#Alternating antibiotics could make resistant bacteria beatable Researchers from the University of Exeter has shown that the use of'sequential treatments'--using alternating doses of antibiotics--might offer effective treatment against bacterial infection.
The researchers used a test-tube model of a bacterial infection to show that, even in bacteria that already harbour drug resistance genes,
although extensive further work is needed now to will be needed before sequential treatments make it in to the clinic,
#Biologists identify brain tumor weakness The study, led by researchers from the Whitehead Institute and MIT's Koch Institute for Integrative Cancer Research, found that a subset of glioblastoma tumor cells is dependent on a particular enzyme that breaks down the amino acid glycine.
Without this enzyme, toxic metabolic byproducts build up inside the tumor cells, and they die. Blocking this enzyme in glioblastoma cells could offer a new way to combat such tumors,
says Dohoon Kim, a postdoc at the Whitehead Institute and lead author of the study,
which appears in the April 8 online edition of Nature. David Sabatini a professor of biology at MIT and member of the Whitehead Institute, is the paper's senior author.
along with members of his lab. GLDC caught the researchers'attention as they investigated diseases known as"inborn errors of metabolism,
Such patients must avoid eating phenylalanine to prevent problems such as intellectual disability and seizures. Loss of GLDC produces a disorder called nonketotic hyperglycinemia,
which causes glycine to build up in the brain and can lead to severe mental retardation. GLDC is also often overactive in certain cells of glioblastoma,
the most common and most aggressive type of brain tumor found in humans. The researchers found that GLDC,
These regions are often found at the center of tumors, which are inaccessible to blood vessels.
which makes them better suited to survive in the ischemic tumor microenvironment, "Kim says. However, this highly active SHMT2 also produces a glut of glycine,
#Study on new treatment for prostate cancer Published in The british Journal of Cancer (BJC), the study is the first time low temperature plasmas (LTPS) have been applied on cells grown directly from patient tissue samples.
It is the result of a unique collaboration between the York Plasma Institute in the Department of physics and the Cancer Research Unit (CRU) in York Department of biology.
and prostate cancer tissue cells from a single patient, the study allowed for direct comparison of the effectiveness of the treatment.
Scientists discovered that LTPS may be a potential option for treatment of patients with organ confined prostate cancer
and a viable, more cost-effective alternative to current radiotherapy and photodynamic therapy (PDT) treatments.
when using LTP treatment is different from other therapies. The active agents in the LTP break up DNA
This is different to some current therapies which cause apoptosis, where cells are prompted to die through natural mechanisms that can result in treatment resistance.
espite continual improvement and refinement, long term treatment for prostate cancer is recognised still as inadequate. In the case of early stage organ confined tumours, patients may be treated with a focal therapy, for example cryotherapy, photodynamic therapy,
or radiotherapy. owever, around a third of patients will experience recurrence of their disease following radiotherapy.
This may be due to the inherent radio-resistance of a small fraction of the tumour the cancer stem-like cells.
Furthermore, numerous side effects are experienced often following treatment. hrough this research we have found that LTPS induce high levels of DNA damage
we have presented the first experimental evidence promoting the potential of LTP as a future focal cancer therapy treatment for patients with early stage prostate cancer.
LTP could be used to treat cancer patients within 10-15 years 1
#Researchers deliver large particles into cells at high speed The researchers created a highly efficient automated tool that delivers nanoparticles, enzymes, antibodies, bacteria and other"large-sized"cargo into mammalian cells at the rate
The new device, called a biophotonic laser-assisted surgery tool, or BLAST, is a silicon chip with an array of micrometer-wide holes,
and help researchers study diseases caused by mutant MITOCHONDRIAL DNA. It also could help scientists dissect the function of genes involved in the lifecycle of pathogens that invade the cell
and understand the cell's defense mechanisms against them.""Now it doesn't matter the size
"The new information learned from these types of studies could assist in identifying pathogen targets for drug development,
or provide fundamental insight on how the pathogen-host interaction enables a productive infection or effective cellular response to occur,
"said Dr. Michael Teitell, chief of the division of pediatric and developmental pathology, and a co-author of the paper.
Dr. Daniel Clemens, adjunct professor of medicine; Bai-Yu Lee, an assistant researcher; Ximiao Wen, a graduate student in mechanical engineering;
and Dr. Marcus Horwitz, professor of medicine and of microbiology, immunology and molecular genetics. The research was supported by a University of California Discovery Biotechnology Award, the National institutes of health, Nanocav and the National Science Foundation n
#Breakthrough finds molecules that block previously'undruggable'protein tied to cancer The findings, which could lead to a new class of cancer drugs,
thus blocking Hur function as a tumor-promoting protein, "said Liang Xu, associate professor of molecular biosciences and corresponding author of the paper.
