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Thursday, September 15, 2011

CYLINDER EXPIRY


"Have U ever heard about LPG gas cylinder's expiry date....!!



Expired Cylinders are not safe for use and may cause accidents. In this regard please be cautious at the time of accepting any LPG cylinder from the Vendor.

Here is how we can check the expiry of LPG cylinders:
On one of the three side stems of the cylinder, the expiry date is coded alpha numerically as follows A B C, or D, and some two-digit number following this e.g., D06.

The alphabet stands for quarters -
1. A for March (First Qtr),
2. B for June (Second Qtr),
3. C for Sept (Third Qtr), &
4. D for December (Fourth Qtr).

The digits stand for the year till it is valid. Hence, D06 would mean December qtr of 2006.
Please Return the Cylinder that you get with an Expiry Date. They are prone to leaks and other Hazardous accidents...
The second example with D13 allows the cylinder to be in use until Dec 2013.

Kindly pass this on to every one, and create awareness among the public

                                           

How to Say I Love in Different Styles

Indian English - 143
English - I love you
Afrikaans - Ek het jou lief
Albanian - Te dua
Arabic - Ana behibak (to male)
Arabic - Ana behibek (to female)
Armenian - Yes kez sirumen
Bambara - M'bi fe
Bangla - Aamee tuma ke bhalo aashi
Belarusian - Ya tabe kahayu
Bisaya - Nahigugma ako kanimo
Bulgarian - Obicham te
Cambodian - Soro lahn nhee ah
Cantonese Chinese - Ngo oiy ney a
Catalan - T'estimo
Cheyenne - Ne mohotatse
Chichewa - Ndimakukonda
Corsican - Ti tengu caru (to male)
Creol - Mi aime jou
Croatian - Volim te
Czech - Miluji te
Danish - Jeg Elsker Dig
Dutch - Ik hou van jou
Esperanto - Mi amas vin
Estonian - Ma armastan sind
Ethiopian - Afgreki'
Faroese - Eg elski teg
Farsi - Doset daram
Filipino - Mahal kita
Finnish - Mina rakastan sinua
French - Je t'aime, Je t'adore
Gaelic - Ta gra agam ort
Georgian - Mikvarhar
German - Ich liebe dich
Greek - S'agapo
Gujarati - Hu tane prem karoo chhoo
Hiligaynon - Palangga ko ikaw
Hawaiian - Aloha wau ia oi
Hebrew - Ani ohev otah (to female)
Hebrew - Ani ohev et otha (to male)
Hiligaynon - Guina higugma ko ikaw
Hindi - Hum Tumhe Pyar Karte hai
Hmong - Kuv hlub koj
Hopi - Nu' umi unangwa'ta
Hungarian - Szeretlek
Icelandic - Eg elska tig
Ilonggo - Palangga ko ikaw
Indonesian - Saya cinta padamu
Inuit - Negligevapse
Irish - Taim i' ngra leat
Italian - Ti amo
Japanese - Aishiteru
Kannada - Naanu ninna preetisuttene
Kapampangan - Kaluguran daka
Kiswahili - Nakupenda
Konkani - Tu magel moga cho
Korean - Sarang Heyo
Latin - Te amo
Latvian - Es tevi miilu
Lebanese - Bahibak
Lithuanian - Tave myliu
Malay - Saya cintakan mu / Aku cinta padamu
Malayalam - Njan Ninne Premikunnu
Mandarin Chinese - Wo ai ni
Marathi - Me tula prem karto
Mohawk - Kanbhik
Moroccan - Ana moajaba bik
Nahuatl - Ni mits neki
Navaho - Ayor anosh'ni
Norwegian - Jeg Elsker Deg
Pandacan - Syota na kita!!
Pangasinan - Inaru Taka
Papiamento - Mi ta stimabo
Persian - Doo-set daaram
Pig Latin - Iay ovlay ouyay
Polish - Kocham Ciebie
Portuguese - Eu te amo
Romanian - Te ubesk
Roman Numerals - 333
Russian - Ya tebya liubliu
Scot Gaelic - Tha gra\dh agam ort
Serbian - Volim te
Setswana - Ke a go rata
Sign Language - (represents position of fingers when signing'I Love You')
Sindhi - Maa tokhe pyar kendo ahyan
Sioux - Techihhila
Slovak - Lu`bim ta
Slovenian - Ljubim te
Spanish - Te quiero / Te amo
Swahili - Ninapenda wewe
Swedish - Jag alskar dig
Swiss-German - Ich lieb Di
Tagalog - Mahal kita
Taiwanese - Wa ga ei li
Tahitian - Ua Here Vau Ia Oe
Tamil - Nan unnai kathalikaraen
Telugu - Nenu ninnu premistunnanu
Thai - Chan rak khun (to male)
Thai - Phom rak khun (to female)
Turkish - Seni Seviyorum
Ukrainian - Ya tebe kahayu
Urdu - mai aap say pyaar karta hoo
Vietnamese - Anh ye^u em (to female)
Vietnamese - Em ye^u anh (to male)
Welsh - 'Rwy'n dy garu
Yiddish - Ikh hob dikh
Yoruba - Mo ni fe..e..

