Recently, the launch vehicle Stardust 1.0 was launched from a former military base in US called Loring Commerce Centre.
Significance of the Launch
The launch of the vehicle is significant in the light that this is the 1st commercial space launch that is powered by biofuel.
Launching the Stardust 1.0 is also significant for Maine because, it is the first commercial rocket launch for the state.
About Stardust 1.0
The launch vehicle Stardust 1.0 is suitable for student and budget payloads.
It is 20 feet in height and approximately 250 kg in weight.
The launch vehicle can carry a maximum payload mass of 8 kg.
In its first launch, the rocket carried three payloads including,
A metal alloy which is designed to lessen vibrations,
A CubeSat prototype which was built by high school students, and
A CubeSat that was procured from software company Rocket Insights.
The launch vehicle will be used to launch the small satellites called CubeSats into space. The satellite will be launched in less toxic and relatively cheaper manner as opposed to the traditional rocket fuel
The Stardust rocket launch vehicle has been manufactured by bluShift.
It is an aerospace company based in Maine, US. This company is involved in developing the rockets powered by bio-derived fuels.
Blushift was manufacturing the Stardust 1.0 launch vehicle since 2014.
The company is also developing other rockets such as Stardust Gen. 2, Starless Rouge, and Red Dwarf.
Fuel produced through the contemporary processes from biomass which can directly be converted into liquid fuels. It is not produced by the usual slow geological processes of formation of fossil fuels like oil.
The state is situated in the New England region of North-eastern United States (US) having its capital city Augusta. It is bordered by New Hampshire in the west, Atlantic Ocean in the southeast and Canadian provinces of New Brunswick and Quebec respectively in the northeast and northwest. The state is the 12th-smallest by area. The most populous city of the state is Portland.
The combination of CDK4/6 inhibitors with endocrine therapy is the standard of care for patients with estrogen receptor-positive (ER+) and HER2-negative (ER+/HER2-) metastatic breast cancer. However, a subset of patients will have tumors with intrinsic resistance to this therapy and most patients will develop resistant disease at some point during treatment.
Researchers at the Lester and Sue Smith Breast Center and the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine examined gene expression data from preclinical models of ER+ breast cancer and from patients with early ER+/HER2- breast cancer who were participating in neoadjuvant trials of CDK4/6 inhibitors and found an association between high interferon (IFN) signaling and resistance to the treatment. The findings published in Clinical Cancer Research, a journal of the American Association for Cancer Research, may aid in helping doctors identify which patients would benefit more from CDK4/6 inhibitor treatment.
“CDK4/6 inhibitors are the standard of care for metastatic disease, and current clinical studies are investigating the use of this treatment in combination with endocrine therapy in early ER+ breast cancer, including in the neoadjuvant and adjuvant settings. It is therefore important to understand the molecular biomarkers of sensitivity and resistance to this therapy,” said Dr. Rachel Schiff, corresponding author of the study and professor at the Lester and Sue Smith Breast Center at Baylor.
The researchers investigated the association between the transcriptomic profiles of ER+ breast cancer cell models and their response to palbociclib, a CDK4/6 inhibitor. They observed an association between high interferon (IFN) signaling and reduced sensitivity to CDK4/6 inhibition. From this data, they developed an IFN-related palbociclib-resistance signature (IRPS) comprised of a subset of 35 genes related to IFN signaling.
The team then analyzed tumor samples from patients enrolled in two neoadjuvant trials of CDK4/6 inhibitor therapy (palbociclib or abemaciclib) and found the IFN-related and IRPS signatures to be highly enriched in patients whose tumors were intrinsically resistant to the therapy. They also found that the IRPS score was significantly higher in clinical ER+ tumors of the luminal B subtype, the more aggressive subtype with poor prognosis, than in the luminal A subtype. But, independent of the subtype, compared to tumors with low IRPS scores, higher IRPS score correlated with increased expression of immune checkpoint genes and immuno-suppressive tumor microenvironment, endocrine resistance and poor prognosis.
“This signature that we defined could be a predictive biomarker and help categorize ER+ breast cancer’s clinical response to anti-CDK4/6 therapy,” said Dr. Xiaoyong Fu, co-first author of the study and assistant professor at the Lester and Sue Smith Breast Center.
When examining breast cancer cell models with acquired resistance to CDK4/6 inhibitors, the team observed a major increase in IFN signaling at time resistance to CDK4/6 inhibitors. The IFN signaling levels in acquired resistance cells were significantly higher than in cells that were untreated or had only short-term treatment with CDK4/6 inhibitors. Further studies will be required to determine the role of IFN signaling in developing resistance.
