(Back to) the Future is here: Lexus builds a working hoverboard


While it isn’t quite a flying car, one highly-anticipated vision of 2015 predicted 30 years ago in ‘Back to the Future’ seems to be just around the corner: Lexus has announced that it managed to build a functional hoverboard.

Still from YouTube video/Lexus International

That’s right: a skateboard that carries the rider above the ground.

The board isn’t up for sale yet, but this is still amazing news for anyone disappointed by the present day being a far cry from the 2015 visited by Marty McFly in the 1985 classic ‘Back to the Future’, which famously featured hoverboards in an iconic scene.

The device is billed as the “first real, rideable hoverboard” on the Lexus website and is branded under the name SLIDE. Indeed, a video demonstrates it sliding through the air like a floating skateboard, although a rider is conspicuously absent.

The gravity-defying board is made possible with magnetic levitation, using nitrogen cooled superconductors, according to the website. It is designed to utilize materials familiar to users of Lexus products, such as those that the car brand’s interiors are often built with, including bamboo.

“When technology, design, and imagination come together, amazing things can be achieved. Presenting SLIDE,” Lexus said in a tweet.

The promotional video shows the board working on pavement, rather than just on metal tracks like previous attempts at creating a hoverboard.

The technological principles behind this board already have serious commercial applications. The L0 series of maglev train set a rail speed record of 375 mph (603 km/h) in April.

Advances in such technology should give those who are who want to see a flying car reason to rejoice.

“It’s very confidential information but we have been studying the flying car in our most advanced R&D area,” Hiroyoshi Yoshiki, a managing officer in Toyota’s Technical Administration Group, told Bloomberg. A “flying car means the car is just a little bit away from the road, so it doesn’t have any friction or resistance from the road.”

Watch the video. URL: https://youtu.be/7zTCgMPZRuo

 

Cuba becomes first nation to eliminate mother-to-child HIV .


Cuba’s success demonstrates that universal access and universal health coverage are feasible and indeed are the key to success.

Cuba, Cuba HIV, Cuba HIV transmission, HIV, HIV patients, HIV Cuba, Mother to child HIV, Cuba mother to child HIV, WHO, Cuba latest news, HIV latest news, World latest news

Each year, 1.4 million women living with HIV around the world become pregnant. Left untreated, they have a 15 to 45 per cent chance of passing the virus to their children during pregnancy, labor, delivery or breastfeeding. (Source: Reuters)

By: AFP | Wasington | Published on:July 1, 2015 8:20 am

Cuba has become the first country in the world to eliminate mother-to-child transmission of HIV and syphilis, the World Health Organisation has said.

“Eliminating transmission of a virus is one of the greatest public health achievements possible,” WHO Director-General Margaret Chan said yesterday.

“This is a major victory in our long fight against HIV and sexually transmitted infections, and an important step towards having an AIDS-free generation.”

Universal health coverage, improved access to tests and increased attention to maternal care were credited with the success, defined by health authorities as fewer than 50 cases of mother-to-child transmission of syphilis or HIV per 100,000 live births.

A small number of cases are allowed to persist, despite the certification, because antiretroviral treatment to prevent mother-to-child-transmission of HIV is not 100 per cent effective.

Rather, WHO and the Pan American Health Organisation (PAHO) define the milestone as “a reduction of transmission to such a low level that it no longer constitutes a public health problem.”

Health authorities have been working in Cuba since 2010 to “ensure early access to prenatal care, HIV and syphilis testing for both pregnant women and their partners, treatment for women who test positive and their babies, caesarean deliveries and substitution of breastfeeding,” said a WHO statement.

“Cuba’s success demonstrates that universal access and universal health coverage are feasible and indeed are the key to success, even against challenges as daunting as HIV,” said PAHO Director Carissa Etienne.

Each year, 1.4 million women living with HIV around the world become pregnant. Left untreated, they have a 15 to 45 per cent chance of passing the virus to their children during pregnancy, labor, delivery or breastfeeding. But the risk of transmission is just over one per cent if antiretroviral medicines are given to both mothers and children.

