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One sample fits all: a microfluidic-assisted methodology for label-free isolation of CTCs with downstream methylation analysis of cfDNA in lung cancer.

Lung cancer (LC) is a major cause of mortality. Late diagnosis, associated with limitations in tissue biopsies for adequate tumor characterization contribute to limited survival of lung cancer patients. Liquid biopsies have been introduced to improve tumor characetrization through the analysis of biomarkers, including circulating tumour cells (CTCs) and cell-free DNA (cfDNA). Considering their availability in blood, several enrichment strategies have been developed to augment circulating biomarkers for improving diagnostic, prognostic and treament efficacy assessment; often, however, only one

Effective posttransplant antitumor immunity is associated with TLR-stimulating nucleic acid-immunoglobulin complexes in humans.

Donor lymphocyte infusion (DLI), whereby donor mononuclear cells are infused into patients, is one of the few effective immunotherapeutic strategies that generate long-lasting tumor remissions. We previously demonstrated that chronic myelogenous leukemia (CML) patients treated with DLI develop high-titer plasma antibodies specific for CML-associated antigens, the majority of which have been reported to bind nucleic acids These observations led us to predict that circulating antibody-antigen complexes in DLI-responsive patients carry nucleic acids that can engage innate immune sensors. Consiste

Redox-responsive dual-drug nanomedicine integrating cisplatin and trypsin for synergistic reversal of tumor chemoresistance.

To overcome cisplatin resistance without increasing systemic toxicity, we rationally elaborated a glutathione-activatable prodrug nanomedicine that chemically co-encapsulates cisplatin and a masked protease. First, a redox-labile succinimide linker (NC-ss-COOH) was covalently grafted onto the ε-amino groups of trypsin to create a "pro-protease" (ssTrypsin) whose catalytic activity is completely silenced in circulation but instantly restored (≥96%) upon cleavage by intratumoral GSH. Simultaneously, cisplatin was stably coordinated to the carboxyl-rich backbone of cRGD-PEG-polyglutamic acid and

The Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies.

The study of cell-free DNA (cfDNA) and other peripheral blood components (known as "liquid biopsies") is promising, and has been investigate … stance in real time. However, there are limitations, such as the difficulty in obtaining sufficient circulating tumor DNA for achieving a high sensitivity to assess the minimal residual disease, or the lack of standardization of the method, and clinical studies, to confirm its prognostic impact. This review focuses on the clinical applications of cfDNA on the minimal r …

Alteration of oncogenic IGF-II gene methylation status associates with hepatocyte malignant transformation.

BACKGROUND: Oncogenic insulin-like growth factor-II (IGF-II) is overexpressed in hepatocellular carcinoma (HCC). The present study aimed to analyze the dynamic alteration of IGF-II CpG site methylation status and its molecular mechanism in HCC progression. METHODS: IGF-II alterations were observed in rat hepatocarcinogenesis models induced by 2-acetylaminofluorene. Liver IGF-II expression was compared by immunohistochemistry or tissue IGF-II specific concentration (nmol/mg protein). Status of human IGF-II promoter 3 (P3) or rat IGF-II P2 CpG site methylation was amplified by methylation-speci

Peri-interventional neutrophil extracellular traps and immune surveillance in hepatocellular carcinoma: mechanisms, biomarkers, and recurrence after liver resection or thermal ablation.

Recurrence remains common after curative-intent liver resection or thermal ablation for hepatocellular carcinoma (HCC). These interventions transiently remodel the hepatic and treatment-bed immune microenvironment through overlapping but distinct processes, including tissue injury, vascular and coagulation activation, neutrophil recruitment, and, particularly during resection, hepatic ischemia-reperfusion. We organize the evidence using a peri-interventional two-component heuristic: chronic liver disease and tumor-associated inflammation may shape baseline susceptibility, whereas acute treatme

Malondialdehyde and Oxidative Stress in Cancer: Biological Insights and Clinical Perspectives.

