Telomere Length and Telomerase Activity in Cancer

Telomere Length and Telomerase Activity in Cancer Conducted on the mean telomere length and the activity of telomerase in bone marrow samples to measure the survival and prognosis of B cell chronic lymphocytic leukemia and found that the patients with a mean telomere length under 6Kb correlated with high telomerase activity similarly the telomere length over 6Kb had a significant correlation with lower telomerase activity (Bechter and Eisterer et al, 1998). This study portrays that telomere length alone is not sufficient enough information to provide prognostic characteristic in cancer therapy but together with the activity of telomerase it is more useful in clinical medicine. Table 2: Mean telomere length and telomerase activity measured and detected in different types of cancer The telomere length for most cancers range from very low to higher than normal somatic cell telomere length. Telomerase activity was also detected in most cancers except in pediatric bone where certain types of bone cancers were did not show detectable telomerase activity (Remes and Norrback et al, 2000, Hiyama and Gollahon et al, 1996, Tasumoto and Hiyama et al, 2000, Sotillo-Pineiro and Sierrasesumaga et al, 2004, Sommerfeid and Meeker et al, 1996, Albanell and Engalhardt et al, 1997). However there are some problems with this technique that makes this topic debatable like for example each type of cancer is unique which make is harder to pick a biological marker that is universally reliable hence the telomerase activity for each type of cancer must be studied individually. Another issue is that this method used highly sensitive assays to obtain telomere length and telomerase activity which in return means that it is more susceptible to false positive results or false negative results. A false positive result can arise due to contaminated lymphocytes as a result of inflammation in the surrounding issues that have no malignant cancer spread may also show telomerase activity. To overcome this issue Kinoshita, et al suggested, in a study evaluating telomerase activity in bladder cancer, that telomerase assays should be performed after antibiotic treatment. False negative results on the other hand may arise from PCR taq polymerase inhibitors in the sample such as bile s alt, heparin and hemoglobin. A highly sensitive telomerase activity assay has been proposed by Yaku and Murashima, et al (2013) that includes the use of magnetic beads which enables the washing process of PCR products to remove any inhibiting contaminants from the samples and hereby limiting the detection of false negative results. What are the current methods of telomere detection? Table 3: Different technique used to measure telomere length and their advantages and disadvantages. There are many different assays that have been developed to measure the activity of telomerase though the most common method used is the telomeric repeat amplification protocol also known as the TRAP/PCR assay. Although this technique is more sensitive and rapid compared to the conventional assays TRAP assay is not suitable for diagnostic purposes in large clinical samples due to its high technicality, obtains time consuming stages and cannot provide reliable quantitative data however many modification of the TRAP assay has been constructed to achieve a better suitable and more efficient way to detect telomerase activity some of which include bioluminescent TRAP-ELIPA (Zu and He et al, 2002), real time quantitative TRAP or (RTQ-TRAP) (Hou and Xu et al, 2001) and the fluorescent TRAP assay (Table 3). On the other hand, several studies have demonstrated enzymatic amplification rather than PCR based amplification to determine telomerase activity such as the DNAzyme assay (Wang and Donov on et al, 2013) however although this assay showed higher sensitivity than the TRAP assay, the enzymes used in the assay are also prone to inhibitions by other biological molecules in the sample. A more indirect approach in detecting telomerase activity has also been carried out by measuring the components of telomerase such as the hTERT mRNA using RTQ-PCR. As the hTR component of telomerase is found in all types of cells whereas hTERT mRNA is only found in cells that express telomerase therefore due to the strong correlation between hTERT mRNA levels and telomerase activity it becomes the next ideal target for detecting telomerase activity and hence cancer. This method was evaluated in peritoneal disseminated cells of gastrointestinal cancers by Botchkina and Rivadeneira et al, (2008) and the study concluded that this method had 100% sensitivity and 100% negative predictive value hence have an important diagnostic value. Furthermore additional longitudinal studies on larger clinical samples are required to fully benefit from its clinical cancer diagnostic values nonetheless telomerase activity can be combined with present cytological diagnosis methods to make a more accurate diagnosis. Telomerase activity can also be used to detect poor prognosis and help identify those that