The number children born annually with HIV was 400,000 in 2009. By 2013, the number was down to 240,000 in 2013. But intense effort is needed to meet the global target of less than 40,000 new child infections per year by 2015, health authorities say.

“It shows that ending the AIDS epidemic is possible and we expect Cuba to be the first of many countries coming forward to seek validation that they have ended their epidemics among children,” said Michel Sidibe, executive director of the United Nations AIDS agency.

Suicide by soda: Sugary drinks kill 184,000 people a year, study says — RT News


Reuters / Sam Hodgson

If you love the taste of an ice cold soda, you may want to determine whether the flavor is actually worth the risk. Sugary drinks are killing around 184,000 people each year, according to a new study.

The research, published in the American Heart Association’s Circulation journal, points the finger at sugar-laden drinks ranging from sodas to sweetened iced tea, fruit drinks, and sports/energy drinks.

“Many countries in the world have a significant number of deaths occurring from a single dietary factor, sugar-sweetened beverages,”said study author Dariush Mozaffarian from Tufts University in Boston.

According to the research, most of the 184,000 global deaths are from people who die of diabetes due to the consumption of“sugar-sweetened beverages” (SSBs).

Another 45,000 die globally from cardiovascular diseases caused by sugary drink consumption, and 6,450 people die from cancers linked to sugar-laden beverages.

Those numbers prompted Mozaffarian to advise soda lovers to “substantially reduce or eliminate sugar-sweetened beverages from [their] diet.”

“There are no health benefits from sugar-sweetened beverages, and the potential impact of reducing consumption is saving tens of thousands of deaths each year,” he added.

Although the numbers cite global deaths, Mexico had the highest death rate due to sugary drinks, with 450 deaths per million adults. It was followed by the US, with 125 estimated deaths per million adults.

Seventy-six percent of deaths related to sugary drinks occur in low-to-middle income countries, according to the report.

The findings “indicate the need for population based efforts to reduce SSB consumption throughout the world through effective health policies and targeted interventions directed at stemming obesity-related disease,” the report states.

The research examined 62 dietary surveys from more than 611,000 people, conducted between 1980 and 2010 across 51 countries. The participants represented almost two-thirds of the world’s adult population.

Published on Monday, the study is the first comprehensive assessment of worldwide deaths attributable to sugar-sweetened beverages (SSBs). It was conducted by an international team of researchers from Harvard, Tufts, and Washington universities in the US, and Imperial College London.

Why Do Pets Make Us Feel Better?


When we are sad, stressed, scared, or wondering how we can possibly deal with whatever life has thrown our way, animals have the ability to make us feel better. Why else would there be millions of cat videos on YouTube and not one, but four, “panda cams” in the United States alone?

But while Grumpy Cat and Bao Bao can make us smile, our pets can actually have a positive effect on our health.

Studies have shown that interacting with animals (even fish!) helps lower blood pressure, reduce anxiety, and decrease depression. Scientists have also observedthat interacting with animals increases levels of the hormone oxytocin. Oxytocin has a number of important effects on the body. It slows a person’s heart rate and breathing, reduces blood pressure, and inhibits the production of stress hormones. All of these changes help create a sense of calm and comfort.

In an interview with National Public Radio, Rebecca Johnson, PhD, RN, FAAN, Director of the Research Center for Human-Animal Interaction at the University of Missouri College of Veterinary Medicine, said: “Oxytocin has some powerful effects for us in the body’s ability to be in a state of readiness to heal, and also to grow new cells, so it predisposes us to an environment in our own bodies where we can be healthier.”

This healing can be emotional as well as physical, as oxytocin makes us feel happy, encourages trust, andpromotes bonding. This helps explain why we literally fall in love with our pets.

At the same time, pets offer us their unconditional love—and yes, even empathy—in return. After a cancer diagnosis and during treatment, pets don’t judge or try to give advice. They don’t ask questions or need reassurance that everything will be okay. Pets are just there when you need them, to show affection, to provide companionship, and to offer comfort.

