Wednesday, 10 May 2017

Cancer Treatment Centers

- there's a very littledifference between a cancer cell and the rest of the cells in our body. - with cancer, it's not suchthat we're normal one day and it's a cancer cell the next day. it's an evolutionary process, so we have multiple mutations that allow a cancer to become cancer. - [voiceover] and that'sthe crux of the issue in seeking a cure for cancer.

finding better ways todetermine when cells go bad. (gentle music) - there is no way thatany particular discipline or let alone an individual can really make asubstantive contribution. i really believe that it takesan interdisciplinary effort. we need computer scientists, engineers, physicians, nurses, psychologists, psychiatrists, basic scientists.

we need a truly multidisciplinary team working together to really address cancer problems. i think that we have what it takes, we have expertise and we have what's most important, which is people. the physicians here, the clinicians, the surgeons, the scientists,

they are willing to work together. they are motivated to work together. i think they genuinelywant to work together to make a difference. i believe strongly that without the multidisciplinary expertise, we cannot address problemsas complex as cancer. - [voiceover] doctor soaresfound the team approach

already in place at the jumptrading simulationand education center at osf saint francismedical center in peoria. - [voiceover] it's quiteimpressive when you first visit, to realize how much there is here. the jump simulation center is invaluable. that i think is unique in so many ways and it was very appealing to me.

- [voiceover] in the lab,doctor soares is investigating whether transgenerational inheritance of epigenetic genes can occur. in other words, what a father eats may affecthis son's prostate health. - there is a lot ofevidence in prostate cancer that men who have morefat around the prostate have prostate cancer thattends to be more aggressive, more invasive, morerefractory to treatment.

so, there have been some studies using a transgenic mousemodel that indicate that too. presumably if dietwould make a difference, the hypothesis would be that it would be throughepigenetic alterations. so, epigenetics refer to alterations in the dna and in the tails of the histones. that even though they arenot encoded on the dna,

they can be inherited and they can influence and determine, in many ways, whether genes are goingto be active or inactive. so, these epigenetic alterations are very important in thecontrol of gene expression. the hypothesis is that diet may cause epigentic alterations.

so, if we identify differences in the two groups of mice that were exposed todifferent types of diet, and by differences i mean, let's imagine that the groupthat was on a high fat diet will show an aggressive disease, and the low fat diet group would not. we would do epigeneticanalysis of the two groups to try to identify epigenetic profiles

that would be characteristicof a low fat diet that would be associated witha less aggressive phenotype. if we found that, my next step would be totest the diet of the father and see whether the diet of the father would in any way influence development of prostatecancer in the male offspring. - [voiceover] studycontinues on the connection between lifestyle choices and cancer,

and the evidence is growing that diet and exerciseplay an important role. - we generally feel thatobesity is often times a risk factor for many cancers. we find that folks that are diagnosed with various cancers likecolon cancer, breast cancer, who are with high bodymass indexes or obese have inferior survivorship. so, working on energybalance as we say it,

which involves adipose tissue, exercise, and intake are all key. how do they all fit together to give us the bestanswer to avoid cancer, we really have not worked out, but clearly they all havean important aspect of that. - we know that two things are risk factors for breast cancer, overweightand a lack of exercise. so we are focusing on these two things,

and we have a nutritionist at the mills breast cancer institute to help patients to keep their weight stable. - do we know exactly what foods will keep us away from cancer? not exactly. do we think that fruits and vegetables, and lack of red meat,

and fish and chicken areprobably good choices? absolutely. do i have a study that i can tell a person that if you don't dothis you'll be harmed? no. so we have a long ways to go in terms of nutrition andenergy balance aspects. - [voiceover] a cell needs to maintain a proper balance of elements,

both in and outside it's walls. small charged particles, called ions, are able to move throughopenings, or channels, in the cell membranes. these ion channels are proteins that control the flow ofions across the cell wall. a protein coating generegulates the movement of the calcium ions in healthy cells, but cancer in the prostategland degrades this process,

so the membrane is nolonger calcium permeable. doctor ella zakharian is researching how best to prevent theprotein degradation. - calcium, it's a small cation, and it's very importantfor keeping this balance inside of cell and outside of cell. but the channel will be, should be, activated for some particular agonist, and in the case now of the prostate cells,

we found that it will beactivated with testosterone and that will lead tothe calcium absorption, calcium uptake into the cell. when there's enough calcium, then the channel willgo into an activation. cancer cells specifically target this channel for degradation. so, they removing itfrom the plasma membrane by cleaving it, chopping it to pieces.