It Only Rains On Me




Yajna“Those who perform the sacrifice of chanting Shri Rama’s holy name with love, faith and full attention receive their share of rewards from the Creator; thereby making even the unfortunate person fortunate.” (Dohavali, 36)
tulasī prīti pratīti soṃ rāma nāma japa jāga |
kiem̐ hoi bidhi dāhino dei abhāgehi bhāga ||
Those who believe in a God, a higher power who is in charge of the complex workings of nature and the fate of man, follow standard religious practices and rituals. Indeed, to say that you perform something “religiously” shows that you have dedication to adherence and practice, without deviation due to sentiment, emotion, or the desire to meet a specific end. Since God is the most powerful person, following His regulations would mean that other priorities could be neglected and life still maintained, while the law codes given by Him shouldn’t be cast aside as being secondary in importance. While the adherence to rituals and regulations shows great deference on the part of the worshiper, a level of respect held towards the esteemed Lord that should be praised, there is a higher platform that can be reached. Not only does this higher state of consciousness bring about more personal and fulfilling interactions with the Supreme Person, it also takes care of the previous obligations pertaining to religious life. The same can’t be said when the reverse order is followed.
What does this mean exactly? Let’s cover some of the basic regulations and rituals to see what effect they have on consciousness. Our thought processes serve as the key determining factor in our happiness and well-being. We may work hard to procure some material reward or to remove distress, but in the end the real change comes in the situation of the mind, its ability to concentrate on thoughts and ideas that don’t cause pain. Since consciousness plays an integral role in every area of life, its importance is not diminished when worshiping God, or that Supreme Controller in the sky that we are looking to not offend.
For a large portion of the world, a common regulation adhered to is that of attending church on Sundays. “Go to church at least once a week to thank the Lord for His blessings and pray to Him for the well-being of yourself and your family. You spend the other six days of the week frantically engaged in your own business, so why not dedicate a few hours during one day each week to prayer and healing?” This is certainly a wonderful practice, as it is very easy to get caught up in our own affairs and forget that there is a higher power, someone who is guiding the workings of matter. In theBhagavad-gita, the Song of God sung on the battlefield of Kurukshetra a long time ago, it is said that all beings, moving and nonmoving, are working under the direction of the Supreme Lord Krishna, who is the same God that has been worshiped since time immemorial by people of every persuasion. Though some may refer to the Lord by a specific name, this doesn’t mean that there are many different Gods. Even the atheists acknowledge God through His form of death. God is the higher power, the supreme controlling force. Though the atheist will not acknowledge the presence of this person, they must bow down to death, which can come at any time and doesn’t leave without getting what it wants.
“The Supreme Lord is situated in everyone's heart, O Arjuna, and is directing the wanderings of all living entities, who are seated as on a machine, made of the material energy.” (Lord Krishna, Bhagavad-gita, 18.61)
Lord KrishnaBesides going to church every Sunday, there are other regulations such as observing holidays and fasting periods and going through different rites performed by priests. In other traditions, the regulations are similar, with people praying a certain number of times each day, worshiping celestial figures through rituals, or visiting temples and other houses of worship. In the Vedic tradition, the oldest system of spirituality in the world, the basic functional unit of religious life is theyajna, or sacrifice. In a standard yajna, there is a pit of fire created inside of a square, with the different participants seated around the pit. The head priest manages the ceremony and chants the mantras necessary to ensure the ritual’s success. The participants give offerings with the right hand into the fire, saying “svaha” after each pour.
How the yajna operates and yields results is pretty straightforward. In addition to the Supreme Lord, there are numerous elevated living entities who are in charge of managing the different departments of creation. One person is in charge of air, another water, another the sun, and so on. The offerings in the fire sacrifice, which usually consist of clarified butter, or ghee, are then eaten up by these different controllers, who are known as devas, or demigods. Therefore the secondary purpose of the yajna is to satisfy the higher authorities, who in turn will kindly bestow their benedictions on man. The process is similar to having a plant in the garden that needs regular watering and sunlight. Through proper care, the plant will yield fruits in the form of flowers, vegetables, grains and other items that can be utilized.
“In the beginning of creation, the Lord of all creatures sent forth generations of men and demigods, along with sacrifices for Vishnu, and blessed them by saying, ‘Be thou happy by this yajna [sacrifice] because its performance will bestow upon you all desirable things.’” (Lord Krishna, Bg. 3.10)
When the demigods are pleased, there is no chance of drought, natural disasters, and so many other calamities. Yajna is also a great way for the individual to realize their fallibility and their inferior position with respect to the higher authorities. Each of us is God in a sense since we control the movement of our body. But this godly power is very limited, as our consciousness does not spread beyond our own experiences. Moreover, we still must succumb to the forces of nature and suffer through the threefold miseries of life [those brought on by the demigods, the mind and body, and other living entities].
