IMPORTANCE Late recurrence (more than 2 years) after liver resection for hepatocellular carcinoma (HCC) is generally considered as a multicentric tumor or a de novo cancer. OBJECTIVE To investigate the risk factors, patterns, and outcomes of late recurrence after curative liver resection for HCC. DESIGN, SETTING, AND PARTICIPANTS This study was a multicenter retrospective analysis of patients who underwent curative liver resection for HCC at 6 hospitals in China from January 2001 to December 2015. Among 734 patients who were alive and free of recurrence at 2 years after resection, 303 patients developed late recurrence. Data were analyzed from June 2017 to February 2018. INTERVENTIONS Liver resection for HCC. MAIN OUTCOMES AND MEASURES Risk factors of late recurrence as well as patterns, treatments, and long-term outcomes of patients with late recurrence. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors of late recurrence. RESULTS Of the included 734 patients, 652 (88.8%) were male, and the mean (SD) age was 51.0 (10.3) years. At a median (interquartile range) follow-up of 78.0 (52.8-112.5) months, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that male sex, cirrhosis, multiple tumors, satellite nodules, tumor size greater than 5 cm, and macroscopic and microscopic vascular invasion were independent risk factors of late recurrence. Of the 303 patients with late recurrence, 273 (90.1%) had only intrahepatic recurrence, 30 (9.9%) had both intrahepatic and extrahepatic recurrence, and none had only extrahepatic recurrence. Potentially curative treatments were given to 165 of 303 patients (54.5%) with late recurrence, which included reresection, transplant, and local ablation. Multivariate Cox regression analysis showed that regular surveillance for postoperative recurrence (hazard ratio [HR], 0.470; 95% CI, 0.310-0.713;

No abstract

BackgroundCancer cachexia is a progressive and multi-factorial metabolic syndrome characterized by loss of adipose tissue and skeletal muscle. White adipose tissue (WAT) lipolysis and white-to-brown transdifferentiation of WAT (WAT browning) are proposed to contribute to WAT atrophy in cancer cachexia. Chronic inflammation, mediated by cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), has been reported to promote cancer cachexia. However, whether chronic inflammation promotes cancer cachexia by regulating WAT metabolism and the underlying mechanism remains unclear.MethodsIn this study, we first analyzed the association between chronic inflammation and WAT metabolism in gastric and colorectal cancer cachectic patients. In cachectic mice treated with anti-IL-6 receptor antibody, we clarified whether WAT lipolysis and browning were regulated by IL-6.ResultsClinical analyses showed positive significant association between serum IL-6 and free fatty acid (FFA) both in early- and late-stage cancer cachexia. However, serum TNF-α was positively associated with serum FFA in the early- but not late-stage cachexia. WAT lipolysis was increased in early- and late-stage cachexia, while WAT browning was detected only in late-stage cachexia. Anti-IL-6 receptor antibody inhibited WAT lipolysis and browning in cachectic mice.ConclusionsBased on these findings, we conclude that chronic inflammation (especially that mediated by IL-6) might promote cancer cachexia by regulating WAT lipolysis in early-stage cachexia and browning in late-stage cachexia.

Bcl-2-associated transcription factor 1 (BCLAF1) is known to be involved in multiple biological processes. Although several splice variants of BCLAF1 have been identified, little is known about how BCLAF1 splicing is regulated or the contribution of alternative splicing to its developmental functions. Here we find that inclusion of alternative exon5a was significantly increased in colorectal cancer (CRC) samples. Knockdown of the BCLAF1 protein isoform resulting from exon5a inclusion inhibited growth and that its overexpression increased tumorigenic potential. We also found that the splicing factor SRSF10 stimulates inclusion of exon5a and has growth-inducing activity. Importantly, the upregulation of SRSF10 expression observed in clinical CRC samples parallels the increased inclusion of BCLAF1 exon5a, both of which are associated with higher tumour grade. These findings identify SRSF10 as a key regulator of BCLAF1 pre-mRNA splicing and the maintenance of oncogenic features in human colon cancer cells.