and we found the enzymes that responsible for this degradation, when we knock them downthat helps to rescue protein back to the plasma membraneand activate a channel, then increases the calcium uptake on that cancer cell and that basically kills the cancer cell. so this is significantly diminishes the survival of the prostate tumor.

we're trying to see whether we can inhibit this enzymatic activity toprevent the protein degradation. that will be one of the scenarios, but i think it will bemore strategically advanced to use the purified proteinand just inject it directly to the tumor and suppressthe tumor growth. - [voiceover] doctor zakharianuses electrical current instead of a microscopeto monitor the results. it is called a planarlipid bilayer technique

that studies functionalactivities of ion channels at the single molecule level. - we incorporate purified protein into artificial membranes,insert the electrodes, and then we can record the currents of magnitude of pico amperes. that's a really, a small current. in the bilayer we can really know exactly what are the concentrations

that are required for channel activation. also, we know how it can be inhibited, which compound can directlyinhibit this channel activity. so, all this technique reallygives us an opportunity to record the channel, toestimate it's electrical current, to see how it's inhibited,so we can regulate it. now we're working on a cell model using prostate cancer cells. next step would be totake it to the animals.

so, we will be inducingthe prostate tumors in the animals and willbe trying to treat that with purified protein, and see whether we can suppress the cancer growth and proliferation. - [voiceover] at theuniversity of illinois, several doctors arestudying the extent to which patients with prostatecancer should be treated. - of all the prostatecancers that we find,

most of them, about 80% of them, are not actually goingto be fast enough growing that even for somebodyin their 60s or 70s, it would cause any cause for alarm. but we don't know which 20% are lethal and which 80% are slow-growing. so this is the biggest issue in prostate cancer and healthcare today, is figuring out which particular cancers

would lead to potentially lethal disease, would grow outside the prostate, would go to other partsin the body and colonize, and which ones will remain stagnant or which ones will remain very slow-growing within the prostate. all the tools that we have todayare based on gleason grade. gleason grade, gleason score is by far, even today after 30 years,

it's still the best singlepredictor of disease, and it's not very good. the other predictors are family history, age, psa status and so on. so, the most popular tools today to predict if a cancer is dangerous combine age, psa, gleason score, all this into a mathematical equation, and they come up with arisk score for a patient.

so risk score works extremelywell for low gleason scores, a younger person whohas no family history, for example, and so on. so, if all the risk factorsare low, your risk is low. but for an individual patient,for an individual cancer, we cannot say that thiscancer is gonna grow and this cancer is not gonna grow. statistically we can do a reasonable job, but not very confident,

and most people are not veryconfident of the chances or of the probabilities that are given. so, in this country, more than 90% of people who are diagnosed with prostate cancer go in for pretty aggressive therapy. whereas many of themprobably did not need it. - the problem we have with many patients is we don't know which patientsbenefit from treatment.

because we don't know which patients benefit from treatment, we give them all thisheavy gun, if you will, of chemotherapy or even surgery. prostate cancer andsurgery is the big gun, so we have to identify again which patients are the ones that would benefit from treatment and that's for two things,

one is to not give themtreatment that won't work, and also to minimize toxicity, because chemotherapy orsurgery or radiation, they all have toxicities. so we have to better identify, not just for cost purposes butalso minimizing side effects, long-term side effects from chemotherapy or other treatments as well. - we're over-treating from a clinical

and public health perspective. but if you ask the individual, then you're doing the right thing. so there's this tension between statistical averagingand individualized care. so where we're moving to inmedicine or in diagnosis, and where our researchis moving to in imaging, is going into more precise predictions. can we precisely predict,

that for this particular patient, for this particular cancer, the risk is high or low or what kind of intervention should we do. so that's what thesenew imaging techniques promise to do for us, is add molecular information,add local information, go beyond simple structure and try to do a better prediction

of precise risk for an individual. - we're learning more aboutthe biology of cancer, and with that biologydictates the treatment, not just the stage andextent of the disease. so, we're looking more athow the cancer cells grow, what are the characteristics of which those cancer cells grow, and targeting those folksparticularly at high risk, minimizing treatment toindiscriminate populations,

which was the standard of caremaybe five, 10, 20 years ago. - you want to do right, or you want to get the righttherapy to the patients so that they're minimally inconvenienced, yet they're not at danger ofsuccumbing to the disease. so at the individual level, that obviously is a great concern. at the national level, ofcourse health care costs, as you well know,

they're just going through the roof, and if we don't have to treat patients or we can identify that we don't have totreat a certain segment, then we'll be much better off. - we have to realize that the diseases that are most killing people now, at some point it will become impossible to sustain.

