The aim of this study is to search the most powerful prognostic factor from routine blood test for esophageal squamous cell cancer (ESCC) patients. Multiple laboratory tests were evaluated including those reflecting red blood cell parameters (hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and red blood cell distribution width (RDW)), platelet morphological parameters (mean platelet volume (MPV) and platelet count (PLT)), blood coagulation status (D-dimer), and tumor biomarker (CA19-9). Known inflammatory indices (NLR and PLR) were also calculated. A total of 468 patients who were diagnosed with ESCC between December 2005 and December 2008 were retrospectively analyzed in this study. By utilizing univariate and multivariate Cox proportional hazard analyses, we found that PLT and MPV were significantly associated with overall survival (OS) and disease-free survival (DFS) of ESCC patients, with optimal cutoff values of 212 and 10.6, respectively. Moreover, the combination of the preoperative PLT and MPV (COP-MPV) was calculated as follows: patients with both PLT (≥212 × 109 L−1) and MPV (≥10.6 fL) elevation were assigned a score of 2, and patients with one or neither were assigned a score of 1 and 0. The COP-MPV was an independent prognostic factor for OS (hazard ratio (HR) 0.378, 95 % confidence interval (CI) 0.241 to 0.593, P < 0.001, 0/2) and DFS (HR 0.341, 95 % CI 0.218 to 0.534, P < 0.001, 0/2) in multivariate analyses. In subgroup analyses for early (stages I and II) and locally (stage III) advanced stage patients, COP-MPV was found significantly associated with OS and DFS in each group (P = 0.025 and P = 0.018 for OS and P = 0.029 and P = 0.002 for DFS). In conclusion, we considered that COP-MPV is a promising predictor for postoperative survival in ESCC patients.

Limited penetration of chemotherapeutic drugs through the blood brain barrier (BBB), and the increased chemo-resistance of glioma cells due to macroautophagy/autophagy, result in high tumor recurrence and extremely limited survival of glioma patients. Ultrasound-targeted microbubble destruction (UTMD) is a technique of transient and reversible BBB disruption, which greatly facilitates intracerebral drug delivery. In addition, sonodynamic therapy (SDT) based on ultrasound stimulation and a sonosensitizer, can be a safe and noninvasive strategy for treating glioma. We innovatively designed a smart "all-in-one" nanosensitizer platform by incorporating the sonoactive chlorin e6 (Ce6) and an autophagy inhibitor-hydroxychloroquine (HCQ) into angiopep-2 peptide-modified liposomes (designated as ACHL), which integrates multiple diagnostic and therapeutic functions. ACHL selectively accumulated in the brain tumors during the optimal time-window of transient UTMD-mediated BBB opening. The nanosensitizer then responded to a second ultrasonic stimulation, and simultaneously unloaded HCQ and generated ROS in the glioma cells. The sonotherapy triggered apoptosis as well as MAPK/p38-PINK1-PRKN-dependent mitophagy, in which the antioxidant relieved the sonotoxicity and MAPK/p38 activation, while the inhibition of MAPK/p38 attenuated the progression toward mitophagy by compromising redistribution of PRKN. Moreover, HCQ blocking autophagosome degradation, augmented intracellular ROS production and resulted in an oxidative-damage regenerative loop. ACHL-SDT treatment using this construct significantly inhibited the xenograft-tumor growth and prolonged the survival time of tumor-bearing mice, exhibiting an improved therapeutic efficiency. All together, we demonstrated a precision sonotherapy with simultaneous apoptosis induction and mitophagy inhibition, which served as an intelligently strategic sense of working alongside, providing new insights into the theranostics of brain tumors.

A bunch of microRNAs (miRNAs) have been demonstrated to be aberrantly expressed in cancer tumor tissue and serum. The miRNA signatures identified from the serum samples could serve as potential noninvasive diagnostic markers for breast cancer. The role of the miRNAs in cancerigenesis is unclear. In this study, we generated the expression profiles of miRNAs from the paired breast cancer tumors, normal, tissue, and serum samples from eight patients using small RNA-sequencing. Serum samples from eight healthy individuals were used as normal controls. We identified total 174 significantly differentially expressed miRNAs between tumors and the normal tissues, and 109 miRNAs between serum from patients and serum from healthy individuals. There are only 10 common miRNAs. This suggests that only a small portion of tumor miRNAs are released into serum selectively. Interestingly, the expression change pattern of 28 miRNAs is opposite between breast cancer tumors and serum. Functional analysis shows that the differentially expressed miRNAs and their target genes form a complex interaction network affecting many biological processes and involving in many types of cancer such as prostate cancer, basal cell carcinoma, acute myeloid leukemia, and more.

Photodynamic therapy (PDT) is an emerging theranostic modality for various cancers and diseases. Photosensitizers are critical components for PDT. Sinoporphyrin sodium, referred to as DVDMS, is a newly identified photosensitizer that was isolated from Photofrin. Here, we evaluated the effects of DVDMS-mediated PDT (DVDMS-PDT) on tumor cell proliferation and metastasis in the highly metastatic 4T1 cell line and a mouse xenograft model. DVDMS-PDT elicited a potent phototoxic effect in vitro, which was abolished using the reactive oxygen species (ROS) scavenger N-acetylcysteine. In addition, DVDMS-PDT effectively inhibited the migration of 4T1 cells in scratch wound-healing and transwell assays. Using an in vivo mouse model, DVDMS-PDT greatly prolonged the survival time of tumor-bearing mice and inhibited tumor growth and lung metastasis, consistent with in vitro findings. PDT with DVDMS had a greater anti-tumor efficacy than clinically used Photofrin. Moreover, preliminary toxicological results indicate that DVDMS is relatively safe. These results suggest that DVDMS is a promising sensitizer that warrants further development for use in cancer treatment with PDT or other sensitizing agent-based therapies.

No abstract