Tuesday 29 December 2009

Hanoi and Ha Long bay


So there's been a bit of a break since the last post. After Saigon I flew to Danang then shared a taxi with two other solo travellers to Hoi An. Everyone on the flight was going to Hoi An I think. Its a very pretty town, ridiculously so in fact, it looks like a set from a Disney musical. There are lots of tailor shops there but the only thing I bought was a fake North Face bag to use as a day sack. I stayed at the Hop Yen hostel, which was $7 per person for a twin room, cheapest in town I think. I shared with a German fellow, who left the next day but paid for the room while I was out - thanks for that, you didn't leave any contact though! It rained constantly in Hoi An so I didn't make it to the beach.

I took a day trip from Hoi An to the My Son ruins, which are the remains of some Cham temples in the jungle. They weren't a patch on Angkor but it was good just to walk around in the jungle for a day. The most interesting thing was the several large pools which were actually in bomb craters. There is one temple which is in pretty good shape, the rest were in bits and under heavy restoration. I booked the trip through the hostel, I think pretty much every time I've booked a tour or bus here it has picked me up from the hostel and then drove around in circles for about an hour picking people up, I saw my hostel about three times in Hoi An. Surely it could be better organised. The souvenir shop at My Son was a treat - fridge magnets depicting Paris and Marseilles, nothing to do with Vietnam or the temples. There's a lot of that in Vietnam - rows of shops selling the same things, men trying to sell you books, always the same ones (photocopied versions of Mr Nice, Irvine Welsh, the same South East Asia Lonely Planet...). Speaking of fridge magnets, I've lost my Angkor magnets somewhere along the line, the folks at home will be disappointed.

It was a 3hr trip from Hoi An to Hue, some nice scenery as we went through the mountains. The bus takes you through a fairly long tunnel; The train actually goes over the top of the mountains which would have been spectacular but it would have meant a journey to Danang first and then getting a train, the bus won out as it was easier. One of the people I met at Danang airport was traveling north so I teamed up with her (I'm mentioning no names here), and together with two others we met on the bus, we decided to walk from the bus stop to the hostel we had looked up, and so avoid the taxi touts. Felt good to find the place in an unfamiliar city. It's turning out to be quite easy to meet people, and it feels a bit less stressful walking around trying to find a place to stay or eat. Not much going on in Hue I thought, we stayed in Hue Backpackers, which was very good for the price, good food too (I had a chicken burger for the first time ever, don't know why apart from I saw someone else's and it looked good). I was there three nights, and spent two evenings in the DMZ bar across the road as the beer was cheaper than the hostel. There is a great vegetarian restaurant by the river, can't remember the name. Vietnam is actually turning out to be quite easy to be a vegetarian, there is a tradition here among hte buddhists of having a few days each month when they don't eat meat (only the monks are truly vegetarian though.) The main part of Hue is a huge walled citadel with a smaller walled area inside it (the Forbidden City), I spent the best part of a day there but it wasn't that impressive to be honest. Its more interesting to read about the history, the place was bombed to bits by both the French and the Americans.

I spent a day with my travel buddy walking out to visit the Tomb of Du Doc, Hue is surrounded by tombs of all the past emperors. It was worth the three hour hike as the tomb area was well preserved, a nice lake, some temples, some statues of the emperors mandarins. The walk back to Hue was insane, rush hour, roads chocked with bikes but no pavements. Made it back alive somehow. Took an overnight bus from Hue to Hanoi, 14 hours, cost $10. Arrived about 7am and again walked to a hostel rather than take a taxi. I got ripped off in Saigon I think (paid three times what I should have done according to my friend who lives there, even though the meter was on), wherever possible I walk anyway, I never take a cab at home unless I'm with other people. The first hostel in Hanoi I stayed at was Central Backpackers, not far from the Hoan Kiem lake and by the St Joseph church. I arrived on Christmas day so it was nice to see a procession there, all Vietnamese bishops and nuns and so on. The Central Backpackers is a new place run by young Vietnamese so I thought I 'd give it a try. It was ok, room clean enough, and there was always people hanging out downstairs, a couple of guys had guitars so it was good to have a strum. On the downside, the free beer tasted off, there was no sink in the bathroom so people were spitting on the shower floor while brushing their teeth, and I got messed around on which bed I was sleeping in. Also, once in the evening I asked for a cup of tea, which they advertise as being free, the young man just sort of brushed me away, and sat down behind the reception desk and stared at me. So I started to feel a bit weird about the place. My friend had booked into the Little Hanoi on Hang Ga street, I went to check it out and it seemed a lot better. I booked my Ha Long bay tour there (that's the picture above). It was $45 for two days, one night on a boat. That was enough for me, to float around the amazing limestone karst islands, explore a cave, do a bit of kayaking. The cabins on the boat were ok, not as cramped as I expected, they even had their own bathroom with shower. 14 people stayed on the boat; some people got off at Cat Ba island for the night, they were going back to Hanoi the next day, I couldn't understand that as it meant no kayaking and very limited cruising time through the bay. The meals were included, but not drinks. It was 30,000 dong per bottle of Tiger, no other beer. Some cocktails or fruit juice would have been good, hardly anyone was drinking. I met some interesting people, Brazillians, Germans, Americans, and a Maori woman. (Just for the record it is 18,000 Dong to the dollar, so the beer cost a pound - still twice as much as in the street side bars). Ha Long bay was definitely worth it, it was my main reason for coming to Vietnam.