“Measuring IFN signaling could be important in identifying who is less likely to respond to CDK4/6 inhibitors so they can be directed to other therapies,” said Dr. Carmine De Angelis, co-first author of the study, currently an oncologist at the University of Naples Federico II and at the time of this study, a postdoctoral fellow at the Lester and Sue Smith Breast Center.
“Targeting these agents to the right patients and learning how to mitigate or overcome resistance is important. These results shed light on a potential important mechanism of resistance that we also observed on correlative studies on samples from the PALLET trial that we collaborated on with NSABP and the Royal Marsden,” said Dr. Mothaffar Rimawi, study co-author and professor and executive medical director at the Dan L Duncan Comprehensive Cancer Center.
For a full list of contributing authors and financial support, see the publication.
Reference: Carmine De Angelis, Xiaoyong Fu, Maria Letizia Cataldo, Agostina Nardone, Resel Pereira, Jamunarani Veeraraghavan, Sarmistha Nanda, Lanfang Qin, Vidyalakshmi Sethunath, Tao Wang, Susan G. Hilsenbeck, Matteo Benelli, Ilenia Migliaccio, Luca Malorni, Lacey M Litchfield, Jiangang Liu, Joshua Donaldson, Pier Selenica, David Norman Brown, Britta Weigelt, Jorge S. Reis-Filho, Ben H. Park, Sara A. Hurvitz, Dennis J. Slamon, Mothaffar F. Rimawi, Valerie M Jansen, Rinath Jeselsohn, C. Kent Osborne and Rachel Schiff, “Activation of the interferon signaling pathway is associated with resistance to CDK4/6 inhibitors and immune checkpoint activation in ER-positive breast cancer”, Clinical Cancer Research, 2021. https://clincancerres.aacrjournals.org/content/early/2021/02/01/1078-0432.CCR-19-4191DOI: 10.1158/1078-0432.CCR-19-4191
Researchers at Baylor College of Medicine found that while most individuals responded to respiratory syncytial virus (RSV) natural reinfection with a typical sustained antibody response associated with protection, a few individuals surprisingly responded atypically, not being able to sustain the antibody response, which declined to levels that made the individuals susceptible to RSV reinfection.
The researchers highlight in their study, published in the journal Vaccine, that their findings point at a subpopulation of people who also may not maintain an antibody response to vaccines and suggest the need to characterize patient-specific responses to respiratory viral infections, such as COVID-19.
“RSV is the leading cause of childhood acute lower respiratory illness worldwide and a significant cause of morbidity and mortality in older adults,” said corresponding author Dr. Pedro A. Piedra, professor of molecular virology and microbiology, pediatrics and of pharmacology and chemical biology at Baylor. He also is the director of Baylor’s Clinical Laboratory Improvement Amendments (CLIA)-Certified Respiratory Virus Diagnostic Laboratory. Piedra also is a leader in the fight against COVID-19.
In response to RSV infection, the body produces specific antibodies that have been correlated with protection from infection and reduction of severe disease, but reinfection is still frequent.
“To understand RSV reinfection, we studied the levels of the natural RSV-specific antibody response on an adult population during an RVS season in Houston,” said first author Brittani N. Blunck, graduate student in the Piedra lab.
The researchers found that the 19 individuals they studied could be placed in one of three categories according to their antibody profiles: A) those whose RSV antibody profile did not change, an indication that they did not get reinfected during the study period. B) those who showed an increase in RSV antibodies, a typical response showing that they had a reinfection that boosted the antibody response, and C) a surprising, small group that showed good antibody levels at the beginning of the study followed by a quick decline in antibodies to levels that made them susceptible to reinfection.
The ‘original antigenic sin’
“The other important finding was what we call the ‘original antigenic sin,’” Piedra said. “This phenomenon, which has been demonstrated for the influenza virus and others, refers to the immune system responding more to older infections than to recent infections.”
In this original antigenic sin case, the immune system produced a stronger antibody response to RSV strains it had encountered long ago than to other strains of the same virus it encountered more recently.
“That was surprising but not totally unexpected because we see that with other viruses. However, we had not seen that for RSV before,” Piedra said.
“We think that our main findings, the existence of a small portion of a human population that does not sustain an RSV antibody response after reinfection and the original antigenic sin, have important implications for vaccine development and deserve further study,” Blunck said.
“Understanding natural reinfection is essential for vaccine development because it helps us design more effective vaccines,” said co-author Dr. E. Lynn Zechiedrich, Kyle and Josephine Morrow Chair in Molecular Virology and Microbiology at Baylor.
“This study is also relevant to the current COVID-19 epidemic, as in some ways RSV and SASRS-Cov-2 are similar,” said co-author Dr. Brian Gilbert, associate professor of molecular virology and microbiology at Baylor. “We need more detailed studies on the immune responses to SARS-CoV-2, the virus that causes COVID-19.”
