For this analysis, Roswell Park researchers measured genes that were specifically induced in human prostate cancer cells by the Src oncogene, a known driver of metastatic progression and recurrence in this disease. They compared these genes to genes that are only active in prostate cancer cells and tumors that have recurred after androgen-deprivation therapy. Through this process, the scientists identified an 11-gene signature that is unique to advanced recurrent prostate cancer.
The researchers also characterized how the Src oncogene drives recurrent prostate cancer through direct activation of the androgen receptor, thereby allowing it to function even after therapy has removed detectable levels of serum androgens. They found that this 11-gene pattern is a biomarker that correlates with a more rapid progress to metastasis and decreased overall survival from prostate cancer.
“This study adds to our understanding of why some men experience metastatic progressive disease after androgen-deprivation therapy,” says Dr. Gelman. “Our data strengthen the idea that combining therapies that inhibit the oncogene Src with those that constrain the androgen receptor may help prevent recurrence of aggressive, lethal prostate cancer.”
Now a team led by researchers at the Duke Cancer Institute have identified a cellular process that cancer cells hijack to hoard cholesterol and fuel their growth. Identifying this process could inform the development of better ways to control cholesterol accumulation in tumors, potentially leading to improved survival for prostate cancer patients.
The findings are published online this month in the journal Cancer Research.
“Prostate cancer cells, as well as some other solid tumors, have been shown to contain higher cholesterol levels than normal cells,” said senior author Donald McDonnell, Ph.D., chairman of the Department of Pharmacology and Cancer Biology at Duke. “All cells need cholesterol to grow, and too much of it can stimulate uncontrolled growth.
“Prostate cancer cells somehow bypass the cellular control switch that regulates the levels of cholesterol allowing them to accumulate this fat,” McDonnell said. “This process has not been well understood. In this study, we show how prostate cancer cells accomplish this.”
McDonnell and colleagues began by identifying genes involved in cholesterol regulation in prostate tumors. They homed in on a specific gene, CYP27A1, which is a key component of the machinery that governs the level of cholesterol within cells.
In patients with prostate cancer, the expression of the CYP27A1 gene in tumors is significantly lower, and this is especially true for men with aggressive cancers compared to the tumors in men with more benign disease. Downregulation of this gene basically shuts off the sensor that cells use to gauge when they have taken up enough cholesterol. This in turn allows accumulation of this fat in tumor cells. Access to more cholesterol gives prostate cancer cells a selective growth advantage.
“It remains to be determined how this regulatory activity can be restored and/or whether it’s possible to mitigate the effects of the increased cholesterol uptake that result from the loss of CYP27A1 expression,” McDonnell said.
He said statin use alone might help, but perhaps not enough, since tumors could simply rev up the regulation of the cholesterol manufacturing process in tumors to compensate.
McDonnell said is lab is continuing the research, including finding ways to induce cells to eject cholesterol, reverse the inhibition of CYP27A1 activity, or introduce compounds that interfere with cholesterol-production in the tumor.
Even more than the Roman Empire, the Silk Road shaped the world we know today. Weaving from Europe to Asia, Russia to the Indian Subcontinent, and everywhere in between, it was along this network of ancient trading routes that people, ideas, inventions, and goods made their way.
At the centre of the Silk Road, and waiting to be discovered, is Uzbekistan. From April 2017, British passport holders (and nationals of more than a dozen other countries) will no longer need a tourist visa: you’ll pay a flat fee of US$50 on arrival, and be able to stay for up to 30 days. When you combine this change with the fact that Uzbekistan Airways also flies directly from London to Tashkent, it’s never been easier, or cheaper, to go.
What are the attractions which make Uzbekistan a must-visit destination? As the author of the Bradt Guide to Uzbekistan, I’ve been fortunate enough to explore almost every corner of the country. Here are my recommendations of what to see, do, and experience in Uzbekistan.
The Silk Road Cities
First and foremost are the great Silk Road cities of Samarkand, Bukhara, and Khiva, which have been inspiring visitors with their architectural masterpieces for centuries. All UNESCO World Heritage Sites, these cities are bejewelled with majolica tiles, stained glass, gilded ceilings, and exquisite paintings and carvings.