Yesterday I went to see the preserved corpse of Ho Chi Minh, the highly revered former President, it was a bit strange really, everyone sort of shuffles past staring at this waxy looking figure in a glass case. Cameras are not allowed (they get confiscated before entry and handed back afterwards), clothing must be respectable, and people were getting told off for having their hands in their pockets or talking. I also visited the Ho Chi Minh museum, lots of pictures and letters giving the life story of the man, I think it would be better to read a book first though. After that I went to the "Hanoi Hilton", or Hoa Loa prison, which was first used by the French to imprison the Vietnamese during colonial times, the conditions being horrific. There is a room with statues of Vietnamese prisoners in stocks, that was a bit spooky. Overall it was similar to the Tiger prison in the War Remnants Museum in HCMC, which had far more interesting stuff in it. The Hoa Loa was later used by the Viet Cong to imprison American POWs (mostly pilots, including Republican John McCain), the pictures show a deliberate contrast with the conditions endured by the Vietnamese prisoners - the Americans are shown eating Christmas dinner, receiving gifts from home and playing volleyball.

One day left in Hanoi before I go to Luang Prabang in Laos for New Years Eve. I'm flying again, which is not really in the spirit of backpacking, but I'd heard too many stories about 36 hour bus rides, people waiting hours for a driver to appear, drivers being drunk and so on. A 1 hour flight is just too tempting, although they are expensive - cost me 126 Euros.

Saturday 19 December 2009

Saigon


Picture shows my room mate in Saigon... Only kidding. I was really tired yesterday after getting the nightbus from Ha Tien to Ho Chi Minh city. It took 7 hours, and I didn't really sleep on it. When I arrived I had no idea where I was, took a taxi to the Phu Ngam Lau area which is basically the tourist area. Staing at the Ngoc Minh guesthouse, which is off a narrow street from the main road. Today I took a walk round the city. Although it is heavily built up and there are thousands of bikes, there are also some quite nice parks. The traffic is not totally chaotic, there are a lot of one-way streets and traffic lights that even the motorbikes obey. When crossing hte road you just have to wait for a small break in the traffic and go for it, helps if there's a local crossing too. I got asked a lot whether I wanted a motorbike or my shoes shined but after Bangkok and Siem Reap I'm used to it, don't make eye contact and keep walking. It felt rude intially to ignore people but it gets very tiring saying no thanks to everyone you pass.

I went to see the War Remnants Museum. Outside are some models of tanks and planes used by the US army. The picture is from a reconstruction of prison cells used to detain suspected VC sympathisers. There are some barbed wire "Tiger" cages that looked particularly gruesome, and images of tortured victims with teeth pulled out, nails driven into their heads and so on. Most of the displays inside detail what the US forces and their allies got up to during the war. The worst bit was the pictures of children which are thought to have been born malformed due to agent orange. There was a photo of a woman selling fruit, even when the villages where being bombed people were still trying to go about there normal lives.

After that I went round the Independence Palace, which did not have much in it but it wasn't much to get in (less than a dollar). Mainly some stately rooms and some phoney set ups of war rooms and communications rooms and so on. After that I just walked around, seeing the Notre Dam cathedral, Post Office and a quick look in Saigon Square, a very busy mall packed with clothes shops (mostly women's clothing so hundred of teenage girls - scary stuff). I found a vegetarian restaurant which was ok, portions very small though so I had two meals. They charged me for using the towel which was placed on my table, so I'll have to watch out for that in future. Tomorrow I go north, hopefully find my way to Hoi An.

over.

