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Every Single Patient in This Small Experimental Drug Trial Saw Their Cancer Disappear

Every Single Patient in This Small Experimental Drug Trial Saw Their Cancer Disappear | Bioscience News - GEG Tech top picks | Scoop.it
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In what appears to be a very promising breakthrough for the treatment of rectal cancer, a small drug trial conducted in the US found every patient treated in the experiment had their cancer successfully go into remission.

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The impact of gene amplification in virus adaptation through intermediate hosts

The impact of gene amplification in virus adaptation through intermediate hosts | Bioscience News - GEG Tech top picks | Scoop.it
Researchers assessed the impact of gene amplification on cross-species adaptation.
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In a recent study published on the bioRxiv preprint server, researchers evaluated the impact of gene amplification on cross-species adaptation. The researchers demonstrated that the impact of RhTRS1 gene amplification could effectively rescue viral replication in fibroblasts from partially resistant African green monkeys (AGMs). The team infected A549 cells with vaccinia virus (VACV) + RhTRS1 or the VACV strain named Copenhagen, expressing a beta-galactosidase (bg) reporter gene. The team explored whether amplification of rhtrs1 could increase the extent of viral replication in the absence of PKR. The team also infected RNase L competent A549 cells or regularly spaced short palindromic repeats with CRISPR in clusters of RNase L deletion present in existing A549 cells with VACV-RhTRS1, VACV-bg or AGM-A. The results of the study showed that A549 cells restricted VACV + RhTRS1 replication by nearly 10,000-fold compared to VACV-bg replication. The team noted that deletion of A549 PKR cells enhanced VACV + RhTRS1 replication by up to 1000-fold compared to PKR-competent cells. The team observed that RNAase L had no impact on VACV-bg replication. 

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Human umbilical cord mesenchymal stem cell-derived treatment of severe pulmonary arterial hypertension | Nature Cardiovascular Research

Human umbilical cord mesenchymal stem cell-derived treatment of severe pulmonary arterial hypertension | Nature Cardiovascular Research | Bioscience News - GEG Tech top picks | Scoop.it
Here we report application of human umbilical cord mesenchymal stem cell (HUCMSC)-derived therapy for pulmonary arterial hypertension (PAH). A 3-year-old female presented with heritable PAH associated with hereditary hemorrhagic telangiectasia and was treated for 6 months with serial intravascular infusions of conditioned media (CM) from allogenic HUCMSCs. The treatment markedly improved clinical and hemodynamic parameters and decreased blood plasma markers of vascular fibrosis, injury and inflammation. A comparative analysis of single-cell RNA sequencing data collected from three HUCMSCs and two human umbilical vein endothelial cell (HUVEC) controls identified eight common cell clusters, all of which indicated regenerative potential specific for HUCMSCs. The properties of HUCMSCs were validated by untargeted label-free quantitation of the cell and CM proteome, suggesting increased activity of regeneration, autophagy and anti-inflammation pathways and mitochondrial function. Prostaglandin analysis demonstrated increased HUCMSC secretion of prostaglandin E2, known for its regenerative capacity. Additional prospective clinical studies are warranted to confirm and further explore the benefits of HUCMSC-derived therapy for PAH. Hansmann et al. show that serial intravascular infusions of conditioned media produced by allogenic umbilical cord mesenchymal stem cells markedly improved the clinical features of a young child with severe pulmonary arterial hypertension. The multi-omic approach analyzing the transcriptome and the proteome of these stem cells isolated from four donors provides initial insight into their beneficial paracrine function.
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A young girl survived an inherited form of pulmonary arterial hypertension thanks to umbilical cord cells.

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Every Single Patient in This Small Experimental Drug Trial Saw Their Cancer Disappear

Every Single Patient in This Small Experimental Drug Trial Saw Their Cancer Disappear | Bioscience News - GEG Tech top picks | Scoop.it
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Identifying the wide diversity of extraterrestrial purine and pyrimidine nucleobases in carbonaceous meteorites | Nature Communications

