Personalized Medicine

Oncotarget

Oncotarget published this research paper on August 30, 2023 in Volume 14, entitled, “Analytic validation of NeXT Dx™, a comprehensive genomic profiling assay" by researchers from Personalis, Inc., Fremont, CA.

DOI - https://doi.org/10.18632/oncotarget.28490

Correspondence to - Richard Chen - richard.chen@Personalis.com

Abstract

We describe the analytic validation of NeXT Dx, a comprehensive genomic profiling assay to aid therapy and clinical trial selection for patients diagnosed with solid tumor cancers. Proprietary methods were utilized to perform whole exome and whole transcriptome sequencing for detection of single nucleotide variants (SNVs), insertions/deletions (indels), copy number alterations (CNAs), and gene fusions, and determination of tumor mutation burden and microsatellite instability. Variant calling is enhanced by sequencing a patient-specific normal sample from, for example, a blood specimen. This provides highly accurate somatic variant calls as well as the incidental reporting of pathogenic and likely pathogenic germline alterations. Fusion detection via RNA sequencing provides more extensive and accurate fusion calling compared to DNA-based tests. NeXT Dx features the proprietary Accuracy and Content Enhanced technology, developed to optimize sequencing and provide more uniform coverage across the exome. The exome was validated at a median sequencing depth of >500x. While variants from 401 cancer-associated genes are currently reported from the assay, the exome/transcriptome assay is broadly validated to enable reporting of additional variants as they become clinically relevant. NeXT Dx demonstrated analytic sensitivities as follows: SNVs (99.4%), indels (98.2%), CNAs (98.0%), and fusions (95.8%). The overall analytic specificity was >99.0%.

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Keywords - cancer, comprehensive genomic profiling, whole exome sequencing, whole transcriptome sequencing, tumor-normal, precision medicine

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Analytic Validation of NeXT Dx™, a Comprehensive Genomic Profiling Assay | Oncotarget

Aging (Aging-US)

Aging-US published this research perspective on July 20, 2023 in Volume 15, Issue 14, entitled, “Towards disease-oriented dosing of rapamycin for longevity: does aging exist or only age-related diseases?" by Dr. Mikhail V. Blagosklonny from Roswell Park Comprehensive Cancer Center, Buffalo, NY.

DOI - https://doi.org/10.18632/aging.204920

Corresponding author - Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com

Abstract

Both individuals taking rapamycin, an anti-aging drug, and those not taking it will ultimately succumb to age-related diseases. However, the former, if administered disease-oriented dosages for a long time, may experience a delayed onset of such diseases and live longer. The goal is to delay a particular disease that is expected to be life-limiting in a particular person. Age-related diseases, quasi-programmed during development, progress at varying rates in different individuals. Rapamycin is a prophylactic anti-aging drug that decelerates early development of age-related diseases. I further discuss hyperfunction theory of quasi-programmed diseases, which challenges the need for the traditional concept of aging itself.

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Keywords - aging, mTOR, hyperfunction, lifespan, health span, cancer, Alzheimer’s disease

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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Does Aging Exist or Only Age-Related Diseases?: Dosing of Rapamycin for Longevity | Aging-US

Oncotarget published this trending research paper on May 26, 2023 in Volume 14, entitled, “Value of chemotherapy post immunotherapy in stage IV non-small cell lung cancer (NSCLC)" by researchers from the Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon; Department of Internal Medicine, Division of Hematology and Oncology, Hotel Dieu de France University Hospital, Beirut, Lebanon.

DOI - https://doi.org/10.18632/oncotarget.28444

Correspondence to - Fadi El Karak - Felkarak@yahoo.com

Abstract

Background: Lung cancer is the number one cause of mortality among all types of cancer worldwide. Its treatment landscape has shifted from the classic chemotherapy alone to newer regimens based on the discovery of new immunotherapy and targeted therapy drugs. However, chemotherapy is still an option for treatment of advanced non-small cell lung cancer (NSCLC) after progression on immunotherapy alone or in combination with first-line chemotherapy.

Methods: This is a retrospective study based on chart review of patients diagnosed with advanced NSCLC cases who received Docetaxel as second or third line after being treated by immunotherapy and/or chemotherapy in previous lines. The data was collected from the medical records of physicians’ clinics in three different hospital centers in Lebanon over the period of 5 years from July 2015 until December 2020. February 2021 was data analysis cut off time. The main aim was to assess the role of Docetaxel post-chemoimmunotherapy for patients with diagnosed NSCLC.