Wednesday 16 December 2009

Sihanoukville to Ha Tien


I've made my way along the coast of Cambodia to Ha Tien, which is in Vietnam just after the border. Along the way I went to Kampot, which had a nice sunset over the river but not much else of note. Quite a dirty town, and loads of dogs - howling and barking all night. Next I went ot Kep, which is an old French resort, lots of crumbling villas overlooking the sea. I hooked up with someone I'd met in Kampot and we had a day on the Rabbit Island. To be honest there's not much to do in Kep apart from swim in the (murky) sea or swing in a hammock, but it was a cool way to pass three days. And a bit of a relief after some of the other places in Cambodia which were quite intense. We did eat some great crab in Kep, seafooded-out at the moment. Also I saw a vivid green preying mantis, just outside my hotel room (Kep Seaside Villa), which rocked.

I took a moto from Kep over the border to Ha Tien in Vietnam this morning. It took about an hour and cost $12. I was the only one crossing at that time (about 9.30AM) so I breezed through. Ha Tien is a quiet place, I'm taking the night bus to Ho Chi Minh city from here at 10PM, should get in about 5AM. Saves on paying for a room!

Til next time, I'm batman

Sunday 6 December 2009

Siem Reap, Cambodia

Sok Sabai,

After two sleepless nights in Bangkok I got on a plane to Cambodia. Siem Reap is a town that has built up around the temples of Angkor, from the old Khmer empire. I'm staying at a very nice guesthouse (the European), and have my own driver to take me around to places in his tuk-tuk. So far I've been on a boat on the floating market and seen some of the temple sites. So far, so chilled. There is a lot of poverty here, at every stop there are children trying to sell you water, postcards and various tat. I bought a hat of one of them, within five minutes the band around the top came off. Well, you get what you pay for. I'm here for another two nights then I'm planning on heading East to the capital, Phnom Penh. Weirdest thing I've seen is the crocodile farm at the back of the guesthouse. Whoever owns the building behind here has two swimming pools and about 30 big crocodiles lounging about, apparently bred for food. No, I haven't tried any croc burgers yet...

Unfortunately the net is too slow here to upload any images so you'll have to wait until next time.

Rob

Thursday 19 November 2009

Travel plan

This shows the flights I have booked. Bit of a strange route, it looks like it would make more sense to start in Japan and travel down Asia to Malaysia and then on to New Zealand. However, I wanted to get to NZ before Winter. The trip is basically three legs, the first in South East Asia:
The blue arrows show flights, the black lines are the potential overland routes. The first flight is to Cambodia, where I'm planning to spend some time at the Ankor temple sites and then travel to Vietnam. Vietnam looks like a long, long country. There are tons of motorbikes and little in the way of road rules. I'm travelling North, making a few stops (probably at Hoi An, for instance), and I'll probably be in Hanoi (the capital) for Christmas. After that, I'm planning to fly into Laos and stay around Luang Prabang for a bit (flying rather than taking the 24hr+ bus journey from Vietnam!). I need to get back into Thailand for the next flight, so I'll probably cross over at Chong Mai (probably spelt that wrong) and travel down to Bangkok via train, stopping at a couple of places (like the old capitals, Sukothai and Ayyuthaya).

After that, I haven't planned much, so I'll save that for the next blog. New Zealand I might do a bit of work, and I definitely want to do some hiking. Japan I'll visit a couple of cities and maybe stay in a Buddhist temple. I want to get to China via South Korea, and visit Beijing and Xi'an, finally getting to Hong Kong. That's as much as I want to plan really.

Rob

Tuesday 17 November 2009

Flatulence

As a vegetarian, people often say to me, "You smelly b@stard!". This is due to my farts. I always say they are due to stress, but...

I was reading about yeast metabolism and raffinose breakdown, something that humans cannot do, as we do not have the required enzyme. Raffinose is found in high amounts in plants, especially beans and green cruciferous vegetables such as brocolli and spinach. Well, we've always known these make you fart the most. Just ask Benjamin Franklin. In humans, the raffinose, along with complex sugars, ends up getting fermented by bacteria in the gut, giving rise to wind. Although this is not harmful, its not ideal. After all, as a social animal you don't want to isolate yourself due to your full-bodied bum-aroma. I'm not sure you would survive on a diet that excluded meat/animal products and beans/green vegetables. What's left? Although some people think they can survive off just sunlight.

