Characterization of T cell receptor repertoire in penile cancer.

Tumor-infiltrating lymphocytes (TILs) play a key role in regulating the host immune response and shaping tumor microenvironment. It has been previously shown that T cell infiltration in penile tumors was associated with clinical outcomes. However, few studies have reported the T cell receptor (TCR) repertoire in patients with penile cancer. In the present study, we evaluated the TCR repertoires in tumor and adjacent normal tissues from 22 patients with penile squamous cell carcinoma (PSCC). Analysis of the T cell receptor beta-variable (TRBV) and joining (TRBJ) genes usage and analysis of complementarity determining region 3 (CDR3) length distribution did not show significant differences between tumor and matched normal tissues. Moreover, analysis of the median Jaccard index indicated a limited overlap of TCR repertoire between these groups. Compared with normal tissues, a significantly lower diversity and higher clonality of TCR repertoire was observed in tumor samples, which was associated with clinical characteristics. Further analysis of transcriptional profiles demonstrated that tumor samples with high clonality showed increased expression of genes associated with CD8 + T cells. In addition, we analyzed the TCR repertoire of CD4 + T cells and CD8 + T cells isolated from tumor tissues. We identified that expanded clonotypes were predominantly in the CD8 + T cell compartment, which presented with an exhausted phenotype. Overall, we comprehensively compared TCR repertoire between penile tumor and normal tissues and demonstrated the presence of distinct T cell immune microenvironments in patients with PSCC.

Identification and molecular mechanism of action of antibacterial peptides from Flavourzyme-hydrolyzed yak casein against Staphylococcus aureus.

Antibacterial peptides can be released from yak milk casein. To date, the amino acid sequences and mechanism of action of yak casein-derived antibacterial peptides remain unknown. The current study identified antibacterial peptides from yak casein and their molecular mechanism of action. Our results showed that yak α-casein, ß-casein, and κ-casein could be effectively hydrolyzed by Flavourzyme (Solarbio Science and Technology Co. Ltd.), and the 2-h hydrolysate showed the highest antibacterial rate of 43.07 ± 2.59% against Staphylococcus aureus. The 1,000 to 3,000 Da fraction accounted for 23.61% of the 2-h hydrolysate and had an antibacterial rate of 62.64 ± 4.40%. Three novel peptides with antibacterial activity were identified from this fraction, and the ß-casein-derived peptide APKHKEMPFPKYP showed the strongest antibacterial effect (half-maximal inhibitory concentration = 0.397 mg/mL). Molecular docking predicted that APKHKEMPFPKYP interacted with 2 important enzymes of Staph. aureus, dihydrofolate reductase and DNA gyrase, through hydrophobic, hydrogen bonding, salt bridge, and π-π stacking interactions. Our findings suggest that the yak casein-derived peptides may serve as a potential source of natural preservatives to inhibit Staph. aureus.

Managing Follicular Lymphoma in the Elderly Population.

Follicular lymphoma (FL) is one of the most commonly diagnosed types of indolent non-Hodgkin lymphoma (NHL). The median age of diagnosis for FL is 65 years old. Although the median life expectancy after diagnosis is approximately 10 years, the incurable disease has a high risk of transformation. This case report focuses on an 80-year-old patient diagnosed with low-grade follicular lymphoma which subsequently transformed leading to the patient's eventual demise as the patient took on the palliative intent. This case report aims to highlight the importance of clinical markers or prognostic factors to identify patients, specifically the elderly population who are at risk of transformation to aggressive forms when their FL remains at stage I-II phases. Currently, elderly patients with FL tend to be quickly dismissed with curative intent with chemotherapy, given their age and comorbidities, despite forming the majority of the population with follicular lymphoma. Age more than 60 years old has been shown to be one of the most powerful yet poor prognostic features in follicular lymphoma international prognostic index (FLIPI)-the main scoring system used for FL. Hence, further studies are required to look into the tailoring treatment for elderly patients with follicular lymphoma after risk stratifying them with appropriate clinical and prognostic markers.

Degradation Characteristics of Cellulose Acetate in Different Aqueous Conditions.