The researchers are continuing their studies by investigating the responses of other branches of the immune system, such as the cellular immune response, to RSV reinfection, as well as the mechanism that mediates the atypical antibody response observed in this work.
Other contributors of this work include Letisha Aideyan, Xunyan Ye, Vasanthi Avadhanula and Laura Ferlic-Stark, all at Baylor.
Financial support of this study was provided by discretionary funds and NIH grant R01GM115501.
New research has identified a nanostructure that improves the anode in lithium-ion batteries
Instead of using graphite for the anode, the researchers turned to silicon: a material that stores more charge but is susceptible to fracturing
The team made the silicon anode by depositing silicon atoms on top of metallic nanoparticles
The resulting nanostructure formed arches, increasing the strength and structural integrity of the anode
Electrochemical tests showed the lithium-ion batteries with the improved silicon anodes had a higher charge capacity and longer lifespan
New research conducted by the Okinawa Institute of Science and Technology Graduate University (OIST) has identified a specific building block that improves the anode in lithium-ion batteries. The unique properties of the structure, which was built using nanoparticle technology, are revealed and explained today in Communications Materials.
Powerful, portable and rechargeable, lithium-ion batteries are crucial components of modern technology, found in smartphones, laptops and electric vehicles. In 2019, their potential to revolutionize how we store and consume power in the future, as we move away from fossil fuels, was notably recognized, with the Nobel Prize co-awarded to new OIST Board of Governors member, Dr. Akira Yoshino, for his work developing the lithium-ion battery.
Traditionally, graphite is used for the anode of a lithium-ion battery, but this carbon material has major limitations.
“When a battery is being charged, lithium ions are forced to move from one side of the battery – the cathode – through an electrolyte solution to the other side of the battery – the anode. Then, when a battery is being used, the lithium ions move back into the cathode and an electric current is released from the battery,” explained Dr. Marta Haro, a former researcher at OIST and first author of the study. “But in graphite anodes, six atoms of carbon are needed to store one lithium ion, so the energy density of these batteries is low.”
With science and industry currently exploring the use of lithium-ion batteries to power electric vehicles and aerospace craft, improving energy density is critical. Researchers are now searching for new materials that can increase the number of lithium ions stored in the anode.
One of the most promising candidates is silicon, which can bind four lithium ions for every one silicon atom.
“Silicon anodes can store ten times as much charge in a given volume than graphite anodes – a whole order of magnitude higher in terms of energy density,” said Dr. Haro. “The problem is, as the lithium ions move into the anode, the volume change is huge, up to around 400%, which causes the electrode to fracture and break.”
The large volume change also prevents stable formation of a protective layer that lies between the electrolyte and the anode. Every time the battery is charged, this layer therefore must continually reform, using up the limited supply of lithium ions and reducing the lifespan and rechargeability of the battery.
“Our goal was to try and create a more robust anode capable of resisting these stresses, that can absorb as much lithium as possible and ensure as many charge cycles as possible before deteriorating,” said Dr. Grammatikopoulos, senior author of the paper. “And the approach we took was to build a structure using nanoparticles.”
While experimenting with different thicknesses of the silicon layer to see how it affected the material’s elastic properties, the researchers noticed something strange.
“There was a point at a specific thickness of the silicon layer where the elastic properties of the structure completely changed,” said Theo Bouloumis, a current PhD student at OIST who was conducting this experiment. “The material became gradually stiffer, but then quickly decreased in stiffness when the thickness of the silicon layer was further increased. We had some ideas, but at the time, we didn’t know the fundamental reason behind why this change occurred.”
Now, this new paper finally provides an explanation for the sudden spike in stiffness at one critical thickness.
Through microscopy techniques and computer simulations at the atomic level, the researchers showed that as the silicon atoms are deposited onto the layer of nanoparticles, they don’t form an even and uniform film. Instead, they form columns in the shape of inverted cones, growing wider and wider as more silicon atoms are deposited. Eventually, the individual silicon columns touch each other, forming a vaulted structure.
“The vaulted structure is strong, just like an arch is strong in civil engineering,” said Dr. Grammatikopoulos. “The same concept applies, just on a nanoscale.”
Importantly, the increased strength of the structure also coincided with enhanced battery performance. When the scientists carried out electrochemical tests, they found that the lithium-ion battery had an increased charge capacity. The protective layer was also more stable, meaning the battery could withstand more charge cycles.
These improvements are only seen at the precise moment that the columns touch. Before this moment occurs, the individual pillars are wobbly and so cannot provide structural integrity to the anode. And if silicon deposition continues after the columns touch, it creates a porous film with many voids, resulting in a weak, sponge-like behavior.