Identifying the wide diversity of extraterrestrial purine and pyrimidine nucleobases in carbonaceous meteorites | Nature Communications | Bioscience News - GEG Tech top picks | Scoop.it
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The lack of pyrimidine diversity in meteorites remains a mystery since prebiotic chemical models and laboratory experiments have predicted that these compounds can also be produced from chemical precursors found in meteorites. Here the authors report the detection of nucleobases in three carbonaceous meteorites using state-of-the-art analytical techniques optimized for small-scale quantification of nucleobases down to the range of parts per trillion (ppt). In addition to previously detected purine nucleobases in meteorites such as guanine and adenine, they identify various pyrimidine nucleobases such as cytosine, uracil, and thymine, and their structural isomers such as isocytosine, imidazole-4-carboxylic acid, and 6-methyluracil, respectively. Given the similarity in the molecular distribution of pyrimidines in meteorites and those in photon-processed interstellar ice analogues, some of these derivatives could have been generated by photochemical reactions prevailing in the interstellar medium and later incorporated into asteroids during solar system formation. This study demonstrates that a diversity of meteoritic nucleobases could serve as building blocks of DNA and RNA on the early Earth. All DNA/RNA nucleobases were identified in carbonaceous meteorites. Having been provided to the early Earth as a component in carbonaceous meteorites, these molecules might have played a role for the emergence of genetic functions in early life.

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A Woman Is Cured of H.I.V. Using a Novel Treatment - The New York Times

A Woman Is Cured of H.I.V. Using a Novel Treatment - The New York Times | Bioscience News - GEG Tech top picks | Scoop.it
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She’s the third person ever to be cured. Researchers announced that the new approach holds the potential for curing more people of racially diverse backgrounds.

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Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy - Cancer Cell

Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy - Cancer Cell | Bioscience News - GEG Tech top picks | Scoop.it
Recruitment of lymphocytes into tumors is critical for anti-tumor immunity and efficacious immunotherapy. We show in murine models that tumor-associat…
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These studies provide critical insights into the mechanisms governing lymphocyte trafficking in cancer immunity and immunotherapy.

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Research could lead to new treatment option for breast cancer patients with brain metastases

Research could lead to new treatment option for breast cancer patients with brain metastases | Bioscience News - GEG Tech top picks | Scoop.it
Breast cancer patients whose cancer spreads to the brain may soon have new treatment options, thanks to research led by CU Cancer Center member Diana Cittelly, PhD.
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Brain metastases from breast cancer develop in patients with metastatic breast cancer. Current treatment options for brain metastases include surgery, radiation, chemotherapy and targeted therapies, but these have limited success and may worsen neurological function. Because 80% of women with brain metastases from breast cancer die within a year of diagnosis, Cittelly and her team want to find a way to target cancer cells after they have spread to the brain.

Working with cells in the lab, they have identified the interleukin 13 receptor alpha 2 (IL13Ra2) as a likely target for treatment. This is a protein that is found at increased levels in cancer cells that metastasize to other locations in the body, particularly the brain and lungs. In addition, the protein has shown vulnerability to treatment with CAR T cells in clinical trials of brain tumors. The researchers' next step is to initiate a collaboration with CAR T cell experts to better understand how CAR T cell therapy might target IL13Ra2.

Ultimately, Cittelly hopes to see clinical trials for patients with breast cancer that has metastasized to the brain, as they are currently excluded from clinical trials.

 

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Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial - Nature

Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial - Nature | Bioscience News - GEG Tech top picks | Scoop.it
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A new study published by researchers at CHU Sainte-Justine in the medical journal Nature Medicine conclued that convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

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Moffitt Cancer Center presents new data from dozens of clinical research studies at ASCO

Moffitt Cancer Center presents new data from dozens of clinical research studies at ASCO | Bioscience News - GEG Tech top picks | Scoop.it
Moffitt Cancer Center, a national leader in cancer care and research and the only National Cancer Institute-designated Comprehensive Cancer Center based in Florida, is presenting new data from dozens of clinical research studies at this year's American Society of Clinical Oncology (ASCO) Annual Meeting, the world's largest clinical cancer research meeting.
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Moffitt Cancer Center, a national leader in cancer care and research and the only National Cancer Institute-designated cancer center in Florida, is presenting new data from dozens of clinical research studies at this year's American Society of Clinical Oncology (ASCO) Annual Meeting, the largest clinical cancer research meeting in the world. Moffitt investigators will lead 25 abstract presentations, five educational sessions, two cancer panels and two clinical science symposia. The virtual meeting will take place June 4-8, 2021. Among those presenting will be Dr. Bijal Shah, who will discuss the results of the Phase 2 ZUMA-3 trial evaluating CAR T-cell therapy for adults with acute lymphoblastic leukemia, a difficult-to-treat malignancy in this patient population. Also on hand will be Dr. Frederick Locke, who will present data from the ALPHA2 trial evaluating ALLO-501, an allogeneic CAR T-cell therapy product, in combination with ALLO-647, a monoclonal antibody that depletes lymphocytes in the body to help prepare the patient to receive new immune cells, in patients with large B-cell lymphoma.

