Saturday, February 29, 2020

UCI neuro-oncologist uses comprehensive approach to battle brain cancer

When you're facing a cancer diagnosis with an average survival span of 12 to 18 months, every milestone is a victory. That makes each wedding invitation, graduation announcement and birthday photo that UCI neuro-oncologist Dr. Daniela Bota receives from her patients a cherished validation of her 12 years of groundbreaking research on glioblastoma multiforme, the most aggressive form of brain cancer. "Because of our work, these people have been able to move on with their lives," she says.

Bota has pushed the boundaries of innovation in her quest to increase the survival rates of individuals with brain tumors, especially glioblastomas. The esteemed physician-scientist has taken a truly comprehensive approach to battling this rare disease, which has a five year survival rate of only 10 percent and claimed the lives of U.S. Sens. Ted Kennedy and John McCain. Bota has conducted clinical trials of multiple cutting-edge treatments that are improving the quantity as well as the quality of life for glioblastoma patients at UCI and beyond.

'So much potential, so much growth'

Bota grew up in Romania, in a family of engineers. It was assumed she'd follow them into the profession – she was a national mathematics champion in her youth – but Bota had another path in mind. "I wanted to make a more significant contribution," she says. "I wanted to combine my analytical side with a place where I could help others. I ended up becoming an M.D.-Ph.D. to blend both."

At USC, Bota earned a doctorate in molecular biology, focusing on neural degeneration. She then went to the University of Kansas for medical school and a residency in neurology. During her shifts, Bota found herself caring for people with brain tumors – and discovered a new direction for her medical career.

The generosity and gratitude of brain tumor patients make it so rewarding to care for them. I see it again and again at UCI. Many of these patients have a terminal diagnosis, but they're volunteering their time and energy to participate in our clinical trials to help us build a better treatment and, hopefully, in the future, a cure."  Dr. Daniela Bota, UCI neuro-oncologist

After a neuro-oncology fellowship at Duke University, Bota joined the faculty of UCI's School of Medicine and the Chao Family Comprehensive Cancer Center in November 2007. "Both my career and UCI in general have grown so tremendously over the dozen years since," says Bota, who's now co-director of the UCI Health Comprehensive Brain Tumor Program. "There has been so much potential, so much growth, so many changes and so much scientific revolution helping us move forward in so many different directions. It's a very exciting time."

A comprehensive approach

The word "comprehensive" carries significant weight in the realm of cancer care centers. The "comprehensive" designation from the National Cancer Institute recognizes an added depth and breadth of research that bridges multiple scientific areas. Just 51 cancer centers in the U.S. carry the designation; the Chao Family Comprehensive Cancer Center is the only one in Orange County. "We offer one of the most innovative and complex portfolios of clinical trials anywhere in the world," Bota says.

Her own multipronged attack against glioblastoma multiforme reflects the center's comprehensive approach. Bota's work on the experimental drug marizomib has generated significant attention and hope. Unlike traditional chemotherapy drugs, marizomib can penetrate the blood-brain barrier – the filtering mechanism that prevents many blood-borne substances from passing into brain tissues – and inhibit cancer growth without causing damage to other parts of the brain.

Over the past 12 years, Bota has shepherded marizomib from preclinical development all the way through a 700-person international phase III clinical trial now underway. "We have a number of patients from our clinical trials who are surviving this tumor for longer periods of time than usually expected," she says.

Amanda Johnson, a 32-year-old freelance writer in Mission Viejo, has been receiving marizomib for two years under Bota's care. Her large glioblastoma tumor – which straddled both sides of her brain – has shrunk so much that it's no longer measurable. She has returned to work on her novel and even joined a gym. "I feel so happy just to be alive," Johnson says.

Larry Johnson, her father, told Fox News, "I don't think [Amanda] has come to realize how important her survival is to other people and families who are going to find themselves in a similar situation."

Bota strives to reach a point where such cases will be so commonplace that they don't make the news. "That's what success looks like – not having a prominent publication or being part of a game-changing discovery," she says. "It's having patients like Amanda still be here and doing well."

Vaccine trials and right to try
To achieve that goal, Bota tenaciously pursues multiple avenues of treatment. She has been a leader in the use of Optune, a device worn on the head that generates an electrical field that disrupts the growth of cancer cells. "We were among the first in the country to explore and use this technology," Bota says. "Now we're working with physicians from other countries to help them adopt it in their practices."

She is also spearheading two clinical trials on cancer vaccines. "Brain tumors hide behind the blood-brain barrier, so the body doesn't recognize them as not being a normal part of the body," Bota explains. "With our vaccines, we extract cellular markers from the patient's tumor and inject them back into the patient to stimulate the immune system to recognize those tumors, attack them and, if possible, eliminate them."

She adds: "Both studies have been well-received in our neuro-oncological community, which is highly promising. And a significant benefit is that the vaccines function with minimal or no toxicity."

In January 2019, one of Bota's patients who was ineligible for both clinical trials was able to access one of the vaccines through the first successful application of the national Right to Try Act. Passed in May 2018, it allows people with terminal illnesses, in consultation with their doctors, to seek treatment with experimental drugs not yet approved by the Food and Drug Administration directly from pharmaceutical companies. "The law puts patients in charge of their care; they initiate contact with the manufacturer and request therapy," Bota says. "It gives patients who don't qualify for clinical trials another option."

"We offer one of the most innovative and complex portfolios of clinical trials anywhere in the world."

Sharing her expertise
Bota eagerly offers her knowledge beyond the doors of the Chao Family Comprehensive Cancer Center. Whenever she and her husband, Robert, a local psychiatrist, travel back to their home country of Romania, she consults with medical colleagues there, as there are no certified neuro-oncologists in the nation. On days when the couple work on their farm in the Transylvanian Alps, locals come to them – often on foot – for medical advice. The two hope to eventually establish a clinic in the area. "I want to make sure that Romania also benefits from my medical expertise," Bota says.