While pleasing the demigods through yajna and adhering to other regulations can help to insulate us from trouble, there is still a higher platform to be reached in spiritual life. The soul, which is the identifiable aspect within all forms of life, has distinct properties, the foremost of which are eternality, bliss and knowledge. Not surprisingly, these traits are inherited from the Supreme Soul, that person we refer to as God. Since the soul has these wonderful features, its primary business cannot be to avoid fear and pain by performing ritualistic functions and adhering to dictates and law codes. Rather, the highest engagement for the soul is to find that one person who gives it the most pleasure. Not surprisingly, that person is God.
Radha and KrishnaThe followers of the bhakti school, the highest system of philosophy and sentiment that can exist, take exclusively to loving the Supreme Lord in any of His non-different forms. In His original feature as Bhagavan, God is the most fortunate. He possesses the qualities of beauty, wealth, strength, fame, renunciation and wisdom to the fullest degree and simultaneously. According to the Vedas, His original form is called Krishna, which means all-attractive. Krishna has many incarnations, of which one of the most celebrated and worshiped is Lord Rama, whose name means one who gives transcendental pleasure to others.
Bhakti-yoga, the system of linking the individual’s consciousness with the Supreme Consciousness through acts of love and devotion, is meant exclusively for Lord Krishna or one of His different Vishnu forms. GoswamiTulsidas, a celebrated Vaishnava poet, especially loves Shri Rama. Even when discussing topics and incidents pertaining to Lord Krishna, Vishnu, or any other non-different form of Godhead, Tulsidas identifies them as being the same Rama, the beloved lord of his life breath.
How do we practice bhakti? How is it any different from going to church once a week or performing a yajna with a fire? Bhakti can actually be practiced through any activity, provided the beneficiary is properly identified and satisfied. For instance, when we sing songs on stage or in the car to ourselves, the beneficiaries are the audience or our mind. If we take the same practice, however, and make Bhagavan the beneficiary, the activity can be considered bhakti. If we prepare elaborate food for our own pleasure or the pleasure of others, the activity is of the material variety, as it aims to please the material senses. But when the same food is prepared and offered to Krishna, the effort becomes the most sublime activity, a central component of a bhakti-yoga routine.
Lord RamaThe most universally appealing and applicable activity of bhakti is the chanting of the holy names, “Hare Krishna Hare Krishna, Krishna Krishna, Hare Hare, Hare Rama Hare Rama, Rama Rama, Hare Hare”. The holy name is the key; it allows any person at any time to link to the spiritual world. No need to wait until Sunday to worship if you have the holy name resting comfortably on the tip of your tongue. This non-different expansion of God, a sound vibration which perfectly represents His ultimate feature as Bhagavan, can be produced and enjoyed at any time. The same can’t be said of any other religious practice. Therefore the bhaktas, the devotees, chant the holy name as often as possible and expound on its glories to others.
In the above referenced verse from his Dohavali, Tulsidas says that anyone who lovingly, attentively and knowingly chants the holy name of the Lord gets all fortunes, for their chanting is their yajna. This is a very important point to understand because it addresses the misgivings that those new to bhakti may have about the process. The initial concern is over the neglect of the previously performed rituals and regulations. “Sure, loving God is great, but won’t I get punished for not going to church? What if I don’t perform my rituals? Won’t the demigods be angry and punish me as a result?” The fear of punishment from the Supreme Lord and the higher authorities is quite natural, as one who is more powerful has the ability to make the lives of the inferiors unpleasant.
But Rama is Bhagavan, or the most fortunate and powerful living entity. Anyone who connects with Him through love and devotion, regularly chanting His name, has no need to fear anyone or anything. In fact, all the rituals and regulations of spiritual life are meant to eventually lead one to the bhakti platform. It is rare to find bhakti active at full levels in a conditioned living entity, someone who is forgetful of their position as eternal servant of God. Therefore other processes are introduced and recommended as a way to maintain some link to religious life. The hope is that the more one maintains their adherence to the rules and regulations of religious life, the greater their chances for ascending to the bhakti platform will be.
Hanuman chantingBy comparing the chanting, or japa, of Rama’s name to a sacrifice where rewards are distributed to the right hand of the worshiper by Vidhi, or Lord Brahma, Tulsidas advises that instead of worrying about what will happen as a result of giving other religious processes secondary importance, just understand that your japa is itself the highest yajna. In the Bhagavad-gita, Lord Krishna confirms that He is the enjoyer of sacrifice, Yajneshvara. Even a yajna aimed at pleasing the demigods must go through Vishnu first; only then can the demigods take their portion of the sacrifice and thus be satisfied. Though Vishnu is the ultimate enjoyer, if the consciousness of the performer isn’t focused on the Lord, the benefit of bhakti is not there. But when there is love and devotion, an awakening of transcendental attachment to the Supreme Lord, the chanting process itself becomes the most potent yajna, a sacrifice that yields the greatest benefits.
