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Newsfeed; Sunday, October 18 2020
18 Oct 2020 Share this post
Ghani: Ghor Attack Reflects Taliban's War Approach, Undermining Hopes For Peace
President Ashraf Ghani on Sunday condemned the Taliban attack in Firozkoh, the capital of Ghor, where at least 12 people were killed and 100 were wounded in a car bomb explosion.
The statement released by the Presidential Palace said that such attacks reflect the Taliban's attitude regarding the war and undermines the aspirations of Afghans to end the conflict through peaceful dialogue.
"The government of Afghanistan emphasizes that these attacks, contrary to Islamic and human values, are a continuation of the unjust war against the people of Afghanistan and the deliberate killing of Muslims," the statement says.
The Presidential Palace again states that continuing Taliban attacks and violence will seriously challenge the peace effort.
They said that Afghanistan wants an end to the war and once again called on the Taliban to renounce their "unjust and un-Islamic" war and accept a ceasefire.
Ongoing war in Helmand
Taliban spokesperson Qari Yousuf Ahmadi issued a veiled threat to the U.S. regarding the airstrikes in Helmand.
They warned the U.S. Forces in Afghanistan (USFOR-A) that the Americans violated their commitments to the Doha agreement by carrying out "excessive" airstrikes following the Taliban attacks in Helmand.
"All responsibility and consequences from continuation of such actions shall fall squarely on the shoulders of the American side," Ahmadi said.
He said that the airstrikes were carries out in areas other than combat zones and where there was no active fighting.
Danesh: National Standards Authority Needs Comprehensive Reforms
Second Vice President Sarwar Danesh said the Afghanistan National Standards Authority (ANSA) is facing many challenges and needs to implement comprehensive reforms.
Speaking at the World Standards Day celebrations being held by ANSA on Sunday, Danesh said reforms were needed, along with the review of policies and plans to seriously combat corruption.
He said that ANSA had so far approved 656 standards, which is a big step, but more work is needed to identify failures and problems.
Danesh highlighted that some of the problems and challenges were the lack of coordination between government departments and the private sector, lack of necessary staff and capacities, lack of sufficient budget, weak communication with international institutions, instability in the leadership of ANSA, and financial mismanagement, among others.
The vice president said that the expectation of the government and people of Afghanistan from the leadership of ANSA is to accurately identify obstacles, weaknesses and problems and work to eliminate them.
Aziz Ahmadzai, head of ANSA also addressed the event and said that along with developing a number of policies, they were working hard to fight corruption.
He also called on Afghan security agencies, traders and the private sector to work with them to implement the standards and assess the quality of commercial materials.
AIHRC: While Fighting Crime, Address Root Cause And Respect Human Rights Norms
The Afghanistan Independent Human Rights Commission (AIHRC) issued a statement on Sunday, expressing concern over the escalation of criminal activity and insecurity in Kabul and other provinces.
The rights body called on the government to address the root causes of the economic and social factors that lead to criminal activities in order to fight crime.
"Citizens' right to life and enjoyment of physical, mental and psychological security are fundamental human rights," they said.
They evoked the Universal Declaration of Human Rights and other international and national laws, to protect and safeguard the right to life and security of their citizens.
They emphasise that even when dealing with the perpetrators of the crimes, the government must respect human dignity and the principles of fair trial.
The statements come at a time when security officials have been recorded ordering the criminals resisting arrest can be shot at by the police, or that words such as "compassion" do not exist in their dictionary while dealing with crime.
Abdullah: Ghor Attack Runs Counter To Principles Of Peace Talks In Doha
Abdullah Abdullah, chairman of the High Council for National Reconciliation, said that attacks, such as the one in Ghor, are against the principles of peace being discussed in Doha.
Abdullah, who is on an official trip to Iran, shared a Facebook post on Sunday, condemning the car bomb explosion near the police headquarter in Ghor centre, Firozkoh, that killed at least 12 civilians and wounded 100 more.
Preliminary information by the Ministry of Interior (MoI) showed that most of the victims, if not all, were civilians.
"Any attack on the lives of civilians and committing murder and bloodshed is against Islamic, human and moral standards and is not allowed in any religion," Abdullah said.
"While peace talks are taking place in Doha, such attacks run counter to the principle of commitment to peace and an end to war and violence through dialogue."
He added that the increase in terrorist attacks and violence in Afghanistan is also affecting the peace negotiations and expressed hope that the warring parties, especially the Taliban, will demonstrate "goodwill for peace" and stop killing civilians.
It is to be noted that no group, including the Taliban, has claimed responsibility for the blast.
3 Security Personnel Killed In Kunduz
Provincial officials confirmed that three government forces were killed during an attack by the Taliban in Kunduz on Saturday night.
Kunduz governor's spokesperson Esmatullah Moradi told Reporterly on Sunday, that the Taliban had launched attacks on Afghan Local Police (ALP) checkpoints in the Dehqan Qeshlaq area of Imam Sahib district.
The Taliban attack was repulsed after several hours of fighting, he said.
Moradi added that two members of the People's Uprising Forces and an ALP officer were also wounded in the attack.
The Taliban also suffered casualties, but the exact number is not known.
COVID-19: 59 New Cases Reported From 476 Samples
The Ministry of Public Health (MoPH) reported 59 new Coronavirus cases from the 476 samples tested in the government's laboratories in the past 24 hours in Afghanistan.
The MoPH reported four deaths and 53 recoveries, pushing those figures to 1,492 dead and 33,614 recovered from COVID-19.
The new cases were reported in the provinces of Kabul, Herat, Kandahar, Balkh, Takhar, Baghlan, Parwan, Farah and Zabul.
Afghanistan has 40,200 confirmed COVID-19 cases, of which 5,094 are active.
MoI: 20 Killed, Wounded In Ghor Car Bomb Blast
The Ministry of Interior (MoI) said that at least 20 people were killed and wounded in an explosion near the Ghor Police Command compound on Sunday.
Tariq Arian, spokesperson for the MoI, said an explosion was reported at around 11 a.m. in Firozkoh city (Chaghcharan), the provincial centre.
He said "terrorists" blew up an explosive-laden Corolla in front of the Department of Women, Martyrs and Disabled Affairs.
Ghor Police spokesperson Abdul Maruf Ramesh had said that the casualties are expected to be high.
No group has claimed responsibility for the explosion so far.
Taliban Kill School Principal And Teacher In Takhar For Being Pro-Government
Takhar police officials said that a school principal and a teacher were killed by the Taliban in the provincial capital of Taloqan city on Saturday night for being pro-government.
Khalil Asir, spokesperson for Takhar Police Command, told Reporterly on Sunday, that the Taliban had killed Saif al-Rahman, principal of the Shamar High School, and Maulvi Abdul Karim, a teacher at the school and a mullah at the local mosque.
He emphasised that the men were killed by the Taliban as school officials and clerics were being targeted for "promoting support" for the Afghan government.
He said that the Taliban had killed them after being defeated by security forces in the province.
The Taliban, however, has not yet commented.
Saleh: Criminals Have Two Choices, Behind Bars Or Stop Crimes
First Vice President Amrullah Saleh, who is in charge of Kabul city's security, said he will return "real and mental security" back to the people of the capital, in a Facebook post on Sunday.
"Criminals have two choices – behind prison bar or stop crimes," he said.
He warned that undocumented vehicles, which have been a problem for years, will be confiscated.
Such vehicles make it difficult to track down criminals.
He said the government may decide to legalise the vehicles after confiscating them and then distribute it to the families of those killed in the war.
The first vice president said those who have undocumented vehicles, can pay their taxes and get the vehicle registered. "The choice is yours."
He also shared his support for the police hotline number "119" and the two WhatsApp numbers where people can send text messages.
"This is an urgent initiative," Saleh wrote. The number allows people to report crimes and sent tips. "If you have photos and addresses of criminals and outlaws, send them to these numbers as well."
Even the Taliban had announced their readiness to curb crimes and assassinations in Kabul.
A campaign called #Kabul_is_not_safe has also started across social media with people criticising the government and complaining about the increasing insecurity.
3 Arrested In Herat For Stealing 140 Sheep And Goats
Herat security officials said they managed to locate 140 stolen sheep and goats in Injil and Guzara districts of the province and handed them over to their owners.
Abdul Ahad Valizadeh, spokesperson for the Herat Police Command, told Reporterly on Sunday, that the livestock was stolen from Guzara district, and three people from Injil had been arrested in connection with the theft.
Faryab police had also arrested two people on Saturday for stealing camels.
2 Women Killed In Uruzgan After 'Taliban' Rocket Hits Their Home
Two women were killed and two children were injured after a rocket hit a civilian home in the Dehrawood district of Uruzgan on Saturday evening.
Ahmad Shah Sahel, spokesperson for the Uruzgan governor's office, told Reporterly on Sunday, that the rocket was fired by the Taliban.
It hit a home belonging to a trbial elder in the Zartala village of the district.
Sahel said the two injured children were critically injured and had been moved to a hospital in Kandahar for treatment.
The Taliban have not yet commented.
100 New District Police Chiefs Appointed
New police chiefs were appointed to 100 districts across 29 provinces on Saturday during a ceremony at the Presidential Palace.
President Ashraf Ghani, First Vice President Amrullah Saleh and National Security Adviser Hamdullah Mohib addressed the ceremony.
Mohib said the police commanders were selected in a transparent process by a committee appointed by Ghani.
He told the commander that they were waging a "just" struggle and their actions would reflect on the country.
Zia Asi, head of the Office of the National Security Council's Security Sector Development, said that the entire appointment process took 45 working days.
Addressing the new commanders, Ghani said that as they move to the districts, there will be motivation, management, commitment and mobility that will be unparalleled in Afghanistan's history.
"You have been elected because you believe in the country with all your heart and have made sacrifices. The nation wants commitment and sacrifice, and you are the children of commitment and sacrifice," Ghani said.
He assured the new commanders that they have the support of the national security and defence officials in their fight against the enemies of the country.