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Vaccine Breakthrough Infections with SARS-CoV-2 Variants | NEJM

Vaccine Breakthrough Infections with SARS-CoV-2 Variants | NEJM | Bioscience News - GEG Tech top picks | Scoop.it
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Summary Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of clinical concern. In a cohort of 417 persons who had received the second dose of BNT162b
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Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 - Nature

Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 - Nature | Bioscience News - GEG Tech top picks | Scoop.it
BigField GEG Tech's insight:

The recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. This study reports that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of the spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinee sera. Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely owing to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants13,14 with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.

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Intranasal influenza vaccine spurs strong immune response in Phase 1 study

Intranasal influenza vaccine spurs strong immune response in Phase 1 study | Bioscience News - GEG Tech top picks | Scoop.it
An experimental single-dose, intranasal influenza vaccine was safe and produced a durable immune response when tested in a Phase 1 study. The investigational vaccine, called Ad4-H5-VTN, is a recombinant, replicating adenovirus vaccine designed to spur antibodies to hemagglutinin, a protein found on the surface of influenza viruses that attaches to human cells.
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Study opens up a new avenue for the development of selective drug therapies

Study opens up a new avenue for the development of selective drug therapies | Bioscience News - GEG Tech top picks | Scoop.it
Researchers at the Department of Energy's Oak Ridge National Laboratory have definitively linked the function of a specific domain of proteins important in plant-microbe biology to a cancer trigger in humans, knowledge that had eluded scientists for decades.
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Scientists set out to prove experimentally what they had first deduced from computational studies: that the apple plasminogen-nematode domain, or PAN, is linked to cell proliferation that drives tumor growth in humans and defense signaling during plant-microbe interactions in bioenergy crops. The association was first made when researchers explored the genomes of crops like poplar and willow. In the latest study, the research team identified four core amino acids called cysteine residues in the HGF protein essential for PAN domain function and studied their behavior in human cancer cell lines. They found that mutation of one of these amino acids, achieved using CRISPR-9, disabled the signaling pathway known as HGF-c-MET that is abnormally high in cancer cells, forcing them to multiply and spread rapidly. The team's findings, published in Nature Communications Biology, open a new avenue for the development of selective drug therapies to fight a variety of cancers such as those that start in the breast and stomach.

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The metastatic spread of breast cancer accelerates during sleep - Nature

The metastatic spread of breast cancer accelerates during sleep - Nature | Bioscience News - GEG Tech top picks | Scoop.it
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The metastatic spread of cancer is achieved by the haematogenous dissemination of circulating tumour cells (CTCs). Generally, however, the temporal dynamics that dictate the generation of metastasis-competent CTCs are largely uncharacterized, and it is often assumed that CTCs are constantly shed from growing tumours or are shed as a consequence of mechanical insults1. Here the scientists observe a striking and unexpected pattern of CTC generation dynamics in both patients with breast cancer and mouse models, highlighting that most spontaneous CTC intravasation events occur during sleep. Further, they demonstrate that rest-phase CTCs are highly prone to metastasize, whereas CTCs generated during the active phase are devoid of metastatic ability. Mechanistically, single-cell RNA sequencing analysis of CTCs reveals a marked upregulation of mitotic genes exclusively during the rest phase in both patients and mouse models, enabling metastasis proficiency. Systemically, they find that key circadian rhythm hormones such as melatonin, testosterone and glucocorticoids dictate CTC generation dynamics, and as a consequence, that insulin directly promotes tumour cell proliferation in vivo, yet in a time-dependent manner. Thus, the spontaneous generation of CTCs with a high proclivity to metastasize does not occur continuously, but it is concentrated within the rest phase of the affected individual, providing a new rationale for time-controlled interrogation and treatment of metastasis-prone cancers. A study of patients with breast cancer and mouse models demonstrates that most circulating tumour cells are generated during the rest phase of the circadian rhythm, and that these cells are highly prone to metastasize.

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Elon Musk’s Neuralink Rival Synchron Selects Patient for Brain Computer Trial - Bloomberg

Elon Musk’s Neuralink Rival Synchron Selects Patient for Brain Computer Trial - Bloomberg | Bioscience News - GEG Tech top picks | Scoop.it
Elon Musk’s Neuralink is overtaken by a rival in a race to regulatory review.
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Synchron Inc., which develops a so-called brain-computer interface and competes with Elon Musk’s Neuralink Corp., enrolled the first patient in its U.S. clinical trial, putting the company’s implant on a path toward possible regulatory approval for wider use in people with paralysis.