As if these truths weren’t enough to allay the fears of those newly initiated into bhakti, Tulsidas touches on another issue to further solidify the supremacy of divine love. When we go to church or perform a ritual, there is typically an accompanying prayer, an inherent understanding that by showing deference to the law codes of God, one will be insulated from punishment and misfortune. As we all know, though, sometimes bad things can happen anyway, despite the most heartfelt and sincere prayers. If our loved one is terminally ill and we pray to God every day to save them, there is still the chance that they will die.
This happens because of karma, or fruitive work. The managers of the departments of the material creation use the basic cause and effect of fruitive activity to instigate outcomes. This is quite easy to understand, for we see how this works all the time. If we drop something out of our hands, it will fall to the ground. If we eat too much food, we will feel discomfort later. If we don’t sleep enough at night, we will be tired throughout the day. Expanding out to the largest scope, all of the results we see in life pertaining to the material body are due to karma. Even the rituals and adherence to religious sacrifice are acts of karma, as they have accompanying results. Therefore at every second the results of past work are coming in, like the election returns that pour in, even from those who voted weeks prior. One person may have voted by an absentee ballot and sent their ballot in the mail many weeks before election day. Thus their votes can be tallied later on, sometimes weeks after the election was held. Similarly, the results of our past work can come to us many years later, sometimes even in another lifetime. Only the Supreme Lord can make sense of these results and predict them.
Lord RamaChanting Rama’s name with love and devotion guarantees the performer their share of the results of the sacrifice, even if they are the most unfortunate. In this way we see that not only does bhakti insulate one from the potential negative reactions of neglecting other spiritual practices, but it actually delivers better results in the long run. The most unfortunate person, one who has very bad karma, can follow dry regulations and procedures all they want, but they will still never become fortunate, as that is not in their destiny. With Rama there is no consideration taken about one’s caste, family heritage, level of sinfulness, wealth, gender, or overall karma. Just the fact that one wants to associate with Him in a mood of love and devotion is enough to satisfy the Lord, who in turn will effuse some of His tremendous fortune onto the worshiper.
There are many historical incidents that support these claims. Probably the most famous example was when Krishna cajoled the residents ofVrindavana to neglect the annual puja to Lord Indra, the king of the heavenly realm, the leader of the demigods. Nanda Maharaja, Krishna’s foster father during the Lord’s time on earth in Vrindavana some five thousand years ago, was set to offer sacrifice to Lord Indra when Krishna stepped in and asked him to perform a puja for the neighboringGovardhana Hill instead. The residents were a little hesitant to follow this advice for fear of the consequences, but since Krishna was asking they did not deny the request. They had taken complete shelter of the Lord, the jewel of Vrindavana. Performing the puja inaugurated by Krishna, the residents faced an onslaught of rain from a vengeful Indra afterwards. The residents took to bhakti by obeying and satisfying Krishna, and now they were seemingly being punished for it.
Krishna lifting Govardhana HillKrishna then stepped in to save the day by holding up the massive hill that had just been worshiped. Keeping it above the residents for seven days as an umbrella, Indra was forced to give up and beg forgiveness for his sin. In this way the residents performed their sacrifice at the Supreme Lord’s direction and received their share of the offerings in the form of God’s protection and association. The higher authority figures may be unhappy if we neglect to pay them tribute, but the Supreme Lord’s satisfaction supersedes anyone else’s concerns. If Rama is happy, no one can do anything to harm His devotee and their exercise of bhakti. On the other hand, if one is unfortunate due to their karma, no demigod or repeated sacrifice can bring them the tremendous fortune that is Bhagavan’s mercy. Presented with the two options, the wise and sober man would always follow the prescription so nicely passed on by Tulsidas.
In Closing:
If in the Supreme Lord of creatures you do believe,
Follow sacrifices and rituals, rewards to receive.
Pious around the world do take their seat on church pew,
Every Sunday worship God, pray for benedictions they do.
Vedic tradition calls for yajna, demigods to please,
Sit around pit of fire, drop oblations of ghee with ease.
Yet of all rituals and rites is Vishnu the enjoyer,
Supreme Godhead, of misfortunes He is the destroyer.
One who worships Him through chanting His name,
The Lord’s favor and company do they gain.
Rama means the Lord who gives transcendental pleasure,
His vision so sublime, His name the saints do treasure.
Tulsidas says do japa of Rama’s name with full attention,
Harbor love for the holy name, give to it your affection.
By this formula does the Creator become favorable,
Lord Brahma, who in his rewards can be most charitable.
If one is unfortunate karma will always cause them pain,
But luck even they can find by chanting Rama’s name.
By avoiding bhakti, rituals may or may not help us.
But Rama can favor the unlucky, in His name do you trust.

