[vc_row][vc_column][vc_column_text]By Monika Kundu Srivastava

Scientists at the Pune-based National Chemical Laboratory (NCL) of Council of Scientific and Industrial Research (CSIR) have developed a mathematical model that promises to deliver better protocols for cancer treatment.

The model has three main components — one for core tumour and other cells that subsequently get affected by cancer; the second for immune stimulators or boosters that help protect normal cells from getting affected; and the third for immune suppressors or dampeners that allow cancer to spread. The model describes most of the ways by which the three ‘actors’ could affect or influence each other.

It is expected to be of significance as treatment protocols could be developed based on accurate calculations, thus avoiding the preventable and uncomfortable side-effects of cancer treatment, researchers said.

A cancer tumour consists mainly of cancer stem cells (94.6%), followed by cancer cells (4.5%), resistant cancer cells (1%) and drug-resistant stem cells (0.001%). The stem cells, depending on the kind of stimulation received, are capable of changing into any type of cell and multiply rapidly. The spread of the disease can be limited significantly, if within 400 days of tumour detection cancer stem cells can be stopped from multiplying and resistant cancer cells stopped from changing into cancer stem cells and drug-resistant stem cells respectively.

After 400 days, when the cells multiply rapidly, it becomes difficult to treat. Many structural changes happen due to mutation, breakages and other factors, which can result in the cells becoming resistant to traditional drugs or radiation and treatment becomes ineffective.

Researchers tested two treatment protocols based on various interactions: one using only radiation and medication while the second included immunotherapy. They found that there was vast improvement in latter protocol in the form of a huge reduction in multiplication rate of tumour cells. This was because radiation had no effect on resistant stem cells, and chemotherapy impacted both stem and cancer resistant cells. Immunotherapy, on the other hand, was found to be beneficial both at early and later stages. In the early stage (till 400 days), it did not allow the number of resistant cells to increase and in later stages it did not allow the tumour to have its full effect due to an increase in the number of protective cells fighting cancer cells.

“The model can be used as a potential tool for the prediction of cancer prognosis and calculation of fold changes in the tumour subpopulations in response to a new treatment regimen. The study opens up new avenues for further research in cancer treatment,” researchers said.

Commenting on the new model, Dr. Radhika Nair, Ramanujan Faculty Fellow at the Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, said it was a novel study and the model could be applied to most cancers.

Researchers at National Chemical Laboratory (NCL), Pune

“The mathematical basis can help predict optimal drug dosage and treatment cycles which can have a huge benefit in avoiding unnecessary side effects of treatment. The model can also tell us how much intra-tumor heterogeneity as well as drug resistant cell population evolves in response to a new treatment regimen, that is, how the cancer might progress,” Dr Nair said.However,she said, while researchers have verified the model with known experimental data, it is essential to prove its clinical applicability as patients may have a unique manifestation of the disease.

The scientists – PiyaliGanguli and Ram Rup Sarkar of Chemical Engineering and Process Development Division at NCL – have published findings of their research in journal, PLOS One. The work was funded by the Science and Engineering Research Board (SERB). (India Science Wire)[/vc_column_text][/vc_column][/vc_row]

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~By Ratneshwar Thakur

Earlier studies had shown that during embryonic development of vertebrates, the axial growth is contributed by a small number of stem cells

New Delhi: For normal birth or physical development of animals, regulation of their size, shape, and number of organs is very critical when embryo is developing. Researchers are trying to understand mechanisms that regulate this process.

A team of researchers led by Dr. Ramkumar Sambasivan at the Bangalore-based Institute of Stem Cell Biology and Regenerative Medicine (InStem) has shown how a genetic switch controls development of organs and body plan of animals.

The team used mouse model for this study and has found that when a gene called Tbx6 was mutated in mouse embryos, it led to development of five spinal cords instead of one seen in normal embryos. The extra spinal cords were formed at the expense of a tissue, which in normal course would have given rise to muscles and skeleton, according to results of the study published in journal Development.

“The novel observation in mutants highlighted the important role of Tbx6 and led us to investigate the connection between spinal cord and muscle-skeleton development,” explained Alok Javali, a member of the research team.

Earlier studies had shown that during embryonic development of vertebrates, the axial growth is contributed by a small number of stem cells called neuro-mesoderm progenitors (NMPs). These cells generate spinal cord (neural tissue) as well as muscle-skeleton system (mesodermal tissue). However, it was not clear how NMPs with dual potential end up making a particular choice.

“We were trying to generate NMP-like cells in the dish from embryonic stem cells and made a surprising find that these cells express Tbx6. This led us to hunt for similar populations in developing embryos,” added Aritra Misra, another co-author of the paper.

Researchers observed Tbx6 expression in NMPs in mouse embryos. They found that the gene is specifically expressed in NMPs fated to become mesoderm, which goes on to make muscle and skeleton. When Tbx6 is absent (in the case of mutant embryos), instead of giving rise to both mesoderm and spinal cord, NMPs make only spinal cord, resulting in extra spinal cords. This means Tbx6 is critical in regulating ‘fate choice’ of NMP stem cells.

“Studying bizarre mutants with multiple limbs or heads or spinal cords is not driven by caprice, but is rather an important exercise in elucidating how nature generates tissues and organs during embryonic development. This knowledge could possibly be harnessed to design methods in the repair or regeneration of damaged tissues such as in spinal cord injuries in patients,” said Dr. Ramkumar, who is a recipient of the DBT-Ramalingaswami Fellowship.