the cost is so high, and most of them can be prevented. so, there will have tobe policies in place that will really incentivize in ways that will lower thefrequency of these diseases. and we should not be in the long term be aiming to address problemsthat can be prevented. - some of the newer drugs that are being fda approved

are those that actually allowthe body's immune system to ramp up and those arenow in clinical trials and fewer are fda approvedfor certain disease sites. we're also learning that immunotherapy has a role in breast cancer, which we never thought existed. so using the immune systemto help fight cancer is huge. - [voiceover] there is a clinical trial studying immunotherapy

for a brain tumor called glioblastoma. clinical trials arecomprised of three phases before a new treatmentprotocol can be approved. phase one determines safe dosage levels and common side effects. phase two determinesthe drug's effectiveness and with a larger test group, finds less common side effects. and phase three confirms the effectiveness

of the new drug againstthe standard of care across a broad group of patients. the national cancer instituteoversees the trials. - nci directs the resources that allow us to do the clinical trials and throughout the united states. so, they're the funding mechanism by which these clinical trialsare allowed to take place. - [voiceover] a treatmentcalled dendritic cell vaccine

currently is in a phase three trial to test it's ability to extend the life of aperson with a glioblastoma. that's a primary brain tumor that even after surgical removal, chemotherapy, and radiation,recurs 100% of the time. glioblastoma is notcurrently a curable cancer. - although it will not, as a rule, spread outside the brain,it will remain confined,

but it certainly causes significant damage while in the central nervous system. the current standard isthe best possible surgery followed by radiation witha chemotherapy pill called temodar, and as a rule wewill do six to 12 months of the pill by itself in patients after completion of radiation. - for a glioblastoma,median survival times are around 14 and a half to 20 months.

it usually is only aboutseven months however, before we can identifyit again on our scans. - the current trial weare participating in, which is going on across the country, involves the use of dendritic cells from the patient to stimulate the immune system, to encourage it to participate in the fighting of thecancer on an immune basis.

- dendritic cell vaccinemade of your own blood cells. that's new. for a scientist and forthe patient as well, that's very personalized. - this particular clinical trialtakes the standard of care, which is the optimal surgery,radiation, and temodar, and to that adds a vaccination which is actually administeredin a two to one fashion. two patients out of everythree receive the vaccination,

and one out of every threewill receive a placebo. the procedure is randomized, neither the physician nor the patient can choose what they are to receive, and the patient and thephysician are also blinded. we do not know what is being administered. - [voiceover] in many cases,the body's immune system is not able to differentiate between cancer cells and healthy cells.

so it must be trained to do so. in the lab, dendritic cellslearn to recognize cancer cells, and the dendritic cells,once returned to the body, will train the immune system'st-cells to fight the cancer. - we take the tumor outat the time of surgery, we mince it, or kindacrush it into small pieces, suspend it in a solution... - we then obtain somemononuclear cells from the blood, through a process called pheresis,

and if you've ever donatedplatelets, for example, that is a pheresis process, allowing us to isolate platelets, but giving you back allyour other blood products. - we mix the two together,and with some added chemicals, activate the immune cells to recognize the gbmcells more accurately. after that, we filter out the cancer cells and we take those immunecells, which are purified,

and the patient's own cells,and inject those intradermally. - those cells will thenmigrate to the lymph glands, present these new found antigens,these foreign particles, to your immune system. your immune system hopefully will generate an immune response, and hopefully that willallow your immune system to assist in the killing of the cancer. - the hope with our clinical trials

is that we can extend the time before that recurrence happens. so by treating by a different means than our standard availablechemotherapy and radiation, that we're able to make it perhaps a year, perhaps a year and a half, maybe even two years before wesee it reappear on our scans. - it is not a curing therapy, and we are striving tocontinue to improve.