In Samarkand, tourists typically head straight for the Registan Square, which is comprised of three madrassahs (Islamic schools), the earliest of which dates from the 15th century. Each of the structures is highly ornamented, and the facade of the Sher For madrassah depicts strange tigers with human faces upon their backs: they are grotesque and beautiful in equal measure, and clearly challenge the orthodox Islamic view that living creatures should not be depicted in art.
My favourite site in Samarkand, however, is a 10 minute walk away. It’s called the Shah-i Zinda, and it is an extraordinary necropolis of decorated tombs, some of which are more than 1,000 years old. Each of the mausoleums in the complex is unique and beautiful, and together they will take your breath away.
Termez: off the beaten track
I like to get beyond the beaten track, however, and so it’s necessary to leave the charms of the cities behind and head out into the hinterland. Tourists rarely travel as far south as Termez, but as a result, they miss out: this was one of the great Graeco-Bactrian cities at the time of Alexander the Great, and the archaeological discoveries made here are eye-opening.
The most important finds (and well-done displays explaining where they came from) are in Termez Archaeological Museum, but it is well worth visiting the open air excavations, too. In my view, the most impressive of these is at Kampir Tepe, where you can still walk what remains of the city walls, follow the streets, and enter into homes and shops, even though the last residents left two millennia ago.
Savitsky Collection in Nukus
Uzbekistan’s history is rich, without doubt, but there’s also a lot to be said for exploring its more contemporary culture. The Savitsky Collection in Nukus (also known as Nukus Art Museum or The State Art Museum of the Republic of Karakalpakstan), in the northwestern part of Uzbekistan, has one of the most important collection of avant garde art in the world, and the story of how the collection was amassed and protected is the subject of the documentary Desert of Forbidden Art. The museum is undergoing an aggressive expansion programme, so more and more works of art will be put on display throughout the year.
Head to the capital, Tashkent
Tashkent, Uzbekistan’s capital, is a regional hub of culture, too. The glorious Navoi Opera and Ballet Theatre has recently reopened after major renovations, and the affordable tickets offer a chance to see world-class classical performances in a remarkable setting.
There are a large number of museums in the city, of which the Uzbekistan State Museum of Applied Art and the Fine Arts Museum of Uzbekistan are particularly worth exploring.
Make sure you also have time to people watch and shop at Chorsu Bazaar — the modern manifestation of the Silk Road markets of the past — and, funny as it may sound, take a ride on the Tashkent Metro, the stations of which are decorated with carved alabaster, mosaics, chandeliers, engraved metalwork, and more.
And then there is the food! Uzbek food is little known outside of Uzbekistan (with the notable exception of Samarkand in London, tipped to become the world’s first Michelin-starred Uzbek restaurant), but even the smell of the grilled meats, soups, and plov (the local variant of pilau, or biryani) will have your mouth watering. Uzbekistan is a major producer of fresh fruits and vegetables, as well as nuts, so you can expect to spend a lot of your visit snacking on healthy treats.
Uzbekistan: an up and coming destination
Uzbekistan ticks all the boxes for an exciting, up and coming destination. The country is developing rapidly, and particularly if you travel out of high season, it’s relatively easy to stay away from other tourists and surround yourself with authentic experiences and warm local hospitality. The Uzbeks have been welcoming travellers for thousands of years, and if you are lucky, you’ll soon be among their honoured guests.
Getting to Uzbekistan
Uzbekistan Airways flies directly from London to Tashkent twice a week, from £427. If you don’t mind routing via Istanbul, Turkish Airlines has return flights from £320.
Tourist Visas for Uzbekistan
If you are a British passport holder and plan to travel to Uzbekistan after 1 April 2017, you will not need a visa, but can instead pay a $50 entry fee on arrival. Additional information will be available closer to the time from the Uzbek Embassy in London, and so are visas if you decide to go on a last minute winter break before the new rules comes into effect.