In a study of therapy dogs at Mount Sinai Beth Israel in New York City, researchers followed 42 people who were receiving six weeks of intense chemotherapy and radiation therapy for head and neck cancer. Before each treatment session, all of the participants visited with a trained therapy dog for about 15 minutes. At the end of the study, the researchers found that although the participants’ physical well-being decreased during treatment, their emotional and social well-being increased.

It is no wonder, then, that even Florence Nightingale believed that “a small pet animal is often an excellent companion for the sick, for long chronic cases especially.

​2-week inactivity may leave kids with pensioner’s muscle strength


Reuters / Michael Kooren

Parents who allow their kids to ditch football practice for video games may want to re-think their strategy. A new study says it only takes two weeks for children to lose one-third of their muscle strength, putting them on par with someone 50 years older.

The research, conducted by the Center for Healthy Aging and the Department of Biomedical Sciences at the University of Copenhagen and published in the Journal of Rehabilitation Medicine, immobilized one leg of both younger and older men by attaching a pad to that limb.

To determine the effects of immobilization on muscle mass, the researchers measured maximal voluntary contraction, leg work capacity, and leg lean mass by dual energy X-ray absorptiometry. Muscle biopsies were also performed, and were evaluated for fiber type, fiber area and capillarization.

The findings showed that it took just two weeks for the young participants to lose one-third of their muscle strength, leaving them with the same physical ability as someone 40 to 50 years older.

That loss in muscle strength is very similar to what is found in older men, according to researcher Andreas Vigelsoe.

“Having had one leg immobilized for two weeks, young people lose up to a third of their muscular strength, while older people lose approx. one fourth,” Vigelsoe said in a university press release.

The research also stated that while both young and older men lose muscle mass when immobilized for two weeks, young men lose more – 485 grams compared to 250 grams. However, young men have more to lose in the first place, as they carry approximately 1kg more muscle mass in each leg than older men.

But the “loss of muscle mass is presumably more critical for older people, because it is likely to have a greater impact on their general health and quality of life,” researcher Martin Gram said.

Once the two-week immobilization period was over, the participants trained on a bicycle three to four times a week, for six weeks. Cycling was enough to regain muscle mass, but not muscle strength.

“Unfortunately, bicycle-training is not enough for the participants to regain their original muscular strength. Cycling is, however, sufficient to help people regain lost muscle mass and reach their former fitness level. If you want to regain your muscular strength following a period of inactivity, you need to include weight training,” Vigelsoe said.

And although biking aided with the return of muscle mass, re-gaining it wasn’t as quick or easy as losing it.

“It’s interesting that inactivity causes such rapid loss of muscle mass, in fact it’ll take you three times the amount of time you were inactive to regain the muscle mass that you’ve lost. This may be caused by the fact that when we’re inactive, it’s 24 hours a day,” Gram said.

Can you teach people to have empathy?


 

Two men facing each other

Empathy is a quality that is integral to most people’s lives – and yet the modern world makes it easy to lose sight of the feelings of others. But almost everyone can learn to develop this crucial personality trait, says Roman Krznaric.

Open Harper Lee’s classic novel To Kill A Mockingbird and one line will jump out at you: “You never really understand another person until you consider things from his point of view – until you climb inside of his skin and walk around in it.”

Human beings are naturally primed to embrace this message. According to the latest neuroscience research, 98% of people (the exceptions include those with psychopathic tendencies) have the ability to empathise wired into their brains – an in-built capacity for stepping into the shoes of others and understanding their feelings and perspectives.

The problem is that most don’t tap into their full empathic potential in everyday life.

You can easily find yourself passing by a mother struggling with a pram on some steps as you rush to a work meeting, or read about a tragic earthquake in a distant country then let it slip your mind as you click a link to check the latest football results.

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Can you read someone’s mind through their eyes?

The empathy gap can appear in personal relationships too – like when I find myself shouting in frustration at my six-year-old twins, or fail to realise that my partner is doing more than her fair share of the housework.

So is there anything you can do to boost your empathy levels? The good news is that almost everyone can learn to be more empathic, just like we can learn to ride a bike or drive a car.

