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Category: biotech/medical – Page 2256

Intracranial hemorrhage can be a devastating complication associated with needle biopsies of the brain. Hemorrhage can occur to vessels located adjacent to the biopsy needle as tissue is aspirated into the needle and removed. No intraoperative technology exists to reliably identify blood vessels that are at risk of damage. To address this problem, we developed an “imaging needle” that can visualize nearby blood vessels in real time. The imaging needle contains a miniaturized optical coherence tomography probe that allows differentiation of blood flow and tissue. In 11 patients, we were able to intraoperatively detect blood vessels (diameter, 500 μm) with a sensitivity of 91.2% and a specificity of 97.7%. This is the first reported use of an optical coherence tomography needle probe in human brain in vivo. These results suggest that imaging needles may serve as a valuable tool in a range of neurosurgical needle interventions.

Stereotactic brain biopsies are a minimally invasive procedure used to obtain samples of intracranial tissue for diagnostic purposes, most commonly related to brain tumors. Approximately 80,000 new cases of primary brain tumor are diagnosed, and 14,000 brain biopsies are performed each year in the United States (1, 2). Hemorrhage is the most frequent and devastating complication associated with this procedure. Perioperative hemorrhage is associated with rates of transient and permanent morbidity of 1.7 to 8.5% and 1.4 to 4.8%, respectively, and mortality rates of 0.6 to 2.8% (3–7).

The standard clinical practice is to identify blood vessels at risk of injury on preoperative imaging, using either contrast-enhanced magnetic resonance imaging (MRI) or x-ray computed tomography. Frameless stereotactic navigation techniques, guided by preoperative imaging, are then used to direct the biopsy needle trajectory to sample the target lesion, while avoiding vasculature or eloquent brain tissue (8).

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#EndOfDiabetes

Researchers at the Icahn School of Medicine at Mount Sinai have discovered a novel combination of two classes of drugs that induces the highest rate of proliferation ever observed in adult human beta cells—the cells in the pancreas that produce insulin. The result is an important step toward a diabetes treatment that restores the body’s ability to produce insulin.

The finding involved one that inhibits the enzyme dual specificity tyrosine-regulated kinase 1A (DYRK1A) and another that inhibits transforming growth factor beta superfamily members (TGFβSF). Together, they caused the cells to proliferate at a rate of 5 to 8 percent per day. The study, titled “Combined Inhibition of DYRK1A, SMAD and Trithorax Pathways Synergizes to Induce Robust Replication in Adult Human Beta Cells,” was published today in Cell Metabolism.

Continue reading “Researchers discover new drug cocktail that increases human beta cell proliferation at rapid rates” | >

Two Nature papers show that it is possible to make T cells that target some of the few neoantigens expressed by glioblastomas and that T- cell responses can be boosted in cancers. This News & Views discusses the findings.

Clinical trials reveal that personalized vaccines can boost immune-cell responses to brain tumours that don’t usually respond to immunotherapy. The findings also point to how to improve such treatments. Personalized vaccines boost immune responses targeting brain tumours.

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In a small and preliminary clinical trial, Johns Hopkins researchers and their collaborators have shown that an experimental gene therapy that uses viruses to introduce a therapeutic gene into the eye is safe and that it may be effective in preserving the vision of people with wet age-related macular degeneration (AMD). AMD is a leading cause of vision loss in the U.S., affecting an estimated 1.6 million Americans. The disease is marked by growth of abnormal blood vessels that leak fluid into the central portion of the retina called the macula, which we use for reading, driving and recognizing faces.

The study published on May 16 in The Lancet, reports an exciting new approach in which a virus, similar to the common cold, but altered in the lab so that it is unable to cause disease, is used as a carrier for a gene and is injected into the eye. The virus penetrates retinal cells and deposits a gene, which turns the cells into factories for productions of a therapeutic protein, called sFLT01.

The abnormal blood vessels that cause wet AMD grow because patients have increased production of vascular endothelial growth factor (VEGF) in their retinas. Current treatments require injections of proteins directly into the eye that bind and inactivate VEGF, reducing fluid in the macula and improving vision. However, the therapeutic proteins exit the eye over the course of a month, so patients with wet AMD usually need to return to the clinic for more injections every six to eight weeks in order to stave off vision loss. Eye specialists say the burden and discomfort of the regimen is responsible for many patients not getting injections as frequently as they need, causing vision loss.

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In the past few years, artificial intelligence has advanced so quickly that it now seems hardly a month goes by without a newsworthy AI breakthrough. In areas as wide-ranging as speech translation, medical diagnosis, and gameplay, we have seen computers outperform humans in startling ways.

