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Category: genetics

Hmmm; I do know for many there is a set of genetic mutations that seem to sit dormat and eventually triggered by environment conditions.

(Reuters Health) — The risk of some childhood cancers might vary depending on where a child’s mother was born, a new study suggests.

For example, some brain and kidney cancers occurred less often in children whose Hispanic mothers were born outside the U.S. than in youngsters whose Hispanic or white mothers were born in the U.S., researchers found.

However, the Hispanic children had a higher risk of certain blood cancers regardless of where their mothers were born.

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Very promising.

The explosion of sequencing technologies such as next generation sequencing (NGS) means it is now possible to tailor individual cancer therapies based on patients’ genetic make-up and tumour molecular profiling. The challenge lies in determining which genetic alterations are important in driving disease, so called ‘actionable mutations’.

Sequencing the entire genome or even a limited region reveals large numbers of alterations. Most are harmless, normal changes that do not promote the transformation of a normal cell to a cancer cell. Being able to sort out which changes are drivers in a cancer is a significant, but critical challenge in being able to guide therapy in clinical trials.

Our scientists at AstraZeneca are taking a leading position, defining a genetic classification strategy for how patients can be characterised at the molecular level, integrating knowledge from the drug’s mechanism of action combined with disease biology to help guide cancer therapy in early stage exploratory clinical trials. The article published in the May 2016 issue of Nature Reviews Cancer describes approaches taken by external groups alongside our own efforts to tackle this problem.

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In a new study, researchers detail the culturing and transfecting of cells with genetic material on an array of carbon nanotubes, which appears to overcome the limitations of other gene editing technologies.

Gene editing techniques hold great promise. They allow targeted and specific edits of genes, and have nearly limitless possibilities in the field of medicine.

Which is not to say that they are perfect. These techniques still have a range of limitations, from precision to toxicity. But a new study shows that can be changed.

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Sharing for fellow researchers and others who have interest in GBM news.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal brain. However, the diffuse and infiltrative nature of these tumors in the brain parenchyma may pose an exceptional hurdle to successful immunotherapy in patients. Areas of invasive tumor are thought to reside behind an intact blood brain barrier, isolating them from effective immunosurveillance and thereby predisposing the development of “immunologically silent” tumor peninsulas. Therefore, it remains unclear if adoptively transferred T cells can migrate to and mediate regression in areas of invasive GBM. One barrier has been the lack of a preclinical mouse model that accurately recapitulates the growth patterns of human GBM in vivo. Here, we demonstrate that D-270 MG xenografts exhibit the classical features of GBM and produce the diffuse and invasive tumors seen in patients. Using this model, we designed experiments to assess whether T cells expressing third-generation chimeric antigen receptors (CARs) targeting the tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, would localize to and treat invasive intracerebral GBM. EGFRvIII-targeted CAR (EGFRvIII+ CAR) T cells demonstrated in vitro EGFRvIII antigen-specific recognition and reactivity to the D-270 MG cell line, which naturally expresses EGFRvIII. Moreover, when administered systemically, EGFRvIII+ CAR T cells localized to areas of invasive tumor, suppressed tumor growth, and enhanced survival of mice with established intracranial D-270 MG tumors. Together, these data demonstrate that systemically administered T cells are capable of migrating to the invasive edges of GBM to mediate antitumor efficacy and tumor regression.

Glioblastoma (GBM) is the most common form of primary malignant brain tumor in adults and remains one of the most deadly neoplasms. Despite multimodal therapy including maximal surgical resection, radiation, and temozolomide (TMZ), the median overall survival is less than 15 months [1]. Moreover, these therapies are non-specific and are ultimately limited by toxicity to normal tissues [2]. In contrast, immunotherapy promises an exquisitely precise approach, and substantial evidence suggests that T cells can eradicate large, well-established tumors in mice and humans [3] –[7].

Chimeric antigen receptors (CARs) represent an emerging technology that combines the variable region of an antibody with T-cell signaling moieties, and can be genetically expressed in T cells to mediate potent, antigen-specific activation. CAR T cells carry the potential to eradicate neoplasms by recognizing tumor cells regardless of major histocompatibility complex (MHC) presentation of target antigen or MHC downregulation in tumors, factors which allow tumor-escape from treatment with ex vivo expanded tumor-infiltrating lymphocytes (TILs) [8] and T-cell receptor (TCR) gene therapy [9], [10].

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A simple blood test can rapidly and accurately detect mutations in two key genes in non-small cell lung tumors, researchers at Dana-Farber Cancer Institute and other institutions report in a new study – demonstrating the test’s potential as a clinical tool for identifying patients who can benefit from drugs targeting those mutations.

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Bringing awareness on a syndrome that makes it hard for families and patients trying to have genetic testing on cancers in their families. I first came across this syndrome with a researcher at Swedish Medical Center’s Cancer Research Group. Some families can have so many various cancers that genetic testing is extremely costly to patients and may not be able to pinpoint the mutation due to this syndrome.

Yet misdiagnosis remains an ongoing challenge, and a recent international study involving more than 100 countries and nearly 2000 patients revealed the average case takes between 5 and 9 years to properly diagnose after the first symptoms appear, and the average patient may see five or six doctors, noted Richard R.P. Warner, MD, in an interview with Oncology Nursing News.

“You can’t detect it, if you don’t suspect it,” said Warner, who directs the Center for Carcinoid and Neuroendocrine Tumors at Mount Sinai Hospital. Most doctors will only see one or two cases in their lifetime, and symptoms of NETs, like diarrhea and recurrent episodes of flushing, are associated with other, more commonly seen conditions.

He added that to complicate matters even further, “no two samples of tumors are exactly identical.” The treatment has to be customized for each case and depends on where the tumor is located and how much it has spread.

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DARPA taking on the designer viruses and resistant fighting viruses that we hate. Who knows; they may finally find the fountain of youth in the process.

Vaccines are great, but they’re no match for most viruses in play at any given time. This is due largely in part to the ever-changing nature of viruses and the expense and difficulty in developing new vaccines to target them. DARPA wants that reality to change, citing the numerous concerning viruses, past and present, that affect humanity. Under the “INTERCEPT” program, DARPA seeks “shape-shifting” vaccines that adapt to kill off viruses as they evolve.

One of the biggest virus scares at the moment is the zika virus, but ebola was just recently a big issue and other viruses, including influenza and dengue, are a continuous problem. Once someone is infected, the virus is able to “mutate and morph as they reproduce inside their hosts,” says DARPA, making any vaccines quickly obsolete. If the agency’s new INTERfering and Co-Evolving Prevention and Therapy (INTERCEPT) program proves successful, though, things will change in a big way.

Under the program, DARPA seeks a solution that uses something called TIPs — Therapeutic Interfering Particles — which are described as small entities similar to viruses that are made in labs. TIPs are essentially genetic material packed within a protein shell, something that mimic the way a virus is structured. Because of their similarities, TIPs can enter cells like viruses but don’t proceeded to hijack that cell as viruses do.

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