The research team included Alok Javali, Aritra Misra, Karolis Leonavicius, Debalina Acharyya, Bhakti Vyas and Ramkumar Sambasivan. The study was funded by the Department of Biotechnology.

(This article has been published through a syndicated feed provided by the India Science Wire. It has not been edited by the APNLive staff.)

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[vc_row][vc_column][vc_column_text]By Yogesh Sharma

Colorectal cancer is the third leading cause of cancer deaths worldwide. Dietary fibre and lifestyle changes have been recommended as measures for preventing colorectal cancer.

A team of researchers from Stem Cells and Regenerative Medicine Centre at the Yenepoya University, Karnataka has now found that high doses of water-soluble Vitamin C and niacin or Vitamin B3 can kill cancer stem cells.

In a study published in journalCell Biology International, researchers have shown for the first time the opposing effects of the low and high dose of vitamin C and vitamin B3 on colon cancer stem cells isolated from certain colorectal carcinoma cell lines.

Research team lead by Dr Bipasha Bose and DrSudheer Shenoy investigated the effects of high doses and low doses of the two vitamins and found that low doses (dose range 5-25 micromolar) of Vitamin C and B3 lead to high proliferation and aggressiveness of colon cancer stem cells thereby indicating a need to be cautious while prescribing low doses of these vitamins to colon cancer patients.

Sitting from left to right: Dr Sudheer Shenoy and Dr Bipasha Bose; Standing from left to right: Mr DebajitChaudhury, Mr Muhammad Nihad and Mr Utsav Sen

However, high doses of the two vitamins (dose range 100 to 1000 micromolar) were successful in killing cancer stem cells. Such high doses of vitamins can only be achieved through intravenous injections in colon cancer patients.

“The next step of our research is to delineate the mechanisms involved in such opposing effects of low versus high concentrations of the two vitamins,” said Dr Bipasha Bose, a member of the research team. “We want to decipher the mechanisms of action of high doses of Niacin and Vitamin C involving PPARγ pathway and oxidative stress induced killing of colon cancer stem cells. We also want to establish the same dose effect of in-vitro studies under in vivo conditions in tumor xenografts models in mice.”

This work is of significance and researchers hope to establish a therapeutic dose of Vitamin C and B3 for colon cancer stem cell therapy. “If the therapeutic dose gets well validated under in vivo animal models, clinical trials can be a possibility in the long run,” added Dr Bose.

Research Team included Dr.Sudheer Shenoy, Dr.Bipasha Bose, UtsavSen, DebajitChaudhury and Muhammad Nihad. (India Science Wire) [/vc_column_text][/vc_column][/vc_row]

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By Ratneshwar Thakur

Planaria are fresh water flatworms with an ability to regenerate from almost any number of pieces to form a completely new being

New Delhi: In an ideal world, one would like to live with no deformities. How often you think about being able to re-grow limbs after an amputation or any injury. Imagine being able to regenerate your spinal cord after an accident has left you paralyzed. Nature has many examples of some tiny organisms completely re-growing from their small pieces. Scientists are studying such organisms to learn important lessons in regeneration.

Researchers at the Bengaluru-based Institute for Stem Cell Biology and Regenerative Medicine have reported that deformities in the epidermis (outer skin layer) of an organism called planaria cause the defect in their stem cell function and regeneration. This is significant because epidermal cells are not stem cells.

Planaria are flatworms that live in fresh water and have the ability to regenerate from almost any pieces to form a completely new animal with all functional organ systems. Researchers used planaria as a model organism to understand the mechanism behind its immense regenerative ability.

“Our study has shown how the organization of epidermal cells during planarian regeneration is crucial for regulating stem cell function,” said Dr. Dasaradhi Palakodeti, a scientist at the Bengaluru based Institute, and a co-author of the study published in the journal Development.

Regeneration is often synonymous with stem cells and most of the studies focus on understanding factors essential for ‘stemness’. “Here, for the first time we show how planarian epidermis (non- stem cell) plays a critical role in wound healing and stem cell function,” said Dhiru Bansal, first author of this paper.

However, it is still unclear how the environment surrounding stem cells regulates their function. Researchers believe stem cells are instructed by surrounding cells to make right decisions to proliferate and differentiate for regeneration, to give rise missing tissues. The team is working to understand the role of a specific protein called PABPC2 (cytoplasmic poly A binding protein) in regeneration.

“Our report about a crosstalk between stem cells and epidermis in planaria opens new possibilities that can be addressed in other systems as well,” said Jahnavi Kulkarni, one of the authors of this paper.

The study opens up a new possibility to discover the role of non-stem cells in the skin regeneration. Skin is often well-thought-out for its protective function but this new study highlights other potential roles of the skin.

The research team included Dhiru Bansal, Jahnavi Kulkarni, Kavana Nadahalli, Vairavan Lakshmanan, Srikar Krishna, Vidyanand Sasidharan, Shilpa Dilipkumar, Akash Gulyani, Srikala Raghavan and Dasaradhi Palakodeti (Institute for Stem Cell Biology and Regenerative Medicine, Bangalore); Jini Geo and Renu Pasricha (National Centre for Biological Sciences, Bangalore).

(This article is from a syndicated feed provided by the India Science Wire)

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