This has sparked a discussion about how AI will impact employment. Some fear that as AI improves, it will supplant workers, creating an ever-growing pool of unemployable humans who cannot compete economically with machines.

This concern, while understandable, is unfounded. In fact, AI will be the greatest job engine the world has ever seen.

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Here, we demonstrated that intradermal administration of clinically relevant vaccines efficiently induces Trm cells specific for tumor-specific and self-antigens that accumulate in vaccinated and non-vaccinated skin. Interestingly, vaccination-induced Trm cells strongly suppress the growth of melanoma, independently of circulating CD8 T cells, and were able to infiltrate melanoma tumors. Therefore, our work highlights the therapeutic potential of vaccination-induced Trm cells to achieve potent protection against skin malignancies.

Memory CD8+ T cell responses have the potential to mediate long-lasting protection against cancers. Resident memory CD8+ T (Trm) cells stably reside in non-lymphoid tissues and mediate superior innate and adaptive immunity against pathogens. Emerging evidence indicates that Trm cells develop in human solid cancers and play a key role in controlling tumor growth. However, the specific contribution of Trm cells to anti-tumor immunity is incompletely understood. Moreover, clinically applicable vaccination strategies that efficiently establish Trm cell responses remain largely unexplored and are expected to strongly protect against tumors. Here we demonstrated that a single intradermal administration of gene- or protein-based vaccines efficiently induces specific Trm cell responses against models of tumor-specific and self-antigens, which accumulated in vaccinated and distant non-vaccinated skin. Vaccination-induced Trm cells were largely resistant to in vivo intravascular staining and antibody-dependent depletion. Intradermal, but not intraperitoneal vaccination, generated memory precursors expressing skin-homing molecules in circulation and Trm cells in skin. Interestingly, vaccination-induced Trm cell responses strongly suppressed the growth of B16F10 melanoma, independently of circulating memory CD8+ T cells, and were able to infiltrate tumors. This work highlights the therapeutic potential of vaccination-induced Trm cell responses to achieve potent protection against skin malignancies.

KEYWORDS: Cancer vaccines, DNA vaccines, intradermal vaccination, melanoma, models of anticancer vaccination, protein vaccines, tissue resident memory CD8+ T cells.

Immunotherapy is emerging as a new form to treat cancer by harnessing the activity of cytotoxic CD8+ T lymphocytes (CTLs) that specifically recognize tumor-associated antigens. Transfusion of autologous tumor-specific CTLs1–4 and blockade of T cell inhibitory receptors5–7 have demonstrated to elicit durable clinical benefit in a significant proportion of patients with melanoma, leukemia, lymphoma and other cancers, who failed to respond to conventional treatments. Vaccination strategies eliciting CTL responses specific for tumor-specific and self-antigens have shown promising results in recent clinical trials.8–10 Long-lasting protective immunity relies on the efficient establishment of long-lived memory CD8+ T cells, which have the potential to eradicate primary and disseminated tumors.11 They have been typically classified in two subsets: effector-memory (Tem) and central-memory (Tcm) CD8+ T cells.

Continue reading “Vaccination-induced skin-resident memory CD8+ T cells mediate strong protection against cutaneous melanoma” | >

In a new #Stanford study explaining the cellular mechanisms behind cognitive impairment from chemotherapy, scientists have demonstrated that a widely used chemotherapy drug, #methotrexate, causes a complex set of problems in three major cell types within the brain’s white matter. The study also identifies a potential remedy.

In a new study explaining the cellular mechanisms behind cognitive impairment from chemotherapy, scientists have demonstrated that a widely used chemotherapy drug, methotrexate, causes a complex set of problems in three major cell types within the brain’s white matter. The study also identifies a potential remedy.

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Scientists in India have hit out at speakers at a major conference for making irrational claims, including that ancient Hindus invented stem cell research.

Some academics at the annual Indian Science Congress dismissed the findings of Isaac Newton and Albert Einstein.

Hindu mythology and religion-based theories have increasingly become part of the Indian Science Congress agenda.

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The results from a human pilot study that focused on treating idiopathic pulmonary fibrosis with senescent cell-clearing drugs has been published. The drugs target aged and damaged cells, which are thought to be a reason we age and get sick, and remove them from the body.

Senescent cells and aging

As we age, increasing numbers of our cells become dysfunctional, entering into a state known as senescence. Senescent cells no longer divide or support the tissues and organs of which they are part; instead, they secrete a range of harmful inflammatory chemical signals, which are collectively known as the senescence-associated secretory phenotype (SASP).

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