Afghan Pine Nut Exports To China Help Nuristan Farmers
Xinhua reports that the pine nut business has changed the lives of the Nuristan farmers since Afghanistan started exporting it to China via the air corridor.
Khost, Paktika and Paktika provinces are known for their quality pine nuts production, but since the opening of the air corridor with China in 2018, plantations have also developed in Nuristan, Laghman, Kapisa and other provinces.
Nuristan businessman Marouf Khan told Xinhua, "Pine nut exports to China over the past couple of years have increased the country's income and also changed living conditions of those involved in the business."
Presently many local farmers are working to collect and process pine nuts.
"If the people of Nuristan with the support of government protect and develop the pine nut forests and properly process it with modern machines, definitely they will earn enough livelihood much more than expected to change their living conditions," Khan told Xinhua.
Since Nuristani farmers started exporting pine nuts, local investments have increased as have job opportunities and incomes.
The provincial agriculture department expected produce to be over 200 tons this year.


What are the best video games of all time? What are the most important? The World Video Game Hall of Fame® at The Strong recognizes individual electronic games of all types—arcade, console, computer, handheld, and mobile—that have enjoyed popularity over a sustained period and have exerted influence on the video game industry or on popular culture and society in general. Inductees to the World Video Game Hall of Fame—Donkey Kong, DOOM, Final Fantasy VII, Grand Theft Auto III, Halo: Combat Evolved, John Madden Football, The Legend of Zelda, The Oregon Trail, Pac-Man, Pokémon Red and Green, Pong, The Sims, Sonic the Hedgehog, Space Invaders, Spacewar!, Street Fighter II, Super Mario Bros., Tetris, Tomb Raider, and World of Warcraft—are on permanent view in the museum's eGameRevolution exhibit.
Anyone can nominate a game to the World Video Game Hall of Fame. Final selections will be made on the advice of the Player's Choice ballot and an International Selection Advisory Committee composed of journalists, scholars, and other individuals familiar with the history of video games and their role in society.
The Strong is a highly interactive museum devoted to the history and exploration of play. Through the World Video Game Hall of Fame and its other key programmatic elements—the International Center for the History of Electronic Games, the Brian Sutton-Smith Library and Archives of Play, the National Toy Hall of Fame, the Woodbury School, and the American Journal of Play—The Strong explores play and the ways in which it encourages learning, creativity, and discovery and illuminates cultural history.
At 60,000 items and growing, The Strong's collection of video games, other electronic games, and electronic game-related historical materials is the largest and most comprehensive public assemblage of such items anywhere. These materials sit alongside and complement more than 400,000 other objects held by The Strong, and altogether they make up the world's largest and most comprehensive collection of toys, dolls, board games, video games, books, photographs, documents, and other historical materials related to play.


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redpajama_set_name: RedPajamaCommonCrawl


The Ministry of Health and Social Development is the authority responsible for safeguarding and promoting the health and social wellbeing of the people of the Virgin Islands (British).
The Ministry is led by the Minister for Health and Social Development who has constitutional responsibility as assigned under section 56 of the Virgin Islands Constitution Order, 2007. The Permanent Secretary has oversight responsibility for the management and coordination of the operations of the Ministry and its related departments. In an advisory capacity, the Chief Medical Officer provides technical guidance on local, regional and international public health matters.
All these activities are performed through close collaboration with other sectors, ensuring community participation, and promoting self-reliance by increasing the assets and capabilities of individuals and social groups to improve their standard of living.
That all inhabitants of the Territory are able to maximise their opportunities for health and social well-being as key resources for life and development.
To provide leadership that promotes health, social well-being and a safe environment as positive resources for living and sustainable development.
What's Happening Within Our Ministry?
Can anyone collect the food establishment licence?
Can anyone sign up for the Partnership for Peace Programme without being sent by the court? And if so, how?
Can I open a new food establishment with the food preparation being done at my home?
Can I report a case to the Social Development Department anonymously?
Can I ring my family member?
The Minister for Health and Social Development's subjects include: Cemeteries, Charities, Clinics, Community Centres, Community Development, Drug Control, Environmental Health, Gender Affairs, Hospital Administration, Medical Services, Mental Health, National Health Insurance, Non-Profit Organisations, Parole and Probation, Public Health, Social Security, Social Welfare and Waste Management.


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Al Nasr Club
Great History
The Vice President
Al Nasr Honorary Board
Board of Directors of Al Nasr Cultural & Sport Club
Board of Directors of Investment Company
Board of Directors of Al Nasr Football Company
Board of Directors of Sports Games Company
Al Nasr Songs
Al Nasr crowned Arabian Gulf Cup Champions
Saturday, 18 January 2020 - 1:45am
Al Nasr won the Arabian Gulf Cup championship after defeating Shabab Al Ahli team by two goals to one in the match that gathered them on Friday evening at Zabeel Stadium, amid a huge public presence by the fans of both teams.
Jurcic: I invite the fans to come and support the players on the field, Habib Al Fardan: Kronuslav managed to solve the technical problems in the team
Saturday, 14 December 2019 - 1:30pm
Kronuslav Jurchic, the club's first football team coach, spoke at the beginning of the introductory press conference for Al Nasr and Sharjah match, within the framework of the 9th round of the Arabian Gulf League, saying : another strong and important match against the Sharjah team is considered to be the derby games, and I am excited to face Sharjah, because the big team matches have a special nature, and everyone is watching with passion, especially the players.
Touzé's double leads Al Nasr to a positive draw away from home with Al Ain
Wednesday, 11 December 2019 - 11:30pm
Al Nasr returned with a valuable point after draw with Al Ain team with by goals for each team, in the match held this evening Wednesday at Hazza Bin Zayed Stadium in Al-Ain, in the framework of the 8th round of the Arabian Gulf League, to raise the Al Nasr's score to the 14 point.
Al Nasr supports Expo 2020 and its stars will wear the blue bracelets of the global event in the league matches, after the approval of the Professional League
Monday, 9 December 2019 - 10:00pm
Al Nasr Cultural and Sports Club believing the great value of the international event "Expo 2020 Dubai", and the resulting contributions that will help in building a better future for all, Al Nasr Club organized the "Expo Support" event on Monday evening at Al Maktoum Stadium.
Jurcic: I feel lucky to lead a team that has a strong reaction against big teams, Glauber Lima: We will do everything against Al Ain to achieve a positive result
Monday, 9 December 2019 - 7:30pm
At the beginning of the introductory press conference of Al Nasr vs. Al Ain match, in the framework of the eighth round of the Arabian Gulf League, the club's first football team coach, Kronuslav Jurcic, said: We have another big match against Al Ain, which has a great history and is led by an excellent coach, besides it includes high ranks and a group of distinguished players, and we respect the Al Ain team like all the teams we face, but we are also a great team, which has a wonderful group of players, and we will do everything we can to achieve victory and harvest three points.
Al Nasr secure a spot in the Arabian Gulf Cup semi-finals at Fujairah Stadium
Friday, 6 December 2019 - 8:15pm
Al Nasr secure a spot in the Arabian Gulf Cup semi-finals after defeating the Fujairah team with a clean goal in the match held this evening Friday at the Fujairah Club Stadium.
Jurjic: We have a strong team capable of competing against the big ones, and Hussain: Krunoslav made a big difference
Wednesday, 4 December 2019 - 6:00pm
Croatian Krunoslav Jurjic, the first football team coach, started his speech at the introductory press conference for Al Nasr vs. Al Fujairah match in the quarter-finals of the Arabian Gulf Cup, saying: We have an important match against Fujairah team, and we aim to continue to offer the upward performance that the team has provided since the first match, and achieve positive results during the next phase.
Negredo and Lima double lead Al Nasr to the quarter-finals of the Arabian Gulf Cup
Saturday, 30 November 2019 - 8:15pm
Al Nasr qualified to the quarter-finals of the Arabian Gulf Cup, after achieving a 2-0 victory over Al Dhafra in a match between held on Saturday evening at Hamdan bin Zayed Al Nahyan Stadium, within the framework of the final round of the group stage of the Arabian Gulf Cup.
Josip: We seek to qualify the by defeating Al Dhafra, Ibrahim Issa: the game is crucial and our only goal is three points
Thursday, 28 November 2019 - 7:00pm
On Thursday evening, the press conference was held for the match between Al Nasr and Al Dhafra in the last round of the group stage of the Arabian Gulf Cup, it was attended by assistant coach Joisp Ohrcen as a replacement for Croatian first team coach Kronislav Jurcic, He was absent from the press conference because he left for his country after receiving the news of his father's death, along with the presence of the first team goalkeeper Ibrahim Issa.
Al Nasr defeated Kalba and won their fourth consecutive win
Thursday, 7 November 2019 - 11:15pm
Al Nasr continued the strong performances with coach Kronaslav Jurcic, and achieved their fourth consecutive victory in the Arabian Gulf League at the expense of Ittihad Kalba 2-0 in the match between them on Thursday evening at Al Maktoum Stadium in the seventh rounds of the Arabian Gulf League, bringing the Al Nasr to Point 13 and in fourth place.
Al Nasr FC vs
Bani Yas
Arabian Gulf League // Round 13
Thursday, 23 January 2020 - 9:00pm, Al Maktoum Stadium
Al Nasr FC
Shabab Al Ahli FC
Arabian Gulf Cup // Final Match
Friday, 17 January 2020 - 8:00pm, Zabeel Stadium
Al Nasr defeated Hatta 2-1 in the Arabian Gulf League
Mon, 09/12/2019 - 9:30pm
Al Nasr lost from Sharjah in the Arabian Gulf League
Al Nasr first soccer team lost against Sharjah, by three goals to a goal, in the match that gathered them this Sunday evening at Al Maktoum Stadium, in the framework of the ninth round of the Arabian Gulf League.