Malondialdehyde (MDA) is one of the main end-products of lipid peroxidation (LPO) and represents a widely investigated marker of oxidative stress (OS) and oxidative tissue damage. Beyond its role as a measurable byproduct of polyunsaturated fatty acid peroxidation, MDA can interact with proteins and nucleic acids, generating adducts that may contribute to mutagenic, genotoxic, and cytotoxic events involved in carcinogenesis and tumor progression. This narrative review summarizes current evidence on the role of MDA in cancers, including breast, lung, head and neck, colorectal, cervical, and cut

Blood-Based Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma, Including the Viral Genome and Glycosylated Proteins.

Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) development and is a global public health issue. … use, including colony stimulating factor 1 receptor (CSF1R), extracellular vesicles, and cell-free, circulating tumor DNA. The clinical use of such surrogate markers may lead to a better understanding of the risk of disease progression and early detection of HCC in HBV-infected patients, thereby improving their prognosis.

Towards precision medicine: advances in 5-hydroxymethylcytosine cancer biomarker discovery in liquid biopsy.

Robust and clinically convenient biomarkers for cancer diagnosis, early detection, and prognosis have great potential to improve patient survival and are the key to precision medicine. The advent of next-generation sequencing technologies enables a more sensitive and comprehensive profiling of genetic and epigenetic information in tumor-derived materials. Researchers are now able to monitor the dynamics of tumorigenesis in new dimensions, such as using circulating cell-free DNA (cfDNA) and tumor DNA (ctDNA). Mutation-based assays in liquid biopsy cannot always provide consistent results across

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… Fiala C Diamandis EP Utility of circulating tumor DNA in cancer diagnostics with emphasis on early detection BMC Med. 2018 16 1 166 10.1186/s12916-018-1157-9 30285732 PMC6167864 38. … Warton K Mahon KL Samimi G Methylated circulating tumor DNA in blood: power in cancer prognosis and response Endocr Relat Cancer 2016 23 3 R157 R171 10.1530/ERC-15-0369 26764421 PMC4737995 64. …

ctDNA from body fluids is an adequate source for EGFR biomarker testing in advanced lung adenocarcinoma.

OBJECTIVES: Epidermal growth factor receptor (EGFR) biomarker testing using blood-based liquid biopsies remains challenging due to the low concentration of circulating tumor DNA (ctDNA) in certain plasma samples. The aim of this study is to evaluate the usefulness for EGFR biomarker testing of ctDNA from pleural effusions, cerebrospinal fluids, ascites and pericardial effusions obtained during the clinical management of lung adenocarcinoma patients. METHODS: For comparison purposes, 23 paired plasma and body fluid samples were collected from 17 patients with EGFR-positive lung adenocarcinoma.…

Total Neoadjuvant Treatment for Locally Advanced Rectal Cancer Patients: Where Do We Stand?

The therapeutic landscape in locally advanced rectal cancer (LARC) has undergone a significant paradigm shift in recent years with the rising adoption of total neoadjuvant treatment (TNT). This comprehensive approach entails administering chemotherapy and radiation therapy before surgery, followed by optional adjuvant chemotherapy. To establish and deliver the optimal tailored treatment regimen to the patient, it is crucial to foster collaboration among a multidisciplinary team comprising healthcare professionals from various specialties, including medical oncology, radiation oncology, surgica

Liquid Biopsy of HPV Cell-Free DNA Enables Blood-Based Early Detection and Molecular Stratification of HPV-Associated Cancer and Precancer Stages.

Liquid biopsies targeting circulating tumor DNA enable noninvasive cancer detection but lack sensitivity in pre- and early- cancer stages, where clinical benefits would be greatest. Human papillomavirus (HPV) causes six cancer types, accounting for 5% of all cancers worldwide. Targeting HPV cell-free (cf)DNA offers a compelling opportunity to overcome current liquid biopsy constraints due to its unique tumor-specific origin, lack of sequence homology to the human genome, and the high viral-to-human copy ratio per cell. Utilizing HPV-associated anal cancer and precancer as a model, here we appl…

Neoadjuvant triplet chemotherapy enables radiotherapy avoidance in human papillomavirus-associated oropharyngeal cancer: a multicentre Phase II trial.