A good warm up is to do a quick assessment of your empathic abilities. Neuropsychologist Simon Baron-Cohen has devised a test called Reading the Mind in the Eyes in which you are shown 36 pairs of eyes and have to choose one of four words that best describes what each person is feeling or thinking – for instance, jealous, arrogant, panicked or hateful.

The average score of around 26 suggests that the majority of people are surprisingly good – though far from perfect – at visually reading others’ emotions.

Going a step further, there are three simple but powerful strategies for unleashing the empathic potential that is latent in our neural circuitry.

Make a habit of “radical listening”

“What is essential,’ wrote Marshall Rosenberg, psychologist and founder of Non-Violent Communication, “is our ability to be present to what’s really going on within – to the unique feelings and needs a person is experiencing at that very moment.”

Listening out for people’s feelings and needs – whether it is a friend who has just been diagnosed with breast cancer or a spouse who is upset at you for working late yet again – gives them a sense of being understood.

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Let people have their say, hold back from interrupting and even reflect back what they’ve told you so they knew you were really listening. There’s a term for doing this – “radical listening”.

Radical listening can have an extraordinary impact on resolving conflict situations. Rosenberg points out that in employer-employee disputes, if both sides literally repeat what the other side just said before speaking themselves, conflict resolution is reached 50% faster.

Look for the human behind everything

A second step is to deepen empathic concern for others by developing an awareness of all those individuals hidden behind the surface of our daily lives, on whom we may depend in some way. A Buddhist-inspired approach to this is to spend a whole day becoming mindful of every person connected to your routine actions.

So when you have your morning coffee, think about the people who picked the coffee beans. As you button your shirt, consider the labour behind the label by asking yourself: “Who sewed on these buttons? Where in the world are they? What are their lives like?”

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Think about all the people you take for granted

Then continue throughout the day, bringing this curiosity to who is driving the train, vacuuming the office floor or stacking the supermarket shelves. It is precisely such mindful awareness that can spark empathic action on the behalf of others, whether it’s buying Fairtrade coffee or becoming friends with the office cleaner.

Bertolt Brecht wrote a wonderful poem about this called A Worker Reads History, which begins: “Who built the seven gates of Thebes? / The books are filled with the names of kings / Was it the kings who hauled the craggy blocks of stone?”

Become curious about strangers

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I used to regularly walk past a homeless man around the corner from where I live in Oxford and take virtually no notice of him. One day I stopped to speak to him.

It turned out his name was Alan Human and he had a degree in Philosophy, Politics and Economics from the University of Oxford. We subsequently developed a friendship based on our mutual interest in Aristotle’s ethics and pepperoni pizza.

This encounter taught me that having conversations with strangers opens up our empathic minds. We can not only meet fascinating people but also challenge the assumptions and prejudices that we have about others based on their appearance, accents or backgrounds.

It’s about recovering the curiosity everyone had as children, but which society is so good at beating out of us. Get beyond superficial talk but beware interrogating people. Respect the advice of oral historian Studs Terkel – who always spoke to people on the bus on his daily commute: “Don’t be an examiner, be the interested inquirer.”

These are the kinds of conversations you will find happening at the world’s firstEmpathy Museum, which is launching in the UK in late 2015 and will then be travelling to Australia and other countries.

Amongst the unusual exhibitions will be a human library, where instead of borrowing a book you borrow a person for conversation – maybe a Sikh teenager, an unhappy investment banker or a gay father. In other words, the kind of people you may not get to meet in everyday life.

Empathy is the cornerstone of healthy human relationships.

As the psychologist and inventor of emotional intelligence Daniel Goleman puts it, without empathy a person is “emotionally tone deaf”.

It’s clear that with a little effort nearly everyone can put more of their empathic potential to use. So try slipping on your empathy shoes and make an adventure of looking at the world through the eyes of others.

New class of compounds shrinks pancreatic cancer tumors, prevents regrowth .


A chemical compound that has reduced the growth of pancreatic cancer tumors by 80 percent in treated mice has been developed by researchers. The compound, called MM41, was designed to block faulty genes. It appears to do this by targeting little knots in their DNA, called quadruplexes, which are very different from normal DNA and which are especially found in faulty genes.