Cellulose acetate (CA) is widely used in cigarette filters and packaging films, but due to its acetylation, it is difficult to degrade in the natural environment, and the problem of pollution has become a serious challenge. Understanding the degradation behavior and performance of CA in different environments is the basis and prerequisite for achieving its comprehensive utilization and developing efficient degradation methods. In this study, we investigated the degradation performance of CA in different aqueous environments to evaluate the effects of pH, salinity and microorganisms on CA degradation. The CA tows and films were immersed in HCl, NaOH solution, river water, seawater or homemade seawater for 16 weeks and the degradation mechanism was investigated by the changes in weight loss rate, degree of substitution, hydrophilicity, molecular structure and surface morphology. The results showed that the degradation of CA tow and film were the fastest in NaOH solution; the weight loss rates after 16 weeks were 40.29% and 39.63%, respectively, followed by HCl solution, and the degradation performance of CA tow was better than that of film. After 16 weeks of degradation in river water, seawater and homemade seawater, all the weight loss rates were less than 3%. In summary, this study illustrated that the environmental acidity, basicity and high concentration of inorganic salts had a critical promotion effect on the non-enzymatic hydrolysis of CA, whereas the number and type of microorganisms were the key factors affecting the biodegradation of CA.

Association of lncRNA H19 polymorphisms with cancer susceptibility: An updated meta-analysis based on 53 studies.

The association between polymorphisms in lncRNA H19 and cancer susceptibility remains to be inconsistent. This study aimed to provide a more precise estimation of the relationship between lncRNA H19 polymorphisms and the risk of cancer based on all available published studies. 53 studies encompassing 32,376 cases and 43,659 controls were included in our meta-analysis by searching the Pubmed, Embase, Web of Science, WanFang, and China National Knowledge Infrastructure databases. Pooled ORs and their 95% CIs were used to estimate the strength between the SNPs in H19 (rs217727, rs2839698, rs2107425, rs3024270, rs2735971, rs3741216, and rs3741219) and cancer susceptibility. The results showed that H19 rs2839698 polymorphism was associated with increased cancer risk in all participants under three genetic models. However, no significant association was identified between the other six SNPs as well as an overall cancer risk. Stratification by ethnicity showed that rs2839698 mutation indicated to be an important hazardous factor for the Asian population. While rs2107425 mutation had a protective effect on the Caucasian population. Stratification by cancer type identified that rs217727 mutation was linked to increased susceptibility to oral squamous cell carcinoma, lung cancer, and hepatocellular carcinoma; whereas rs2839698 mutation was associated with an elevated risk of hematological tumor and digestive system tumor (p < 0.05). Besides, the rs2735971 mutation was connected with the digestive system tumor. In summary, the rs217727, rs2839698, rs2107425 and rs2735971 polymorphisms in H19 have associations with cancer susceptibility.

ING5 Inhibits Migration and Invasion of Esophageal Cancer Cells by Downregulating the IL-6/CXCL12 Signaling Pathway.

Esophageal squamous cell carcinoma (ESCC) is a common cancer in East Asia and in other parts of the world and exhibits a poor prognosis. Growth inhibitor 5 (ING5) is a new member of the growth inhibitor (ING) protein family and is involved in many important cellular functions, such as the cell cycle, apoptosis, and chromatin remodeling. As a newly discovered tumor suppressor, ING5 has been shown to inhibit lung cancer proliferation and distant metastasis through the AKT pathway. In lung cancer tumors, ING5 can attenuate the ability of cancer cells to invade normal tumor-adjacent tissues. However, ING5 has rarely been studied in ESCC. Here, we found that in ESCC EC-109 cancer cells, ING5 overexpression inhibited cell proliferation and tumor invasion, whereas, in ESCC TE-1 cancer cells, ING5 knockdown promoted cell invasion. In a nude mouse xenograft model, ING5 overexpression inhibited tumor growth and the invasion ability of ESCC cells. Further studies revealed that ING5 overexpression inhibited IL-6/CXCL12 expression at both the mRNA and protein levels as well as morphological changes. We found for the first time that ING5 inhibits ESCC cell migration and invasion by downregulating the IL-6/CXCL12 signaling pathway.

Metal Modulation: An Easy-to-Implement Tactic for Tuning Lanthanide Phototheranostics.