Concentration and Seriousness, the slogan of Al Nasr teams training in preparation for the new season
Al Nasr crowned the Table Tennis President's Cup
Al Nasr wins in the Abu Dhabi International Jujitsu Championship
Al Nasr Sports Games company celebrates Athletics team
Sun, 05/03/2017 - 11:15pm
البطولة | 🏆 الجزء الثاني .. ما بعد المباراة #الكأس_يا_نصر
البطولة | 🏆 الجزء الأول.. ما قبل المباراة #الكأس_يا_نصر
جمهورنا الوفي 💙 لدينا رسالة خاصة لكم من الثعلب الكرواتي كرونو 🔥 #الكأس_يا_نصر
رسالة من نيجريدو قائد الفريق قبل النهائي
تمنياتنا بالتوفيق للاعبي الفريق الأول لكرة القدم بالنادي في نهائي كأس الخليج العربي. 💙
Alvaro Negredo
Mohamed Ali Ayed
Mohamad Alakberi
Ibrahim Essa
Mohammad Ibrahim Sarwashi
Mohamed Al Jasmi
Rashed Mohammad Omar
Ghaith Hussain
Jassim Yaqoob
Amir Mubarak
Mahmoud Khamis
Ahmed Shambih
Dubai, UAE, P.O.Box 2226 - Dubai
Tel: +9714 - 3372220 / 3375845
Fax: +9714– 3370024
Email Address: info@alnasr-club.ae


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6 Jersey St, Bloomfield Twp., NJ, 07003-2619
Courtesy of: WEICHERT REALTORS
BloomfieldElementary School
BloomfieldMiddle School
BloomfieldHigh School
Address: 6 Jersey St
City: Bloomfield Twp.
Amazing opportunity to renovate or totally reimagine this colonial style home in an exceptionally convenient neighborhood. The first level lends itself to an open layout for kitchen and dining purposes, while also offering access to the large rear yard. An ample sized living room and additional room tucked away off of the foyer could be the perfect space for a den or private office. The second level has three bedrooms, a full bathroom and another room to be used as you desire. The lower level is large enough to finish into a fantastic recreational space and has a full bathroom already in place. This home's true value is in its location, being less than half a mile to Glen Ridge NYC train station, approximately a third of a mile to Bloomfield College which will soon to become part of Montclair State University, a quick ride to Newark International Airport, just a short distance to parks, downtown and the ever vibrant Bloomfield Avenue.
Courtesy of: WEICHERT REALTORS All information deemed to be reliable but not guaranteed. The data relating to real estate for sale on this website comes in part from the IDX Program of Garden State Multiple Listing Service, L.L.C. Real estate listings held by other brokerage firms are marked as an IDX Listing and reference the listing brokerage. This information is provided for consumers' personal, non-commercial use and may not be used for any purpose other than to identify prospective properties consumers may be interested in purchasing. The dissemination of listings on this website does not constitute the consent required by N.J.A.C. 11:5.6.1 (n) for the advertisement of listings exclusively for sale by another broker. Any such consent must be obtained in writing from the listing broker. Copyright © 2022 Garden State Multiple Listing Service, L.L.C. All rights reserved. Updated: 2nd February, 2023 1:22 AM (UTC)


With a show of hands, about half of those listening to the presentation in Jake Kraayenbrink's back 40 near Moorefield, Ont., confessed to having a smartphone of some sort.
Ocheda Dairy Inc. of rural Worthington, Minn., cleared another hurdle recently in its plans to construct a permanent pipeline for liquid manure.
Federal environmental programs have drastically overestimated the poultry industry's contributions to water pollution, according to a University of Delaware-led study that could trigger changes to river and bay cleanup plans around the country.
The recent groundbreaking for the building of a manure digester facility just outside of Enumclaw brought out many key players in the effort to lessen the burden on local dairy farmers as well as improve agricultural sustainability.


Premier Scale Services is a major supplier of a wide selection of industry leading scales and measurement systems including weighbridges, counter scales, balance scales, kitchen scales, platform scales, platform bases, livestock weighers and moisture meters. The company also stocks a huge range of spare parts for its systems.
Tri-Pump and Engineering is the official sole exclusive distributor for the Goodman series of locomotives and Eimco range of rocker shovels. The company is also a preferred supplier for the Man-Dirk group of companies, providing general and specialist tools in the applications of safety, maintenance, repair and operations.
CP Engineering is an authorized dealer of HEYCO tools and the principal supplier of all major tools of Mercedes Benz, Audi, Volvo, VW, Man Trucks and a wide range of industrial tools. In the field of machining tools for workshop CP Engineering is also the exclusive agent in Zambia for Pilot.
Fuel Systems products cater for diverse industries, focussing on the petroleum oil market. Their product range includes meters for delivery and receiving of bulk liquids, fuel dispensers for commercial and retail use, registers for various applications, flow meters, heavy duty and standard filtration units, nozzles, couplings and hoses.
Global Weighing Equipment provides a comprehensive range of scales that withstand the challenges of rugged environments. It offers accurate and reliable industrial weighing solutions for such sectors as pharmaceutical, chemistry, food, vehicle and transport, and logistics, with offices in Lusaka and Kitwe.
Whether you like to sew items as a hobby or as a business, you will find a selection of domestic and industrial electric sewing machines at the Madina Sales shop in Lusaka, together with all the accessories you're likely to need. Also available are treadle sewing machines which do not require electric power.
WACO Africa in Zambia offers professional maintenance access related services such as thermal insulation, corrosion protection, industrial plastic encapsulation and asbestos removal. It provides industrial services for power stations, refineries, steel and petro-chemical plants, construction, building projects and maritime repairs.
Steeplejack Services Zambia has vast expertise in the movement of heavy plant, machinery or structures. The company uses conventional methods such as craneage or alternative methods, if cranes are unavailable, such as derricks and winches, or tirfors, chain blocks and rollers in confined and inaccessible areas.
Proplast Zambia is a major supplier of machinery for the plastic industry. The company is an exclusive agent for Windsor, Cirmech, Cirwind, Prasad group of companies and Botheven machinery in Zambia. The company's procuring network enables it to respond quickly to specific requirements no matter how large or small.
Whether it is structural steel erection, precast panel installation, mechanical plant installation, high bay rack erection, or rigging that is required, Mega Earth Movers has the expertise and capacity to deliver an exceptional service. The company has offered its services to a wide array of clients – small and large.
Pex Hydraulics Zambia offers comprehensive re-manufacturing of hydraulic components. The company rebuilds a wide range of hydraulic equipment regardless of size or condition. Pex is also able to upgrade hydraulic equipment, adding the latest parts during rebuilding.
Ingco Zambia Ltd is one of the major suppliers of a broad range of industrial tools, machines and accessories. The company believes that top quality means not only great functionality and appearance, but also high efficiency and performance, as well as low maintenance.
A lawn can be a source of pride as well as a place for the family to play. Regular mowing of grassy areas is one of the most important aspects of landscape maintenance. It's worth choosing the best tools, like those from Mowtec which supplies domestic and commercial lawn mowers.
This is a fully owned Zambian company that specialises in industrial tools and equipment for construction, mining and precision heavy lifting. As well as retailing these products, Ginoka Enerprises also imports, exports and distributes them, as well as providing a procurement service for companies in the region.


Taken on Mount Olive Road off Highway 174.
Snow falling on horses off of Red Rock in Reno.
Resident squirrels enjoying some sunflower seeds here on the San Juan Ridge.
Waterfall right before the Highway 49 bridge.
Bear Valley Creek in snow.
Big snowflakes on a snowy evening on Mill Street.
Hummer feeder at Turkey Flats Ranch.
Sad daffodil in the snow.


Brain tumors are a large and heterogeneous group of neoplasms affecting the central nervous system that, despite the progress of the modern medicine, still represent a great challenge for physicians all over the world. The annual global age-standardized incidence of primary malignant brain tumors is ~3.7 per 100,000 for males and 2.6 per 100,000 for females. Rates appear to be higher in more developed countries (males 5.8, and females 4.1 per 100,000) than in less developed countries (males 3.0 and females 2.1 per 100,000). Conversely, the incidence of both primary malignant and non-malignant brain tumors is about 10 - 14 cases per 100,000/year all over the world, with white males having the highest rate. Males also generally have higher rates of primary malignant brain tumors while females have higher rates of non-malignant tumors, primarily meningiomas. Worldwide age-standardized mortality for primary malignant brain tumors is ~2.8 for male and 2.0 for females per 100,000. Mortality rates differ significantly by histology and age. For example, glioblastoma multiforme (GBM) has a 5-year survival rate of 3.3%, low grade gliomas, such as pilocytic astrocytomas, oligodendrogliomas, and ependymomas have 5-year survival rates of over 70%, while anaplastic astrocytoma, malignant gliomas and lymphomas have 5-year survival rates less than 40% .
Due to these dramatic epidemiological data, in the past decades we assisted to the birth of an intensifying interest in understanding the causes of brain tumors among the scientific community. Despite notable advances achieved during recent years in both surgical and chemo/radiotherapeutic approaches, an improved survival has not been clearly documented, especially for primary malignant brain tumors. This is partially due to the tumors' intrinsic clinical and molecular heterogeneity. As a matter of fact, choice of initial treatment, prediction of survival, stratification of patients, prediction and monitoring of response to therapy, still represent some of the greatest challenges in the management of patients affected by brain tumors. In these settings, different studies have been performed to better understand the pathophysiology of cerebral neoplasms, with the aim to identify new molecular prognostic markers and therapeutic targets. However, until now, molecular biomarkers that effectively predict response to therapy and/or survival outcomes in brain tumors are limited. Consequently, there is a strong need to develop novel and independent markers of prognosis for these neoplasms. One of the cellular structure candidate to accomplish this role is represented by telomeres.