We don't seem too well adapted to digesting vegetables. So are vegetarians in denial of their true self?

Friday 6 November 2009

Hygiene

This week I decided to see how long I could go without changing my shirt. Also, I didn't use any deoderant, and I walked to work and back each day (about 3 miles one way). Why? I am going travelling soon and I want to minimise the number of clothes I take. I already don't hardly ever shave, so I'm halfway to being a vagabond.

The results? Actually, the t-shirt didn't smell too bad. Maybe its made of a magic fabric (I think its just cotton though). I would take it on holiday but the design on the front has a VW camper van with a Union Jack on it, might not be the best idea in some parts of the world.

Of course, this is November in the UK, a week in the tropics might be a different story.

blip blip

Monday 28 September 2009

Drugs Don't Work?

Following on from the last post, which looked at new research on a way to overcome multi-drug resistance (MDR) in cancer cells (MacDiarmid et al., 2009. Nat Biotech 27:643), I thought I'd try and find some information on both the prevalence of MDR, and the effectiveness of current chemotherapy treatments.

This was partly inspired by an article by Mike "Health Ranger" Adams comments in a national newspaper, where he basically says that Patrick Swayze was killed by the chemotherapy, and not by the cancer itself (goto article)

So according to Macmillan Cancer Support, there are over 200 types of cancer and over 50 different chemotherapy drugs currently in use. The main effect of these drugs is to stop cancer cells dividing by interfering with DNA replication. For example, cisplatin, a commonly used drug in chemotherapy, causes the DNA to cross-link or stick together irreversibly. The result of interfering with cell division is that either the cell will commit suicide (apoptosis) or at least stop growing. The aim is to either kill the tumour or prevent further growth so it can be operated on. Chemotherapy is often used as an adjuvant with surgery, to try and kill of any cancer cells that may remain after the tumour has been surgically removed.

Unfortunately, cancer cells become resistant to the drugs used on them. The response to this has been to increase dosages and/or use combinatorial therapy (several drugs at once). As most drugs have some kind of side effect, increasing the drug load will increase the toxicity to the patient. The side effects of chemotherapy are generally due to its effects on cells which have high rates of division, such as bone marrow (which makes blood cells), hair follicles, and the lining of the mouth and digestive system. In younger people, it may also affect the germ cells, reducing fertility. The loss of bone marrow cells is the most serious, as this can lead to anaemia and infection from lack of red and white blood cell production. Basically the drugs are non-selective, once they are in the blood they will have an effect on any cell which divides. This is why therapies which use a targeted delivery system such as the one I discussed earlier are really important if we want to fight cancer. At the moment, the strategy is largely, give the patient drugs for a certain period of time, then stop the treatment to let the patients own (non-cancerous) cells recover, while hoping that all the cancer cells have been killed.

How do cancer cells become drug resistant? The main mechanism seems to be by pumping out the drug molecules from the cell. Essentially there will be a mutation leading to over-expression of one of the ATP-binding cassette transporter proteins, which are able to pump out a wide variety of foreign molecules from the cell. The two main ones identified are p-glycoprotein (or MDR1, this was targeted in the MacDiarmid minicell study) and MRP (Pajic et al 2009 Cancer Res 69:6396, Cole et al., 1992 Science 258:1650). Other mechanisms could include activation of DNA-repair pathways or enzymatic pathways that break down the drugs, although these are mostly unknowns.

So the point of this post was to find out the effectiveness of chemotherapy. A fairly recent study looked at 5-year survival rates after cancer treatment with or without chemotherapy. Chemotherapy was found to only increase survival by 2.3% in Australia and 2.1% in the USA, which is not much, but better than nothing (Morgan et al., 2004. Clin Oncol R Coll Radiol 16:549). For comparision, 5-year survival of cancer without chemotherapy is 60%, this varies a lot according to the type of cancer.

There a numerous papers comparing the effectiveness of treatment with and without specific drugs for various different cancers. One suggested that chemotherapy for elderly prostate cancer sufferers may not increase survival rates (i.e. lifetimes) but significantly reduced pain, i.e. gave a better quality of life (Mike et al., 2006. Cochrane Database Syst Rev. 18:CD005247). This theme was found in the other studies I looked at. Humber et al. suggested that increasing the dosage of chemotherapy against womb cancer does not improve survival but worsens the side-effects (Humber et al., 2005. Cochrane Database Syst Rev 20:CD003915). finally, a study looking at the effects of using the drug gemcitabine after surgery to remove pancreatic cancer found that the drug prolonged the cancer-free period after the surgery, but ultimately did not result in an extended lifespan when the cancer recurred (Ueno et al., 2009. British J Cancer 101:908).