Breakthrough opens new avenues for hepatitis C vaccine

“Isolation of hepatitis C ‘founder virus’ reveals weakest links in virus makeup.”
Hopes for an effective vaccine and treatment against the potentially fatal hepatitis C virus (HCV) have received a major boost following the discovery of two ‘Achilles’ heels’ within the virus.
A team of medical researchers from the University of New South Wales (UNSW) studied individuals at high risk of HCV infection, including a number identified within a few weeks of the onset of infection.
Using a new technique called next generation deep sequencing and sophisticated computer analytics the team, led by Professor Andrew Lloyd and Associate Professor Peter White, were able to identify the ‘founder’ virus responsible for the initial infection and then track changes within the virus as it was targeted by the immune system.
“We discovered that hepatitis C has not one but two ‘Achilles’ heels’ that provide opportunities for vaccine development,” said Dr Fabio Luciani, from UNSW’s Inflammation and Infection Research Centre and the research team’s biostatistician.
“If we can help the immune system to attack the virus at these weak points early on, then we could eliminate the infection in the body completely,” he said.
A paper describing the breakthrough appears in the leading scientific journal in the field of virology, PLoS Pathogens.
Hepatitis C virus infection is a global pandemic with more than 120 million people infected worldwide, including some 200,000 Australians. The virus causes progressive liver disease leading to cirrhosis, liver failure and cancer. Current antiviral treatments are arduous, costly, and only partially effective.
Team member and virologist Dr Rowena Bull said the discovery of the weakest links meant vaccine researchers could now focus their attentions on the most likely avenues for success.
“The first weak point was identified at transmission, when the virus has to survive the transfer from one individual to another,” Dr Bull said.
“The second weakness, and surprise finding, was the significant drop in the diversity of the viral variants in each individual studied, occurring about three months after transmission, around the time where the immune system is starting to combat the virus. A lower number of variants means the virus is easier to target.”
Study leader Professor Lloyd said the discoveries were significant because of their potential to overcome longstanding barriers to hepatitis C vaccine development.
“To date hepatitis C has been difficult to target with single interventions because there are many different strains of the virus,” he said. “In addition, like HIV, the hepatitis C virus mutates very rapidly and exists as a complex family of mutated viruses within every infected individual, meaning the virus can avoid efforts by the immune system to keep it under control,” Professor Lloyd said.
“What’s more, a third of infected people can have an effective immune response that eliminates the virus early on. This means key initial immune responses were difficult to identify and study because early infection and elimination can go unrecognised.”
Professor Lloyd said work is now underway to identify the key immunological features of the founder viruses in order to guide new vaccines.
“Further research will test the extent of the immune response against these founder viruses in a cohort of very early infected individuals,” he said.
_________________
The research team included members from UNSW’s Kirby Institute, The University of Western Australia and Murdoch University, and was supported by a National Health and Medical Research Council of Australia (NHMRC) Program Grant and by grants from Australian Centre for HIV and Hepatitis Virology.

Small molecule receptor detects lipid’s telltale sign of cell death