Pancreatic cancer is the most lethal of any common cancer. Only three in every 100 people diagnosed will live for five years or more and this survival rate has barely improved in the last 40 years.

Scientists from UCL (University College London) have designed a chemical compound that has reduced the growth of pancreatic cancer tumors by 80 percent in treated mice.

The compound, called MM41, was designed to block faulty genes. It appears to do this by targeting little knots in their DNA, called quadruplexes, which are very different from normal DNA and which are especially found in faulty genes.

The findings, published in Nature Scientific Reports, showed that MM41 had a strong inhibiting effect on two genes — k-RAS and BCL-2 — both of which are found in the majority of pancreatic cancers.

Funded by the UK charity, Pancreatic Cancer Research Fund, the UCL team, led by professor Stephen Neidle, conducted a small-scale trial, treating two groups of eight mice with pancreatic tumors with different doses of MM41 twice a week for 40 days (12 doses). A further control group received no treatment. The tumors in the group given the larger dose decreased by an average of 80 percent during the treatment period, and after 30 days, tumor regrowth stopped in all the mice. For two of the mice in this group, the tumor disappeared completely with no signs of regrowth after treatment ended for a further 239 days (the approximate equivalent to the rest of their natural life span).

Analysis of the mice tumors showed that the MM41 compound had been taken up into the nucleus of the cancer cells showing that it was able to effectively target the pancreatic cancer tumor.

The team also saw no significant side effects on the mice during the study: there was no damage to other tissue or organs, and none of the mice showed any significant weight loss.

Discussing the results, Neidle explained: “This research provides a potentially very powerful alternative approach to the way that conventional drugs tackle pancreatic cancer, by targeting a very specific area of the DNA of faulty genes. One of the genes that MM41 blocks — the BCL-2 gene — is involved in regulating apoptosis, the body’s natural process which forces cells to die if they become too damaged or unhealthy to be repaired. BCL-2 is present in high amounts in many tumors and helps cancer cells to survive, but when the BCL-2 gene is blocked by MM41 in mice, the cancer cells succumb to apoptosis and die.”

Neidle stressed that although these results are exciting, MM41 is not ideal for trialling in humans and further refinements are needed. “We are now working to optimise this class of compounds, but it’s clearly worthy of further investigation for potential use in treating pancreatic cancer in people,” he said.

Pancreatic cancer is the most lethal of any common cancer. Only three in every 100 people diagnosed will live for five years or more and this survival rate has barely improved in the last 40 years. The majority of patients are diagnosed too late for surgery — currently the only potentially curative treatment — and 80 per cent of those who have surgery will see the cancer return.

Maggie Blanks, Pancreatic Cancer Research Fund’s CEO, said: “It’s because of these bleak facts that our funding strategy focuses on finding and developing alternative, effective treatments for patients as well as finding a way to diagnose pancreatic cancer at an early stage. To find a potential new way to kill pancreatic cancer tumor cells is an exciting development.”

Russian Government Calls For International Investigation Into U.S. Moon Landings


http://organichealth.co/russian-government-calls-for-international-investigation-into-u-s-moon-landings-for-good-reasons/

Glioblastoma and Other Malignant Gliomas


Importance  Glioblastomas and malignant gliomas are the most common primary malignant brain tumors, with an annual incidence of 5.26 per 100 000 population or 17 000 new diagnoses per year. These tumors are typically associated with a dismal prognosis and poor quality of life.

Objective  To review the clinical management of malignant gliomas, including genetic and environmental risk factors such as cell phones, diagnostic pitfalls, symptom management, specific antitumor therapy, and common complications.

Evidence Review  Search of PubMed references from January 2000 to May 2013 using the termsglioblastoma, glioma, malignant glioma, anaplastic astrocytoma, anaplastic oligodendroglioma,anaplastic oligoastrocytoma, and brain neoplasm. Articles were also identified through searches of the authors’ own files. Evidence was graded using the American Heart Association classification system.