This reveal of the vaulted structure and how it gains its unique properties not only acts as an important step forward towards the commercialization of silicon anodes in lithium-ion batteries, but also has many other potential applications within material sciences.
“The vaulted structure could be used when materials are needed that are strong and able to withstand various stresses, such as for bio-implants or for storing hydrogen,” said Dr. Grammatikopoulos. “The exact type of material you need – stronger or softer, more flexible or less flexible – can be precisely made, simply by changing the thickness of the layer. That’s the beauty of nanostructures.”
Journal: Communications Materials Title: Nano-vault architecture mitigates stress in silicon-based anodes for lithium-ion batteries Authors: Marta Haro, Pawan Kumar, Junlei Zhao, Panagiotis Koutsogiannis, Alexander James Porkovich, Zakaria Ziadi, Theodoros Bouloumis, Vidyadhar Singh, Emilio J. Juarez-Perez, Evropi Toulkeridou, Kai Nordlund, Flyura Djurabekova, Mukhles Sowwan, Panagiotis Grammatikopoulos DOI: 10.1038/s43246-021-00119-0
Method to enable quantum optical circuits that use photons–heralds a new future for secure communication and quantum computing
The modern world is powered by electrical circuitry on a “chip” — the semiconductor chip underpinning computers, cell phones, the internet, and other applications. In the year 2025, humans are expected to be creating 175 zettabytes (175 trillion gigabytes) of new data. How can we ensure the security of sensitive data at such a high volume? And how can we address grand-challenge-like problems, from privacy and security to climate change, leveraging this data, especially given the limited capability of current computers?
A promising alternative is emerging quantum communication and computation technologies. For this to happen, however, it will require the widespread development of powerful new quantum optical circuits; circuits that are capable of securely processing the massive amounts of information we generate every day. Researchers in USC’s Mork Family Department of Chemical Engineering and Materials Science have made a breakthrough to help enable this technology.
While a traditional electrical circuit is a pathway along which electrons from an electric charge flow, a quantum optical circuit uses light sources that generate individual light particles, or photons, on-demand, one-at-a-time, acting as information carrying bits (quantum bits or qubits). These light sources are nano-sized semiconductor “quantum dots”-tiny manufactured collections of tens of thousands to a million atoms packed within a volume of linear size less than a thousandth of the thickness of typical human hair buried in a matrix of another suitable semiconductor.
They have so far been proven to be the most versatile on-demand single photon generators. The optical circuit requires these single photon sources to be arranged on a semiconductor chip in a regular pattern. Photons with nearly identical wavelength from the sources must then be released in a guided direction. This allows them to be manipulated to form interactions with other photons and particles to transmit and process information.
Until now, there has been a significant barrier to the development of such circuits. For example, in current manufacturing techniques quantum dots have different sizes and shapes and assemble on the chip in random locations. The fact that the dots have different sizes and shapes mean that the photons they release do not have uniform wavelengths. This and the lack of positional order make them unsuitable for use in the development of optical circuits.
In recently published work, researchers at USC have shown that single photons can indeed be emitted in a uniform way from quantum dots arranged in a precise pattern. It should be noted that the method of aligning quantum dots was first developed at USC by the lead PI, Professor Anupam Madhukar, and his team nearly thirty years ago, well before the current explosive research activity in quantum information and interest in on-chip single-photon sources. In this latest work, the USC team has used such methods to create single-quantum dots, with their remarkable single-photon emission characteristics. It is expected that the ability to precisely align uniformly-emitting quantum dots will enable the production of optical circuits, potentially leading to novel advancements in quantum computing and communications technologies.
The work, published in APL Photonics, was led by Jiefei Zhang, currently a research assistant professor in the Mork Family Department of Chemical Engineering and Materials Science, with corresponding author Anupam Madhukar, Kenneth T. Norris Professor in Engineering and Professor of Chemical Engineering, Electrical Engineering, Materials Science, and Physics.
“The breakthrough paves the way to the next steps required to move from lab demonstration of single photon physics to chip-scale fabrication of quantum photonic circuits,” Zhang said. “This has potential applications in quantum (secure) communication, imaging, sensing and quantum simulations and computation.”
Madhukar said that it is essential that quantum dots be ordered in a precise way so that photons released from any two or more dots can be manipulated to connect with each other on the chip. This will form the basis of building unit for quantum optical circuits.
“If the source where the photons come from is randomly located, this can’t be made to happen.” Madhukar said.
“The current technology that is allowing us to communicate online, for instance using a technological platform such as Zoom, is based on the silicon integrated electronic chip. If the transistors on that chip are not placed in exact designed locations, there would be no integrated electrical circuit,” Madhukar said. “It is the same requirement for photon sources such as quantum dots to create quantum optical circuits.”