Phototheranostics constitute an emerging cancer treatment wherein the core diagnostic and therapeutic functions are integrated into a single photosensitizer (PS). Achieving the full potential of this modality requires being able to tune the photosensitizing properties of the PS in question. Structural modification of the organic framework represents a time-honored strategy for tuning the photophysical features of a given PS system. Here we report an easy-to-implement metal selection approach that allows for fine-tuning of excited-state energy dissipation and phototheranostics functions as exemplified by a set of lanthanide (Ln = Gd, Yb, Er) carbazole-containing porphyrinoid complexes. Femto- and nanosecond time-resolved spectroscopic studies, in conjunction with density functional theory calculations, revealed that the energy dissipation pathways for this set of PSs are highly dependent on the energy gap between the lowest triplet excited state of the ligand and the excited states of the coordinated Ln ions. The Yb complex displayed a balance of deactivation mechanisms that made it attractive as a potential combined photoacoustic imaging and photothermal/photodynamic therapy agent. It was encapsulated into mesoporous silica nanoparticles (MSN) to provide a biocompatible construct, YbL@MSN, which displays a high photothermal conversion efficiency (η = 45%) and a decent singlet oxygen quantum yield (ΦΔ = 31%). Mouse model studies revealed that YbL@MSN allows for both photoacoustic imaging and synergistic photothermal- and photodynamic-therapy-based tumor reduction in vivo. Our results lead us to suggest that metal selection represents a promising approach to fine-tuning the excited state properties and functional features of phototheranostics.

Biomaterial-based platforms for cancer stem cell enrichment and study.

Cancer stem cells (CSCs) are a relatively rare subpopulation of tumor cell with self-renewal and tumorigenesis capabilities. CSCs are associated with cancer recurrence, progression, and chemoradiotherapy resistance. Establishing a reliable platform for CSC enrichment and study is a prerequisite for understanding the characteristics of CSCs and discovering CSC-related therapeutic strategies. Certain strategies for CSC enrichment have been used in laboratory, particularly fluorescence-activated cell sorting (FACS) and mammosphere culture. However, these methods fail to recapitulate the in vivo chemical and physical conditions in tumors, thus potentially decreasing the malignancy of CSCs in culture and yielding unreliable research results. Accumulating research suggests the promise of a biomaterial-based three-dimensional (3D) strategy for CSC enrichment and study. This strategy has an advantage over conventional methods in simulating the tumor microenvironment, thus providing a more effective and predictive model for CSC laboratory research. In this review, we first briefly discuss the conventional methods for CSC enrichment and study. We then summarize the latest advances and challenges in biomaterial-based 3D CSC platforms. Design strategies for materials, morphology, and chemical and physical cues are highlighted to provide direction for the future construction of platforms for CSC enrichment and study.

Diagnostic values of Xpert MTB/RIF, T-SPOT.TB and adenosine deaminase for HIV-negative tuberculous pericarditis in a high burden setting: a prospective observational study.

The diagnosis of tuberculous pericarditis (TBP) remains challenging. This prospective study evaluated the diagnostic value of Xpert MTB/RIF (Xpert) and T-SPOT.TB and adenosine deaminase (ADA) for TBP in a high burden setting. A total of 123 HIV-negative patients with suspected TBP were enrolled at a tertiary referral hospital in China. Pericardial fluids were collected and subjected to the three rapid tests, and the results were compared with the final confirmed diagnosis. Of 105 patients in the final analysis, 39 (37.1%) were microbiologically, histopathologically or clinically diagnosed with TBP. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) for Xpert were 66.7%, 98.5%, 96.3%, 83.3%, 44.0, 0.338, and 130.0, respectively, compared to 92.3%, 87.9%, 81.8%, 95.1%, 7.6, 0.088, and 87.0, respectively, for T-SPOT.TB, and 82.1%, 92.4%, 86.5%, 89.7%, 10.8, 0.194, and 55.8, respectively, for ADA (≥ 40 U/L). ROC curve analysis revealed a cut-off point of 48.5 spot-forming cells per million pericardial effusion mononuclear cells for T-SPOT.TB, which had a DOR value of 183.8, while a cut-off point of 41.5 U/L for ADA had a DOR value of 70.9. Xpert (Step 1: rule-in) followed by T-SPOT.TB [cut-off point] (Step 2: rule-out) showed the highest DOR value of 252.0, with only 5.7% (6/105) of patients misdiagnosed. The two-step algorithm consisting of Xpert and T-SPOT.TB could offer rapid and accurate diagnosis of TBP.

Capillary morphogenesis protein 2 is a novel prognostic biomarker and plays oncogenic roles in glioma.