Findings  Only radiation exposure and certain genetic syndromes are well-defined risk factors for malignant glioma. The treatment of newly diagnosed glioblastoma is based on radiotherapy combined with temozolomide. This approach doubles the 2-year survival rate to 27%, but overall prognosis remains poor. Bevacizumab is an emerging treatment alternative that deserves further study. Grade III tumors have been less well studied, and clinical trials to establish standards of care are ongoing. Patients with malignant gliomas experience frequent clinical complications, including thromboembolic events, seizures, fluctuations in neurologic symptoms, and adverse effects from corticosteroids and chemotherapies that require proper management and prophylaxis.

Conclusions and Relevance  Glioblastoma remains a difficult cancer to treat, although therapeutic options have been improving. Optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment.

New Device Uses Patient Tumors as High-Throughput Screen Tool


 

Literature Review: Inpatient HTS?
  • Efforts to replace traditional cell culture–based testing of drug candidates with models that carry better predictive power, as relates to effect in human patients, have proliferated in recent years. These include 3D organotypic models, tissue printing platforms, and organs-on-chips. These two reports take the testing of new oncology drug candidates to the next level, that is, right into the human patient. In Klinghoffer et al., the team reports on a multi-needle-based device for injecting multiple drugs transcutaneously into discrete loci within the tumor in an actual patient (figure 1). Through extensive testing, the team demonstrated that up to eight drugs could be injected into mapped locations within the tumor, forming column-like tracks, and to remain acting locally, allowing the post-treatment analysis of drug efficacy and mechanism of action through the measurement of multiplebiomarkers. The biomarker analysis was performed after 24–72 h of treatment by obtaining 4 μm histological sections every 2 mm along the injection column. The authors evaluated three xenograft models either with several oncology drugs or with the same drug dosed at different concentrations. Post-treatment analyses showed that the different drugs acted distinctly based on their previously established molecular mechanisms and that their action exhibited a dose–response effect. Moreover, it was shown that the local responses to the microinjected drugs could be used to predict the corresponding response to the systemically delivered substance, and the system was demonstrated to support a pilot screen of 97 drugs. Last but not least, the authors tested the injection device in human lymphoma patients where the procedure was found to be generally well-tolerated. In a companion paper, the Robert Langer’s team provides an implantable microdevice containing a large number of drug-containing reservoirs that can be implanted inside the tumor. As a prototype, the team used a cylindrical device ∼0.8 mm thick for a delivery via biopsy needle (figure 2). By properly separating the drug-containing cavities along the cylindrical carrier, the team was able to control the crosstalk between adjacent drugs (either to eliminate it to study the individual agents or to retain it in order to test for advantageous drug–drug combinations). At this stage, the device contained 16 reservoirs, although the authors pointed out that further increase in the number would be possible. Further, changing the shape of the cavity, as well as manipulating the drug formulation, afforded control over the rate of delivery of drugs with different physicochemical properties. The two reports thus bring us one step closer to shifting the medium-to-high throughput testing of drug candidates from the laboratory to the patient.

  • Click Image To Enlarge +

    The CIVO tumor microinjection platform. (A) The CIVO platform consists of a handheld array of up to eight needles capable of simultaneously penetrating subcutaneous tumors and delivering microdoses of candidate therapeutics. (B) For preclinical studies, tumors were grown as flank xenografts in immunocompromised mice and injected while mice were anesthetized. A chemically inert ITD was co-injected through each needle. (C) A representative example of the ITD signal from a tumor injected using a five-needle array visualized with a Xenogen In Vivo Imaging System (IVIS). (D) A longitudinal IVIS scan demonstrating the column-like distribution of the tracking dye signal from a single needle spanning the z axis of the tumor. (E) Tumor responses were assessed after resection of the tumor via histological staining of cross sections (4 mm thick) sampled at 2-mm intervals perpendicular to the injection column. (F) High resolution whole-slide scanning captured images of every cell from each 4-mm-thick tissue section. (G) A representative tumor response to microinjected drug at a single injection site. Nuclei, DAPI (4′,6-diamidino-2-phenylindole) (blue); ITD (green); a drug-specific biomarker (orange). (H) The resulting images were processed by a custom image analysis platform called CIVO Analyzer, which classifies the cells within each region of interest as biomarker-positive (green dots) or biomarker-negative (red dots).