The results hold promise for treating a broad array of cancers in people. The researcher said Hur has been detected at high levels in almost every type of cancer tested,
including cancers of the colon, prostate, breast, brain, ovaries, pancreas and lung.""Hur inhibitors may be useful for many types of cancer,
"Xu said.""Since Hur is involved in many stem cell pathways, we expect Hur inhibitors will be active in inhibiting'cancer stem cells,
'or the seeds of cancer, which have been a current focus in the cancer drug discovery field."
"Hur has been studied for many years, but until now no direct Hur inhibitors have been discovered, according to Xu.""The initial compounds reported in this paper can be optimized further
and developed as a whole new class of cancer therapy, especially for cancer stem cells, "he said."
"The success of our study provides a first proof-of-principle that Hur is druggable,
"A cancer-causing gene, or oncogene, makes RNA, which then makes an oncoprotein that causes cancer
or makes cancer cells hard to kill, or both,"Xu said.""This is the problem we're trying to overcome with precision medicine."
"The scientist said the Hur-RNA binding site is like a long, narrow groove, not a well-defined pocket seen in other druggable proteins targeted by many current cancer therapies."
"Hur tightly binds to RNA like a hand, "Xu said.""The Hur protein grabs the'rope
and involved the collaboration of chemists, cancer biologists, computer modeling experts, biochemists and biophysicists at KU--notably the labs of Xu, Jeffrey Aub in the Department of Medicinal Chemistry and Jon Tunge in the Department of chemistry.
For Xu, the findings are reflective of a personal commitment to improving odds for people diagnosed with cancer
the second-largest killer in the U s. after heart disease.""Trained as medical doctor and Ph d.,with both a grandfather and an uncle who died of cancer,
I devoted my career to cancer research and drug discovery--aiming to translate discovery in the lab into clinical therapy,
to help cancer patients and their families, "he said.""We hope to find a better therapy--and eventually a cure--for cancer
#Study revises theory of how PTEN, a critical tumor suppressor, shuts off growth signals Today,
scientists at Cold Spring Harbor Laboratory (CSHL) publish new evidence explaining precisely how the protein encoded by PTEN (called PTEN) works--specifically,
how it is recruited to particular locations in our cells where pro-growth signals need to be shut off.
The new evidence, assembled by a team led by CSHL Associate professor Lloyd Trotman, contradicts a long-held assumption about PTEN function,
and could help scientists design more effective drugs to counteract cancer's hallmark trait, uncontrolled cellular growth."
"A whole generation of cancer investigators, including me, has been taught that PTEN performs its crucial role at the plasma membrane,
And in view of PTEN's critical role as a tumor suppressor, it's also important that the process we uncovered is controlled a one,
--or decoded--the genes of patients with Neuromuscular Disease (NMD) and was then able to identify the genetic source,
"In all six cases of myopathy, or muscle weakness, these children had undergone extensive, expensive and invasive testing--often over many years--without a successful diagnosis,
until they enrolled in our study, "said Dr. Lisa Baumbach-Reardon, an Associate professor of TGEN's Integrated Cancer Genomics Division and the study's senior author.
This is a prime example of the type of"personalized medicine"TGEN uses to zero in on diagnoses for patients,
and to help their physicians find the best possible treatments.""Our results demonstrate the diagnostic value of a comprehensive approach to genetic sequencing,
or disease-causing, genetic variants with a single, timely, affordable test.""In one of the six cases, TGEN researchers found a unique disease-causing variant,
or mutation, in the CACNA1S gene for a child with severe muscle weakness in addition to ophthalmoplegia,
"To our knowledge, this is the first reported case of severe congenital myopathy with ophthalmoplegia resulting from pathogenic variants in CACNA1S,
Learning the specific genetic cause of symptoms is a key step in finding new therapeutic drugs that could treat the patient's disease.
In another closely related case, TGEN's genetic testing found a pathogenic variant in the RYR1 gene in a case of calcium channel myopathy.
Five of the six cases involved patients under the care of Dr. Saunder Bernes, a neurologist at Barrow neurological institute at Phoenix Children's Hospital.
"Without this type of deep genetic analysis, we might never have discovered the source of each of these children's disease,
"said Dr. Bernes, whose young patients'previous tests included muscle biopsies, EMG, MRI, EKG and limited gene sequencing."
"In three of the six cases, the children had Collagen 6 myopathies, or weaknesses. Collagen is essential to holding together muscles, tendons, skin, cartilage and the disks between vertebras.
or disease-causing mutation, in the COL6A3 gene, or likely pathogenic variants in the COL6A6 gene.
