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Hepatocellular carcinoma (HCC) is the most malignant cancer worldwide. Sorafenib (SRF) is a common therapeutic drug used for patients with advanced HCC. Nevertheless, drug resistance frequently occurs in patients treated with sorafenib. Glycyrrhizic acid (GRA) is a natural compound that is identified to exhibit anti-cancer effects. In this work, we aimed to investigate the effects of GRA on SRF-resistant HCC cells and the potential regulatory mechanisms. We established SRF-resistant HCC cell lines and administrated GRA treatment. We performed CCK-8 and colony formation experiments to detect cell proliferation. The accumulation of lipid reactive oxygen species (ROS) and iron levels were measured to evaluate ferroptosis. The protein levels of ferroptosis suppressor glutathione peroxidase 4 (GPX4) and SLC7A11, and the activation of AKT and mTOR were measured with western blotting assay. GRA treatment notably suppressed the viability and proliferation of SRF-resistant HCC cells. SRF-resistant HCC cells exhibited repressed ferroptosis level activated AKT/mTOR cascade, and GRA treatment reversed these effects. Inhibition of ferroptosis and activation of mTOR reversed the anti-proliferation effects of GRA on SRF-resistant HCC cells. Treatment with GRA could effectively reverse the SRF resistance of HCC cells via inducing ferroptosis and inactivating the AKT/mTOR cascade. [ABSTRACT FROM AUTHOR]

Objective: Our aim is to retrospectively compare the disease-free survival (DFS) of adjuvant TACE after surgical resection on patients with tumor less than 5 cm. Methods: A total of 307 patients with HCC underwent hepatic resection between January 2014 to December 2016 were enrolled in this study. Among these, 172 patients underwent surgical treatment only (group A) and 135 patients received surgical resection followed by adjuvant TACE (group B). Propensity score matching (PSM) analysis is used to minimize baseline differences between two groups. DFS was compared between the two groups and Cox proportional hazard model was used to predict the factor for recurrence. Results: Before PSM, the 1, 2, 3 year DFS rate of group A and B were 90.1%, 83.3%, 75.3% versus 85.2%, 73.9%, 68.1%, respectively (p =.286). After PSM, the 1, 2, 3 year DFS rate of group A and group B were 90.3%, 80.8%, 71.9% versus 89.2%, 77.8%, 71.3%, respectively (p =.791). In subgroup analysis where patients presented with microvascular invasion (MiVI), before PSM the 1, 2, 3 year DFS rate were 77.8%, 77.8%, 77.8% and 70%, 70%, 47.3%, for group A and B, respectively (p =.491). After PSM the 1, 2, 3 year DFS rate for group A and B were 71.4%, 71.4%, 71.4% and 100%, 100%, 50%, respectively (p =.440). Cox proportional hazard model identified tumor size ≥3 cm as factor related to recurrence. Conclusions: Adjuvant TACE does not improve the DFS of HCC patients with tumor size less than 5 cm. [ABSTRACT FROM AUTHOR]

During major resection of liver carcinoma, liver regeneration (LR) is induced by various clinical and biological factors. Heme oxygenase (HO)-1 has been found as a key inducer of LR in preclinical trial. The clinical evidence for the role of HO-1 in liver dysfunction (LD) including LR is still unknown and has been included in this study. Therefore, plasma HO-1 were monitored during perioperative period in 65 patients with hepatectomy, with 35 training and 30 validation cohorts. LD were evaluated by liver function serum markers and calculation of regeneration indices, respectively. In the training setting, HO-1 levels were remarkably reduced after liver resection (P < 0.001) and gradually recovered within 7 days after surgery. Preoperative HO-1 specifically predicted LD during the first week after surgery (AUC: 0.757; P = 0.01). In patients with LD and complications after surgery, HO-1 levels decreased throughout the perioperative period. In addition, we had also confirmed that low levels of HO-1 (<169 ng/ml) before surgery were associated with an increase in the incidence of postoperative LD and morbidity (P = 0.007, P = 0.045), and decrease of liver regeneration (P = 0.005). And HO-1 was an independent predictor for poor clinical outcome. We had provided the first clinical data verifying that human HO-1 was related to LD. Consequently, HO-1 levels can be used as effective clinical indicators to predict LD and clinical outcome, and can be used as intervention target before liver resection. [ABSTRACT FROM AUTHOR]

Of all the aerobic respiration by-products, cytotoxic superoxide derived from mitochondrial-leaked electrons, is the only one known to be disposed of intracellularly. Is this fate the only destiny for mitochondrial-leaked electrons? When Cynomolgus monkeys were injected intravenously with reactive oxygen species (ROS) indicators, the connective tissues of dura mater, facial fascia, pericardium, linea alba, dorsa fascia and other body parts, emitted specific and intense fluorescent signals. Moreover, the fluorescent signals along the linea alba of SD rats, did not result from the local presence of ROS but from the interaction of ROS indicators with electrons flowing through this tissue. Furthermore, the electrons travelling along the linea alba of mice were revealed to originate from mitochondria. These data suggest that mitochondrial-leaked electrons may be transported extracellularly to a hitherto undescribed system of connective tissues, which is pervasively networked, electrically conductive and metabolically related. [ABSTRACT FROM AUTHOR]

