Researchers discovers what triggers breast cancer to spread to other body parts

 by Biomechanism 

Research led by Shyamal Desai, PhD, Assistant Professor of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans, has discovered a key change in the body’s defense system that increases the potential for breast cancer to spread to other parts of the body. The results, reported for the first time, are featured in the January 2012 issue of Experimental Biology and Medicine.

For cancer cells shape matters. All cells contain a protein cytoskeleton that acts as a scaffold determining overall shape and function, the position of the cell within an organ or tissue, and the ability of the cell to communicate with its neighbors to prevent the uncontrolled growth typical of cancer cells. However, cell transformations that result in cancer disrupt the genetic programs of the cell and alter the cytoskeleton, leading to changes in shape, function, and cell communication that produce uncontrolled growth and metastatic spreading of the tumor. Understanding these changes to the normal genetic program of a cell and the consequences that ultimately lead to cancer have been major challenges to cancer biologists.

This research, funded by the National Institutes of Health, found that a cellular defense system called the ISG15 pathway, which is normally involved in fighting bacterial and viral infection, is triggered in breast cancer to disrupt normal cytoskeletal function and increase the possibility that the cancer cells will metastasize, or spread.

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“Our findings, for the first time, causally link an alteration in the ISG15 pathway during transformation with metastatic potential,” notes Dr. Shyamal Desai, Assistant Professor of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans, “thus providing a novel therapeutic target for future drug discovery.”

Cells contain a protein quality control pathway termed the Proteasome that breaks down damaged and unneeded proteins to their component amino acids for recycling. Such proteins are marked for degradation by flagging them with a small protein called Ubiquitin, which is then recognized by the Proteasome. Alterations in the genetic program that controls the Ubiquitin/Proteasome system have been known for some time to cause cell transformation and cancer. More recently, Dr. Desai and her colleagues have demonstrated that, unlike normal cells, transformed cancer cells produce increased amounts of a related control system that marks proteins with another small protein called ISG15.

Previous research reports that the amount of ISG15 is increased in high-grade compared with low-grade cancers. The ISG15 system is normally activated by interferon and is part of an ancient cellular immune response designed to counter bacterial and viral infection. By a still unidentified mechanism, cancer cell transformation activates the ISG15 pathway. Dr. Desai and colleagues have previously reported that activation of the ISG15 system interferes with function of the Ubiquitin/Proteasome pathway. In their latest work, Dr. Desai and colleagues show that several key proteins that regulate cell movement, invasion, and metastasis are blocked from Proteasome degradation by the ISG15 system and that genetic manipulation to inhibit this pathway reverses cancer cell transformation, suggesting an approach to blocking cancer progression.

Arthur Haas, PhD, the Roland Coulson Professor and Chairman of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans, discovered the ISG15 pathway and co-discovered the Ubiquitin/Proteasome system that was awarded the 2004 Nobel Prize in Chemistry. “These results provide a functional link between the Ubiquitin and ISG15 pathways that reveals how small cell alterations can yield large overall consequences for cell transformation.”

The research team also included Arthur Haas, PhD, and Dr. Desai’s lab members Ryan Reed, Surendran Sankar, PhD, and Julian Burks in the LSUHSC Department of Biochemistry and Molecular Biology, Jerome Breslin, PhD, in the LSUHSC Department of Physiology, and Ashok Pullikuth, PhD, in the LSUHSC Department Pharmacology, as well as scientists at the UMDNJ-Robert Wood Johnson Medical School in New Jersey, and the University of Pennsylvania School of Medicine in Philadelphia.

“Although this current project focused on breast cancer, ISG15 is also elevated in a variety of cancers,” concludes Dr. Desai. “Therefore, this discovery has important implications in other cancers as well.”

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Courtesy LSU Health Sciences Center, New Orleans