Telomeres consist of long tandem arrays of TTAGGG repeats, bound by proteins, placed at the end of linear chromosomes, which are involved in several essential biological functions [2, 3]. These non-coding telomeric repeats represent a buffer zone preventing the adjacent coding region of the genome from erosion. In normal human cells, the telomeres decreases by some 5-20 repeats with every cell division . Therefore telomere shortening limits the number of times a cell can divide. Hence, they can be considered the mitotic clock by which cells count their divisions and regulate the onset of replicative senescence in somatic cells [6-8]. The alteration of telomere length homeostasis affects telomere structure and leads to genomic instability by generating chromosome end-to end fusion and chromosomal abnormalities . It has been demonstrated that telomeres shortening could initiate successive events, such as aberrant fusions or recombination of the end of chromosomes, genomic instability, loss of cell growth control, and finally cancer development [10, 11]. Hence, cells exhibiting critical telomeres shortening and genomic instability present an increased capacity of dicentric chromosomes formation and susceptibility to oncogenic transformation [5, 12, 13]. Several studies showed the presence of an hypervariability of telomere length in different human solid tumors, including brain tumors, suggesting for telomeres and proteins involved in the modulation of their length a possible clinical role as diagnostic/prognostic marker or therapeutic target for cancer treatment.
Human telomeres are regions of 4-15 kilobases of repetitive hexameric (TTAGGG)n guanine-rich DNA sequences at the ends of each chromosome . They end with a single-stranded 3'-overhang that folds back and invades its complementary strand to form a T-loop . Formation of this structure is presumed to involve the insertion of the 3'-telomeric overhang into duplex telomeric DNA, its hybridization with the cytosine-rich strand, and dislodgment of the guanine-rich strand into a displacement loop (D-loop) . It has been demonstrated that T-loops are especially well-adapted to shield the ends of chromosomes from DNA repair and DNA damage-sensing mechanisms [15, 17]. Moreover, a complex of telomere-specific proteins, named shelterin complex, binds and caps telomeres, further preventing chromosomal ends from being recognized as DNA double strand breaks (DSB) by the DNA damage response (DDR) machinery [18, 19]. As the lagging strands of telomeres are incapable of being fully replicated during each round of cell division, telomeres undergo progressive shortening during normal cellular proliferation. Eventually, they become so short that they trigger the DDR, causing cell crisis [4, 18, 20]. This normally results in replicative senescence and eventually checkpoint-driven cell death and apoptosis, defining cellular lifespan and safeguarding an organism against unlimited cellular proliferation and cancer [19, 21, 22].
Shelterin complex proteins interact selectively with telomeric DNA and localize to telomeres. In its most abundant form, the complex is composed of six core components: TRF1, TRF2, POT1, TIN2, TPP1 and RAP1. TRF1 and TRF2 (Telomeric Repeat Factors 1 and 2) recognize duplex telomeric DNA whereas POT1 (Protection of Telomere 1) associates with the single-strand telomeric DNA present at the 3′-overhang [23, 24]. The scaffolding subunit TIN2 (TRF1-interacting nuclear protein 2) binds simultaneously to TRF1, TRF2 and TPP1, whereas TPP1 (previously known as TINT 1  ) connects POT1 with TIN2 [25-31]. A sixth component, RAP1 (Repressor Activator Protein 1), is a TRF2-associated factor . Via protein–protein interactions, these DNA binding factors bring a number of other proteins to telomeres, where they localize to form a variety of complexes [33, 34], playing a key role in telomere capping and length regulation (see Figure 1).
Schematic representation of the six subunits of the Shelterin complex on the telomeric DNA and of their molecular structure, including domains, protein interactions and DNA binding sites.
In addition to this 6-member complex, Shelterin may also be present in the form of sub-complexes that lack either TRF1 or TRF2/RAP1[30, 34-41]. While the importance of these different sub-complexes remains unclear, the particular function of each of the three DNA binding subunits (TRF1, TRF2 and POT1) is well-understood.
TRF1 has a key role in the modulation of telomere length. Its ADP-ribosylation, allow telomerase to bind telomeres and start their elongation.
TRF2 serves to block recognition of telomeres as double-strand DNA breaks. Loss of TRF2 function leads to the activation of the ATM kinase (Ataxia telangiectasia mutated kinase), formation of telomere dysfunction-induced foci (TIFs), and induction of either senescence or apoptosis [21, 36, 42-45]. Moreover, in cells lacking functional checkpoints, telomeres devoid of TRF2 serve as substrates for the NHEJ (non-homologous end-joining) repair mechanism and give rise to interchromosomal fusions [41, 46]. TRF2 also appears to protect telomeres, at least in part, through its ability to promote T-loop formation and maintenance [15, 17].
POT1 serves to hide the 3′-telomeric overhang from telomerase and from DNA damage sensing mechanisms. Hence, the loss of POT1 leads to the activation of the ATR kinase (ATM and Rad3-related kinase), formation of TIFs, and induction of either apoptosis or cell cycle arrest [38, 42, 47, 48]. In cells that lack functional checkpoints, POT1 dysfunction leads to a loss of telomerase regulation that results in longer telomeres [31, 39].
Therefore, through the interaction with the shelterin complex proteins, telomeres protect chromosomes from recombination, end-to-end fusion, and recognition as damaged DNA, providing a means for complete replication of chromosomes.
In summary, telomeres serve as a molecular clock that controls the replicative capacity of human cells and their entry into senescence, but they also contribute to the functional organization of chromosomes within the nucleus and participate in the regulation of gene expression [49, 50].
During a process of DNA synthesis and cell division, telomeres shorten as a result of the incomplete replication of linear chromosomes. This progressive shortening represent the so-called 'end-replication problem'.
As previously described, in order to prevent degradation by exonucleases or processing as damaged DNA, the telomere 3' single-strand overhang folds back into the D-loop of duplex telomeric DNA to form a protective 'T-loop', which is reinforced with TRF2 and other telomeric DNA-binding proteins that constitute the shelterin complex . These proteins have a fundamental role in the modulation of telomere length, allowing telomeres elongation or conversely promoting their attrition.
In human cells, several pathways regulating telomeres length have been identified.
The most important mechanism is represented by telomerase, a highly specialized ribonuclear reverse transcriptase enzyme that catalyzes extension of 5'-ends of the lagging DNA strand by adding TTAGGG repeats onto the telomeres using its intrinsic RNA as a template for reverse transcription . Two major subunits of the human telomerase core complex have been identified, named h-TERC and h-TERT. The former serves as a template for telomeres elongation; instead, the latter subunit (h-TERT) contains a reverse transcriptase domain that catalyzes this reaction  (see Figure 2).
However, the length and structure of telomeres are also controlled by a variety of proteins, working exclusively at the telomere or contemporarily participating in DNA repair process. Collectively, these telomeric proteins may function to protect telomere integrity and function, to connect the DNA damage/repair network with the controls of cellular senescence, to monitor telomere homeostasis and modify the access of telomerase to telomeres. Two major proteins are the TRF1 and TRF 2 that are localized at telomeres . These proteins play key roles in the maintenance of telomere function and structure modifying telomerase activity [41, 55, 56]. Moreover, a recent evidence shows that TRF1 interacts with other telomere-binding molecules and is integrated into the functional telomere structure . TRF1 accepts adenosine diphosphate (ADP)-ribosylation catalyzed by the tankyrase-poli-ADP-ribose polymerase (TANKs-PARP) complex. The ADP-ribosylation of TRF1 reduces its ability to bind telomeric DNA, allowing telomerase to elongate telomeres and extending the cellular life span [58-60].
In most somatic cells telomerase is produced at very low levels. In contrast, many malignant cells are able to upregulate this enzyme and extend their survival through continuous telomeric elongation .
The vast majority of tumor cells use telomerase as preferred mechanism for telomere maintenance, whereas only 10-15% of all cancer lose the functional activity of telomerase and use the telomerase-independent Alternative Lengthening of Telomeres pathway (ALT) that operates via DNA repair and recombination processes .
Several characteristic features are associated with ALT activity . First, telomere length distribution is highly heterogeneous and ranges from less than 3 kb to more than 50 kb . In contrast, in human telomerase-positive cells all telomeres typically have a similar length of around 10 kb. Second, ALT-positive cells have been described to contain several classes of extrachromosomal telomeric repeats (ECTRs) in the nucleus. ECTRs comprise double- and single-stranded circular molecules, linear telomeric DNA, and t-complex molecules that consist of high molecular weight DNA with highly branched structures [67-70]. These DNA fragments might be products of t-loop resolution by recombination enzymes. The function of ECTRs in the telomere lengthening process is unknown but the amount of partially single-stranded telomeric (CCCTAA)n DNA circles (C-circles) appears to correlate with ALT activity . Third, the occurrence of telomere sister chromatid exchanges (T-SCE) is generally increased in ALT cells [72, 73]. Fourth, in ALT cells promyelocytic leukemia nuclear bodies (PML-NBs) associate with some telomeres [64, 74]. These complexes are called ALT-associated PML-NBs (APBs) [64, 65].
Which type of telomere maintenance mechanism is active seems to depend on the origin of the tumor. ALT is rarely found in carcinomas but frequently activated in tumors of mesenchymal and neuroepithelial origin like osteosarcomas, liposarcomas or astrocytomas [75, 76].
Therefore, at least two mechanisms of telomere maintenance, telomerase activity and the recombination-based ALT, may be more or less prevalent in different tissues undergoing tumour formation, leading to the aforementioned features [77, 78]. The activation of such a mechanisms causes the alteration of telomere length that is reflected by a hypervariability of telomere length already observed in different human solid tumors [79-81], and also in brain tumors [82-87]. Hence, analysis of telomere length variations and of length modulation mechanisms may provide promising information for their potential role as prognostic marker or therapeutic target in cancer.
Aging can be defined as the progressive decline of tissue function that eventually results in mortality . Aging is a natural occurring process and not a disease state. While aging is inevitable for all humans, the speed of age-related functional deterioration varies considerably amongst individuals. Why some individuals reach frailty earlier than others is not understood and genetic factors as well as environmental exposures are believed to modulate the senescence process. Currently, aging is viewed as a generalized process occurring in all organ systems in a parallel fashion . However, recent studies point towards a much higher degree of complexity in the aging process and accumulating data support the notion that diseases incurred during life may accelerate the aging of certain organ systems .