“This advance is an important example of how solving fundamental materials science challenges, like how to create quantum dots with precise position and composition, can have big downstream implications for technologies like quantum computing,” said Evan Runnerstrom, program manager, Army Research Office, an element of the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory. “This shows how ARO’s targeted investments in basic research support the Army’s enduring modernization efforts in areas like networking.”
To create the precise layout of quantum dots for the circuits, the team used a method called SESRE (substrate-encoded size-reducing epitaxy) developed in the Madhukar group in the early 1990s. In the current work, the team fabricated regular arrays of nanometer-sized mesas with a defined edge orientation, shape (sidewalls) and depth on a flat semiconductor substrate, composed of gallium arsenide (GaAs). Quantum dots are then created on top of the mesas by adding appropriate atoms using the following technique.
First, incoming gallium (Ga) atoms gather on the top of the nanoscale mesas attracted by surface energy forces, where they deposit GaAs. Then, the incoming flux is switched to indium (In) atoms, to in turn deposit indium arsenide (InAs) followed back by Ga atoms to form GaAs and hence create the desired individual quantum dots that end up releasing single photons. To be useful for creating optical circuits, the space between the pyramid-shaped nano-mesas needs to be filled by material that flattens the surface. The final chip where opaque GaAs is depicted as a translucent overlayer under which the quantum dots are located.
“This work also sets a new world-record of ordered and scalable quantum dots in terms of the simultaneous purity of single-photon emission greater than 99.5%, and in terms of the uniformity of the wavelength of the emitted photons, which can be as narrow as 1.8nm, which is a factor of 20 to 40 better than typical quantum dots,” Zhang said.
Zhang said that with this uniformity, it becomes feasible to apply established methods such as local heating or electric fields to fine-tune the photon wavelengths of the quantum dots to exactly match each other, which is necessary for creating the required interconnections between different quantum dots for circuits.
This means that for the first time researchers can create scalable quantum photonic chips using well-established semiconductor processing techniques. In addition, the team’s efforts are now focused on establishing how identical the emitted photons are from the same and/or from different quantum dots. The degree of indistinguishability is central to quantum effects of interference and entanglement, that underpin quantum information processing -communication, sensing, imaging, or computing.
Zhang concluded: “We now have an approach and a material platform to provide scalable and ordered sources generating potentially indistinguishable single-photons for quantum information applications. The approach is general and can be used for other suitable material combinations to create quantum dots emitting over a wide range of wavelengths preferred for different applications, for example fiber-based optical communication or the mid-infrared regime, suited for environmental monitoring and medical diagnostics,” Zhang said.
Gernot S. Pomrenke, AFOSR Program Officer, Optoelectronics and Photonics said that reliable arrays of on-demand single photon sources on-chip were a major step forward.
“This impressive growth and material science work stretches over three decades of dedicated effort before research activities in quantum information were in the mainstream,” Pomrenke said. “Initial AFOSR funding and resources from other DoD agencies have been critical in realizing the challenging work and vision by Madhukar, his students, and collaborators. There is a great likelihood that the work will revolutionize the capabilities of data centers, medical diagnostics, defense and related technologies.”
The paper’s co-authors include Qi Huang and Lucas Jordao from USC’s Mork Family Department of Chemical Engineering and Materials Science, Swarnabha Chattaraj from the Ming Hsieh Department of Electrical and Computer Engineering and Siyuan Lu from the IBM Thomas J. Watson Research Center.
Featured image: PHOTON WAVES. IMAGE/WIKIMEDIA COMMONS
A team of scientists from Japan have found success in growing small intestinal cells, akin to those found in the human body, from human-induced pluripotent stem cells. The scientists used a procedure they previously developed on embryonic stem cells for this discovery. They claim that the grown cells can be used for laboratory studies focusing on human small intestinal drug transport and metabolism.
Enterocytes, which line the epithelium of the small intestine, are the sites of absorption and metabolism of most orally consumed medications. For this reason, studies on the absorption of novel oral drugs rely on in vitro or animal models to accurately recreate the environment of the small intestine. Currently, scientists widely use the human colon cancer cell line Caco-2 as a model of the intestinal epithelium. However, this has its drawbacks: Caco-2 cells have been derived from the colon; therefore, they more closely resemble the colon than the small intestine. For example, these cells do not express cytochrome P450 3A4 (CYP3A4), a protein critical for drug metabolism that is abundantly expressed in the small intestine. Moreover, Caco-2 cells tend to show high cell-line to cell-line variations.
To tackle these problems, scientists from the Tokyo Institute of Technology, The University of Tokyo, Kanto Chemical Co. Inc., Shionogi & Co., Ltd. and Shionogi TechnoAdvance Research Co., Ltd., developed novel enterocyte-like cells from human-induced pluripotent stem cells (hiPSCs), which can differentiate into any type of cell when provided with right growth factors.