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Powerhouse-pruning protein may also help make energy rapidly available for growing new blood vessels

Powerhouse-pruning protein may also help make energy rapidly available for growing new blood vessels | Bioscience News - GEG Tech top picks | Scoop.it
A protein that helps keep our cell powerhouses working at a premium appears to also help make energy rapidly available when it's time to make new blood vessels.
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Ushio-Fukai and Dr. Tohru Fukai reported in Nature Cell Biology that ROS rapidly modifies CTR1, a cell surface receptor that usually allows essential mineral copper to enter the interior, where its tasks include aiding angiogenesis. Modification of CTR1 prompts it to bind to the VEGF receptor, VEGFR2, also on the cell surface, and the united pair dives inside. This movement enables the sustained VEGFR2 signaling that is essential for making new blood vessels. The researchers also have evidence that Drp1 is also modified by ROS, prompting it to move from a passive state in the fluid part of the cell, or cytosol, to the mitochondria where it still promotes fission, which also produces the powerful hydrogen peroxide ROS. She says that active mitochondria are high users of oxygen and therefore, like NADPH oxidase, high producers of ROS in endothelial cells. The researchers showed that the ROS generated by mitochondria in turn activates AMPK, a key enzyme for regulating energy levels in cells and known to use glucose to rapidly generate enough energy to support important biological work such as making new blood vessels. 

 

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How artificial intelligence is poised to reshape medicine

How artificial intelligence is poised to reshape medicine | Bioscience News - GEG Tech top picks | Scoop.it
In a recent review published in the journal of Nature Medicine, researchers discussed the results of a two-year weekly effort to track and communicate significant developments in medical (artificial intelligence) AI. They included prospective studies as well as developments in medical image analysis that have narrowed the gap between research and implementation.
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In a recent review published in the journal Nature Medicine, scientists discussed the results of a two-year weekly effort to track and communicate significant developments in medical AI. In particular, AI has been a game-changer in the crucial task of protein folding, which involves predicting the 3D structure of a protein from its chemical sequence. Improvements in protein structure prediction can reveal mechanistic information about a variety of events, including drug-protein interactions and mutation effects. With AI, non-invasive cancer screening, prognosis, and tumor origin identification are now possible. Moreover, deep learning has improved CRISPR-based gene editing by helping predict guide RNA activity and identifying anti-CRISPR protein families. According to one study, BioBERT, a model trained on a large corpus of medical literature, outperformed previous peers on natural language tasks such as answering biological questions.  

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The applications of nanomaterials against viral disease

The applications of nanomaterials against viral disease | Bioscience News - GEG Tech top picks | Scoop.it
The application of nanomaterials in the diagnosis, prevention, and treatment of viral diseases is reviewed in detail, highlighting areas of significant progress or stagnation from the past few decades.
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Therapeutic nanosystems and diagnostic systems are increasingly being applied to various areas of medicine, acting as sensors, delivery vehicles, immunostimulants, radiation sensitizers and viral inhibitors. In an article recently published in the journal Pharmaceutics, the application of nanomaterials in the diagnosis, prevention and treatment of viral diseases is reviewed in detail, highlighting areas of significant progress or stagnation over the past decades. Drug delivery is the primary focus of nanomaterials in disease treatment, generally offering improved pharmacokinetics, drug retention time, and "drug-like" of the administered compound. The physical and chemical properties of the nanoparticle strongly influence the biodistribution of the nanomedicine in the body and the ability and propensity of the particle to enter the target cells. In addition to being used as a delivery vehicle, the nanoparticles themselves can be used as viral therapy, acting to block the viral replication cycle or cell entry. Particles constructed from copper, silver and gold are also capable of generating reactive oxygen species. In addition to being directly damaging to viral genetic material, it can induce apoptosis in infected cells, thus preventing viral propagation.

 

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New immunotherapy becomes activated specifically in tumors - EPFL

New immunotherapy becomes activated specifically in tumors - EPFL | Bioscience News - GEG Tech top picks | Scoop.it
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EPFL scientists have developed a chemical method for targeting the effects of cancer-fighting immunotherapy drugs only to the tumor tissue, making the drugs less toxic to the rest of the human body.