‘Lung cancer gene’ pinned

AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

The research team discovered several genes that are important for the growth of cancer cells. Image: Eraxion/iStockphoto Singapore scientists, headed by Dr Bing Lim, Associate Director of Cancer Stem Cell Biology at the Genome Institute of Singapore (GIS), a research institute under the umbrella of the Agency for Science, Technology and Research (A*STAR), and Dr Elaine Lim, medical oncologist affiliated with Tan Tock Seng Hospital (TTSH) and National Cancer Centre Singapore (NCCS), have, for the first time, identified a gene responsible for lung cancer. The finding, reported in the advanced online issue of Cell on 5 January 2012, is a huge step towards finding a cure for the disease.   A small number of cells, known as cancer stem cells or tumor-initiating cells (TIC), are responsible for the promotion of tumor growth. Dr Bing Lim’s team was successful in finding a marker, known as CD166, to identify these cells. With the finding of this marker, the team then made more inroads into the genomic study of the TICs, and discovered several genes that were important for the growth of cancer cells.   The metabolic enzyme known as glycine decarboxylase (GLDC) is a normal occurring enzyme in cells, present in small quantities. The scientists discovered that in abnormal instances when the level of GLDC rises significantly, it causes changes in the behavior of the cell, making it cancerous.   "The manuscript from Dr Bing Lim's laboratory provides a very exciting breakthrough about the unique metabolism of tumor initiating cells” said Dr Lewis Cantley of Harvard Medical School. “This study builds on recent observations that a subset of cancer cells have enhanced serine/glycine metabolism. Importantly it shows that the enzyme glycine decarboxylase, which contributes to nucleotide synthesis, is elevated in lung tumor initiating cells and that it is critical for the ability of these cells to form tumors in vivo. Since glycine decarboxylase does not appear to be generally required for the growth of normal adult tissues, these results raise the possibility that this enzyme could be a target for cancer therapy."   “This research is exemplary of the synergy between cancer researchers and clinicians that led to a breakthrough in our understanding of the metabolic pathway in lung cancer. I congratulate Dr Bing Lim and Dr Elaine Lim for leading this impressive multi-institutional study,” said Dr Huck Hui Ng, Acting Executive Director of GIS. “The discovery of the biomarker has profound implications in cancer diagnostics and stratified medicine. It is hopeful that the metabolic enzyme GLDC will be a good target for drug development by the pharmaceutical industries."   Dr Bing Lim added “This is one of the most satisfying pieces of work I have orchestrated and the biggest credit must go to my post doctoral fellow, Dr Wen Cai Zhang, who took the project from first establishing a xenograft model for human lung cancer to the identification of CD166 as a marker for lung cancer stem cell and culminating with the amazing discovery of the impact of a regular metabolic enzyme in carcinogenesis. It is doubly satisfying that we may have also identified a major drug target for controlling cancers”.   Dr John Wong, Vice Provost (Academic Medicine) of the National University of Singapore, explained that “Lung cancer is one of the most common causes of cancer death in Singapore and the region. There is an urgent need to better understand what drives this disease, especially as lung cancer in Asians appears to have major biological differences compared to that commonly seen in the West. The authors of this seminal paper should be congratulated as they represent the best of Team Science in Singapore, comprising both basic scientists and clinician investigators, all working to develop better therapies for Singaporeans and the community we live in. The findings from Dr Bing Lim’s team strongly support the cancer stem cell paradigm and similar studies in other cancers need to be done.”   Elaine Lim, co-corresponding author and co-principal investigator in this project said, “This paper is the result of successful co-operation between scientists and doctors from the Singapore Lung Cancer Consortium, with the Stem Cell division in GIS. The thoracic surgeons from TTSH, NCCS and NUHS have made outstanding contributions to this homegrown scientific project”   Prof Soo Khee Chee, Director of NCCS, said that “NCCS has made important contributions to medical research through the years, both in clinical as well as basic research. This paper is an example of a very satisfying outcome when medical doctors and scientists huddle together to produce high-quality work. Co-operation between seemingly disparate disciplines amongst the different institutions in Singapore, led by Elaine and Bing, was critical to this success – and there will be many more to come” -          “This study has made significant contributions to our fundamental understanding of lung cancer,” added Prof Philip Choo, Chief Executive Officer at TTSH. “The study also represents an exceptional step forward for medical research involving doctors and scientists. We look forward to more of such collaborative efforts in the future.” Editor's Note: Original news release can be found here.