Telomeres shorten as we age. Consequently, telomere length has been postulated as a marker of "genetic age" (mitotic clock), as a fundamental explanation for the aging process, and has been marketed as a simple predictor of longevity. Telomere length indeed reflects the cell's past proliferative history and future propensity to apoptosis, senescence, and transformation. However, cellular aging is not equivalent to organ or organismal aging. Studies in humans have attempted to relate short telomeres to longevity. In a provocative initial publication from the University of Utah, individuals around 60 years of age who had the longest telomeres lived longer than did subjects with the shortest telomeres, but the most associated cause of death in the latter group was, inexplicably, infection, and those with shorter telomeres did not have a higher rate of cancer deaths . Heart disease as the cause of death was also more common in subjects with the shortest telomeres. Subsequent studies have produced conflicting findings. The Cardiovascular Health Study of subjects over 65 years of age found that individuals in the shortest quartile for telomere length were 60% more likely to die than those in the longest quartile . Causes of death related to short telomeres were infectious. Two twin studies at older age also correlated shorter telomeres with poorer survival [92, 93]. Finally, a cohort study that looked at participants at time zero and after 10 years found that death within 10 years was significantly more common in those with shorter telomeres . In contrast, these associations have not been confirmed in other studies of older subjects. Njajou and collegues reported that telomere length failed to predict survival, but correlated with years of healthy life . In a Danish study of people aged 73 to 101 years, telomeres correlated with life expectancy in simple univariate analysis but, when corrected for age, did not predict longevity . In Dutch men with a mean age of 78 years, telomere length eroded with aging but failed to correlate with mortality . In a Finnish investigation, telomere length did not predict overall mortality . Finally, in an analysis from California, short telomere length predicted death from cardiovascular disease in women but not in men, where the rate of shortening predicted mortality rather than length itself . Collectively, data on association between telomere length and aging are quite inhomogeneous and contradictory, whereas data on the role of telomere length in human disease are more consistent.
Telomere dysfunction and telomere length alterations have been reported as responsible of various human pathologies, ranging from neurodegenerative to inherited genetic diseases. In the last decade, several studies elucidated telomere's role in the pathophysiology of different diseases at a molecular level. For this reason, measuring of telomeres in peripheral mononuclear cells or in whole blood samples has been applied to patients with a multitude of disease states .
Dyskeratosis congenital (DC), is a rare inherited bone marrow failure disease, and can be considered the classic "telomere disease". The inherited defect in X-linked dyskeratosis congenital was identified in a gene named DKC1 . DKC1 encodes dyskerin, a protein that binds to the RNA component of telomerase and stabilizes the telomerase complex. Inheritance is X-linked recessive, autosomal dominant, or autosomal recessive. In addition to the diagnostic triad of nail dystrophy, lacey reticular pigmentation, and oral leukoplakia, patients with DC are at very high risk of bone marrow failure (BMF), cancer, pulmonary and liver disease, and multiple other medical problems [102, 103]. Several studies demonstrated that patients with dyskeratosis congenita have accelerated telomere shortening and that telomere length measurement by flow fluorescence in situ hybridization in peripheral blood lymphocytes is an important diagnostic test for DC: in particular, age-adjusted values provide a quantitative measure of disease severity, with shortest telomeres associated to severe variants of DC [104, 105].
Much attention has been given to individuals with atherosclerotic disease and, as a common rule, telomeric length of peripheral mononuclear cells seems to be a strong predictor for disease progression. In particular, leukocyte telomere length is associated with measures of subclinical atherosclerosis  and with HDL cholesterol levels . Moreover, cellular aging reflected by shorter leukocyte telomere length is a predictor for advanced atherosclerosis and cardiovascular disease risk . Patients with myocardial infarction have shorter telomeres as compared to controls , and reduced leukocyte telomere length has been linked to increased coronary artery calcium  and reduction in left ventricular mass. Shortened telomeres have been observed also in white blood cells of patients affected by diabetes type I and II,[112-114] neurodegenerative disease including dementia and Alzheimer disease [115-119], ischemic stroke . All these results suggest an important role of telomere and of its length modulation mechanisms in the pathophysiology of several common diseases, often age-related, encouraging new researches to improve the knowledge about telomere biology and to translate these new informations in the clinical practice for a better patient's management in terms of diagnosis, treatment and prognostic stratification.
Functional telomeres protect chromosome ends from recombination and fusion, and are therefore essential for maintenance of chromosomal stability [3, 121, 122]. The alteration of telomere length homeostasis affects telomere structure and leads to genomic instability by generating chromosome end-to-end fusion and chromosomal abnormalities . It has been demonstrated that telomeres shortening could initiate successive events, such as aberrant fusion or recombination of the end of chromosomes, genomic instability, loss of cell growth control, and finally cancer development [10, 11]. Cells exhibiting critical telomeres shortening and genomic instability thus present an increased capacity of dicentric chromosomes formation and susceptibility to oncogenic transformation [5, 12, 13].
The phenomenon of telomeres alteration during carcinogenesis and cancer progression is well known and established at the molecular level [123-125]. Several studies demonstrated the presence of telomere length alterations in different human solid tumors, such as prostate, breast, colorectal, head and neck cancer . These alterations are widely variable, resulting in both telomere attrition and elongation as compared to adjacent normal tissues. In the majority of cases, telomere length seems to be reduced in human tumors [126-131], even if it tends to increase along with malignancy of tumors [79, 132, 133].
In particular, telomere dysfunction has been extensively studied in the most common solid tumors. These studies demonstrated telomere length modification in different histologies as compared to normal tissue due to the alteration of telomere length modulation mechanisms . This differences have been widely analysed in order to identify new cancer biomarkers, to investigate the eventual correlation with patient's prognosis and to discover new targeted molecular therapies.
In breast cancer, multiple studies have showed that telomere shortening is associated with increased risk and poor outcome, and can thus be used as a prognostic factor to predict the course of disease. The first report describing the use of telomere length as a possible prognostic marker in breast cancer was published by Odagiri and collegues . In this study, telomere length analysis was performed in a cohort of 41 patients diagnosed with breast cancer and showed that telomere length was significantly reduced in tumor tissues (8.1 ± 0.6 kb) as compared to that of the adjacent normal breast tissues (9.7 ± 0.5 kb) in 18 of 22 patients (p > 0.05). Subsequent studies confirmed the potential role of telomere length as clinical biomarker in breast cancer, including Fordyce et al.  who reported measurements of telomere length in 2 independent sets of breast tumors containing a total of 140 samples. This study showed that telomere alterations include both telomere attrition and elongation. In fact, only 50% of all tumors had telomere values in the normal range. Moreover, in this study telomere length was associated with tumor size (p = 0.02), TNM stage (p = 0.004), 5-year overall survival (p = 0.0001) and 5-year disease-free survival (p = 0.0004) and, in particular, reduced telomere length was associated with nodal involvement (p < 0.0001).
Recent investigations concerning prostate cancer suggest that reduced telomere length is associated with poor clinical outcome and markers of disease progression [126, 128]. The first reported study was performed by Donaldson and colleagues in 1999 and represented a retrospective investigation of the relationship between clinical outcomes in patients with organ-confined prostate adenocarcinoma and telomere length . In this archival case-controlled study, association analysis for telomere length and survival and telomere length and biochemical recurrence indicated by PSA levels of > 2.5ng/ml, revealed that reduced telomere length correlated with death (p < 0.0001) and disease recurrence (p < 0.0001), even if there was no statistical association with patients' ages at diagnosis, nodal statuses, pathological grades or Gleason sum scores. This finding was recently confirmed in a larger retrospective population-based study comprising 77 men who underwent prostatectomy between 1982 and 1995 . In this cohort, telomere length was a predictor of time to recurrence when adjusted for age at diagnosis, Gleason sum score and pelvic node involvement.
Although relatively rare, researches on the role of telomeres in lung cancer showed that telomerase expression and activity can be considered important contributors to the malignant phenotype in lung epithelial cells, and have been proposed to be of potential prognostic value . Conversely, reports on the use of telomere length to predict lung cancer progression are scarce. Shirotani et al. investigated the relationship between telomere length and various characteristics of tumor cells in 46 lung cancer specimens, comprising 40 primary and 6 metastatic lesions . In partial accordance with recent studies in breast and prostate cancers [126, 127], the authors observed both elongation (2 cases) and reduction of telomere length (13 cases) in the 16 small cell carcinomas of the sample set. The 2 cases with telomere elongation were associated with a poor prognosis. Similarly, in the adenocarcinoma samples of this study, both telomere reduction and elongation were observed, but a clear association with patients prognosis was not reported. Hirashima et al. evaluated the prognostic significance of telomere length alterations in cancer and normal lung tissues obtained from 72 patients with histologically confirmed pathological stage I-IIIA non-small cell lung cancer (NSCLC) . In this study, the 25 patients (34.7%) with alterations in telomere length, elongation or attrition, had significantly shorter survival durations than those of the others.
The use of telomeres as prognostic factors in colorectal carcinoma has been suggested in several studies performed by the groups led by Siewert and coworkers[132, 137] and by Iniesta and collegues . It is interesting that these studies showed an opposite relationship as compared to studies in other cancer types [126-129, 131], with longer telomeres associated with poor prognosis. This difference may be explained considering the different regulation of telomerase expression in colorectal epithelial cells. Normal colorectal epithelium, in fact, has been showed to contain cells of possible stem cell origin that are telomerase-positive and presumably counteract telomere attrition due to physiologically high cell proliferation rates, and total cell loss due to physiological shedding in this specialized cell compartment . Consequently, it is possible that the existing high telomerase activity may affect cells undergoing tumor initiation and results in elongated telomeres in cells of colorectal cancer.