By modifying a procedure that they previously used on human embryonic stem cells, the scientists initially grew cells that resemble the early stages of small intestine cells, called intestinal progenitor cells. Then, they cultured these progenitor cells on a collagen vitrigel membrane (CVM). Further, they treated the progenitor cells with a maturation medium containing 6-bromoindirubin-3′-oxime, dimethyl sulfoxide, dexamethasone, and activated vitamin D3. Their efforts resulted in the development of enterocyte-like cells that closely resembled actual enterocytes, expressing efflux transporter proteins regulating drug absorption as well as CYP3A4, which Caco-2 cells lack. Dr. Nobuaki Shiraki, Associate Professor at Tokyo Institute of Technology, and one of the corresponding authors of this study, adds, “We established an efficient culture procedure for generating enterocyte-like cells from hiPSCs by culturing the hiPSC-derived endoderm or intestine progenitor cells on CVM.”
The scientists claim that these first-of-their-kind enterocyte-like cells can be used as an in vitro model of the small intestine for evaluating the intestinal absorption of drugs in humans. Elaborating on the advantages of using these cells for future studies, Dr. Shoen Kume, Professor at Tokyo Institute of Technology, and co-corresponding author of this study, comments, “The hiPSC-derived enterocyte-like cells established in this study could be used for the quantitative prediction of the intestinal absorption of drugs in humans under special occasions such as alteration of the functions of transporters/metabolic enzymes by drug-drug interactions as well as normal conditions.”
Indeed, let us hope that the hiPSC-derived enterocyte-like cells would aid breakthrough research in future pharmacokinetic studies!
The IMbrave150 trial found median overall survival was 19.2 months in patients treated with atezo+bev vs 13.4 months for those treated with sorafenib alone, the current standard treatment
The IMbrave150 trial found median overall survival was 19.2 months in patients treated with atezo+bev vs 13.4 months for those treated with sorafenib alone, the current standard treatment (HR, 0.66 [95% CI, 0.52-0.85]; P=0.0009). Survival at 18 months was 52% with atezo+bev and 40% in patients treated with sorafenib.
All patients in the trial had nonresectable HCC – the most common form of liver cancer – and had not previously been treated with systemic therapy. A total of 501 patients were treated in the multicentre, open label, randomised controlled trial and the new follow-up figures confirm the superiority of the atezo+bev combination over sorafenib in this group of patients with HCC.
Atezolizumab is an immune checkpoint inhibitor drug, which helps the immune system hunt down and destroy cancer. Bevacizumab is a targeted monoclonal antibody therapy that starves tumours of their blood supply by preventing endothelial growth but also enhances the immune effects of atezolizumab.
The new data, presented today at the European Association for the Study of the Liver (EASL) Liver Cancer Summit 2021, follows the initial publication of trial data[i] with 8.6 months of follow-up which found survival at 12 months was 67.2% with atezo+bev, compared to 54.6% in those treated with sorafenib. This new post-hoc descriptive overall survival analysis included 12 months of additional follow-up from the primary analysis.
Prof. Richard Finn, lead author of the study, commented, “IMbrave150 showed consistent clinically meaningful treatment benefit and safety with an additional 12 months of follow-up. The combination provides the longest survival seen in a front-line Phase III study in advanced HCC, confirming atezo+bev as a standard of care for previously untreated, unresectable HCC.”
“These are highly significant findings for the treatment of patients with HCC. Many thousands of patients worldwide could benefit from this treatment and it can be considered a major breakthrough – the first improvement in treatment for these types of cases in 13 years and a treatment long awaited by doctors.”
The trial enrolled systemic treatment-naive patients with unresectable HCC, ?1 measurable untreated lesion (RECIST 1.1), Child-Pugh class A liver function and ECOG PS 0/1. Patients were randomised 2:1 to atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sorafenib 400 mg bid until unacceptable toxicity or loss of clinical benefit per investigator. Patients were required to have an upper endoscopy within 6 months of starting the study, to assess for high-risk varices.
Survival benefit with atezo+bev vs sorafenib was generally consistent across subgroups and with the primary analysis. The updated objective response rate (ORR; 29.8% per RECIST 1.1) with atezo+bev was in line with the primary analysis, with more patients achieving complete response (CR; 7.7%) than previously reported. Safety was consistent with the primary analysis, with no new signals identified.
“We now need to understand what is next in front-line liver cancer and how will we build on this data to further improve outcomes beyond the 19.2 months we described. Additionally, we need to evaluate the efficacy for this regimen in earlier stages of HCC.”