“Efficient, economical molecule could speed evaluation of some anti-cancer treatments.”

Researchers from Boston College have developed a new class of small molecule receptors capable of detecting a lipid molecule that reveals the telltale signs of cellular death, particularly cancer cells targeted by anti-cancer drugs, the team reports in the current electronic edition of the Journal of the American Chemical Society.

Caption: The cLac molecule developed in the lab of Boston College chemist Jianmin Gao latches onto dying cells, while bypassing living cells. When colored with a fluorescent dye in tests, cLac allows traditional imaging technology to view the volume of apoptotic cells, which could ultimately provide a faster way to evaluate the effectiveness of anti-cancer drugs. As shown here, a fluorescence microscopy image reveals cLac at work in laboratory tests. Credit: Journal of the American Chemical Society
Researchers led by Assistant Professor of Chemistry Jianmin Gao successfully grafted the key residues of the milk protein lactadherin onto the molecular scaffolding of a short but sturdy circular chain of amino acids to create cyclic lactadherin (cLac) mimics capable of binding to apoptotic, or dying, cells.
Gao said his team spent a year and a half focused on a finding a new method of measuring cell death. The team wanted to create an alternative to traditional tests that measure whether or not a tumor has shrunk in size after several weeks of treatment. The team’s focus was on finding a way to measure the presence of dead cells, not the absence of tumor cells.
“We started by looking for a method to detect dying cells,” said Gao. “The sensitivity of scientific and medical imaging is better if you look for the appearance of something, rather than the disappearance. What we wanted to look for is that in the initial stages of treatment the therapy’s molecules are beginning to trigger the death of cancer cells. That can give you an idea a drug is working much sooner than the current methods of evaluation.”
The newly engineered cLac molecules could prove useful as a prognostic tool which could enable oncologists to determine the effectiveness of anti-cancer drugs in a matter of days rather than several weeks, said Gao, who added that further research and testing will need to be conducted.
“Given the small size and ease of synthesis and labeling, cLacs hold great promise for noninvasive imaging of cell death in living animals and, ultimately, in human patients,” Gao said.
The cLac molecule is relatively small, built upon on a cyclic peptide scaffold of approximately a dozen amino acids, yet Gao’s laboratory tests show it is capable of capturing the lipid molecule phosphatidylserine (PS) – a function nature accomplishes by using proteins of several hundred amino acids, Gao said. In apoptotic cells PS flows to the surface where cLac is able to latch onto the dying cells while bypassing living cells. In the current report, researchers colored cLac with a fluorescent dye in order to highlight apoptotic cells for fluorescence microscopy. By using appropriate tracing agents, cLac should be detectable through commonly used imaging technology, including MRI and PET.
The cLac molecule could offer a cost-effective, more stable and cleaner alternative to natural PS-binding proteins used for similar purposes, Gao said. Those proteins are bulky and relatively unstable, contain metal cofactors that make results difficult to interpret and show poor ability to penetrate tissue because of their size.
Gao said cLac could also serve as a useful tool for researchers who use protein as a cell death indicator to screen for millions of compounds. The use of the small, peptide-binding molecule could substantially reduce costs for researchers, Gao said.