Cells choose their own destiny

WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH

B cells - immune system cells that can make antibodies - have some control over their destiny. Image: Henrik5000/iStockphoto In a major shake-up of scientists’ understanding of what determines the fate of cells, researchers at the Walter and Eliza Hall Institute have shown that cells have some control over their own destiny. The researchers, from the institute’s Immunology division, drew their conclusion after studying B cells, immune system cells that can make antibodies. B cells can have multiple fates. Some of the more common fates are to die, divide, become an antibody-secreting cell or change what antibody they make. This all happens while the cells are proliferating in the lymph nodes. The commonly-held view is that a cell’s fate is determined by external cues such as the presence of particular hormones or cell signaling molecules. However the Walter and Eliza Hall Institute’s head of immunology, Professor Phil Hodgkin, and colleagues Dr Mark Dowling, Dr Cameron Wellard and Ms Jie Zhou, predicted that cell fates are, to a large extent, determined by internal processes. To test their theory the research team recreated the conditions required for B cells to develop into the different cell types and then filmed the cells, working with Dr John Markham from National Information and Communications Technology Australia to develop new technology and image analysis methods. The research team’s experimental observations were further enhanced by the expertise of mathematician Dr Ken Duffy from the Hamilton Institute at the National University of Ireland Maynooth. Dr Duffy’s understanding of probabilities was critical for the team to interpret the behaviour of the 2500 cells that were filmed. The team’s research findings have been published today in the international journal Science. Professor Hodgkin said the cells behaved as though there were internal machines that governed the cells’ fates. “Each of these internal machines is like a little clock or timer for division, death, what type of antibody they make and whether they become antibody secreting cells,” he said. Dr Dowling explains it as the different fate outcomes being a competition. “Each cell will, in some sense, set up a clock that starts ticking for each of the outcomes and whatever clock goes off first is the decision that the cell makes,” he said. “The cell is trying to do everything but only one fate wins.” Professor Hodgkin said even though the cells were getting the same external signals there was still considerable variation in what happened to the cell population. “A reliable proportion of the B cells would end up with each of the different fates,“ he said. “This suggests that external factors such as hormones or cell signaling molecules were not telling the cells what to do but were altering the probability of what the cells were going to do anyway.” When the body is responding to an infection many immune cell types, each with a different function, are produced. Dr Dowling said it could be that the body was tweaking the odds of producing particular cell types depending on the situation. “The body produces many different hormones and cell signaling proteins so the odds will be different for different infections. A whole lot of molecules involved in the immune system will affect those odds.” Professor Hodgkin said the hope now was to create mathematical models that accurately predict how external signals will alter the probability of what an immune cell population will do. “The development of such models would help in the design of new immune therapies for autoimmune diseases and improved vaccines,” he said. Editor's Note: Original news release can be found here.

Australians biggest users of weed

THE UNIVERSITY OF NEW SOUTH WALES

Up to 15 per cent of 15 to 64 year olds in the two countries use cannabis. Image: KarenMassier/iStockphoto Australia and New Zealand have the highest rates of cannabis and amphetamine use in the world, according to comprehensive research on illicit drug use. Up to 15 per cent of 15 to 64 year olds in the two countries use cannabis, while 2.8 per cent of the same age group use drugs such as speed and crystal meth. The latter figure does not include use of ecstasy. The data is part of a series of papers published in The Lancet examining global drug use and law enforcement, which was led by Professor Louisa Degenhardt, who is based at UNSW’s National Drug and Alcohol Research Centre (NDARC). In 2009, 10 to 15 per cent of people in Oceania had used marijuana in the previous year, compared with 1.2 to 2.5 per cent in Asia. Between 2 and 2.8 per cent of Australians and New Zealanders used amphetamines in that period, compared to 0.2 to 1.4 per cent of people in Africa and Asia. The authors report that in a high-income country such as Australia, illicit drugs are responsible for 2 per cent of years lost due to disability, compared with 2.3 per cent for alcohol and 7.8 per cent for tobacco. The study has been reported extensively around the world, including in the Sydney Morning Herald. For a review of the research, go to NDARC's website Editor's Note: Original news release can be found here.

Maalai Neram - Short Film

Surprising Turbans...

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Collection of awesome photographs that had no Photoshop touch and look just incredible.