In still another case, TGEN testing identified the genetic culprit of the child's muscle weakness as a pathogenic EMD variant associated with Emery-Dreifuss muscular dystrophy.
"Reporting these cases raises awareness about how often each child with muscle disease is unique,
requiring personalized medical treatment beginning with genetic diagnosis through sequencing like we perform at TGEN.""Dr. Hunter said."
It also reveals clues for enriching desirable bacteria in populations at risk of intestinal diseases--such as preemies.
The research may have applications in a clinical setting for protecting premature infants from a range of intestinal diseases including necrotizing enterocolitis (NEC),
It also reveals clues for enriching desirable bacteria in populations at risk of intestinal diseases--such as preemies."
The early establishment of bifidobacteria has been shown to be associated with improved immune response to vaccines, development of the infants'immature immune system,
and protection against pathogens. Bifidobacterium are known to consume the 2'-fucosylated glycans (sugars) found in the breast milk of women with the fucosyltransferase 2 mammary gene.
She recently received a grant from the Pediatric Medical device Consortium at the Children's Hospital of Philadelphia to research this possibility i
what type of influenza it is, and it can differentiate between a human strain and a bird strain,"said Neethirajan."
#Breakthrough in cancer research: Cancer-suppressing proteins The research was conducted in the laboratory of Distinguished Professor Aaron Ciechanover, of the Technion Rappaport Faculty of medicine.
The team was led by research associate Dr. Yelena Kravtsova-Ivantsiv and included additional research students and colleagues,
as well as physicians from the Rambam, Carmel and Hadassah Medical centers, who are studying tumors and their treatment. kpc1 an important and vital pathway in the life of the cell,
-B has been identified as a link between inflammation and cancer. The hypothesis of the connection between inflammatory processes and cancer was suggested first in 1863 by German pathologist Rudolph Virchow,
and has been confirmed over the years in a long series of studies. Ever since the discovery (nearly 30 years ago) of NF?
It is involved in tumors of various organs (prostate, breast, lung, head and neck, large intestine, brain, etc.
which are vital to tumor growth; and increased resistance of cancerous cells to irradiation and chemotherapy.
The current research was conducted on models of human tumors grown in mice as well as on samples of human tumors,
and a strong connection was discovered between the suppression of malignancy and the level of the two proteins,
clearly indicating that the increased presence of KPC1 and/or p50 in the tissue can protect it from cancerous tumors.
Professor Ciechanover, who is also the president of the Israel Cancer Society, notes that many more years are required"to establish the research
and gain a solid understanding of the mechanisms behind the suppression of the tumors. The development of a drug based on this discovery is a possibility,
although not a certainty, and the road to such a drug is long and far from simple
#Researchers find protein that may signal more aggressive prostate cancers Biomarkers in the body are analogous to the warning lights in cars that signal something might need repairing.
"In the context of prostate cancer) there's a big interest in trying to find biomarkers to discriminate between aggressive and nonaggressive disease,
Prostate cancer can grow so slowly the carrier dies of natural causes before the cancer spreads,
and could provide a potential new drug target for prostate cancer, "Franceschi said.""It could also be a potential biomarker to discriminate between fast and slow growing tumors."
"The U-M researchers made the discovery in a roundabout way, said Franceschi, whose research lab mainly studies bone formation, not cancer."
"We discovered this regulatory mechanism in bone cells, but subsequently found it was also operative in prostate cancer cells,
"This is the first paper the lab has published on cancer.""The idea is that adding a phosphate group, a process called phosphorylation, to the protein Runx2,
However, in prostate cancer cells, Runx2 triggered genes that fuel tumor growth and metastasis."It's unusual that a protein
whose function is to produce bone has this unusual function in prostate cancer, "Franceschi said.
and found that tumor growth was reduced. Franceschi's lab also collaborated with researchers in Italy to analyze tissue samples from 129 patients with prostate cancer.
They found little or no Runx2 phosphorylation in normal prostate, benign prostate or prostatitis, which suggests that Runx2 phosphorylation is associated closely with the more aggressive forms of prostate cancer.
The next step is to establish an actual cause-effect relationship between Runx2 phosphorylation and prostate cancer.
To do this they will compare prostate cancer formation in normal mice and mice lacking Runx2 in their prostates.
Worldwide, prostate cancer is the second-most common cancer in men, according to the World Cancer Research Fund International.
In the U s.,about 221,000 new cases of prostate cancer will be diagnosed in 2015 resulting in roughly 27,500 deaths s
#Hyper-stretchable elastic-composite energy harvester Scientists have developed a hyper-stretchable elastic-composite energy harvesting device called a nanogenerator.