Background: The microbiota plays a critical role in the process of human carcinogenesis. Pancreatic head carcinoma (PHC)-associated tongue coating microbiome dysbiosis has not yet been clearly defined.Objective: Our aim is to reveal the bacterial composition shifts in the microbiota of the tongue coat of PHC patients.Design: The tongue coating microbiota was analyzed in 30 PHC patients and 25 healthy controls using 16S rRNA gene sequencing technology.Results: The microbiome diversity of the tongue coat in PHC patients was significantly increased, as shown by the Shannon, Simpson, inverse Simpson, Obs and incidence-based coverage estimators. Principal component analysis revealed that PHC patients were colonized by remarkably different tongue coating microbiota than healthy controls and liver cancer patients. Linear discriminant analysis effect size revealed that Leptotrichia, Fusobacterium,Rothia, Actinomyces, Corynebacterium, Atopobium, Peptostreptococcus, Catonella, Oribacterium, Filifactor, Campylobacter, Moraxella and Tannerella were overrepresented in the tongue coating of PHC patients, and Haemophilus, Porphyromonas and Paraprevotella were enriched in the tongue coating microbiota of healthy controls. Strikingly, Haemophilus, Porphyromonas, Leptotrichia and Fusobacterium could distinguish PHC patients from healthy subjects, and Streptococcus and SR1 could distinguish PHC patients from liver cancer patients. Conclusions: These findings identified the microbiota dysbiosis of the tongue coat in PHC patients, and provide insight into the association between the human microbiome and pancreatic cancer. [ABSTRACT FROM AUTHOR]

Aim: The majority of available data on the clinical efficacy of sunitinib in patients with imatinib-resistant or -intolerant gastrointestinal stromal tumours (GISTs) are from studies of western populations. We investigated the clinical outcomes of imatinib dose escalation versus sunitinib in first-line imatinib-failure Asian GIST patients to further guide clinical treatment. Methods: Patients received imatinib dose escalation and a shift to sunitinib (Group A) or a direct shift to sunitinib (Group B). The objective tumour response was assessed according to Choi's criteria. Progression-free survival (PFS) and overall survival (OS) were calculated. The relationship between genetic mutation and survival was analysed. Results: In total, 40 patients who fulfilled the inclusion criteria were recruited. The differences in survival between Group A and Group B were not significant for PFS (p = .776) or OS (p = .219). For patients with KIT exon 11 mutation, a trend towards a better PFS was found in Group B (p = .122), OS of Group B was better than Group A (p = .013). The median PFS and OS of sunitinib treatment were 8 and 24 months, respectively, and a clinical benefit was observed in 80%. Patients with KIT exon 11 mutations had better PFS compared to those with KIT exon 9 mutations or wild-type GISTs (p = .017, p = .040, respectively). Conclusions: Both imatinib dose escalation and sunitinib were optional in Asian patients after failure of first-line imatinib, and patients with KIT exon 11 mutation benefited more from a direct shift to sunitinib. [ABSTRACT FROM AUTHOR]

Fractional CO2 laser is one of the most effective treatment options used to resurface scars. However, most previous studies have been performed on mature scars at least 2 months after surgery. Recent studies have emphasized the importance of early treatment to reduce scar formation. In the present study, we described our experience with fractional CO2 laser intervention before skin suture during scar revision surgery in Asians, and found the treatment was safe and effective. [ABSTRACT FROM AUTHOR]

Objective: The management of liver receivers requires intense immunosuppression to prevent graft rejection. Mycophenolate mofetil (MMF) is a common immunosuppressant but frequently suffer dose reduction for gastrointestinal adverse reactions (GI). Hence, the enteric-coated mycophenolate sodium (EC-MPS) is introduced as a substitute for MMF to reduce GI. The study was designed to investigate the efficacy, safety and exposure equation of EC-MPS in liver transplant patients in China. Methods: Ninety-two liver receivers who administered EC-MPS or MMF as a primary immunosuppressant were enrolled in this single-center study and divided into MMF group and EC-MPC group, respectively. Efficacy and safety of EC-MPS were compared with MMF. The MPA exposure was measured at time 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 h after mean 4.5 days of EC-MPS treatment. An equation of limited time points for estimating serum MPA exposure of EC-MPS was established using multiple stepwise regression model. Results: Data show an interpatient variation in MPA AUC,CmaxandTmax. After a first dose of EC-MPS, the mean value of serum AUC0-12 hwas 20.68 mg/L (SD 8.94, range 8.1–46.3).Cmaxwas 9.7 mg/L (SD 6.48, range 2.7–16.3);Tmaxwas 1.90 h (SD 0.97, range 0.5–4). The best equation for estimating the AUC was 6.0 1 4 + 0.946C2 + 0.606C3 + 1.154C4 + 2.479C6 + 5.07C12. Comparing with MMF, EC-MPS not only effectively maintained immunosuppression, but also had similar incidences of infection, renal dysfunction and hematological disorders. However, EC-MPS markedly improved GI, the incidence of GI was half of the MMF group. Conclusion: This analysis presented that EC-MPS is an effective and safe immunosuppressant as similar as MMF. The conversion of MMF to EC-MPS could be administered. [ABSTRACT FROM PUBLISHER]