Uzbekistan waives tourist visas for 27 countries
Guided tours of Uzbekistan
Uzbekistan is a hot destination for 2017, and a number of UK-based tour operators are offering scheduled departures and bespoke itineraries. For example, Wild Frontiers offers adventurous itineraries in Uzbekistan and the neighbouring countries of Kyrgyzstan and Turkmenistan.
Viator also has a selection of local operators:
Recommended Uzbekistan guide books
Bradt Guide to Uzbekistan (published 2016) RRP £17.99
Uzbekistan: The Golden Road to Samarkand (published 2014) RRP £16.95
Lonely Planet Central Asia (published 2014) RRP £19.99
It’s estimated that up to 90 percent of older men experience BPH, or benign prostatic hyperplasia, and quality of life can be severely affected.
“During development, both male and female embryos start out having certain fetal tissue called the Müllerian duct mesenchyme,” said Jose Teixeira, professor of reproductive biology in the College of Human Medicine and lead author of the federally funded study. “Human male embryos need to get rid of this tissue typically between 7 to 10 weeks after conception or else they will develop a uterus.”
According to Teixeira, his latest findings, now published in PNAS, clearly show that some of this tissue remains in male mice and contributes to cells where the prostate is located.
“No one really has known the origin of this disease,” Teixeira said. “But we now have early clues that this remnant tissue in the mice becomes part of the tissue that would go on to develop an enlarged prostate.”
Teixeira and his team also found that a malfunctioning tumor-suppressing gene that’s associated with certain cancers, such as colon and pancreatic, and is known as Stk11, additionally influenced the development of BPH.
“By altering the Stk11 gene, the number of cells in this embryonic tissue multiplied above what is needed and caused the prostate tissue surrounding the urethra to grow,” Teixeira said.
This overgrowth of tissue is what he indicated could cause the lower urinary tract symptoms, such as difficulty urinating, in older men with the disease.
“Most drugs or procedures on the market today just treat the symptoms, not the disease itself,” Teixeira said. “Our study could open up a whole new pathway for targeted treatments to help shrink the prostate tissue or stop it from growing further.”
Before this can happen though, Teixeira said that his team will first have to determine whether the Stk11 gene or the other genes and proteins it controls are similarly affected in the human form of BPH.
If Turkey has a an exotic version of a bucket and spade seaside resort, Alanya on its south eastern coast is it. Its lovely white sand beaches are lapped by the warm waters of the Mediterranean sea and overlooked by the towering Taurus mountains. And as you follow its coastal curve and meander inward too, the mood perceptively changes from historic to bizarre, lively and amusingly, a little cheesy too.
Along the harbour are myriad restaurants, some named after celebrities such as James Dean and Elvis and an open-air segment of cafés, dubbed the tea rooms, that look onto the tens of moored ships. Some of these are private yachts and some take tourists out to sea. Smaller ones dressed in yellows, reds and orange bob on their laurels, offering a colourful eyeful against the deep blue of the sea.
One sun-scorched afternoon, I found myself on the Sea Angel, a wooden pirate ship that looked twee with its a statue of a a silver angel. With Kapten Arif at the helm I was was about to spend four-hours with a rather large gaggle of Russian, German and Dutch tourists. Party music escaped from some overhead speaker while the crew-cum-gymnasts served and entertained. The ship anchored every now and again so we could jump ship and swim in the warm sea water and as we sailed by Alanya’s rich heritage of coves and caves (Phosphorus being the most famous), crew members took to diving off them in all manner of daredevil ways. Even dolphins turned up on cue to a collective joy. A lunch of skewered chicken followed by juicy watermelon was remarkably good. Though not a sophisticated jaunt, young families and those young at heart may find this to be tremendous fun.
Yet everywhere I looked I was reminded that this is an historic town. It’s 13th century castle, built by Seljuq Sultanate of Rum on a rocky peninsula, is perched 820 feet high. It’s now an open-air museum with a palace, villas and a chapel that was converted into a mosque and is testament to a long history of invasions including the Ptolemaic, Seleucid, Roman, Byzantine, and Ottoman Empires.