A research team led by Professor Keon Jae Lee of the Department of Materials science and engineering at the Korea Advanced Institute of Science
For example, wearable/biomedical devices and electronic skins (e skins) should stretch to conform to arbitrarily curved surfaces and moving body parts such as joints, diaphragms, and tendons.
These noteworthy results were achieved by the non-destructive stress-relaxation ability of the unique electrodes as well as the good piezoelectricity of the device components.
It can open avenues for power supplies in universal wearable and biomedical applications as well as self-powered ultra-stretchable electronics
low-cost molecular tumor diagnosis A device developed by Massachusetts General Hospital investigators may bring rapid,
accurate molecular diagnosis of tumors and other diseases to locations lacking the latest medical technology.
"The global burden of cancer, limited access to prompt pathology services in many regions and emerging cell profiling technologies increase the need for low-cost,
"says Cesar Castro, MD, of the MGH Cancer Center and Center for Systems Biology, co-lead author of the report."
"The emerging genomic and biological data for various cancers, which can be essential to choosing the most appropriate therapy,
supports the need for molecular profiling strategies that are more accessible to providers, clinical investigators and patients;
"The device the team has developed--called the D3 (digital diffraction diagnosis) system--features an imaging module with a battery-powered LED light clipped onto a standard smartphone that records high-resolution imaging data with its camera.
and the results rapidly returned to the point of Care for molecular analysis of tumors, a sample of blood or tissue is labeled with microbeads that bind to known cancer-related molecules
and are loaded into the D3 imaging module. After the image is recorded and data transmitted to the server,
A pilot test of the system with cancer cell lines detected the presence of tumor proteins with an accuracy matching that of the current gold standard for molecular profiling,
The investigators then conducted analysis of cervical biopsy samples from 25 women with abnormal PAP SMEARS--samples collected
along with those used for clinical diagnosis--using microbeads tagged with antibodies against three published markers of cervical cancer.
Based on the number of antibody-tagged microbeads binding to cells, D3 analysis promptly and reliably categorized biopsy samples as high-risk, low-risk or benign, with results matching those of conventional pathologic analysis
. D3 analysis of fine-needle lymph node biopsy samples was accurately able to differentiate four patients
whose lymphoma diagnosis was confirmed by conventional pathology from another four with benign lymph node enlargement. Along with protein analyses, the system was enhanced to successfully detect DNA--in this instance from human papilloma virus--with great sensitivity.
and depth of cancer screening in a way that is feasible and sustainable for resource limited-settings, "says Ralph Weissleder, MD, Phd, director of the MGH Center for Systems Biology (CSB) and co-senior author of the paper."
or high-risk cases that could help to offset delays caused by limited pathology services in those regions
and DNA markers of other disease catalysts, including infectious agents and allergens; 2) integrate the software with larger databases;
both in normal conditions and in situations of stress--like the body experiences following a bone marrow transplant.
the discovery opens new lines of inquiry about the Ash1l gene's potential role in cancers known to involve other members of the same gene family,
like leukemia, or those where Ash1l might be expressed highly or mutated.""It's vital to understand how the basic,
and an associate professor in the Division of Hematology-Oncology at the U-M Medical school.""Leukemia is a cancer of the body's blood-forming tissues,
so it's an obvious place that we plan to look at next. If we find that Ash1l plays a role,
Dysfunction of blood-forming stem cells is well known in illnesses like leukemia and bone marrow failure disorders.
and radiation used to treat cancer. The replacement of these cells through bone marrow transplantation is the only widely established therapy involving stem cells in human patients.
But even in the absence of disease, blood cells require constant replacement--most blood cells last anywhere from a few days to a few months,
depending on their type. Over more than five years, Maillard and his collaborators identified a previously unknown
The Ash1l (Absent, small or homeotic 1-like) gene is part of a family of genes that includes MLL1 (Mixed Lineage Leukemia 1),
a gene that is frequently mutated in patients who develop leukemia. The research found that both genes contribute to blood renewal;
Ash1l-deficient stem cells were unable to establish normal blood renewal after a bone marrow transplant.
After the U s. dropped atomic bombs on Hiroshima and Nagasaki, doctors noticed that radiation patients weren't able to generate new white blood cells to fend off infections.
Subsequent experiments on mice showed that bone marrow transplants from healthy animals into irradiated ones could renew their ability to make new blood cells.
including those whose blood stem cells are killed off by cancer treatments. But work continues in the laboratory setting."