The case for chemotherapy then - it may slightly improve your chance of survival, but more importantly, make your final days a bit more comfortable. However, just pumping more and more drugs into the patient is not going to help.

Back to the article by Mike Adams. Swayze died of lung cancer, which is notoriously untreatable. What drug therapies we have do not work very well, one study gave the figure of just two months of extra life following chemotherapy for small-cell lung carcinoma (Suglan et al., J Clin Oncology 20:3750). To repeat what I said above, this is maybe better than nothing. And without testing the drugs, on patients who are dying and are desperate for anything that works, we would not have found out the things we have. The key thing here is though that I have not found any evidence that chemotherapy actually reduces chances of survival for cancer patients.

It seems clear to me that the future of cancer therapies must reside in targeted therapies, such as the minicell strategy I am currently getting very excited by. To be fair to the health ranger, I should have a look at "alternative" therapies for cancer (i.e. not from Western medicine). Maybe next time.

Rob 28/9/9

Tuesday 22 September 2009

Curing cancer with bacteria

It was my turn to do journal club today, which is where we do a talk to our lab group about a science paper that has recently come out. Today's title was "Sequential treatment of drug-resistant tumors with targeted minicells containing siRNA or a cytotoxic drug", by MacDiarmid et al., and it was a strange, though interesting one. (Reference: Nature Biotech 27 643 - 651 (July 2009))

I've had a long standing interest in gene therapy, which is where you would use genetic factors to cure a condition, rather that just administering a drug. This paper focused on an alternative treatment for cancer. A lot of tumours become resistant to the drugs used for chemotherapy, which is often due to a mutation which leads to the cell making lots of a certain type of protein that prevents the drug taking action. Increasing the dosage may only make the patient sick due to side-effects of the drug, while the tumour survives.

MacDiarmid et al. used a combination of small interfering RNA, or siRNA, to reduce the resistance of a tumour cell to drugs, and a novel method of delivering the siRNA directly to the tumour, namely bacterially derived minicells. Minicells are basically bacterial cells lacking any insides that can be loaded up with genetic material or chemical compounds. They are formed from a mutant strain of bacteria that does not divide properly. Usually bacteria have a main chromosome, but minicells lack this and are very small as a result. They are really not much more than a sack surrounded by a lipid (fat) membrane. This can be loaded up with a drug for instance by incubating the minicells and the drug together. The minicell can be programmed to deliver its contents to a target cell by the use of a special antibody. The antibody recognises part of the minicell wall, and also an antigen presented by the target cell, which in this case is the EGF-receptor (EGF = epidermal growth factor) which is found in high concentrations on the outside of many types of cancer cell.

In this case, the target cell was a human tumour that had been grafted onto some unfortunate mice, and was expressing the drug resitance gene MDR1 (for multi-drug resistance). The Minicells get into the tumour cells and get eaten up by the cell, but release the siRNA payload. This activates the RNA silencing system to prevent expression of the MDR1 gene, and thus make the tumour drug-susceptible again. They then followed this up with another treatment, where the minicells were loaded with a drug which could then kill the tumour off.

As for the results, they treated mice bearing various types of tumour with the minicells carrying anti-MDR1 siRNA and then used minicells carrying a drug. The tumours regressed in size, and the mice survived, while the treated ones did not. The controls used were good - minicells which were not targeted to the tumour, ones which has a nonsense siRNA, which has basically a random sequence so does not affect any gene, and various combinations of minicells and standard drug administration. None of the control treatments had any effect.

So this strategy has a lot of potential in humans, assuming that people could accept a treatment involving what is basically the outside of a bacterial cell, and some genetic tinkering. I would imagine there would be a lot of problems with the human immune response as well. One thing the authors did not show was whether the treatment would work against a tumour of mouse origin, as they only used grafted human tumour cell-lines. Their strategy was to use an anitbody against EGF-r, which although it is expressed highly in tumours, is also expressed elsewhere in the cell. They used an antibody against the human EGF-r to target the minicells, which probably doesn't react very well with EGF-r of mouse origin; a good control would have been to use an antibody against mouse EGF-r. Also, although the treated mice survived, it wasn't clear whether the tumour had regressed or been killed off. I suppose if it extends your life by a few years, it still would make a good treatment, but there are obviously a lot more studies to be done.