have a more advantage of benefiting from adjuvant treatments and due to its biological marker properties it can also be useful in the development of anti-cancer therapies. Can telomere length be used to predict life expectancy? A study conducted on domestic dog breeds show that peripheral blood mononuclear cell telomere length is a strong predictor of average life span and the breeds with shorter telomere lengths were found to have an increase probability of deaths caused by cardiovascular diseases. The correlation of telomere length in domestic dogs shows similar telomere biology to humans including telomere length, attrition and absence of somatic cell telomerase activity in comparison to studies conducted in mice models (Fick and Fick et al, 2012). Mice have rodent telomeres which have a significantly different dynamics in contrast to human telomeres and are much longer with shorter life span, making it difficult to address whether or not telomere length can be used to predict life expectancy directly. However studies that have been conducted on mice also show that the rate of increasing short telomere length predicts longevity in mammals providing more evidence for the association between telomere lengt h and life expectancy (Vera and Jesus et al, 2012). As telomere shortening is inversely correlated with age which in return is very likely to correlate with age associated issues including lifespan. One of the largest family studies on telomere length in humans also reported a correlation between telomere length, aging and life span as well as a significant indication that telomere length is also influenced by genetics specifically from the paternal inheritance (Njajau and Cawthon et al, 2007). This study suggests the possibility that the genes that are controlling telomere length may also affect lifespan (Figure 5). Another more recent study conducted by Heidinger and Blount et al, (2011) on Zebra finches, measuring telomere lengths from nesting stage to various points of its natural lifespan producing the strongest available for the relationship between telomere length and life span. This study suggests that telomere length at early stages in life is a strong indicator of lifespan however as humans retain a higher life expectancy co mpared to zebra finches it’s harder to compare these findings to humans. Therefore similar studies should be carried out to evaluate the importance of early life telomere length and lifespan in humans. Figure 5 The mean telomere length in wild type( WT) mice and transgenic telomerase reverse transcriptase (TgTERT) mice both decreased with age whereas the amount of short telomeres measured increased with age (5A). This shows that telomere length is significatly negatively correlated with life span in mice similarly to the strong negative association between age and telomere length in humans supported by results obtained by Njajou et al (5B). There is a distinct market in the industry that includes various privet companies and clinics such as Life length, RepeatD and TeloMe, which are providing the public the ability to determine an individual’s biological age through measuring the length telomeres via blood tests. Most of these companies use flow-PCR, RTQ-PCR or Q-FISH to estimate telomere length however to be able to estimate an individual’s life expectancy is a debateable topic however there are various benefits that comes with obtaining information about how short or long ones telomere is like for example the biological age is an indicator of overall health status and essentially help people proceed a healthier life style with better understanding of how life style actions are effect aging process. It is important to take in to consideration that the telomere length tests that are currently available are not able to predict life span as it is effected by a wide range of factors than telomeres alone. More over these tests can be used to see if there in an improvement in the rate of biological aging and can even be used to monitor the prognosis of current treatments and help disease prevention however the uses of these tests in a clinical environment still requires further longitudinal research and understanding in more depth of telomeres and its involvement in different diseases than what is currently known. This includes more studies of how telomere length is affected during early stages of life and how the inherited and environmental factors affect telomere length. Is it possible to alter telomere length using modern technology or in the near future? Table 4: The population doublings and telomerase activity detected in pBabe, pBabest2 and pBabest2-AS infected BJ cells. The reconstructions of telomerase activity in normal neonatal human fibroblast cell strain (BJ) which do not poses telomerase activity but however express the RNA subunit of telomerase complex (hTR) have been reported to display elongation of telomeres and extend replicative life span. The cells were infected with cDNA coding for hTERT sub-cloned in the retroviral vector pBabe, pBabest-2 and pBabest-2-As. The PBabest-2 