Translational research : the journal of laboratory and clinical medicine
-
Due to tremendous technological advances, radiation oncologists are now capable of personalized treatment plans and deliver the dose in a highly precise manner. However, a crucial challenge is how to escalate radiation doses to cancer cells while reducing damage to surrounding healthy tissues. This determines the probability of achieving therapeutic success whilst safeguarding patients from complications. ⋯ Preclinical studies in mice and nonhuman primates have shown that serum circulating microRNAs can be used to accurately distinguish pre- and postirradiation states and predict the biological impact of high-dose irradiation. First reports from human studies are also encouraging, however biology-driven precision radiation oncology, which tailors treatment to individual patient's needs, still remains to be translated into clinical studies. In this review, we summarize current knowledge about the potential of serum microRNAs as biodosimeters and biomarkers for radiation injury to lung and hematopoietic cells.
-
Hepatocellular carcinoma (HCC) is the world's second leading cause of cancer death; 82.4% of patients die within 5 years. This grim prognosis is the consequence of a lack of effective early detection tools, limited treatment options, and the high frequency of HCC recurrence. ⋯ In an effort to address the current challenges of HCC screening and management, several studies have identified and evaluated liver-cancer-associated molecular signatures such as genetic alterations, methylation, and noncoding RNA expression in the form of circulating biomarkers in body fluids and circulating tumor cells of HCC patients. In this review, we summarize the recent progress in HCC liquid biopsy, organized by the intended clinical application of the reported study.
-
Adjuvant chemotherapy for solid tumors based on platinum-derived compounds such as cisplatin is the treatment of choice in most cases. Cisplatin triggers signaling pathways that lead to cell death, but it also induces changes in tumor cells that modify the therapeutic response, thereby leading to cisplatin resistance. We have recently reported that microRNA-7 is silenced by DNA methylation and is involved in the resistance to platinum in cancer cells through the action of the musculoaponeurotic fibrosarcoma oncogene family, protein G (MAFG). ⋯ We developed specifically selected aptamers against MAFG, with high sensitivity to detect the protein at a nuclear level probed by aptacytochemistry and histochemistry analyses. The inhibition of MAFG activity through the action of the specific aptamer apMAFG6F increased the levels of reactive oxygen species production and the sensitivity to cisplatin. We report first the specific nuclear identification of MAFG as a novel detection method for diagnosis in NSCLC, and then we report that MAFG modulates the redox response and confers cell protection against free radicals generated after platinum administration, thus also being a promising therapeutic target.
-
The aim of this phase 1 clinical trial was to test the safety and feasibility of a single dose of allogeneic umbilical cord-derived mesenchymal stem cells (MSCs) in patients with severe sepsis. This is a single-center, open-label, dose-escalation phase 1 clinical trial of a single dose of intravenous MSCs in patients with severe sepsis. We enrolled 15 patients who averagely divided into low (1 × 106 cells/kg), intermediate (2 × 106 cells/kg), and high (3 × 106 cells/kg) dosing cohorts. ⋯ This study enrolled 15 patients (10 male and 5 female), with a median age of 58. Compared to those in the historical, case-matched group, neither there were infusion-associated serious events or treatment-related adverse events in any of the 15 patients in this trial, nor were there any safety or efficacy signals for serious adverse events or the measured cytokines. A single intravenous infusion of allogeneic MSCs up to a dose of 3 × 106 cells/kg was safe and well tolerated in 15 patients with severe sepsis.