#New biomarker for uterine cancer discovered Researchers at Uppsala University have, together with researchers from Turku and Bergen, discovered a new biomarker
which makes it possible to identify women with uterine cancer who have a high risk of recurrence.
The findings were published recently in the journal Gynecologic Oncology. Endometrial cancer of the uterus is the most common form of gynecologic cancer in Europe and North america.
The treatment primarily consists of removing the uterus and in some cases offering chemotherapy if the risk of recurrence is deemed high.
The current study looks at the amount of protein ASRGL1 present in the tumour cells in uterine cancer.
Turku and Bergen and is collected based on samples from 500 women who were diagnosed with uterine cancer between the years 1981 and 2007.
or partially lost ASRGL1 in the tumour cells had a much higher risk of the cancer recurring
and dying from the disease, while patients with sustained high levels of ASRGL1 had a much lower risk of recurrence.
'I view the results as a first step towards personal treatment of uterine cancer. Today, 10-15 per cent of the patients suffer recurrences,
and offer them more aggressive treatment after their operation increases',says Per-Henrik Edqvist, researcher at Uppsala University's Department of Immunology, Genetics and Pathology,
whether ASRGL1 also can be used for diagnosing tissue biopsies taken before the operation, to identify patients in need of more extensive surgery.'
'Our results are promising, but more research is needed before ASRGL1 can be accepted as a new diagnostic tool in healthcare.
It was within The Human Protein Atlas project that the expression of the ASRGL1 protein was mapped first in the human body's normal tissues and in different forms of cancer.
The discovery point towards the possibility of identifying aggressive melanomas at an earlier stage than is currently possible,
Pigment Cell & Melanoma Research. May be possible to predict disease progression It is the first time that the protein megalin,
which is known otherwise primarily for its function in the kidneys, has been connected with malignant melanomas. The novel knowledge is the result of longstanding research in the field of cell surface receptor proteins at the Department of Biomedicine at Aarhus University."
"Our studies have shown that the protein megalin is almost always detectable in malignant melanomas, while it is rarely found in the benign counterparts.
"says Associate professor Mette Madsen from the Department of Biomedicine at Aarhus University. With the new knowledge, the hope is that pathologists
and oncologists at an early stage will be able--unlike today--to predict whether a patient should expect spreading
and relapse or not from a malignant melanoma.""It is a new and interesting marker that no one has thought of before.
Even though we currently see considerable progress and success from novel treatment strategies for patients with metastatic melanoma,
it remains a very serious illness when it reaches later stages with spreading. In a best case scenario, this discovery can pinpoint those patients who will experience a relapse,
which patients the most,"says Henrik Schmidt, consultant at the Department of Oncology at Aarhus University Hospital,
either medicine affecting the protein and its function thereby inhibiting the proliferation of the cancer cells and their survival,
and could easily be introduced at the hospitals s
#Shape-shifting molecule tricks viruses into mutating themselves to death A newly developed spectroscopy method is helping to clarify the poorly understood molecular process by
But scientists have developed therapeutic antiviral agents for HIV Hepatitis C, and influenza using a strategy called lethal mutagenesis.
This strategy seeks to extinguish viruses by forcing their already high mutation rates above an intolerable threshold.
If viruses experience too many mutations, they can't properly manage their genetic material.""They can't replicate
Toxicology, and Biological engineering. Essigmann is cofounder of a pharmaceutical company that is developing mutagenic inhibitors of HIV."
"KP1212 is about 20 percent of the way toward being an ideal therapeutic mutagen. The hints given us by the spectroscopy guide us toward even better mutagenic molecules,
But together their research teams were able to fruitfully undertake one of the first 2d infrared spectroscopic studies of the therapeutic mechanism of an antiviral drug."
#Electronic micropump to deliver treatments deep within the brain Drugs constitute the most widely used approach for treating brain disorders.
Epilepsy is a typical example of a condition for which many drugs could not be commercialised because of their harmful effects,
During an epileptic seizure, the nerve cells in a specific area of the brain are activated suddenly in an excessive manner.
have developed a biocompatible micropump that makes it possible to deliver therapeutic substances directly to the relevant areas of the brain.
the researchers reproduced the hyperexcitability of epileptic neurons in mouse brains in vitro. They then injected GABA,
such as those used to treat Parkinson's disease, with this micropump, it may be possible to use this technology to treat patients with epilepsy who are resistant to conventional treatments,
and those for whom the side-effects are too great, "explains Christophe Bernard, Inserm Research director. Based on these initial results, the researchers are now working to move on to an in vivo animal model
In addition to epilepsy, this state-of-the-art technology, combined with existing drugs, offers new opportunities for many brain diseases that remain difficult to treat at this time e
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