under the control promotor of the Maloney Murine leukaemia long terminal repeat sense strand exceeded the normal estimated life span of BJ cells of 87-90 PDs and hence showing evidence for forced expression of telomerase activity results in extended life span (Vaziri and Benchimol et al, 1998). This study reveals that pBabest-2 cells can potentially replace genetically unstable cell lines through the expression of telomerase in gene therapy in order to treat age related diseases and cancer. Consequently other studies have shown that the inhibition of telomerase leads to telomere shortening and cell death and therefore can be used as anticancer drugs. Telomerase inhibiting drugs are currently under phase 2 of clinical trials and its effects on telomere shortening is reversible however the process of telomere shortening with inhibition requires a long period of time before a significant change in cell growth is seen due to the presence of the cells alternative telomere lengthening mechanisms (ATL) for maintaining telomeres. Figure 6 The HME50-5E cells underwent apoptosis against number of days after transfected with complementary 2’-O-MeRNA oligomer telomerase inhibitors. More than 50% of cells went under apoptosis after 100 days after the initial transfection (Herbert et al, 1999). Herbert and Pitts et al, 1999, reported that peptide nucleic acid (PNA) and 2-O-MeRNA oligomers inhibit the activity of hTR telomerase in immortal human cell lines HME50-5E and DU145 hence can be used as a potential chemotherapeutic drug (figure 6). The use of targeting telomerase in direct anticancer therapies also has its drawbacks as telomerase activity is also found in some somatic human cells that may also be targeted during treatment. Additionally a small minority of cancers have been reported to exhibit no significant telomerase activity therefore the treatment may not be as effective in certain cancers compared to others due to drug resistance. Another issue with this approach is that chemically related molecules may carry the risk if being unintentionally inhibited which could result in harmful side effects. Based on the research that that has been carried out on telomeres it is well established that telomere length can be easily manipulated however like in most biological pathways when the natural process are disrupted there are always positive and negative consequence. In this case involuntarily altering telomere length requires the manipulation of telomerase activity (Lee and Hills et al, 2013). The increase in telomerase activity has been associated with multiple different cancers which could therefore potentially increase the risk of developing cancer while reducing the risk of developing CHD and other diseases that are associated with telomere shortening. Furthermore additional studies are required to develop a more advanced technique that can alter telomere length and at the same time prevent or repress cancer. Alternatively a follow up study reported that a series of lifestyle changes such as plant based diet, moderate exercise, stress management and increased social support provided to men with low risk for prostate cancer, revealed an increase in relative telomere length in the intervention group compared to the controls after 5 years. This study shows a significant correlation between telomere length and lifestyle changes, indicating that telomere length can also be altered naturally by reducing the environmental risk factors associated with telomere shortening without having to interfere with telomerase activity (Ornish and Lin et al, 2013). Conclusion The discovery of telomeres and telomerase is without a doubt a major revolutionary step in the scientific field which has led to the understanding of biological age and its association with low mortality medical conditions such as CHD and Cancer. However there are still some structural aspects of telomeres and telomerase that are not fully understood, like for example telomere binding factors TRF1 and TRF2 have only a few studies which suggest that they are part of a telomere maintaining control mechanism (Smogorzewska and Steensel et al, 2000). Therefore these negative regulators can also be possibly targeted in therapies in the future as they have been found to be associated with telomerase activity and hence telomere shortening and eventually lead to programed death of cancerous cells through apoptosis. Although most telomerase inhibition drugs have failed due to long lag phase period before effective shortening of telomeres occur, it can still be used in combination with present chemotherapeutic drugs and provide a more efficiently induced cell death (Cerone and Londono-Vallejo et al, 2006). Moreover telomere length is an independent biomarker for assessing cardiovascular diseases therefore telomere length testing can be used in clinical medicine as a risk factor for early diagnosis faster than current biomarkers such as cholesterol levels. The future will undoubtedly point to new discoveries of how telomere and age related diseases are associated and help prevent them.

