Hematol Oncol Clin North Am
December 2024
Circulating tumor DNA (ctDNA) is emerging as a transformative biomarker in the management of non-small cell lung cancer (NSCLC). This review focuses on its role in detecting minimal residual disease (MRD), predicting treatment response, and guiding therapeutic decision-making in radiation oncology and immunotherapy. Key studies demonstrate ctDNA's prognostic value, particularly in identifying relapse risk and refining patient stratification for curative-intent and consolidative treatments.
View Article and Find Full Text PDFMetastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor (AR)-targeted agents is often lethal. Unfortunately, biomarkers for this deadly disease remain under investigation, and underpinning mechanisms are ill-understood. Here, we applied deep sequencing to ∼100 mCRPC patients prior to the initiation of first-line AR-targeted therapy, which detected /enhancer alterations in over a third of patients, which correlated with lethality.
View Article and Find Full Text PDFUp to 430,000 cases of bladder cancer are diagnosed each year worldwide. A proposed method for non-invasive monitoring has been to utilize a "liquid biopsy." Liquid biopsy has been proposed as a non-invasive method of testing biomarkers in bodily fluids in order to detect and survey cancer.
View Article and Find Full Text PDFMotivation: Detection of genomic alterations in circulating tumor DNA (ctDNA) is currently used for active clinical monitoring of cancer progression and treatment response. While methods for analysis of small mutations are more developed, strategies for detecting structural variants (SVs) in ctDNA are limited. Additionally, reproducibly calling small-scale mutations, copy number alterations, and SVs in ctDNA is challenging due to the lack to unified tools for these different classes of variants.
View Article and Find Full Text PDFRetroviruses and their host have coevolved in a delicate balance between viral replication and survival of the infected cell. In this equilibrium, restriction factors expressed by infected cells control different steps of retroviral replication such as entry, uncoating, nuclear import, expression, or budding. Here, we describe a mechanism of restriction against human T cell leukemia virus type 1 (HTLV-1) by the helicase-like transcription factor (HLTF).
View Article and Find Full Text PDFLiquid biopsies using cell-free circulating tumor DNA (ctDNA) are being used frequently in both research and clinical settings. ctDNA can be used to identify actionable mutations to personalize systemic therapy, detect post-treatment minimal residual disease (MRD), and predict responses to immunotherapy. ctDNA can also be isolated from a range of different biofluids, with the possibility of detecting locoregional MRD with increased sensitivity if sampling more proximally than blood plasma.
View Article and Find Full Text PDFRecent breakthroughs in circulating tumor DNA (ctDNA) technologies present a compelling opportunity to combine this emerging liquid biopsy approach with the field of radiogenomics, the study of how tumor genomics correlate with radiotherapy response and radiotoxicity. Canonically, ctDNA levels reflect metastatic tumor burden, although newer ultrasensitive technologies can be used after curative-intent radiotherapy of localized disease to assess ctDNA for minimal residual disease (MRD) detection or for post-treatment surveillance. Furthermore, several studies have demonstrated the potential utility of ctDNA analysis across various cancer types managed with radiotherapy or chemoradiotherapy, including sarcoma and cancers of the head and neck, lung, colon, rectum, bladder, and prostate .
View Article and Find Full Text PDFTraditional cold chain systems of collection, transportation, and storage of biofluid specimens for eventual analysis pose a huge financial and environmental burden. These systems are impractical in pre-hospital and resource-limited settings, where refrigeration and electricity are not reliable or even available. Here, we develop an innovative technology using metal-organic frameworks (MOFs), a novel class of organic-inorganic hybrids with high thermal stability, as encapsulates for preserving the integrity of protein biomarkers in biofluids under ambient or non-refrigerated storage conditions.
View Article and Find Full Text PDFTransient soluble oligomers of amyloid-β (Aβ) are considered among the most toxic species in Alzheimer's disease (AD). Soluble Aβ oligomers accumulate early prior to insoluble plaque formation and cognitive impairment. The cyclic d,l-α-peptide CP-2 () self-assembles into nanotubes and demonstrates promising anti-amyloidogenic activity likely by a mechanism involving engagement of soluble oligomers.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2022
The detection of circulating tumor DNA via liquid biopsy has become an important diagnostic test for patients with cancer. While certain commercial liquid biopsy platforms designed to detect circulating tumor DNA have been approved to guide clinical decisions in advanced solid tumors, the clinical utility of these assays for detecting minimal residual disease after curative-intent treatment of nonmetastatic disease is currently limited. Predicting disease response and relapse has considerable potential for increasing the effective implementation of neoadjuvant and adjuvant therapies.
View Article and Find Full Text PDFBackground: The standard of care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which is typically preceded by neoadjuvant chemotherapy. However, the inability to assess minimal residual disease (MRD) noninvasively limits our ability to offer bladder-sparing treatment. Here, we sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis.
View Article and Find Full Text PDFFifteen -aminoimidazolone (Nai) dipeptides having a variety of 5-position side-chain groups were synthesized by regioselective proline-catalyzed reactions of azopeptide and aldehyde components followed by acid-mediated dehydration of an aza-aspartate semialdehyde intermediate. The introduction of 5-aryl-Nai dipeptides into cluster of differentiation 36 receptor (CD36) peptide ligands has provided insight into the conformation responsible for binding affinity and anti-inflammatory activity.
View Article and Find Full Text PDFPurpose: Cell-free DNA (cfDNA) and circulating tumor cell (CTC) based liquid biopsies have emerged as potential tools to predict responses to androgen receptor (AR)-directed therapy in metastatic prostate cancer. However, due to complex mechanisms and incomplete understanding of genomic events involved in metastatic prostate cancer resistance, current assays (e.g.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2020
Glutamate is the major excitatory neurotransmitter in the brain, and photochemical release of glutamate (or uncaging) is a chemical technique widely used by biologists to interrogate its physiology. A basic prerequisite of these optical probes is bio-inertness before photolysis. However, all caged glutamates are known to have strong antagonism toward receptors of γ-aminobutyric acid, the major inhibitory transmitter.
View Article and Find Full Text PDFIn acute lymphoblastic leukemia (ALL), limited data are available on mTOR gene expression in clinical samples and its role in predicting response to induction chemotherapy. mRNA expression of mTOR gene was determined quantitatively by real-time PCR in 50 ALL patients (30 B-ALL and 20 T-ALL) and correlated with clinical outcome after induction chemotherapy. Expression level of mTOR was upregulated in more than 50% of cases of ALL.
View Article and Find Full Text PDFDescribed herein are the synthesis and photophysical characterization of a library of aryl-substituted oxazole- and thiazole-based dipeptidomimetic analogues, and their incorporation into position 66 of green fluorescent protein (GFP) in lieu of the natural fluorophore. These fluorescent analogues resemble the fluorophore formed naturally by GFP. As anticipated, the photophysical properties of the analogues varied as a function of the substituents at the para position of the phenyl ring.
View Article and Find Full Text PDFA synthesis of the complete tetracyclic framework of the structurally unique Lycopodium alkaloid lycopladine H has been accomplished using a strategy involving a double alkene hydroformylation/intramolecular reductive amination to form the azocane and spiro-piperidine moieties of the natural product.
View Article and Find Full Text PDFHigh incidence of nasopharyngeal carcinoma (NPC) has been reported from China, Southeast Asia and Northeast (NE) region of India. Populations at geographic regions having higher incidence of NPC display human leukocyte antigen (HLA) distribution patterns different from areas having low incidence. The current study has investigated the contribution of environmental risk factors and ethnic variation of microsatellite markers in HLA region for the high incidence of NPC in NE India.
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