sometimes it's incremental improvements, the radiation adds some time. the temodar, temozolomidechemo adds some time. we hope that this also adds some time, and if we can make many small steps, then perhaps in the endwe'll have a bigger step, and we'll have significantly improved the life of our patients. - [voiceover] whiledoctors geoffroy and tsung

work on immunotherapy techniques in treating brain tumors, doctor soares is using mice to determine what factorsexist in the brain that cause malignant transformations of otherwise totally normal cells. those cells and radial glialcells are types of stem cells. - what we found is that if you take these radial glial cells,

before you alter any genes, so these are perfectly normalneural progenitor cells, so these are cells that are the precursors of the neurons. so if you inject them into a specific region of the mouse brain, let's say the mouse, the motor cortex. these are human neural progenitor cells in a mouse motor cortex.

and we label with agreen fluorescent protein so we can recognizewhich are the human cells in the mouse (mumbling). these cells differentiateinto all sorts of neurons. these neurons can even synapsewith the mouse neurons. but what we found was that thevery same radial glial cells, if injected in anotherarea of the mouse brain, the subventricular zone,near the third ventricle, they give rise to tumors

that have all the hallmarks of primitive neuroectodermal tumors. - [voiceover] much likescientists use spectroscopy to measure the gases thatmake up a planet's atmosphere, doctor bargava and his graduate students are using wave lengths of light to identify chemicals in body tissue. specific wave lengths correspond to the chemicalbonds between certain atoms.

if successful, this methodwill better standardize results than the current method of looking at stainedtissue under a microscope. - right now, we have difficulty in looking at molecularcontent in tissues. depending on where the dye came from, who used it, who applied it, under what conditions, andhow the tissue was handled, you might get very different results.

if you take the tissue outthat you've identified, slice it thin, put it on a glass slide, stain it with a non-specific dye or a molecularly specific dye and have a human look atit and make a decision. what we're trying to do in thislab is change that paradigm. we're gonna take the same tissue that you were interested in observing, but we're not gonna put any dyes on it.

we're instead gonna use spectroscopy, which allows us to see thechemical composition directly. so without a dye, we can actually see which chemical species are present in the tissue. and then we're not gonna have a human look at every single chemicalspecie individually, because that's too much data and will just take too long

and we won't be able to find subtle correlations between those things. but we have fantastic computers now, so we'll take computers and use them to analyze those datain an intelligent way and come up with decisions. but the kind of chemistries that we're interested in accessing are the protein content,the carbohydrate content,

and the nucleic acid statusin a piece of tissue. and also, we're doingthis in an imaging format, so it's not just important to know that this chemistry is present, but where it's present, and inrelation to everything else, how it's present, in whichform is also crucial. - [voiceover] cancer clearlyhas a negative connotation. but the medical community hasmade many positive strides in combating cancer in young people.

- one of the striking differences perhaps is that pediatric patientstend to do a lot better when it comes to treatment. like about 80% of the patientswill survive their disease. - the reason for that possibly being that the chemotherapy is more intensive or we just have a better job of getting them to adhere to it. - children tend totolerate the chemotherapy

a lot better than whatadult patients will do. and so that is an advantage for us, and that's part of the reason why our patients tend to do better. - [voiceover] youngpeople coping with cancer want to dream of a future. survivorship programs arecoupled with palliative care to provide patients andtheir families with relief from the stress of a serious illness.

- palliative care is anextra layer of support that helps patients with,not only with cancer, but with many chronic diseases. and particularly for patients that are going to have chronic disease that alter the way they live or the way their life is going to become, or also may shorten their life expectancy. so, there is a trendwithin the united states,

and actually across the world, to introduce palliative care early during the treatment of pediatric cancer. and so, at the children's hospital, we were able to, over the past two years, we were able to utilize theresources we have and so, using our counselors, our nurses, we were able to introduce palliative care very early during thediagnosis of cancer treatment.

that happened within thefirst four weeks of treatment. - survivorship basically starts as soon as you're done with therapy. so we go from treating the actual cancer to monitoring not only for relapse but for side effects fromthe actual treatment. so as soon as you're done with therapy and your cancer is gone, now you're a survivor

and now we need to startmonitoring for side effects of everything that we justdid to treat the cancer. - [voiceover] survivorship, it's more likely than ever before. much of it because of the research work done across central illinois. - you know maybe 30 years ago we might have a dozen drugs, now we have over a hundred drugs.

we have many more options for folks, and they're much more effective options. and this goes alongwith precision medicine, which, in case they were looking at more targeted therapyfor other cancers, and looking exactly how wecan slow their cancer growth. (upbeat music)

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