Studies indicating the prognostic potential of telomeres have also been reported for head and neck cancer. Patel et al. studied telomere alterations in tumor and adjacent normal tissues in 110 patients with head and neck cancer (squamous cell carcinomas of the oral cavity, larynx and pharynx) and 40 patients with precancerous and benign conditions (leukoplakia, submucous fibrosis, erythroplakia, hemangioma) . Telomere lengths in this sample set were significantly lower in malignant tissues as compared with the tumor adjacent normal tissues. In addition, 2-year disease-free survival analysis showed that patients with longer telomeres in malignant tissues had poor disease-free survival. These findings are in agreement with that reported for colorectal carcinoma and lung [132, 133, 135, 137], and in contrast to other cancer histologies [126-129]. A possible explanation for these interesting discrepancies in head and neck cancer is the fact that telomerase activity was observed in over half of the adjacent normal tissues. As before discussed for colorectal carcinoma, altered regulation of telomerase expression in cells undergoing transformation may explain the elongated telomeres in the tumors.
Collectively, these findings suggest that hypervariability of telomere length in various human solid tumors probably reflects the differential regulation of telomerase expression in cancer cells and depends on the different stages of carcinogenesis and tumor progression. Therefore, analysis of telomere length may have a clinical relevance as a prognostic marker in human solid tumors, whereas analysis of the mechanisms of length modulation, such as telomerase and ALT, can suggest new molecular target for advanced therapeutic strategies.
Brain tumors research is being performed worldwide at a remarkable pace, with some of the more recent promising studies focused on identification of aberrant genetic events and signalling pathways, tumor stem cell identification and characterization, modulation of tumor immunological responses, combination therapies, and understanding of the rare long-term survivors. Identification of additional indicators will enable better patients' stratification and individualization of treatment is needed to more accurately determine patient's prognosis and to identify novel therapeutic approaches that can optimize patient's outcome. A growing body of knowledge suggests a potential role of telomere length measurement in different tumors. Nevertheless, even if its clinical use is not completely established, a number of studies demonstrated that it can be helpful to patients stratification, to provide useful information about patient's prognosis and, in some case, to suggest new therapeutic strategies in cancer.
Although not entirely consistent in the type of telomere alteration, i.e., attrition vs. elongation, and unclear on the underlying mechanisms, multiple studies have showed that telomere dysfunctions are associated with parameters of clinical outcome in patients with brain tumors. A possible explanation for these interesting discrepancies in brain tumors is the fact that different expression and/or altered regulation of telomerase expression in tumor cells may reflects the underlying biology of telomere maintenance and its dysfunction over time. In telomerase positive tumor cells, telomere length is balanced by telomere shortening due to cell division and telomere elongation by telomerase. Therefore, telomere length is maintained by telomerase activity that can be influenced in different ways and by various factors. This mechanism keeps tumour cells proliferating and growing by the stabilization of their telomeres which is essential to maintain the unlimited dividing potential and to escape from 'crisis' [49, 123, 139]. As well as in almost all malignant tumors, World Health Organization (WHO) high grade brain tumors are associated to higher telomerase activity than benign tumors, such as schwannomas, meningiomas  or normal brain tissue . Increased telomerase expression has been also associated with higher proliferative index, tumor grading, age, vascular and endothelial proliferation , poor outcome [83, 143, 144], and it increases with malignancy from low-grade to high-grade brain tumors [83, 145].
Therefore, understanding the context and mechanisms by which telomeres length contribute to cancer development is the next logical research step and may represent an interesting research field in order to elucidate brain tumors biology. Moving toward the study of molecular mechanisms controlling telomere length, included telomerase and ALT, will not only provide insight into the complex etiology of brain tumors but also promises to provide novel targets for cancer therapy.
In these settings, several studies have been performed to analyze telomere biology in brain tumors, with the aim to better understand the patophysiology of these tumors for improving prognosis of patients affected by such terrible neoplasms.
Astrocytic tumors represent about the 23% of primary brain and CNS tumours and, in particular, astrocytomas and glioblastomas (GBMs) account for 76% of all gliomas. The incidence of such tumours tends to increase with age, although some histological variants are more frequent in specific age ranges. For example, pilocytic astrocytomas affect exclusively childhood, being the most common brain tumor between 5 and 14 years old. Conversely, the incidence of glioblastomas increases with age, with the highest rates in the 75 to 84 years old. The prognosis can be different according to histology. For low grade astrocytomas (grade I and II), prognosis is usually good and a gross total surgical excision alone represents a sufficient therapeutic strategy. Conversely, for high grade astrocytomas (i.e. glioblastomas WHO IV), although a multimodal therapeutic strategy consisting of radical surgical removal, chemotherapy and radiotherapy, prognosis remains poor. For example, five–year survival rates are 94% for pilocytic astrocytomas but are less than 5% for glioblastomas. Survival generally decreases with older age at diagnosis. Children and young adults have better survival for most histologies .
Several studies focused on astrocytomas showed an association between telomerase activity and reduced telomeres length in high grade tumors. Liu et al. analyzed telomere length in a series of astrocytic tumors. Telomere length measurement was performed using a telomere specific restriction enzyme and Southern blot analysis. The authors observed a progressive shortening of the telomere restriction fragments (TRFs) in astrocytomas from WHO grade I to IV as compared to TRFs of normal brain tissue, with no significant differences between primary and recurrent GBMs . These findings support the hypothesis that telomere shortening is one of the important genetic events during transformation of astrocytomas and progression to higher grades.
Subsequent studies were focused on the analysis of the relationship between telomere length and telomerase activity, suggesting new interesting hypothesis about telomere maintenance mechanisms during the neoplastic transformation and progression of astrocytic tumors. In 1997, Morii and colleagues, analysed telomere length and telomerase activity in a series of 20 gliomas (WHO grade I to IV), including 1 pilocytic astrocytomas, 7 oligoastrocytomas, 1 anaplastic astrocytoma (AA) and 11 GBMs. In their series, telomerase-positive samples had a mean TRF length of <10 kb, whereas telomerase-negative samples all had long heterogeneous TRFs which exhibited an increased signal peak from 10 to 20 kb. The authors concluded that telomerase-negative gliomas had longer TRFs compared with telomerase positive ones, suggesting that, in addition to the telomerase-dependent mechanism, an alternative telomerase-independent mechanism (ALT) for telomere maintenance may be present in human gliomas . Hiraga et al, in 1998, performed the most complete analysis of telomere length in human brain tumors, comparing TRFs length and telomerase activity in 160 neuroepithelial and non-neuroepithelial brain tumors. Among grade I-IV astrocytomas, the authors compared telomere length between telomerase-positive and telomerase-negative samples vs normal brain tissue (NBT). TRFs were shorter in tumors with telomerase activity than telomerase-negative samples and NBT samples. Specifically, the detection rates of telomerase activity were widely different for different histopathological entities. Telomerase activity was detected in none of pilocytic astrocytomas, in 20.0% (3 of 15) of grade II astrocytomas, 40% (6 of 15) of anaplastic astrocytomas and 72.3% (34 of 47) of glioblastomas, suggesting that telomerase activity tend to increase with the malignancy of astrocytic tumors. In particular, all pilocytic astrocytomas (3 of 3) were telomerase negative and showed longer TRFs as compared to normal brain tissue. TRFs in grade II astrocytomas and anaplastic astrocytomas with telomerase activity were shorter as compared to the same tumors without telomerase activity. Lastly, 80% of the progression GBMs exhibited reduced mean TRF length (7.747 kb) compared with NBT and origin tumors, and telomerase was reactivated in 100% (10 of 10) of cases. In summary, the mean TRF length of tumors with telomerase activity was significantly shorter than that of tumors with undetectable telomerase activity for each tumor entity .
These results suggest that telomerase activity strongly correlates with malignancy and potential progression of the astrocytic tumors, being often associated with reduced telomere length.
These findings were confirmed by Le et collegues, in 1998 . The authors performed an analysis of telomere length and telomerase activity in a series of 69 grade I-IV gliomas. From the analysis of all series, the authors concluded that telomerase activity is present in most glioma samples (72%), but that the frequency of such activity increases with malignancy, being higher in high grade gliomas (HGGs) than in low grade gliomas (LGGs), and is often associated with telomeres shortening. This can be explained with the relative low replicative rate of LGG tumor cells. When the proliferative activity increases, such as during the progression to HGGs, the increased mitotic activity causes a progressive telomeres shortening. In this condition, the activation of telomerase activity represents the only way to escape from cell crisis and apoptosis. This can explain the presence of high telomerase activity and reduced TRFs only in a small percentage of LGGs that probably presents a more aggressive behavior than the telomerase negative LGGs with normal or elongated telomeres. This demonstrates an increasing telomerase activity with the more malignancy of gliomas samples, underlying the role of telomerase and TRFs length as marker of malignancy.
Similar findings were found by Maes and collegues in 2007 . They conducted a study focusing on the relationship between telomerase activity and telomere length in a series of 53 intracranial tumors, including 2 low grade astrocytomas, 1 anaplastic astrocytomas, and 11 GBMs. Again, in this study the authors demonstrated that telomere length was reduced in high-grade tumours, whereas it was compatible or elongated as compared to normal brain tissues in low-grade astrocytomas, suggesting that telomerase activity with shortened telomeres correlates with the aggressive growth of high-grade gliomas.
Harada and colleagues  analyzed possible differences of telomerase activity and telomere length among primary and secondary GBMs. Summarizing their findings, TRFs were always shorter than NBT samples, but not statistically significant differences between primary and secondary GBMs were found. Interestingly, although the latter presented significantly higher levels of telomerase activity and hTERT expression than the former, telomere length was anyway shorter than normal brain tissue. The authors explained this apparent discrepancy suggesting that telomerase activation occurs late in carcinogenesis, when the high replication rate of tumor cells already caused telomeres shortening. At this point, activation of telomerase represents the principal mechanism to escape from apoptosis and cell death. Conversely, in primary GBMs, shorter telomere length can be explained by a reduced telomerase activity that might have less influence on carcinogenesis and, hence, other unknown factors might facilitate their cellular immortality.