Results: A total of 21 patients were included in this study. The majority of our patients were males (81%). As for histologic type, most patients had non-squamous lung cancer (67%) as compared to 33% who had squamous lung cancer. Overall, our study reported a 24% response rate to Docetaxel including stable disease and partial response and a median progression free survival (PFS) of 3 months. The mean time interval elapsed from diagnosis to the initiation of Docetaxel was 11.5 months.

Conclusion: New therapeutic options should be validated for the treatment of NSCLC in the second and subsequent lines of therapy considering the poor prognosis of this disease. The chemotherapy in second and third line may keep an important role in the treatment after progression on newer agents, but it needs more evidence in prospective studies including a larger number of patients.

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Keywords - chemotherapy, immunotherapy, non-small cell lung cancer

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Value of Chemotherapy Post Immunotherapy in Stage IV Non-Small Cell Lung Cancer (NSCLC)

Aging-US published this editorial on March 1, 2023 in Volume 15, Issue 5, entitled, "Parsing chronological and biological age effects on vaccine responses" by Chris P. Verschoor and George A. Kuchel from Health Sciences North Research Institute, Sudbury, Ontario, Canada.

DOI - https://doi.org/10.18632/aging.204572 (PDF Download)

Corresponding author - Chris P. Verschoor: cverschoor@hsnri.ca

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Keywords - aging, biological age, frailty, vaccination, influenza

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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Parsing Chronological and Biological Age Effects on Vaccine Responses

Aging-US published this research paper as the cover for Volume 15, Issue 3, entitled, "Immune-mediated platelet depletion augments Alzheimer’s disease neuropathological hallmarks in APP-PS1 mice" by researchers from Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria, Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Austria, Department of Transfusion Medicine, University Clinic, Paracelsus Medical University, Salzburg, Austria, Austrian Cluster for Tissue Regeneration, Vienna, Austria.

DOI - https://doi.org/10.18632/aging.204502

Corresponding author - Kathrin Maria Kniewallner - kathrin.drerup@pmu.ac.at 

Abstract

In Alzheimer’s disease (AD), platelets become dysfunctional and might contribute to amyloid beta deposition. Here, we depleted platelets in one-year-old APP Swedish PS1 dE9 (APP-PS1) transgenic mice for five days, using intraperitoneal injections of an anti-CD42b antibody, and assessed changes in cerebral amyloidosis, plaque-associated neuritic dystrophy and gliosis. In APP-PS1 female mice, platelet depletion shifted amyloid plaque size distribution towards bigger plaques and increased neuritic dystrophy in the hippocampus. In platelet-depleted females, plaque-associated Iba1+ microglia had lower amounts of fibrillar amyloid beta cargo and GFAP+ astrocytic processes showed a higher overlap with thioflavin S+ amyloid plaques. In contrast to the popular hypothesis that platelets foster plaque pathology, our data suggest that platelets might limit plaque growth and attenuate plaque-related neuritic dystrophy at advanced stages of amyloid plaque pathology in APP-PS1 female mice. Whether the changes in amyloid plaque pathology are due to a direct effect on amyloid beta deposition or are a consequence of altered glial function needs to be further elucidated.

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Keywords - Alzheimer’s disease, platelets, amyloid-beta, microglia, astrocytes

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

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Platelet Depletion Augments Alzheimer’s Disease Neuropathological Hallmarks

Teach Me in 10

Oligonucleotide therapeutics have attracted much attention recently. They represent an up-and-coming class of therapeutic options that can lead to major advances in the treatment or cure of diseases, holding great potential for further development in human medicine. 

In this Teach me in 10 we are joined by Chris Rosenau, product manager of nucleic acid therapeutics at Thermo Fisher Scientific. He covers the basics of oligonucleotide therapeutics, their trends and challenges, considerations for phosphoramdites in oligonucleotide synthesis, and resources from Thermo Fisher Scientific that are available to you in oligonucleotide therapeutic development.

What Are Oligonucleotide Therapeutics?

Analytical Cannabis 

Speaking at the Analytical Cannabis Expo Europe Online 2022, Oliver Zugel delivered his talk on the cannabis industry in Germany.

Will Germany Be the Turning Point for a Troubled Cannabis Industry?

Speaking at the Analytical Cannabis Expo Europe Online 2022, Alex Fray discussed the regulatory roadmap for medicinal cannabis in Europe.

Medicinal Cannabis in Europe – A Regulatory Roadmap

Speaking at the Analytical Cannabis Expo Europe Online 2022, Russ Hudson delivered his talk on the state of the cannabis market in Spain.

Personalized Medicine

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