A recent study has shown that nanosecond pulsed electric fields (nsPEF) can affect the intracellular structures of melanoma within weeks. nsPEF is a non-drug, non-thermal treatment using ultrashort, intense pulsed electric fields with nanosecond durations. In the current study we followed up melanoma histopathology and metastasis with tissue micro-array 5 months post-nsPEF. After nsPEF treatment, tumor growth, tumor histology, metastasis, peri-tumor vessel and micro-vessel density were examined for the effect of nsPEF treatment on melanoma in vivo. The 17 nsPEF-treated mice were tumor-free for 169 days, significantly longer than those 19 control mice bearing melanoma without nsPEF. Histopathology follow-up showed that melanoma did not recur to the primary injection place after complete elimination. Compared with the control tumor, nsPEF-treated tumors present decreased micro-vessel density in a time-course manner in this survival study. Treatment with nsPEF caused continuous histopathological changes in melanomas, eliminated melanoma without recurrence at the primary site and prolonged animal survival time by inhibiting tumor blood supply and leading to tumor infarction. Thus, nsPEF could be applied in a non-ionizing therapeutic approach, without other agents, to locally treat tumors within a defined boundary. [ABSTRACT FROM AUTHOR]

Objective: Chronic or acute rejection is a leading cause of allograft loss after solid organ transplantation and the presence of memory T cells is associated with increased propensity for allograft rejection. The purpose of this study was to investigate the correlation between immunophenotypic shift of memory CD8+ T cells and immune status in the patients after liver transplantation. Material and methods: Seventy-three blood samples were collected and varied compartments of memory CD8+ T cells were analysed in non-rejected and rejected patients. Results: The results show that with time elapsed, the immunophenotypes of memory CD8+ cells shifted from naive T cells to central or intermediate memory cells, and then to effector or terminal memory cells in non-rejected patients. This course was correlated with the expression of CD127 on CD8+ T cells. In rejected patients, the main proportion of CD8+ cells were dominated by naive CD8+ cells and then rapidly restored to the immunophenotypes of memory T cells after effective treatment. Conclusion: These results demonstrated that immunophenotypic shift of memory CD8+ T cells was closely related to the change of the immune status in the patients after liver transplantation. Monitoring the immunophenotypic shift of memory CD8+ T cells is of great importance in the prediction for allograft rejection and treatment effectiveness after liver transplantation. [ABSTRACT FROM AUTHOR]

TLR4 (Toll-like receptor 4) and B7-H1, which were known to be restricted to immune cells in the past, were found to be aberrantly expressed in a majority of tumor cells, facilitating tumor evasion from immune surveillance. Our study demonstrated that activation of TLR4 signaling in bladder cancer cells up-regulated B7-H1 expression. Furthermore, this regulation was significantly attenuated by ERK or JNK inhibitor. Our results elucidated the molecule mechanism of regulation of B7-H1 expression through TLR4 signaling and may suggest new strategies of down-regulating the cancer-associated B7-H1 expression for bladder cancer treatment. [ABSTRACT FROM AUTHOR]

In addition to the effects on T lymphocytes, Cyclosporin A can inhibit dendritic cells allostimulatory capacity, but its precise mechanism remains unknown. The data in this study demonstrated that Cyclosporin A has no effect on the expression of major histocompatibility complex class II and costimulatory molecular CD80, CD86, CD40 on matured DC induced by Lipopolysaccharide in vitro, but can up-regulated B7-DC expression on DC in an Interleukin-4-dependent manner, which is associated with reduced allostimulatory ability of DC. Furthermore, Cyclosporin A treatment inhibited production of Interferon-γand TNF-α, Interleukin-12p70, but increased production of the Interleukin-10 of DC. Thus, up-regulated expression of B7-DC may be responsible for Cyclosporin A-mediated inhibitory effects on allostimulatory capacity of DC. [ABSTRACT FROM AUTHOR]

Calcitriol has important immunomodulation action and can prolong recipient survival after organ transplantation. The data in this study demonstrated that treatment of liver allograft recipient with calcitriol can protect allograft from acute rejection and prolong recipient's survival. Calcitriol inhibited expression of proinflammatory cytokine such as Interleukin-2 and Interferon-γ intragraft. It also inhibited expression of nuclear factor κB (NF-κB) significantly as a result of enhancing its inhibitory protein I kappa B (IκB). As well, expression of zinc-finger protein A20 (A20) was enhanced significantly. The results suggest that calcitriol exerts its immunosuppression action in part through inducement of the A20, IkB, inhibition of NF-kB, and resultant proinflammatory expression pathway. [ABSTRACT FROM AUTHOR]