Although the vast majority of the researches have been performed focusing their attention to telomere length and telomerase expression in astrocytic gliomas, recently several studies showed an increasing interest also to the analysis of the relation between ALT mechanism, telomere length and patients prognosis.
The presence of elongated telomeres and of an alternative mechanism of telomere length maintenance (ALT) was demonstrated to be associated to a better prognosis in patients affected by GBMs by Hakin-Smith et al. in 2003 . Their work represents the first report describing the relationship among ALT pattern, telomere length, and prognosis in human GBMs. In this study, the authors analyzed telomerase activity and telomere lengths in 77 GBM patients. ALT phenotype patients had a median survival of 542 days compared with 247 days in those without the ALT phenotype. Moreover, ALT phenotype was associated with elongated telomeres, benign biology and better prognosis. Therefore, the presence of ALT could be a positive prognostic marker in glioblastoma multiforme.
The first study that analyzed the ALT prevalence among different grades of astrocytic tumors was performed by Henson and coworkers in 2005. In their study, the authors analyzed the prevalence of ALT phenotype and telomerase activity in a series of 40 astrocytomas, composed by 7 WHO grade II-III astrocytomas and 33 GBMs. This study showed for the first time that the prevalence of ALT associated to elongated telomeres is significantly higher in grade II to III astrocytomas as compared to GBMs.
On the basis of Henson's results, in 2010 Slatter and collegues conducted a study focusing on the analysis of ALT prevalence in a series of 48 astrocytic tumors from grade I to IV. In agreement with previous studies by Hakin-Smith and Henson [148, 149], ALT phenotype was more frequent in low grade astrocityc tumors, whereas telomerase activity was prevalent in the higher grades.
Collectively, these studies demonstrated that telomerase activity correlates with malignancy of astrocytic tumors, being higher with the increasing WHO grading [83, 86, 87, 139, 145, 147, 150]. Therefore, telomerase activity and reduced telomeres should be considered a potential biomarker of aggressive behaviour of these neoplasms. Conversely, low grade astrocytomas are usually telomerase-negative and have compatible or elongated telomeres as compared to normal brain tissue [83, 86, 139, 145, 149]. In these tumors, the only telomere length maintenance mechanism is represented by ALT [149, 150]. Henson et al  and Slatter and collegues  documented that ALT phenotype is associated to elongated telomeres and it is more frequent in low grade astrocityc tumors as compared to GBMs. Moreover, Hakin-Smith and collegues  demonstrated that, despite the ALT phenotype associated to elongated telomeres is rarely documented in GBMs, when present it is associated to a longer survival, suggesting its possible role as a positive prognostic markers in GBMs. These findings can be explained considering the biological role of telomeres. In normal tissues as in neoplastic cells, telomeres undergo progressive shortening during each cell replication. When telomeres are critically shortened, the cell cannot preserve anymore its own chromosomic ends and goes toward cell crisis and subsequent apoptosis. Therefore, telomeres represent the biologic clock of cells and constitute one of the most important structure that can preserve cells from senescence. This is the reason why tumor cells need a robust telomere maintenance mechanism to allow an high replicative activity, escaping from cell death. It is well known that high grade brain tumors are malignant neoplasms with an high replicative activity. Consequently, they need a mechanism of telomere maintenance that allows cell division avoiding excessive telomere shortening that can determine cell death. Telomerase seems to accomplish this role with success, especially in high grade tumors. This can be the explanation of the higher telomerase activity found in brain tumors with the increasing of WHO grading. Hence, the highest levels of telomerase expression are found in GBMs. Conversely, low grade astrocytic tumor have a slow replication rate and thus they does not need telomerase. According to the aforementioned studies, in these tumors the slow growing rate is accompanied by a sluggish cell division rate. This can be the reason why the most part of the studies in the literature documents elongated telomeres in low grade tumors. In these neoplasms, the main telomere length maintenance mechanism is represented by ALT. Being specific of benign or slightly aggressive tumors, ALT and elongated telomere are associated to a better survival [149, 150] even if these features are found in a low percentage of high grade brain tumors, such as GBMs . When low grade tumors progress to higher grade, the increasing replicative activity causes a progressive telomere shortening. In this condition, the only way to escape from cell death is the activation of telomerase activity. This is typically observed in progression GBMs .
In summary, high telomerase activity and reduced telomere seem to be features of high grade astrocytic tumors, whereas elongated telomeres and ALT phenotype are specific of low grade ones and, therefore, correlates with a better prognosis.
Different studies have also been performed to analyze the role of the Shelterin proteins in the pathophysiology of several neoplasms, including brain tumors. Telomere-specific DNA-binding proteins, such as TRF1, have been put forward as additional candidates for the role of molecules modifying telomerase activity, and they have been suggested to play key roles in the maintenance of telomere function [41, 55, 56]. It has been demonstrated that overexpression of TRF1 inhibits telomere elongation in telomerase-positive cells , resulting in gradual and progressive telomeres shortening to the "mortality stages," the proliferative barriers that lead to a non-dividing state and cell death [24, 151, 152]. The mutation or deletion of TRF1 can result in telomere elongation and extend cell survival . Overexpression of a dominant negative TRF1, which removes endogenous TRF1 from telomeres, results in telomere lengthening in telomerase-positive cells  . Therefore, the expression of TRF1 is considered a physiological homeostatic mechanism that controls the proliferative potential of normal cells by inhibiting the activity of telomerase .
It has been demonstrated that TRF1 is expressed in astroglial brain tumors of different grades, whereas it is not expressed in normal brain tissue. Such expression decreases from low-grade through high grade astrocytomas . This finding may suggest that the loss of TRF1 expression capability, being the result of down- regulation of TRF1 expression in malignant gliomas cells, may play a role in the cell immortalization of astroglial brain tumors.
Furthermore, according to the role of telomerase in the elongation of telomeres in high grade astrocytic tumors, several studies suggested its possible role as molecular target for new therapeutic strategies. Marian et al demonstrated that the telomerase antagonist Imetelstat efficiently targets glioblastoma tumor-initiating cells leading to a decreased proliferation and tumor growth . Gurung and collegues showed that Thymoquinone induces telomere attrition, DNA damage, cell cycle arrest and apoptosis in the glioblastoma cells by inhibiting the activity of telomerase . Lin et al documented that Butylidenephthalide (BP) inhibits proliferation and induces senescence in human glioblastomas by downregulating hTERT expression and consequently telomerase activity . From this perspective, telomerase represent a promising target for new specific therapeutic approaches for the personalized treatment of telomerase-positive high grade astrocytic tumors.
Ependymomas are tumors that arise from ependymal cells lining the cerebral ventricles and the central canal of the spinal cord. They represent the 5-6% of intracranial gliomas ( 69% occur in children) and 60% of spinal cord gliomas ( 96% occur in adult) . In pediatrics they are usually intracranial (the most common localization is the posterior fossa), whereas in adults they tend to be spinal. The treatment of choice is the radical surgical excission followed by radiotherapy (XRT), whereas the role of chemotherapy is very limited. The operative mortality is 5-8%, the 5 year survival is 20-30% in pediatrics and 80% in adults [158, 159].
Data on telomeric alterations in adult and pediatric intracranial ependymomas are slightly inhomogeneous. In 2008 Ridely et al. performed an analysis of telomere length in a series of 21 primary and recurrent pediatric intracranial ependimomas from 7 patients (6 primary tumors and 15 recurrences) . Telomerase activity was detected in 19 tumors (86%), and particularly it was evident in 11 of 14 primary tumors and in all recurrent tumors. Mean telomere length ranged from 7.3 to 16.7 kb, with telomere maintenance observed in five of seven patients (71%). Of these five cases, four showed telomere lengthening and one had compatible TRFs in relapsed tumors as compared to the primary tumor. Conversely, telomere shortening occurred in two of seven recurrent cases (29%).
The authors concluded that variable TRFs length and evidence for telomerase-mediated telomere maintenance were present in the majority of pediatric ependymoma recurrent cases (71%), whereas TRFs shortening was evident in a minority (29%). These results implicate telomerasemediated telomere maintenance as a key mechanism facilitating tumor progression in pediatric ependymoma.
This was demonstrated by the fact that all recurrent tumors analyzed were telomerase positive, although telomere length was reduced only in small percentage of cases.
In the same year, Tabori et al evaluated TRFs length in a series of 26 pediatric intracranial ependymomas (grade II and III), analyzing an eventual correlation with patients' prognosis . Telomerase activity was detected in 73% of tumor samples but TRFs length was widely variable (mean 6.5 kb,range 3.6–9.1 kb). Based on these findings, although ependymomas rely predominantly on telomerase activity to maintain their telomere length, the authors concluded that there was no correlation between telomere length and telomerase expression or survival. Although it seems to emerge that the majority of intracranial ependymomas (especially in children) shows telomerase activity, telomere length appears to be widely variable. Therefore, there is a lack of a firm correlation of telomere length with telomerase expression that do not allows to get definitive conclusions about their possible role as prognostic marker in these neoplasms. It is more probable that these findings reflect an high molecular variability of intracranial ependymomas.
Oligodendrogliomas arise from oligodendroglia cells. They represent 25-33% of glial tumors [160, 161] and have an incidence peak at 40 years, with a smaller earlier peak in childhood between 6-12 years . They show a slight preference for male, with a male-female ratio of 3:2. In 90% of cases they are supratentorial. Surgery is the treatment of choice; chemotherapy is recommended, whereas XRT is suggested only for anaplastic variants . The median survival for surgically treated lesions is 35 months , although the ten-year survival is about 10-30% . According to Nurnberg  and Hiraga , oligodendrogliomas seem to have compatible or longer telomeres than normal brain tissues and detectable telomerase activity. The lack of reduced telomeres in telomerase positive tumor samples can be considered a marker of the less aggressive behavior of such tumors.