Reference: Richard S. Finn, M.D., Shukui Qin, M.D., Masafumi Ikeda, M.D., Peter R. Galle, M.D., et al., for the IMbrave150 Investigators, “Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma”, N Engl J Med 2020; 382:1894-1905 DOI: 10.1056/NEJMoa1915745 https://www.nejm.org/doi/full/10.1056/NEJMoa1915745
All neuroblastomas arise from developmental cells not normally found in children, making them a promising target for drug development
The largest single cell study to date of the childhood cancer, neuroblastoma, has answered important questions about the genesis of the disease. The researchers from the Wellcome Sanger Institute, Great Ormond Street Hospital (GOSH) and their collaborators, discovered that all neuroblastomas arise from a single type of embryonic cell called sympathoblasts.
The study, published today (5 February 2021) in Science Advances, sought to understand why neuroblastomas range in severity, with some easy to treat and others having relatively low five-year survival rates. The fact that all neuroblastomas arise from sympathoblasts makes them an attractive drug target, because these cells exist only in the tumour after the child is born.
Neuroblastoma is a rare cancer that generally affects children under five years old. It begins in the abdomen, usually in the adrenal glands – hormone-producing glands above the kidneys. Neuroblastoma is remarkable in that its severity can vary greatly between individuals. In some children the cancer will disappear without treatment, whereas in others the cancer is relentless. The five-year survival rate for neuroblastoma is one of the lowest of all childhood cancers*.
This varied outlook prompted the researchers to ask whether the range of severity could be caused by neuroblastomas arising from different cell types at different stages of the child’s development in the womb. This was made possible by the advent of single cell mRNA sequencing, a high-resolution technology that can identify different cell types present in a tissue according to the genes expressed by individual cells.
In this study, gene expression of 19,723 cancer cells was analysed and compared to a reference of 57,972 developmental adrenal cells in the hope of identifying the cell types from which neuroblastomas arise and to find novel treatment targets.
“What is most striking about our findings is that despite the great diversity of clinical behaviour of neuroblastoma, there is a patient overarching neuroblastoma cell type. The identification of sympathoblasts as the root of all neuroblastoma is an important step towards understanding how the disease develops and, hopefully, how we can treat it.”
— Dr Jan Molenaar, a senior author of the study from the Princess Maxima Centre for Pediatric Oncology in the Netherlands
Currently, many cancer treatments cause serious side-effects for the patient. But in recent years, technological advances have sped up drug development by allowing researchers to identify differences between the biological processes, such as the expression of a particular gene, within healthy human cells and those within cancerous ones. These differences can be exploited to attack cancer cells without affecting the patient’s healthy cells.
The presence of sympathoblasts, a developmental cell type not normally found in children after they are born, makes it a promising drug target for the treatment of neuroblastoma.
“Neuroblastoma is an unusual cancer in that some tumours resolve without intervention, yet the disease still has one of the lowest five-year survival rates of any childhood cancer. This study fills important gaps in our knowledge of what neuroblastoma cells are and revealed novel treatment targets. My hope is that new, less intrusive therapies can be developed by targeting sympathoblasts, a developmental cell type that exists only in neuroblastoma tumours after a child is born.”
— Dr Karin Straathof, a senior author of the study from Great Ormond Street Hospital
As well as facilitating the discovery of sympathoblasts as the root of neuroblastoma, the single-cell reference map of the developmental adrenal gland will also contribute to the Human Cell Atlas project**. The project aims to create comprehensive reference maps of all types of human cells – the fundamental units of life – as a basis for understanding human health and diagnosing, monitoring, and treating disease.
“Our study shows the power of looking at individual childhood cancer cells in revealing not just one, but a plethora of novel treatment ideas. This raises the exciting prospect that a single cell atlas of all types of paediatric tumours may transform our understanding of childhood cancer.”
— Dr Sam Behjati, a senior author of the study from the Wellcome Sanger Institute and Cambridge University Hospitals
Featured image credit: Adobe stock
Reference: Gerda Kildisiute, Waleed M. Kholosy, Matthew D. Young, Kenny Roberts, Rasa Elmentaite, Sander R. van Hooff, Clarissa N. Pacyna, Eleonora Khabirova, Alice Piapi, Christine Thevanesan, Eva Bugallo-Blanco, Christina Burke, Lira Mamanova, Kaylee M. Keller, Karin P.S. Langenberg-Ververgaert, Philip Lijnzaad, Thanasis Margaritis, Frank C.P. Holstege, Michelle L. Tas, Marc H.W.A. Wijnen, Max M. van Noesel, Ignacio del Valle, Giuseppe Barone, Reinier van der Linden, Catriona Duncan, John Anderson, John C. Achermann, Muzlifah Haniffa, Sarah A. Teichmann, Dyanne Rampling, Neil J. Sebire, Xiaoling He, Ronald R. de Krijger, Roger A. Barker, Kerstin B. Meyer, Omer Bayraktar, Karin Straathof, Jan J. Molenaar, Sam Behjati, “Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell”, Science Advances 05 Feb 2021: Vol. 7, no. 6, https://advances.sciencemag.org/content/7/6/eabd3311 eabd3311 DOI: 10.1126/sciadv.abd3311
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Neanderthals’ gut microbiota already included some beneficial micro-organisms that are also found in our own intestine. An international research group led by the University of Bologna achieved this result by extracting and analysing ancient DNA from 50,000-year-old faecal sediments sampled at the archaeological site of El Salt, near Alicante (Spain).