A Cultured Upbringing

“The unsuccessful yogi, after many, many years of enjoyment on the planets of the pious living entities, is born into a family of righteous people, or into a family of rich aristocracy.” (Lord Krishna, Bhagavad-gita, 6.41) It is stated in the Bhagavad-gita that the unsuccessful yogi does not have to worry about having his efforts go for naught or worshiping the Supreme Self in vain. There is no progress lost on the path towards ultimate liberation   , which provides the identifiable aspect within every living creature its supreme satisfaction, of which it is most certainly deserving. With other ventures, an unplanned occurrence, something terrible happening at the wrong time, can wipe the slate clean, but the same does not apply with steps made towards the origin of all life and matter. From the statements in the Gita pertaining to this subject, there may be some confusion, for the next destination of the unsuccessful yogi can be a place seemingly not very conducive to spiritual life. A quick review of the matter, however, shows that Lord Krishna    - the speaker of the Gita and the object of yoga, the beneficiary of every religious practice performed in the past, present or future - is correct about the fate of the unsuccessful yogi being beneficial. What is a yogi and how can one be successful as a yogi? Yoga is the linking of the individual soul with the Supreme Soul. The difference between the two entities is subtle yet stark at the same time. The qualification of subtle is made because the individual spirit soul is the same in quality as the Supreme Soul. Juxtapose two human beings. One may be in the stage of infancy while the other is in adulthood. One might have been born in a certain land while another is a native of another area. Despite the differences in circumstances and maturation of external features, the two entities are identical in where they take their identity from. Those sources of identity are also of the same quality. Just as ice and vapor are two different manifestations of the same matter, the living beings in different material bodies are spirit souls with different outer coverings. The Supreme Soul resides within every living being as well. This spiritual entity is the same in quality as the individual soul. Both are transcendental to matter, eternal, knowledgeable and blissful. But there are differences between the two entities; otherwise one wouldn’t be called Supreme. The Supreme Soul, who is also known as the Paramatma, is all-pervading. The individual soul within is only conscious of its present life’s activities. Since the soul is eternal, it has existed in the past and will continue to exist in the future. The body types are inhibiting towards knowledge, however, sort of like how a lampshade covers up the brilliant light emitted by a lamp. Forgetfulness, the darkness of ignorance, is concomitant with association with matter. Not only is the Paramatma conscious of the previous lives of the localized being, but it is also connected to every other living entity as well. Hence the Paramatma is referred to as antaryami, or the all-pervading witness. As this ability is not present in the individual soul, the Paramatma automatically becomes superior. From the Bhagavad-gita, we learn that the Paramatma is an expansion of God, a localized representation of the Supreme Lord which acts as an impartial witness to the activities of the individual soul. “I am seated in everyone's heart, and from Me come remembrance, knowledge and forgetfulness. By all the Vedas am I to be known; indeed I am the compiler of Vedanta, and I am the knower of the Vedas.” (Lord Krishna, Bhagavad-gita   , 15.15) Yoga is the linking of the individual with the Supreme within the body. Every endeavor actually descends from the search for this link. In ignorance, however, the link will be sought with worldly objects, people and things that are not attached to spirit. Another living entity is obviously a spirit soul as well, but if the source of the attachment to them is related to their bodily manifestation, there is no connection with spirit. The Paramatma is as pure as you get, so the connection that results inherits the same properties as the corresponding entity. Hence yoga is the ultimate activity, the most worthwhile aim to achieve. Just learning of the need for yoga is rare enough. In the modern age the word “yoga” has turned into a synonym for stretching exercises and gymnastics. The health benefits are but a small aftereffect of the ancient system that was always intended to bring about a fruitful union between the two souls residing within the body. After learning of the need for yoga, practicing it properly is rather difficult. For starters, through many lifetimes spent attached to matter, the conditioned soul is confident that just finding gratification for the senses will be enough to provide happiness. The serpents that are the senses are the greatest inhibitors to achieving the perfect union that is yoga. So the first step in yoga is to provide some type of sense control through austerity and penance. Whether you try the type of yoga involving the renunciation of the fruits of work, the study of matter and spirit, or work in full devotion to the Supreme Lord, there is always some type of austerity involved. In bhakti-yoga, which is the easiest to implement but the most difficult to accept with firm conviction, the emphasis is placed on the positive activities of devotion, such as hearing about God in His personal form, worshiping His non-different manifestation of the deity   , and chanting His names, like those found in the maha-mantra, “Hare Krishna Hare Krishna, Krishna Krishna, Hare Hare, Hare Rama Hare Rama, Rama Rama, Hare Hare   ”. Coupled with these positive activities is restraint from sinful behavior like meat eating, gambling   , intoxication   , and illicit sex   . Since the Gita was a discourse between the original spiritual master    of the world and one of His students, there was some back and forth, several question-and-answer periods. When hearing about the principles behind yoga and how difficult it is to practice yoga to fruition, the receiver became a little worried. The fruit of yoga practice is samadhi, or more specifically, sharanagati, which is the