BACKGROUND: This prospective Phase 2 trial assessed a novel de-escalation strategy for upfront neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (NAC-TPF) to avoid postoperative radiotherapy (PORT) and chemoradiotherapy (POCRT) for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Patients with HPV-associated resectable OPSCC were enrolled. Invasive surgery or PORT/POCRT was an inclusion criterion if upfront surgery was performed. Treatment started with three cycles of NAC-TPF, followed by surgery. The primary endpoint was the c

Beyond molecular classification: integrating signaling, subcellular, and immune reprogramming in endometrial cancer.

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries, with rising incidence rates that have not been m … filing as an emerging complementary immune biomarker. We also discuss emerging frontiers, including circulating tumor DNA as a minimal residual disease tool, single-cell and spatial transcriptomics revealing tumor microenvironment architecture, and artificial intelligence-augmented digital pathology. Building on these axes, we propose an integrated conceptual model in …

The logarithmic phase as a therapeutic direction: evaluating pharmacological strategies against cancer progression.

Cancer remains a significant medical crisis and health burden globally, with an estimated 20 million new cases and nearly 10 million deaths … ence highlighting excellent tolerability and adjunctive benefits. Real-time monitoring using Ki-67, circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs) enables dynamic evaluation of kinetics and heterogeneity shifts. Targeting the logarithmic phase, while accounting for tumor heterogeneity through multimodal, adaptive and biomarker-guided approaches combi …

Targeted liquid biopsy for brain tumors.

Cerebrospinal fluid (CSF) is a promising source of molecular biomarkers in the detection and monitoring of brain malignancies. Unlike peripheral blood, where biomarker detection is hindered by the blood-brain barrier and the complex nature of biofluids, CSF offers a more direct and enriched source of tumor-derived markers, including circulating tumor DNA (ctDNA), microRNA (miRNA), proteins, and extracellular vesicles (EVs). These biomarkers, originating from brain tumor cells, are often more concentrated in CSF than in peripheral blood due to the proximity of CSF to the central nervous system …

Predictive and Prognostic Biomarkers and Tumor Antigens for Targeted Therapy in Urothelial Carcinoma.

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have … DNA damage response and repair (DDR) mutations, poly (ADP-ribose) polymerase (PARP) expression and circulating tumor DNA (ctDNA), as well as their clinical utility in UC. We also evaluate recent advancements in precision oncology in UC, while illustrating limiting factors and challenges related to the clinical application of these biomarkers in clinical practice.

Extensive mutational ctDNA profiles reflect High-grade serous cancer tumors and reveal emerging mutations at recurrence.

OBJECTIVE: Circulating tumor DNA (ctDNA) offers a minimally-invasive alternative to study genomic changes in recurrent malignancies. With a high recurrence rate, the overall survival in high-grade serous ovarian carcinoma (HGSC) has remained low. Our objectives were to determine whether ctDNA from plasma adequately represents HGSC, and to find mutational changes at relapse suggesting therapy options that could alter patient outcome. METHODS: We collected 152 longitudinal plasma and 92 fresh tissue samples from 29 HGSC patients, sequencing and detecting mutations with a gene panel of more than…

Polymerase chain reaction diagnosis of t(14;18) from paraffin-embedded tissues fixed with Holland Bouin fluid.

The t(14;18) translocation and its molecular counterpart, the bcl-2/IgH gene rearrangement, are highly characteristic of follicular non-Hodgkin lymphomas. The identification of the tumor-specific t(14;18) clone is mandatory for any molecular studies on residual disease because of the existence of circulating t(14;18)-bearing benign cells. In this study, the ability to specifically polymerase chain reaction (PCR) amplify t(14;18) with DNA purified from tissues fixed with Holland Bouin fluid is demonstrated. The specificity of the PCR product was confirmed by internal probe hybridization and wit

[Stratification of the risk of malignization of intraductal papillary mucinous neoplasms of the pancreas].

The purpose of this review was to analyze the most perspective methods for risk stratification of malignant transformation of pancreatic intraductal papillary mucinous neoplasms (IPMN). Advisability of humoral predictors (tumor markers, inflammatory markers, circulating leptin and branched-chain amino acids, etc.) is in identifying prognostic signs suitable for risk stratification of IPMN malignant transformation and, therefore, determining treatment strategy for a particular patient. According to data screening, the most advisable predictors of malignant transformation of neoplasms are carboh