Welfare Reform

All Forms of Government Welfare Should be Abolished By: Michelle M. Flores 12/11/08 Strayer University PHI 210 Professor James Poteet All Forms of Government Welfare Should be Abolished Welfare is defined as â€Å"governmental provision of economic assistance to persons in need. † (wordnet. princeton. edu). There are many programs that are currently implemented to aid and assist families in need. Under new laws, Maryland has re-named its assistance programs to Family Investment Programs.Some of these programs include: TCA- Temporary Cash Assistance, Food Stamps, WIC – Women Infants and Children Program, Child Care Assistance, Medical Assistance, Section 8- housing assistance, Energy Assistance and many other programs. To qualify for such programs, a family must have a minor child or a pregnant woman, and the parent must have applied for child support from the absent parent. It is said that the family applying must show a need for assistance. (peoples-law. org). Currentl y, the United States is in a financial recession. This recession has made many Americans rely and depend on such assistance from the Government.With all of these and many more programs implemented, when is enough, enough? How much assistance should be offered to a single family or person? What programs are actually necessary and/or beneficial? I will provide a brief synopsis of a few programs below. Temporary Cash Assistance Temporary Cash Assistance is a government allowance in the form of cash. Qualifications for this program are as follows: Household sizeGross Income 1 person or a pregnant woman$216. 00 a month or less 2 persons$380. 00 a month or less 3 persons$482. 0 a month or less 4 persons$583. 00 a month or less 5 persons$675. 00 a month or less (peoples-law. org). The current minimum wage in Maryland is $7. 25. (epi. org). This means that a single person or pregnant woman cannot work anymore than thirty two hours a month or eight hours a week to qualify for this benefit. T he average person works at least thirty to forty hours per week, which is about four times the qualifying allowance. What kind of job will allow a person to work only eight hours a week?How is this fair to those who work more than that and are still struggling to get by living paycheck to paycheck? It’s not! Are these families using this cash assistance to help pay bills or to live lavishly? What type of control is used here? There is no control, so absolutely none. Now, I am not saying that families who receive cash assistance should not be able to buy luxury or feel good items, but these items should not be a priority before bills are paid. If you cannot afford to keep your lights on, you should not be in the bar buying alcohol or in the salon getting your hair and nails done. This is absurd!I love to see my tax dollars going to hair nails on a woman that is not working, but yet I work full time and cannot afford to have my hair and nails done as often as those women do. SN AP SNAP otherwise known as the Supplemental Nutrition Assistance Program is the new name for the Food Stamp Program. SNAP is a government allowance that provides needy families with the benefit to buy food. This program provides a family with a card similar to a debit or credit card that holds the benefits allotted to said family. If a person or family qualifies for cash assistance, they will automatically qualify for SNAP.The income guidelines are as follows: Household SizeGross IncomeNet Income 1 person$1,127. 00$867. 00 2 persons$1,517. 00$1,167. 00 3 persons$1,907. 00$1,467. 00 4 persons$2,297. 00$1,767. 00 5 persons$2,687. 00$2,067. 00 (peoples-law. org). With minimum wage at $7. 25 per hour, a person can work an average of one hundred and seventy two hours a month for an average of about thirty two hours a week.What are the problems with this program? How do we make certain that the needy families and children of those needy families are actually receiving the allotted benefit s? The government cannot control this either. Many times these benefits are sold to those who are not needy for half or less than what they are really worth. Meaning, a person not being supplied with this benefit can buy the card from a needy person and go into a market and buy a hundred dollars worth of groceries for only fifty dollars. The non-needy person has then saved a lot, but the child of a needy family is at home with less available food.This sickens me that a parent can literally take out of their child’s mouth just to get cash to do God knows what with. WIC WIC is the Women, Infants and Children Program. This program covers pregnant women, new mothers and children under five who have a nutritional need. The income guidelines here are: Family SizeIncome per monthIncome per year 1 person$1,604. 00$19,240. 00 2 persons$2,159. 00$25,900. 00 3 persons$2,714. 00$32,560. 00 4 persons$3,269. 00$39,220. 00 5 persons$3,824. 00$45,880. 