Back on campus, in her capacity as senior associate dean for clinical research, she uses her vast clinical trial experience to help colleagues in UCI's School of Medicine advance their own research projects into the clinical arena.

"I'm excited by the ability to impact the lives of so many people through this role," Bota says. "Whether it's for burns or vascular disorders or other conditions, people come to UCI for the same reason: We can offer what community hospitals cannot. Being able to make that happen, to create new options for our patients, is what wakes me up in the morning."

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Tuesday, September 03, 2019

MIT reserchers catalogue 7,757 gut microbes that can help develop new treatments

Researchers have created a comprehensive catalogue of human gut bacteria by isolating and preserving samples of 7,758 strains of the microbes-- an advance that may help develop new treatments for several diseases.

The human digestive system houses thousands of different strains of bacteria, many of which are beneficial, while some have been linked to metabolic disorders and inflammatory bowel diseases for over a decade.


To know more about how these microbes changed in individuals over time, the researchers at MIT, in the US collected stool samples from about 90 people from an area, for up to 2 years.


Results from the data set (BIO-ML) should help in understanding the way in which microbial populations change in the human gut, researchers said.


This may also help scientists develop new treatments for a variety of diseases, said a Prof. of biological engineering and of civil and environmental engineering at MIT.


There's a lot of excitement in the microbiome field because there are associations between thesee bacteria and health and disease. But we're lacking in being able to develop to understand why that is, what's the mechanism, and what are the functions of those bacteria that are causing them to associate with the disease, she said.


More than ever before, modern techniques allow us to isolate previously uncultured human gut bacteria. Exloring this genetic and functional diversity is fascinating-- everywhere we look, we discover new things, said one of the lead authors.


I'm convinced that enriching biobanks with a large diversity of strains from individuals living diverse lifestyles is essential for future advancements in human microbiome research, she added. This is the first time we're getting a glimpse of these really different dynamics, she said.


In a case, the researchers found 3 related strains of Bacteroides vulgatus coexisting within a single person, all of which appeared to have diverged from one ancestor strain within the host.


In another case, the study noted one strain of Turicibacter snaguinis completely replacing a related strain of the same species nearly overnight.


For the most part of the research, the team focused on microbes found in about a dozen individuals who had provided samples over an extended period.


That was a unique opportunity, and we thought that would be a great set of individuals to really try to dig down and characterise the microbial populations more thoroughly, she said.


To date, there hadn't been a tonne of longitudinal studies, and we wanted to make that a key focus of our study, so we could understand what the variation is day-to-day , she said.


The team was able to isolate a total of 7,758 strains from the 6 major phyla of bacteria that mostly make up the human GI tract, and for 3,632 of these, they sequenced the full genomes.


For the remaining strains, they sequenced partial genomes. They also measured the quantities of different metabolites found in the stool samples, revealing that, within a single person, changes in amino acid levels were closely linked with changes in microbial populations over time.
However, when looking at the differences in the composition of microbial populations across people, the variations were closely associated with changes in the levels of bile acids that help in digestion.


The researchers don't know exactly procedures these differences, but say they could be influenced by diet-- a link they hope to study in the future. Comprehensive and high-resolution collections of bacterial isolates open the mechanistically investigate how our lifestyle shapes out gut microbiome, metabolism and inflammation. 


We aim to provide such a resource to the research community worldwide, including to lower-income research community worldwide, including to lower-income research institutions, said MIT research associate.


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Saturday, May 10, 2014

Country's first end-stage heart failure, transplant unit launched

Patients of end-stage heart disease will no longer have to look to the West for succour, as Fortis Healthcare Limited has launched the country's first comprehensive centre for treatment of end-stage heart failure and transplant in its Chennai hospital. While Chennai continues to do the best in terms of heart failure management, doctors say it's because of government encouragement, and that Mumbai would take a long time to achieve the feat.

Speaking at the inaugural function of the centre in Chennai, Dr KR Balakrishnan, director, cardiac science, Fortis Malar, said: "Our cardiac team of doctors have so far performed 16 heart transplants, 35 ECMO (Extra Corporeal Membrane Oxygenation-to stabilize and act as a bridge to Heart Transplants) and 5 Ventricular Assist Device (a bridge to a heart transplant in case it's required later). We have now decided to make it a centre for heart failure management and heart transplant so that awareness is spread and people utilise the facility instead of going abroad and spending more."

Aditya Vij, CEO, Fortis Healthcare Limited said: "Our Chennai hospital will remain the centre for treatment and management of end-stage heart failure and transplant. This has become possible because, unlike in other parts of the country, we get a lot of support from the government here, and there is a well maintained registry and a very dedicated team of doctors."

Heart failure is a major health concern worldwide, including in India. Twenty million people world-wide suffer from heart failure. India witnesses two million new cases every year with at least a third of them requiring advanced therapy. It is also important to note that the mortality rate in heart patients is as high as 30-40% within a year of diagnosis.

In India, the treatment for heart failure is restricted to medical therapy, revascularization therapy (restoration/augmentation of blood supply to the heart), valvular surgeries and cardiac resynchronization (heart pacing) therapy.

Talking about developing the heart failure management sector in Mumbai Fortis Hospital, Vij said inter-centre trainings were on and soon the Mumbai branch too would have at least an artificial heart pump. "Our centres across the country are connected. Management of heart failure patients and heart transplant are a very specialised area and needs lot of expertise and dedicated teams. We are in the process of training and building such teams in our other centres too," said Vij.


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