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Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer - Nature

Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer - Nature | Bioscience News - GEG Tech top picks | Scoop.it
Emerging data demonstrate that the activity of immune cells can be modulated by microbial molecules. Here, we show that the short-chain fatty acids (SCFAs) pentanoate and butyrate enhance the anti-tumor activity of cytotoxic T lymphocytes (CTLs) and chimeric antigen receptor (CAR) T cells through metabolic and epigenetic reprograming. We show that in vitro treatment of CTLs and CAR T cells with pentanoate and butyrate increases the function of mTOR as a central cellular metabolic sensor, and inhibits class I histone deacetylase activity. This reprogramming results in elevated production of effector molecules such as CD25, IFN-γ and TNF-α, and significantly enhances the anti-tumor activity of antigen-specific CTLs and ROR1-targeting CAR T cells in syngeneic murine melanoma and pancreatic cancer models. Our data shed light onto microbial molecules that may be used for enhancing cellular anti-tumor immunity. Collectively, we identify pentanoate and butyrate as two SCFAs with therapeutic utility in the context of cellular cancer immunotherapy. The activity of immune cells can be regulated by the microbiome. Here, the authors show that the fatty acids pentanoate and butyrate—normally released by the microbiome—increase the anti-tumour activity of cytotoxic T lymphocytes and chimeric antigen receptor T cells through metabolic and epigenetic reprogramming.
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Each person carries about 100 trillion bacterial cells in their digestive tract, belonging to several thousand species, this is called the microbiome. It is believed to be involved in the development of chronic inflammatory bowel diseases, to trigger diabetes, to be responsible for obesity, and even for neurological diseases such as multiple sclerosis and Parkinson's disease, but also for depression and autistic disorders. Scientists from the Universities of Würzburg and Marburg have succeeded for the first time in demonstrating experimentally that bacterial metabolites can increase the cytotoxic activity of certain immune cells and thus positively influencing the efficacy of tumor therapies. Ideally, the bacterial species composition of the microbiome could be used to monitor its influence on the success of therapy. It is the short-chain fatty acids, butyrate and, in particular, pentanoate, that are able to increase the cytotoxic activity of CD8 T cells. Their study shows that treatment with the fatty acid pentanoate increased the ability of tumor-specific T cells to fight solid tumor models. Furthermore, the same effect was observed with CAR-T based treatment.

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Door opened to more permissive research on human embryos | Science

Door opened to more permissive research on human embryos | Science | Bioscience News - GEG Tech top picks | Scoop.it
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The world's largest stem cell society this week signaled a willingness to reconsider a long-standing restriction on laboratory efforts to grow and study human embryos. In new guidelines, the International Society for Stem Cell Research (ISSCR) also spotlights a possible alternative to using embryos that might be less ethically fraught: emerging methods to model stages of human development with stem cells. ISSCR's influential guidelines previously put the culture of human embryos beyond 14 days postfertilization in its most restrictive category three: "prohibited research activities." The new guidelines, drafted by a task force of scientists and ethicists, omit longer embryo culture from this category and encourage a public discussion about allowing it.

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Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera | Bioscience News - GEG Tech top picks | Scoop.it
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Structure-function analysis of the SARS-CoV-2 variant B.1.351 using serum samples from convalescent and vaccinated individuals reveals how mutations in the viral spike protein result in tighter binding to the receptor ACE2 and allow escape from monoclonal antibody neutralization.
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Human ACE2 peptide-mimics block SARS-CoV-2 pulmonary cells infection - Nature Communication

Human ACE2 peptide-mimics block SARS-CoV-2 pulmonary cells infection - Nature Communication | Bioscience News - GEG Tech top picks | Scoop.it
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A team of French researchers has come up with an anti-Covid solution which is an alternative to a vaccination and which could be ready for use  in the form of a nasal spray. They have created a peptide, made up of natural amino acids which lures the virus to it by mimicking the ACE2 lock, and so prevents it from entering into human cells. They have tested it on pulmonary cells and found it has worked without any toxic reaction to humans. These first-in-class blocking peptide mimics represent powerful tools that might be used in prophylactic and therapeutic approaches to fight the coronavirus disease 2019.

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Axicabtagene Ciloleucel Approved in Japan for Relapsed/Refractory LBCL

Axicabtagene Ciloleucel Approved in Japan for Relapsed/Refractory LBCL | Bioscience News - GEG Tech top picks | Scoop.it
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January 22, 2021 — The Japan Ministry of Health, Labour and Welfare has approved the CAR T-cell therapy axicabtagene ciloleucel for use in the treatment of adult patients with certain relapsed/refractory large B-cell lymphomas.

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