0 This program supplies mothers with inf ants or young children with milk, cheese, beans, oatmeal, cereal and several other nutritious items. This program is very beneficial to the family, as it maintains the health of babies, young children and mothers. I feel as though this is a wonderful program. With every up there is a down. Welfare fraud is huge in America. Welfare fraud is described as â€Å"the intentional misuse of various state funded Welfare programs. † (spamlaw. com). Fraud comes in many forms and may consist of withholding income, household size information or providing false information to obtain benefits.Here we have people obtaining benefits and are not deserving of them. One for instance is the purchasing of the SNAP card. Welfare fraud is very expensive. â€Å"It costs the system millions in misused benefits every year. † (spamlaw. com) â€Å"Welfare fraud has been widely criticized by advocates of the system because this abuse makes funds less available to those who actually need the benef it. It has also been criticized by opponents of the system who believe the crime creates situations where hard working taxpayers are supporting the middle class and a lavish lifestyle for criminals.These critics have coined the terms ‘welfare Cadillac’ or ‘welfare Queen’ to instances or individuals associated with welfare fraud† (spamlaw. com). All actions of welfare fraud should be avoided if you are approached to be involved in such acts. These crimes are punishable by the full extent of the law. If a person is convicted of welfare fraud and put in prison, are our tax dollars not going to further take care of them? In prison inmates are fed, clothed and nursed to health. Not to mention they have to be guarded by correctional officers or policing staff.Wow, what a vicious cycle. We take the benefits from them in the free world, but then again support them in the locked up world. I am so glad that my hard earned tax dollars are supporting such trash. The new changes in the Welfare program were created to help families achieve independence. What is the government doing to help achieve such independence? What programs are implemented to get these needy families back into the work force, not to depend on the government? The Welfare reform in the early 1990’s led to a huge reduction in Welfare dependency. Under the old AFDC (Aid to Families with Dependant Children) program, states were given more federal funds if their welfare caseloads were increased, and funds were cut whenever the state caseload fell. This structure created a strong incentive for states to swell the welfare rolls. Prior to the reform, one child in seven was receiving AFDC benefits. † (Conn Carroll). At this time, President Clinton created programs that allowed families to learn new skills and help them transition back into the work force. This reduced Welfare dependence and required welfare recipients to prepare for employment.This is what really nee ds to be done. However, with the new financial crisis that the United States is currently seeing, it is harder for those with minor skills to obtain work. President Obama has enacted stimulus bill that abolishes welfare reform and adds new welfare spending. â€Å"It is clear that – in both the House and the Senate stimulus bills – the original goal of helping families move to employment and self-sufficiency and off long term dependence on government assistance has instead been replaced with the perverse incentive of adding more families to the welfare rolls.The House bill provides four billion per year to reward states to increase their Temporary Cash Assistance case loads; the Senate bill follows the same policy but allocates less money. † (Rector & Bradley). This is crazy. The funds should be allocated by the amount of unemployment per state, not a gross figure overall. There are some states that are better off financially than others. The funds should be divi ded accordingly. â€Å"In the first year after enactment of the stimulus bill, federal welfare spending will explode upward by more than twenty percent, rising from $491 billion in FY 2008 to $601 billion in 2009.This one year explosion in welfare spending would be, by far, the largest in U. S. history. † (Rector & Bradley). Since the enactment of the welfare reform in the early 1990’s, many Americans have become less dependent on the welfare system. Clinton gives great thanks for being re-elected partially due to his signing of the welfare reform bill. Great job and wonderful efforts President Clinton! In my opinion Welfare is an incentive for people to sit at home and not work, to not be responsible for themselves or their families. Don’t get me wrong, I do see a need for assistance programs, only when necessary.Do I think that all forms of government welfare should be abolished? No, I do not. Surprised by this answer? I knew you would be. I agree that these p rograms should be implemented for those who are in crisis and desperately need them. These programs should not be used and abused at American’s leisure. Considering the tough economic times we are in right now, I agree that many Americans need help. Especially those who have lost their jobs and those who are aggressively seeking employment, but cannot find it. However, this help should only be temporary.New reform needs to be implemented. Education and services need to be offered to get people back into the work force and off of government dependency. With all of the current programs offered, me as a single mother has a huge incentive to quit my job, stay at home and collect all the government has to offer. Then, I may be able to buy lobster in the grocery store rather than 80/20 ground beef. WORKS CITED Carroll, C. (2009). Stimulus Bill Abolishes Welfare Reform. Retrieved November 7, 2011 from http://blog. heritage. org/2009/02/11stimulus-bill-abolishes-welfare-reform/print/ Fox, L. 2007). What a new Federal minimum wage means for the United States. Retrieved November 7, 2011 from http://www. epi. org/publications/entry/ib234/ Rector, R. and Bradley, K. (2009, February). Stimulus Bill Abolishes Welfare Reform and Adds New Welfare Spending. Web Memo No. 2287 Published by the Heritage Foundation http://www. peoples-law. org/income/gov-ben/family_investment_program. htm What is Welfare Fraud? Retrieved November 7, 2011 from http://www. spamlaws. com/welfare-fraud. html http://wordnetweb. princeton. edu/perl/webwn? s=welfare