Built by Seljuq Sultanate of Rum on the rocky peninsula part it includes villas and a chapel that was converted into a mosque. Part of the peninsular juts out onto the Mediterranean sea and this is where “man throwing ledge” remembers the gory story of slaves being pushed to their death. Slaves would be given three stones to throw into the sea. If the stones made a splash (an impossible task thanks to the rock formations) they would live another day, if not they would be thrown to their death.
Following the winding floral stone path downwards I was stopped in my tracks by Che Sukru. Clad in just a pair of shorts, his tanned torso was bent over a hand operated juicer making pomegranate juice that he sold for couple of lira a glass. Drinking the juice in his garden café shaded by mandarin and lemon trees while chickens clucked and pottered, was an experience that was beyond quaint.
Following the path as it twisted down to ground level I was led to the now defunct but still fascinating arches of the Tersane shipyard. It serves as a museum to this bygone industry with part-built ships, maps and information describing how it may have been.
Nearby and standing to attention in the harbour is the 13th century octagonal landmark Kızılkule (Red Tower) so called because of its red bricks. Built to protect the town from attack, there are five floors each with a museum of artefacts. Climbing all 86 steps to the roof means getting sensational views over the marina and the beaches.
Reaching the town from the harbour means walking through a bizarre cat sanctuary where stray cats can tuck into bowls of food and shelter in purpose built hutches. It’s part of a serene park where fountains flow while felines and people mingle in quiet reverie.
Just beyond that is a sprawling warren of tiny streets laced with numerous of shops selling fake designer bags, clothes and shoes. Michael Korrs, Prada, Chanel populated the shelves with the odd smattering of Mulberry. It’s common to haggle and it’s impossible to resist.
Amid these streets, restaurants and bars are plentiful with Bar Street being the hotspot for a pulsating night life. It’s also round here that I lunched at Mini Mutfak, a fabulous Turkish restaurant where lamb Kofta (meatballs) never tasted so good and I simply loved the Yavalama – mint beef balls with small chick peas in tzatziki sauce.
Beyond these tiny roads is the main road, Ataturk Street named after Mustafa Kemal Atatürk (1881-1938) a Turkish army officer, revolutionary, and the first President of Turkey who founded the Republic of Turkey. There is an impressive statue of him at the central crossroads where the Turkish flag flies at full mast. Indeed, most buildings in Alanya have the Turkish flag hanging from them.
There are long stretches of beach and perhaps the prettiest is Cleopatra beach. It’s in front of Dalmatas Cave (a tiny two storey cave with impressive stalactites and stalagmites). They say it was named after the Egyptian Queen who stopped by and enjoyed a swim in this bay. Had she done so today she could have also lazed on a comfy cabana or sipped her tipple at a choice of beach side cafes.
One day I joined a jeep tour – a convoy of 18 jeeps filled with people who were encouraged to throw water at each other. I couldn’t fathom out why but on the bright side we clapped eyes on gorgeous pine forests, banana and cotton plantations as we trucked our way through the dirt tracks of the Taurus mountains We stopped for a bbq lunch alongside Dim River and visited an old village to have a peep inside an ancient mosque.
A more sedate day out was to Dim Caye for lunch. Al-freso restaurants are stretched out over the Dim river on platforms. Some restaurants allowed diners to fish for trout for their lunch. Not so at Gol Piknik, where we were seated on cushions and served Turkish cuisine served to a backdrop symphony of a waterfall and the quacking of passing ducks. After a quick finger check of the cold water temperature and I resolved to stay on dry land, though I did spot others – adults and children – splashing and frolicking around the river flumes.
There is a weekly bazaar that takes place in town and although mostly a food and vegetable market with the odd vendor selling flags, it offered a reassuring snapshot of local life.
That afternoon I visited a uniquely Turkish venue, a local Hammam. My lack of Turkish banter was of no concern because no words needed – a knowing look at reception led to a wet sauna followed by dry heat followed by a long dip in a swirling hot tub followed by an eye-watering pummelling given by a slight lady who you’d think couldn’t hurt a fly and soapy deep clean scrub. After a short rest, presumably to recover, a lovely massage pieced me back together again.