Hepatocellular carcinoma (HCC) is one of the most common and deadly gastrointestinal malignancies. Given its insensitivity to traditional systematic chemotherapy, new therapeutic strategies for efficient HCCs treatment are urgently needed. Here, the development of a novel 2D MXene-based composite nanoplatform for highly efficient and synergistic chemotherapy and photothermal hyperthermia against HCC is reported. A surface-nanopore engineering strategy is developed for the MXenes' surface functionalization, which achieves the uniform coating of a thin mesoporous-silica layer onto the surface of 2D Ti C MXene (Ti C @mMSNs). This strategy endows MXenes with well-defined mesopores for on-demand drug release/delivery, enhanced hydrophilicity/dispersity, and abundant surface chemistry for targeting engineering. Systematic in vitro and in vivo evaluations have demonstrated the high active-targeting capability of arginine-glycine-aspartic acid (RGD)-targeting Ti C @mMSNs into tumor, and the synergistic chemotherapy (contributed by the mesoporous shell) and photothermal hyperthermia (contributed by the Ti C MXene core) completely eradicate the tumor without obvious reoccurrence. This work not only provides a novel strategy for efficiently combating HCC by developing MXene-based composite nanoplatforms, but also paves a new way for extending the biomedical applications of MXenes by surface-nanopore engineering.

This paper analyzes changes in the gender earnings gap in urban China over the period 1988-2004 using urban household survey data. The mean female/male earnings ratio declined from 86.3% to 76.2%. Mainly responsible for this diverging trend were rapid increases in returns to both observed and unobserved skills, which accentuated

Hepatocellular carcinoma (HCC) is one of the deadliest malignancies worldwide featured with the poor prognosis and high mortality in affected patients. Given its insensitivity to conventional systemic chemotherapy, the development of novel modalities for HCC management is highly urgent. Sonodynamic therapy (SDT) has gained considerable momentum in cancer therapy. Especially, through synergistic SDT/chemotherapy, SDT would enhance the chemotherapeutic process on inhibiting tumor growth, which holds great potential on combating HCC. In this work, we report on the design/fabrication of targeted biodegradable nanosonosensitizers based on hollow mesoporous organosilica nanoparticles (HMONs), followed by pore-engineering including covalent anchoring of protoporphyrin (PpIX, HMONs-PpIX) and conjugation of arginine-glycine-aspartic acid in order to specifically targeting HCC cells. Such nanosonosensitizers provide efficient loading and controllable stimuli-responsive release of chemotherapeutic agents for HCC-targeting chemotherapy, thus promoting an enhancing chemotherapeutic process via the unique sonotoxicity under ultrasound irradiation. The HMONs matrix with biologically active organic groups in the framework (disulfide bond) are endowed with intrinsic tumor microenvironment-responsive biodegradability and improved biocompatibility/ biosafety. In particular, a synergistic inhibition effect of drug-loaded HMONs-PpIX-arginine-glycine-aspartic acid on HCC growth has been systematically demonstrated both in vitro and in vivo (84.7% inhibition rate), which brings insights and meets the versatile therapeutic requirements for HCC management. Scheme 1. Schematic illustration of the synthetic process of HMONs-PpIX-RGD and synergistic chemo-SDT against HCC tumor xenograft on nude mice. a) Schematic diagram of synthesizing HMONs and further pore engineering with PpIX. b) Schematic process of surface PEG modification, RGD conjugation, and DOX loading on as-synthesized HMONs. c) Schematic illustration of multitherapeutic functions of HMONs-PpIX-RGD, including free transport within blood vessel after intravenous injection, specific recognition between RGD and ligands expressed on HCC cell membranes, GSH/ US-responsive drug release, and enhanced/synergistic chemo-SDT process.www.afm-journal.de www.advancedsciencenews.com 1800145 (3 of 16)

No abstract