Published in Communication Biology, their paper puts forward the hypothesis of the existence of ancestral components of human microbiota that have been living in the human gastrointestinal tract since before the separation between the Homo Sapiens and Neanderthals that occurred more than 700,000 years ago.
“These results allow us to understand which components of the human gut microbiota are essential for our health, as they are integral elements of our biology also from an evolutionary point of view” explains Marco Candela, the professor of the Department of Pharmacy and Biotechnology of the University of Bologna, who coordinated the study. “Nowadays there is a progressive reduction of our microbiota diversity due to the context of our modern life: this research group’s findings could guide us in devising diet- and lifestyle-tailored solutions to counteract this phenomenon”.
THE ISSUES OF THE “MODERN” MICROBIOTA
The gut microbiota is the collection of trillions of symbiont micro-organisms that populate our gastrointestinal tract. It represents an essential component of our biology and carries out important functions in our bodies, such as regulating our metabolism and immune system and protecting us from pathogenic micro-organisms.
Recent studies have shown how some features of modernity – such as the consumption of processed food, drug use, life in hyper-sanitized environments – lead to a critical reduction of biodiversity in the gut microbiota. This depletion is mainly due to the loss of a set of microorganisms referred to as “old friends”.
“The process of depletion of the gut microbiota in modern western urban populations could represent a significant wake-up call,” says Simone Rampelli, who is a researcher at the University of Bologna and first author of the study. “This depletion process would become particularly alarming if it involved the loss of those microbiota components that are crucial to our physiology”.
Indeed, there are some alarming signs. For example, in the West, we are witnessing a dramatic increase in cases of chronic inflammatory diseases, such as inflammatory bowel disease, metabolic syndrome, type 2 diabetes and colorectal cancer.
HOW THE “ANCIENT” MICROBIOTA CAN HELP
How can we identify the components of the gut microbiota that are more important for our health? And how can we protect them with targeted solutions? This was the starting point behind the idea of identifying the ancestral traits of our microbiota – i.e. the core of the human gut microbiota, which has remained consistent throughout our evolutionary history. Technology nowadays allows to successfully rise to this challenge thanks to a new scientific field, paleomicrobiology, which studies ancient microorganisms from archaeological remains through DNA sequencing.
The research group analysed ancient DNA samples collected in El Salt (Spain), a site where many Neanderthals lived. To be more precise, they analysed the ancient DNA extracted from 50,000 years old sedimentary faeces (the oldest sample of faecal material available to date). In this way, they managed to piece together the composition of the micro-organisms populating the intestine of Neanderthals. By comparing the composition of the Neanderthals’ microbiota to ours, many similarities aroused.
“Through the analysis of ancient DNA, we were able to isolate a core of microorganisms shared with modern Homo sapiens”, explains Silvia Turroni, researcher at the University of Bologna and first author of the study. “This finding allows us to state that these ancient micro-organisms populated the intestine of our species before the separation between Sapiens and Neanderthals, which occurred about 700,000 years ago”.
SAFEGUARDING THE MICROBIOTA
These ancestral components of the human gut microbiota include many well-known bacteria (among which Blautia, Dorea, Roseburia, Ruminococcus and Faecalibacterium) that are fundamental to our health. Indeed, by producing short-chain fatty acids from dietary fibre, these bacteria regulate our metabolic and immune balance. There is also the Bifidobacterium: a microorganism playing a key role in regulating our immune defences, especially in early childhood. Finally, in the Neanderthal gut microbiota, researchers identified some of those “old friends”. This confirms the researchers’ hypotheses about the ancestral nature of these components and their recent depletion in the human gut microbiota due to our modern life context.
“In the current modernization scenario, in which there is a progressive reduction of microbiota diversity, this information could guide integrated diet- and lifestyle-tailored strategies to safeguard the micro-organisms that are fundamental to our health”, concludes Candela. “To this end, promoting lifestyles that are sustainable for our gut microbiota is of the utmost importance, as it will help maintain the configurations that are compatible with our biology”.