Different results have been reported for oligoastrocytomas, that show shorter telomeres than normal brain tissue associated to high telomerase activity . This pattern is more frequent in the anaplastic variant, confirming the role of telomerase activity associated to reduced telomeres as markers of aggressive behavior in these neoplasms as in astrocytic gliomas.
Meningiomas are extra-axial, usually benign tumors with a slow growing rate that arise from arachnoid cells. They account for 34% of all primary brain and CNS tumors . The incidence peak is at 45 years with a male-female ratio of 1:2,2. About 1.5% occur in childhood and adolescence between 10-20-yeras age . Surgery is the treatment of choice for symptomatic meningiomas and the five-year survival is 91.3% .
Benign mengiomas (WHO grade I) show a variable telomere length [82, 139, 168], sometimes slightly shorter than normal meningeal tissue , whereas atypical and anaplastic meningiomas show telomerase activity associated with a significant telomere length shortening . This can be explained considering that the slow growth of benign meningiomas and the absence of telomerase activity cause an equally slow shortening of telomeres, whereas the higher replicative capacity of atypical and especially of malignant meningiomas determines a more evident reduction of telomere length. In these settings, the activation of telomerase activity can give to the cell the capacity to escape from senescence and, consequently, an high proliferative strength. Therefore detectable telomerase activity and shortened telomere length suggest that the tumor contains a cell population with the capacity for unlimited proliferation.
These results indicate that telomere shortening together with telomerase activity may be a critical step in pathogenesis of atypical and malignant meningiomas and may correlate with their malignant behavior. Indeed, as previously discussed for astrocytic tumors, the association of telomerase activity with reduced telomeres length may be considered a marker of an aggressive behavior also in meingiomas, being more frequent in atypical and malignant meningiomas.
Schwannomas are benign, usually encapsulated, peripheral nerve sheath tumor composed of neoplastic Schwann cells that can have an intracranial or spinal localization. They account for about 8-10% of intracranial and 25-30% of spinal tumors. The peak of incidence is between the 4th and 6th decades . The vast majority of intracranial Schwannomas develops from vestibular nerve. Tumors of trigeminal or facial nerve are far less common. Management includes many options: surgery, wait and see strategy for little or no growth tumors, radiation therapy alone or in conjunction with surgery, chemotherapy, radiosurgery .
Schwannomas usually show reduced telomeres, benign pathological features, low proliferative indices and a lack of telomerase activity [169, 171]. These peculiarities allows such tumors to have a benign clinical course. Conversely, rarely they can assume an aggressive behaviour that is characterized by malignant pathological features and high replicative potential that are usually associated to elongated telomeres. This can be explained considering that long telomeres allow tumor cells to maintain an high proliferative capacity without the need of telomerase activity. When the length of the telomere is long enough for proliferation, the telomerase activity subsides.
For these reasons, telomeres elongation, even in absence of telomerase activity, can be considered a marker of aggressive clinicopathological behaviour in schwannomas [169, 171].
Primary neuroectodermal tumors (PNETs), also called embryonal tumors, represent 1 % of all primary central nervous system (CNS) tumors. They are frequent especially in children, representing the most frequent brain and CNS tumor in the range between 0 and 4 years old .
They are highly malignant lesions and can disseminate via CSF spontaneously or iatrogenically . Extraneural metastases can also occur. Radical surgical excision is the treatment of choice. XRT is indicated following surgical removal, but it should be avoided at all if possible before 3 years of age to avoid intellectual impairment and growth retardation. Overall survival rate for PNETs is substantially poor with an expected 3 year progression free survival of approximately 50% for localized supratentorial PNETs .
PNETs usually show telomerase activity even if there is not a clear association with telomere length. Despite Hiraga  and Rahman  reported reduced telomeres in the most part of tumor samples, data from Didiano  document a wide variability of telomeres length. Interestingly, Rahman reported shorter telomere length in PNETs cells than GBMs, suggesting an higher replicative activity in the former as compared to the latter. These results underline and explain the aggressive behaviour of neuroectodermal tumors. The same author, reported a minority of cases with elongated telomeres and undetectable telomerase activity, suggesting ALT as alternative mechanism of telomere maintenance in these tumors .
In summary, telomerase activity can be considered a marker of PNETs and can explain the malignancy of these tumors, although there is not an evident correlation with telomere length. Moreover, in a little percentage of cases without telomerase activity, the aggressive behaviour of PNETs is due to ALT and is associated to elongated telomeres, that allow tumour cells to actively replicate .
Pituitary adenomas are usually benign tumors that arise from anterior pituitary cells (adenohypophysis). They represent about 13% of primary brain and CNS tumors with an incidence peak on 3th and 4th decades of life . Treatment of pituitary adenomas include medical treatment (dopamine agonists, somatostatin, etc), surgery (transcranial or transsphenoidal approach) or XRT (in case of recurrence that cannot be surgically removed or treated medically).
Their usually benign behaviour can be explained with the lack of telomerase activity, although telomere length is slightly reduced as compared to normal brain tissue . Sometimes they can recur or, rarely, they can progress to pituitary adenocarcinomas. As demonstrated by Harada and colleagues, during progression to carcinoma, the replicative activity of tumor cells causes a progressive shortening of telomeres and the reactivation of telomerase . Therefore, also in pituitary adenomas, telomerase activity and reduced telomere length can be considered marker of aggressive behaviour and can be used to predict the progression to carcinomas.
Primary central nervous system lymphomas (PCNSL) also known as primary brain lymphomas are a primary intracranial tumors appearing mostly in patients with severe immunosoppression (typically patients with AIDS). They represent the 0.5-1.2% of intracranial tumours and less than 1 % of extranodal non-Hodgkin lymphomas (NHL), although in the last years there was a progressive increase of incidence also in immunocompetent patients. They affect all age groups, but are most commonly diagnosed in people who are over 50 years of age. Histologically they are a form of extranodal, high-grade non-Hodgkin lymphoma. Most PCNSLs (about 90%) are diffuse large B-cell lymphomas (DLBCLs); the remaining 10% are poorly characterized low-grade lymphomas, Burkitt lymphomas, and T-cell lymphomas . PCNSLs originate inside the CNS and typically remain confined, rarely spreading outside the nervous system. Although the origin cells are lymphocytes, PCNSLs can be assimilated to brain tumors for their intracranial localization and relationship with brain parenchyma and brain blood barrier that gives PCNSLs the same therapeutic challenges (i.e. in terms of drug delivery through the blood brain barrier) of the other brain tumors.
Data from the literature demonstrate that in PCNSLs have variable telomere length, usually reduced as compared with normal brain tissue, and show high telomerase activity [139, 178].
Harada et al demonstrated a statistically significant correlation between telomerase activity and the survival period of patients with PCNSL. In particular, patients with high telomerase activity had poor prognosis and short survival, regardless of telomere length .
These findings suggest that telomerase activity represents a common features in PCNSLs and can be considered by itself a marker for predicting a poor prognosis, regardless of telomeres length, the age at onset and the KPS score before the initial treatment. Nevertheless, telomeres are usually shortened in these tumors and this can explain the aggressive behavior of such tumors, even if the association with patients' survival has not been demonstrated.
Only few studies have been performed focusing on the analysis of telomere length and telomerase activity among less common non-neuroepithelial tumors, such as hemangioblastomas, hemangioperycitomas and germ cell tumors.
Hemangioblastomas are benign tumors that usually show normal telomere length and undetectable telomerase activity. Nevertheless, the rare cases of hemangioblastomas with aggressive behavior show shorter telomeres than normal brain tumors and are telomerase-positive .
Conversely, malignant non-neuroepithelial tumors such as hemangioperycitomas and germ cell tumors, usually show high telomerase activity associated to an important shortening of telomere length .
This suggest that, also for these rare non-neuroepithelial brain tumors, telomerase activity associated to reduced telomere length can be considered a marker of malignancy.
There is a desperate need for developing innovative diagnostic tools and therapies for brain tumors.
According to their role in the regulation of cell replication and senescence, telomeres and telomeric proteins represent a new interesting research field to better understand the alterations responsible of carcinogenesis and malignant progression of human brain tumors. In these settings, elucidation of telomeres biology represents the new frontier of cancer research. Although a lot of studies have already been focused on this promising field, further studies should be performed to better understand the pathways involved in the telomeres length maintenance and, consequently, in the process of carcinogenesis and malignant progression of human brain tumors, in order to discover new diagnostic/prognostic tools or new therapeutic strategies for improving prognosis of patients affected by these terrible neoplasms.


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Capturing the excitement, energy and charisma that have made Rod a true rock icon, including those infamous moves and all the hits like Handbags & Gladrags, Maggie May, Baby Jane, Da Ya Think I'm Sexy, Sailing, Tonight's The Night, The First Cut Is The Deepest, and You're In My Heart.
This authentic production, now in its fourth year, includes a stunning stage set, a spectacular light show, an impeccable live band and stage-wide projections.
Thu 10 Mar 2022 at 7.30pm
Members of the Theatres Loyalty Scheme receive a discount of £2.00 per Band A ticket.
"I've seen some 'Rods' in my time, but Paul is the best one I've ever seen." Don Stewart (Rod Stewart's Brother)
The Jive Aces Big Beat Revue
Britain's Got Talent semi-finalists, The Jive Aces, explode onto the stage in their trademark yellow …
Venue: The Brook Theatre
Thu 4 Mar 2021 at 7.30pm
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The Vintage Boys Rock n Roll Show
Step back in time to the Golden Age of Rock 'n' Roll as the sounds of the 50s & 60s are …
Fri 5 Mar 2021 at 7.30pm
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Rose Royce featuring Gwen Dickey
Don't miss the opportunity to experience the fantastic Rose Royce, now reunited with their original …
Sun 7 Mar 2021 at 7.30pm
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