It felt truly exotic.
Where to Stay in Alanya
I stayed in a private luxury villa in the hills above Alanya offered by 5 Star Villa Holidays – read my review: Villa Review: Dream Villas, Alanya, Turkey
Villa Review: Dream Villas, Alanya, Turkey
Other recommended options are Grand Okan Hotel (great for families) and Sunprime C-Lounge (adult-only all-inclusive hotel).
How to Get to Alanya
I flew with Monarch, the scheduled leisure airline, which operates flights to Antalya from London Gatwick in the summer and Leeds Bradford in the winter with fares, including taxes, starting from £40 one way (£104 return).
Alanya is about 115 km from Antalya Airport and 40 km from Gazipasa Airport. You can either catch the bus from the airport to the city, or rent a car, giving you the freedom to explore further afield and, like me, to consider accommodation slightly outside the city centre.
“An estimated 7.7 million children and adolescents participate in organized sports each year and the Centers for Disease Control and Prevention estimates that they sustain between 1.6 and 3.8 million sports-related concussions annually,” said Morrissey. “In response to this, the state of Rhode Island passed the School and Youth Programs Concussion Act (SYPCA) in July 2010. The law outlines both mandatory and recommended provisions in regard to managing student athletes with a suspected concussion. Our study assessed compliance with this law among Rhode Island high schools and community league organizations.”
In a 2013 statewide assessment of Rhode Island concussion law compliance among RIIL member high schools, non-member high schools and selected community league sports organizations, the study team found nearly universal compliance with mandated elements of SYPCA.
All athletic directors surveyed reported that they require concussion information sheets to be signed by both student athletes and parents prior to the start of each sports season. The research team also found that all coaches and 93 percent of volunteers have completed annual concussion training.
One hundred percent of surveyed groups also reported that any student athlete with a suspected concussion is immediately removed from play, and 93 percent reported that those students cannot return to play until they receive written clearance from a licensed physician, all per the SYPCA mandates.
“These SYPCA laws only apply to schools that are RIIL members,” said Michael Mello, M.D., M.P.H., director of the Injury Prevention Center and co-author of the study. “When we explored other non-RIIL schools and sports organizations where SYPCA is recommended but not required, and also any of the recommendations that are not legally required of RIIL members, we found a very different compliance rate.”
Only a handful of schools require student athletes to complete any type of pre-season neurocognitive testing, and nearly 20 percent don’t offer it to student athletes at all. Half of the surveyed groups reported developing a written return to play protocol.
“These compliance statistics show us that in order to best protect youth athletes in Rhode Island, all recommendations outlined in the SYPCA law should be made mandatory,” said Mello. “Additionally, non-RIIL schools, as well as community sports organizations, should also be required to comply with the law.”
Neha Raukar, M.D., director of the Center for Sports Medicine and a co-author of the study, sees many youth athletes in her clinic for concussion treatment. “If a concussion is not treated properly and student athletes return to play too soon, they are at high risk for prolonging their symptoms, meaning more time out of the classroom and on the bench. They are also at risk for experiencing a devastating post-concussion event, such as second impact syndrome, which can be fatal,” said Raukar.
“We are only just beginning to understand the long-term consequences of sustaining repeated head trauma and concussions,” said Raukar. “Physicians, coaches and school staff alike all need to know the importance of properly diagnosing concussions, as well as the criteria for when a student athlete can both return to school and return to sports.”
But, Morrissey also urges that the public needs to play a role and ensure that their school or community sports organization follows all the recommendations in the concussion law. “One example of our community pushing for better concussion protection for our students can be seen in school nurse annual training,” said Morrissey. “At the time of our survey, only one quarter of surveyed groups required school nurses to complete annual concussion training. But now there is a new law in place to try to correct this, and Rhode Island is one of only a handful of states to reach out to school nurses for training. This is a clear step in the right direction.”