  • Click Image To Enlarge +

    In vivo drug sensitivity assay. (A) The device is implanted by needle directly into tissue, and drugs diffuse from device reservoirs into confined regions of tumor. Each region is assayed independently to assess the tumor-specific response to a given drug, such as apoptosis or growth arrest. A second biopsy needle selectively retrieves a small column of tissue that immediately surrounds and includes the device. This tissue contains the regions of drug diffusion and is used for determination of drug efficacy. (B) Three methods for precise control over the release profile of a given drug are demonstrated: reservoir opening size affects the rate of transport; the formulation of a drug in a polymer matrix (for example, PEG slows release of sunitinib versus free doxorubicin); and hydrophilic expansive hydrogels (to achieve rapid tissue uptake of highly insoluble drugs, such as lapatinib). Scale bars, 300 μm.

  • * Abstract from Science Translational Medicine 2015; Vol. 7, Issue 284, p. 284ra58

    A fundamental problem in cancer drug development is that antitumor efficacy in preclinical cancer models does not translate faithfully to patient outcomes. Much of early cancer drug discovery is performed under in vitro conditions in cell-based models that poorly represent actual malignancies. To address this inconsistency, we have developed a technology platform called CIVO, which enables simultaneous assessment of up to eight drugs or drug combinations within a single solid tumor in vivo. The platform is currently designed for use in animal models of cancer and patients with superficial tumors but can be modified for investigation deeper-seated malignancies. In xenograft lymphoma models, CIVO microinjection of well-characterized anticancer agents (vincristine, doxorubicin, mafosfamide, and prednisolone) induced spatially defined cellular changes around sites of drug exposure, specific to the known mechanisms of action of each drug. The observed localized responses predicted responses to systemically delivered drugs in animals. In pair-matched lymphoma models, CIVO correctly demonstrated tumor resistance to doxorubicin and vincristine and an unexpected enhanced sensitivity to mafosfamide in multidrug-resistant lymphomas compared withchemotherapy-naïve lymphomas. A CIVO-enabled in vivo screen of 97 approved oncology agents revealed a novel mTOR (mammalian target of rapamycin) pathway inhibitor that exhibits significantly increased tumor-killing activity in the drug-resistant setting compared with chemotherapy-naïve tumors. Finally, feasibility studies to assess the use of CIVO in human and canine patients demonstrated that microinjection of drugs is toxicity-sparing while inducing robust, easily tracked, drug-specific responses in autochthonous tumors, setting the stage for further application of this technology in clinical trials.

  • * Abstract from Science Translational Medicine 2015; Vol. 7, Issue 284, p. 284ra57

    Current anticancer chemotherapy relies on a limited set of in vitro or indirect prognostic markers of tumor response to available drugs. A more accurate analysis of drug sensitivity would involve studying tumor response in vivo. To this end, we have developed an implantable device that can perform drug sensitivity testing of several anticancer agents simultaneously inside the living tumor. The device contained reservoirs that released microdoses of single agents or drug combinations into spatially distinct regions of the tumor. The local drug concentrations were chosen to be representative of concentrations achieved during systemic treatment. Local efficacy and drug concentration profiles were evaluated for each drug or drug combination on the device, and the local efficacy was confirmed to be a predictor of systemic efficacy in vivo for multiple drugs and tumor models. Currently, up to 16 individual drugs or combinations can be assessed independently, without systemic drug exposure, through minimally invasive biopsy of a small region of a single tumor. This assay takes into consideration physiologic effects that contribute to drug response by allowing drugs to interact with the living tumor in its native microenvironment. Because these effects are crucial to predicting drug response, we envision that these devices will help identify optimal drug therapy before systemic treatment is initiated and could improve drug response prediction beyond the biomarkers and in vitroand ex vivo studies used today. These devices may also be used in clinical drug development to safely gather efficacy data on new compounds before pharmacological optimization.