Protein found in heart may be target for colon cancer therapies




A protein critical in heart development may also play a part in colon cancer progression.
Research led by investigators from Vanderbilt-Ingram Cancer Center and the Vanderbilt Eye Institute suggests that the protein BVES (blood vessel endocardial substance) – which also is key in regulating corneal cells – may be a therapeutic target for halting colon cancer metastasis.
The study, appearing in the October issue of the Journal of Clinical Investigation, further suggests that BVES may be important more broadly in many, or most, epithelial cancers.
About 85 percent of cancers originate in epithelial cells that form the body’s external and internal linings (such as the skin and the lining of the gastrointestinal tract).
However, the main clinical concern is not the primary tumor, but the potential for that tumor to leave its tissue of origin and spread throughout the body (a process called “metastasis”).
A critical step in metastatic progression of epithelial cancers happens when epithelial cells “revert” to a less differentiated state – a process called “epithelial-mesenchymal transition” or EMT.
Ophthalmologist Min Chang, M.D., studies the healing process in the cornea, perhaps the most highly regulated epithelium in the body. From collaborative studies with David Bader, Ph.D., who discovered BVES and showed its importance in heart development, Chang found that BVES was highly expressed and regulated in corneal cells.
When BVES is disrupted in corneal cells, they become disorganized, almost “cancer-like,” noted Chang, an assistant professor of Ophthalmology and Visual Sciences and co-author on the study.
Chang then brought these findings to the attention of colleague Christopher Williams, M.D., Ph.D., assistant professor of Medicine and Cancer Biology and co-author on the study.
“When he described these cells, it sounded a lot like the way cancer cells looked when they were undergoing metastasis,” Williams said. “So it seemed reasonable to look in cancer for BVES-dependent phenotypes.”
Chang and Williams teamed up with the lab of Daniel Beauchamp, M.D., to assess BVES expression in human colorectal cancers. They found that BVES levels were very low in all stages of colon cancer. They also noted decreased BVES levels in many other types of epithelial cancers (including breast) and in several colorectal cancer cell lines.
To uncover why BVES levels were reduced, the investigators enlisted the help of Wael El-Rifai, M.D., Ph.D., and colleagues. They determined that the BVES promoter (a DNA region that controls gene expression) was heavily modified (methylated), which silenced its expression. In cell experiments, the researchers showed that treating cells with a “demethylating” agent (the drug decitabine, which is currently used to treat myelodysplastic disorders) restored BVES expression. When BVES was expressed in colorectal cancer cell lines, they became more epithelial in nature and their tumor-like characteristics (in cell experiments and in animal models) decreased.
These findings suggest that treatment with agents to increase BVES levels might provide a way to decrease aggressive behaviors of colorectal and other epithelial cancers.
“In cancer, typically the primary tumor doesn’t kill you; it’s the metastatic disease that proves lethal,” said Williams. “So if targeting BVES could interfere with metastasis, that would be very exciting.”
The researchers also identified signaling pathways involved in BVES function that may represent other therapeutic targets – and that reveal new insights into the normal biological function of BVES. The findings could have implications in wound healing and other normal functions of epithelial cells, as well as for many types of epithelial cancer.
“We don’t think it’s just isolated to the colon; it pertains to a broad lot of epithelial cancers,” Chang noted. “And that’s a lot of cancers.”