Breakfast Is the Most Important Meal of the Day Essay

Breakfast is considered the most important meal of the day, and for good reason. There are a few reasons people don’t eat breakfast in the morning such as not feeling hungry or to try and limit calories. However, skipping breakfast can lead to a number of problems when it comes to trying to lose weight and keep it off. If you are trying to achieve or maintain a healthy weight, consider the following reasons to eat breakfast each and every morning. It Revs up Your Metabolism Eating breakfast is a great way to get your metabolism working well for the day. When your body receives food in the morning, it tells your brain that you’re going to need to start working to digest it. This wakes up the system and warms up the metabolism so it’s ready to work throughout the day. When you don’t eat breakfast in the morning, your body thinks that it needs to conserve the energy it has because it isn’t getting any more through nutrition. This actually slows your metabolism down, which results in a decrease in the amount of calories you burn all day long. It Keeps You from Binging Not eating breakfast in the morning may save you calories for the time being, but it sets you up for failure throughout the rest of the day. This is because after not feeding your body for several hours overnight, a lack of food in the morning will leave you grumpy and hungry very early in the day. When lunch time rolls around, you’re more likely to choose something high in fat and calories to satisfy your food cravings, because you feel so ravenous. If you can hold off through dinner, chances are you will feel an overwhelming urge to snack all night long, which can really pack on the calories. It Keeps You in a Good Mood Feeding yourself in the morning will keep your spirits up throughout the day for a number of reasons. First and foremost, since your body won’t think that it’s starving after a nutritious meal in the morning, it’s easier to get in a good mood and stay that way. It also provides plenty of needed energy to help you get through the regular tasks of your day, which can help keep your mood bright and optimistic. A healthy meal in the morning can also help to regulate your blood sugar levels through lunch time, which plays a vital role in your mood. Overall, eating something for breakfast is better than eating nothing at all. The more balanced your meal is, the better off you will be. Instead of a breakfast of bacon, eggs and toast that will leave you feeling heavy and sluggish within just a few minutes, consider having a fruit smoothie and a bowl of oatmeal topped with fresh berries, which will invigorate your body and give you the energy needed to get through the day .

Two U.S. Vacation Hot Spots Essay - 566 Words

In all of my travels across the United States of America, the `hottest vacation spot hands down is in Key West, Florida and the `coolest place to travel to is Denali National Park in Denali, Alaska. These vacation destinations are the two most beautiful and most relaxing places in the nation! I personally have experienced a week of enjoyment at both locations and find myself wanting to go back to each of them in the future because I had such a great time. Even though these are both awesome places to spend a week of vacation time, they differ in weather and climate patterns, they each have unique attractions and activities to do, and both vary in travel costs and various other expenses. Weather and climate conditions are one major†¦show more content†¦Since both vacation spots have different climates, they both offer a variety of different activities to do and adventures to have. In Key West, vacationers are literally surrounded by water and have numerous water activities to partake in like deep sea fishing, boating, swimming, snorkeling, scuba diving, jet skiing, going to the beach, etc. I would suggest packing your travel bags full of shorts, tee shirts, water apparel, and extra sunscreen! In the arctic area of Alaska, recreational activities include biking, climbing, camping, fishing, hiking, winter sports, scenic driving, wildlife viewing, and visiting various exhibits. Your travel bags for Denali National Park should consist of warm, water resistant clothing, hiking equipment, camping equipment, and nutritional and energizing camping food. One of the most important issues about traveling and vacations is the cost and the overall expense of the trip. From Allentown, Pennsylvania, a round trip ticket for a week to Key West, Florida is going to cost between four hundred and five hundred dollars, including a rental car and gas. 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