Pancreatic tumours are a particularly horrible type of cancer with 5-year survival rates less than 5% and it is one of the leading causes of death from cancer. Pancreatic cancer received international awareness in 2011, when Steve Jobs the co-founder and CEO of Apple died after his tumour returned.

One of the key biological pathways that is altered in pancreatic cancer is the TGF-beta signalling pathway.

Normally this pathway regulates and keeps the cell growth and proliferation in check. This pathway also suppresses the immune system so that a balance can be achieved where the white blood cells can fight infection and detect cancerous cells but without harming and attacking your own healthy normal cells. TGF-beta can also cause a cell to commit apoptosis, which is a form of cell death. Finally, TGF-beta causes angiogenesis, which means that it promotes a blood supply to the cells, allowing nutrients to reach the cells.

So basically the TGF-beta pathway, suppresses the immune system and promotes angiogenesis (blood supply), however it also leads to cell death (if the cell is out of control) and stop the cell from growing and proliferating.

Below is a detailed schematic of the pathway. Don't worry about the details here, but the key thing to get from this image is that this pathway has different components that ensure the functions of the cell that I described earlier take place.

Source: http://www.genome.jp/kegg/pathway/hsa/hsa04350.html

In pancreatic cancer, parts of the TGF-beta pathway that cause apoptosis (cell death) and inhibit cell growth are mutated whereas TGF-beta itself and the other parts of the pathway are elevated. In this way, pancreatic tumours exploit the TGF-beta to its benefit, so their environment now has a rich supply of blood, the white blood cells are not suppressed.

So in summary, the pancreatic cancer (and other forms of cancer btw), cunningly benefit from the good parts of the TGF-beta pathway whilst avoiding the

In the latest issue of the journal Cancer Research, a German research team led by Professor Max Schnurr published their findings where they knocked out the expression of the TGF-beta gene using shRNA technology (we might talk about that in another post) and at the same time activated the immune system in mice models of pancreatic cancer.

Source: Ellermeier J et al. Cancer Res 2013;73:1709-1720

A group of 20 mice had no treatment. A group of 16 mice had the TGF-beta knockdown treatment only. And a third group of 15 mice had both the TGF-beta knockdown AND the activation of the immune system.

Here is the key finding:

Source: Ellermeier J et al. Cancer Res 2013;73:1709-1720

The above graph is called a survival curve and the different coloured lines represent different groups of mice. The important lines are the black line which represents mice that did not get any treatment (no knockdown of TGF-beta). The green line represents mice that had TGF-beta knockdown. The red line represents mice that had both the TGF-beta knockdown AND the activation of the immune system treatment.

As you can see the untreated mice (black line) do not do so well. By 40 days, they had to be killed because the tumour was so bad.

The mice who recieved TGF-beta knockdown treatment alone did much better and survived on average 39% longer.

The mice who recieved the combined treatment of TGF-beta gene knockout and immune system activation did even better and survived on average 58% longer than mice who recieved no treatment. Importantly, the pancreatic tumour completely regressed in 33% of mice.

Of course treating mice is a long way off from doing the same in humans, however the findings in this paper opens up potentially novel targets

noreply@blogger.com (Gehad Youssef) — Thu, 21 Mar 2013 20:59:00 +0000

Hi, welcome to Scientific Mania!

This is an exciting blog where I will highlight some of the latest and most interesting key scientific and medical findings especially research into cancer biology, treatment, drug targets, patient management. translational and clinical findings etc...

Often these findings will have been published in the same month or even week and often the mainstream media does not cover these kinds of stories.

Here are some of the kind of research, I am talking about:

Biomarkers that can predict whether a person suffering from cancer can beat the disease or not.

New cellular treatments and drug targets that may one day reach the clinic.

...And much more!

SCIENTIFIC MANIA

Bacteria engineered to produce GASOLINE fuel

Machine that was used to ferment the engineered E. coli and to collect the gasoline. Source: Nature 502, 571–574.

The HIIT exercise protocol according to Little and co-workers (2009)

Non-Hodgkin's lymphoma: case studies with DCA

Male with cancer mixes DCA drug with Mountain Dew....and achieves FULL remission!

EphA3 a New potential target in high risk Gliobastoma

Targeting TGF-beta 1 signalling in Pancreatic Cancer

Machine that was used to ferment the engineered E. coli and to collect the gasoline. Source:
Nature 502, 571–574.