merging of the soul into an ocean of bliss through surrender to God. The perfect yogi does not take birth again after the present life is over. Their consciousness is tied to the Supreme Lord, so they get a spiritual body in the next life, one that does not damage the link to the divine consciousness. Arjuna, Krishna’s student in the Gita, was worried about what would happen to the yogi who didn’t achieve full God consciousness by the time of death. So much hard work goes into yoga, and if one doesn’t succeed, will they have to start over again from the beginning in the next life? Krishna responded by allaying Arjuna’s fears and those of countless future generations by stressing the fact that the unsuccessful yogi never goes backwards. Even if they should fall off of the devotional platform, they get to start again in the next life from the place where they left off. How does this work exactly? Krishna says that the next birth is in an environment which is conducive to yoga practice. Being born into a family that is God conscious or already devoted to yoga would naturally increase the chances of a person continuing their yoga from the previous life. But Krishna also mentions a family of aristocracy as being a destination for the unsuccessful yogi, who first enjoys in the heavenly planets for many, many years. Yoga corresponds with righteousness, or piety, so there are merits relating to temporary rewards simultaneously accumulated through the link in consciousness, though the target objective is to connect with God and not to find enjoyments that relate to the body that one is trying to transcend. The concern may be raised that a family of an aristocracy can create circumstances that actually inhibit yoga practice. Sort of like being born with a silver spoon in your mouth, taking birth in a rich family means that sense gratification will be easily available. We know that regularly meeting sense demands will only add fuel to the fire of material existence, making it more difficult to satisfy the same senses in the future. Think of the spoiled kid who is used to getting so many gifts for Christmas that they get angry if they don’t get enough presents on one particular year. How can birth in such a family be conducive to yoga? In the context of the statements of the Gita, aristocracy actually refers to culture. A family that is cultured can be considered an aristocracy, especially during the time that Krishna was delivering His wonderful message to Arjuna. A non-aristocratic family is more focused on the senses and meeting its demands through hard labor. In ancient times, the laborer class was not educated. They were protected by the higher classes, and they would remain steadfast to their dharma, or occupational duties, through service. Though it is possible for any person in any class or gender to be able to achieve perfect yoga within one lifetime, the circumstances of a non-aristocratic birth make it difficult to even learn about yoga, let alone take up the practice. If the mind is constantly worried about how to procure food and keep a roof over the head, how is it going to pay attention to words of spiritual wisdom? In modern times, we can liken a non-aristocratic birth in the context of the Gita to being born in abject poverty, where there is no guarantee of eating on a particular day. If there is no peace of mind, how can there be any happiness? If there is no comfort of knowing when and where to eat, how is the mind going to contemplate higher topics like the meaning of life and the need for transcending the senses? A sannyasi, a person accepting the renounced order with fearlessness and firm conviction in the path, can perhaps survive in such unpleasant conditions, but for the normal person the uncertainty would be too much to handle. At least in an aristocracy there is a chance to become cultured, to be educated on higher matters. Even if yoga shouldn’t be the first avenue chosen, one who is satisfied to the limit with the senses will have a better chance of questioning the meaning of life. If, on the one hand, you have one person who just wants to have a secure life of material amenities and on the other you have one who has already lived that life, obviously the latter person can eliminate more options as being candidates for the ultimate aim in life. No amount of wealth or opulence can make a person truly happy. If it could, the wealthy would never take to philanthropy or seek further expansion of their business. “Persons who have acted piously in previous lives and in this life, whose sinful actions are completely eradicated and who are freed from the duality of delusion, engage themselves in My service with determination.” (Lord Krishna, Bg. 7.28) When the individual who has everything becomes bewildered about the meaning of life, they have every opportunity for reviving the divine consciousness and remaining connected to God in yoga. It is said in the Gita that one who has exhausted all of their sinful activities is eligible for coming back home, back to Godhead. At the root level, any behavior not dovetailed with yoga practice can be considered sinful, so the person who has tried every type of sinful engagement and eliminated them as being necessary can very easily accept yoga and thereby continue from where they left off in the previous life. Regardless of the specific circumstances of birth, whether in this life or the next, there is always something to be gained by taking steps towards Krishna. The spiritual energy is like a sun that never sets. Its warmth is always there for whoever wants to take advantage of it. Even if success in yoga is hard to come by right now, through determination it will eventually arrive. The dedicated devotee is always in good graces with Krishna, who then takes the responsibility for their welfare. In Closing: In yoga practice there is no need to hurry, Even if unsuccessful in this life no worry. In next life take birth in family of aristocracy, Or in pious family full of enlightened yogis. Upon that renewed opportunity seize, To again start in yoga and Krishna please. But isn’t it a problem to be born rich, To gratify senses all the time like unending itch? To a cultured family is what aristocracy means, To find spiritual life and sinful reactions clean.