Capillary morphogenesis protein 2 (CMG2) was originally identified through its participation in capillary morphogenesis, and subsequently identified as the second receptor for anthrax toxin (ANTXR2). Although tumor-associated functions of CMG2 have also been reported, the clinical significance and functional mechanism of CMG2 in glioma remain to be elucidated. We assessed the clinicopathological relevance of CMG2 in a cohort of 48 glioma patients as well as through public glioma databases, and explored the function of CMG2 using glioblastoma (GBM) models in vitro and in vivo. CMG2 overexpression was associated with increased tumor grade and poor patient survival. CMG2 promoted G2/M-phase transition during the cell cycle of GBM cells in vitro and contributed to tumor growth in vivo. We also observed that CMG2 is implicated in the activation of extracellular signal-regulated kinases (ERKs), epithelial-mesenchymal transition (EMT), migration, and invasion in GBM cells. Transcriptomic analysis of GBM cells with or without CMG2 overexpression indicated that a panel of oncogenic signaling pathways was altered with CMG2 upregulation, implying that CMG2 might orchestrate these signaling pathways to regulate the growth of GBM cells. Yes-associated protein 1 (YAP1) activity was enhanced by CMG2 overexpression but suppressed with CMG2 deficiency. Since YAP1 is critically implicated in GBM, the oncogenic roles of CMG2 in GBM cells might thus be mediated, at least partially, by YAP1. Altogether, CMG2 functioned as an oncogene in glioma cells and is a potential prognostic biomarker or therapeutic target for the clinical treatment of glioma. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

High-mobility group box 1 released by autophagic cancer-associated fibroblasts maintains the stemness of luminal breast cancer cells.

Cancer stem cells/cancer-initiating cells (CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer-associated fibroblasts (CAFs) are major components of the niche of breast cancer-initiating cells (BCICs), and their interactions may profoundly affect breast cancer progression. Autophagy has been considered to be a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance has not been determined. In this study, we found that the presence of CAFs containing high levels of microtubule-associated protein 1 light chain 3 (LC3II), a marker of autophagosomes, was associated with more aggressive luminal human breast cancer. CAFs in human luminal breast cancer tissues with high autophagy activity enriched BCICs with increased tumourigenicity. Mechanistically, autophagic CAFs released high-mobility group box 1 (HMGB1), which activated its receptor, Toll-like receptor (TLR) 4, expressed by luminal breast cancer cells, to enhance their stemness and tumourigenicity. Furthermore, immunohistochemistry of 180 luminal breast cancers revealed that high LC3II/TLR4 levels predicted an increased relapse rate and a poorer prognosis. Our findings demonstrate that autophagic CAFs play a critical role in promoting the progression of luminal breast cancer through an HMGB1-TLR4 axis, and that both autophagy in CAFs and TLR4 on breast cancer cells constitute potential therapeutic targets. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Poly-γ-glutamic acid-based GGT-targeting and surface camouflage strategy for improving cervical cancer gene therapy.

Polycation-based delivery presents a major method for non-viral gene therapy. However, the disadvantages of cationic vectors are their tendencies to be captured and eliminated by the reticuloendothelial system due to their excessive positive charges and nonspecific interaction with normal cells that leads to adverse effects. PEGylation was applied to solve these major problems. Yet, PEG chains can severely compromise cellular uptake and yield unsatisfying efficiency resulting in a so-called PEG dilemma. We developed a γ-PGA-based GGT-targeting and surface camouflage strategy by constructing a ternary complex system via a layer-by-layer self-assembly method. The biodegradable polyanion γ-PGA could protect the PEI/pDNA complexes from interaction with the body fluid components; however, in endosome, the polyanion facilitated the intracellular release of PEI/pDNA. The γ-PGA/PEI/pDNA nanoparticles possessed a markedly improved serum-tolerant capability. More importantly, γ-PGA interacts with the tumor-associated γ-glutamyl transpeptidase (GGT) that can mediate endocytosis of the nanoparticles. With pTRAIL as the therapeutic gene, the γ-PGA/PEI/pTRAIL nanoparticles effectively inhibited tumor cell proliferation by inducing cell apoptosis and arresting cell cycles. The in vivo results displayed effective suppression of tumor growth, and high treatment efficacy in the mice bearing cervical tumor. The γ-PGA-based GGT-targeting and surface camouflage strategy is a potential method for improved gene delivery and cancer therapy.

Poly lactic-co-glycolic acid controlled delivery of disulfiram to target liver cancer stem-like cells.

Disulfiram (DS), an anti-alcoholism drug, shows very strong cytotoxicity in many cancer types. However its clinical application in cancer treatment is limited by the very short half-life in the bloodstream. In this study, we developed a poly lactic-co-glycolic acid (PLGA)-encapsulated DS protecting DS from the degradation in the bloodstream. The newly developed DS-PLGA was characterized. The DS-PLGA has very satisfactory encapsulation efficiency, drug-loading content and controlled release rate in vitro. PLGA encapsulation extended the half-life of DS from shorter than 2minutes to 7hours in serum. In combination with copper, DS-PLGA significantly inhibited the liver cancer stem cell population. CI-isobologram showed a remarkable synergistic cytotoxicity between DS-PLGA and 5-FU or sorafenib. It also demonstrated very promising anticancer efficacy and antimetastatic effect in liver cancer mouse model. Both DS and PLGA are FDA approved products for clinical application. Our study may lead to repositioning of DS into liver cancer treatment.

[Cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy].

To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.

Gene therapy using the human telomerase catalytic subunit gene promoter enables targeting of the therapeutic effects of vesicular stomatitis virus matrix protein against human lung adenocarcinoma.

The catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), is highly active in immortalized cells and more than 90% of human cancer cells, but is quiescent in the majority of normal somatic cells. Thus, the hTERT promoter has been extensively used in targeted cancer gene therapy. Vesicular stomatitis virus (VSV) matrix protein (MP) induces the apoptosis of tumor cells in the absence of other viral components. In our previous studies, we successfully constructed the pVAX-M plasmid from the pVAX plasmid, which expressed wild-type VSV MP (VSV MP is under the control of the CMV promoter) and demonstrated that pVAX-M efficiently suppresses the growth of malignant tumors via the induction of apoptosis in vitro and in vivo. The present study was designed to construct the plasmid phTERTM (VSV MP is under the control of the hTERT promoter) and investigate whether it had a targeted antitumor effect in nude mice bearing human lung adenocarcinoma. In vitro, A549 human lung adenocarcinoma cells were treated with NS, Lip-null, etoposide, Lip-pVAX-M or Lip-phTERT-M, and examined for cell viability through MTT assays or for apoptosis by flow cytometry and TUNEL assays. In vivo, A549 human lung carcinoma models in nude mice were established. Mice were treated with 10 4-weekly intravenous administrations of NS, Lip-null, etoposide (2 mg/kg), Lip-pVAX-M or Lip-phTERT-M. Subsequently, Lip-phTERT-M was found to be the most efficient inhibitor of tumor growth and inducer of tumor cell apoptosis when compared with the other groups in vivo and in vitro (P<0.05). Notably, immunohistochemical staining showed that Lip-phTERT-M significantly limited the overexpression of VSV MP to the tumor tissues and reduced VSV MP expression in other organs in comparison with Lip-pVAX-M (P<0.05). Therefore, it can be concluded that phTERT-M demonstrates a targeted antitumor effect on A549 human lung adenocarcinoma cells. These observations suggest that phTERT-M gene therapy may be a novel and potent strategy for targeting human lung adenocarcinoma.

Immunosafety evaluation of a multilayer flat-plate bioartificial liver.

INTRODUCTION: To study and evaluate the immunosafety of our newly developed multilayer flat-plate bioartificial liver (BAL) in treatment of canines with acute liver failure. METHODS: Fresh porcine hepatocytes and bone marrow mesenchymal stem cells were cocultured in new BAL. Ten canine models with acute liver failure were set up through D-galactosamine administration; 24 hours after administration, the beagles were randomly allocated to a 6-hour treatment with the BAL. The beagles were divided into 2 groups by treatment times. Group 1 beagles (n = 5) received a single BAL treatment. Group 2 beagles (n = 5) received 3 BAL treatments. The hemodynamic, hematologic response and humoral immune responses to BAL therapy were studied before and after treatments. RESULTS: All beagles remained hemodynamically and hematologically stable during BAL treatments. The levels of IgG and IgM were similar before and after treatment after a single treatment. In addition, the level of CH50 in group 1 slightly decreased after the initiation of BAL treatment, and then the level recovered to baseline quickly after treatments. Time-course changes of the levels of antibodies and CH50 after 3 treatments in group 2 were similar to group 1. Only trace levels of IgG were detected in BAL medium after treatments. CONCLUSION: The multilayer flat-plate BAL showed a great immunosafety in the treatment of canines with acute liver failure and exhibited a good prospect of its use in clinic.

Diluted povidone-iodine inhibits tumor growth through apoptosis-induction and suppression of SOD activity.

Povidone-iodine (PVP-I) is widely used in clinical practice as an antiseptic and flushing agent after surgery to remove a tumor. Our present study was designed to determine whether diluted PVP-I is cytotoxic to colon cancer cells and ascetic tumor cells in vitro and to examine its antitumor effects in vivo. In vitro, CT26 and H22 cells treated with different concentrations of diluted PVP-I (0-1.56 µg/ml) were analyzed using the mononuclear cell direct cytotoxicity assay (MTT) and a flow cytometry assay. In vivo, Balb/c mice injected in the abdominal cavity with CT26 cells or H22 cells were treated intraperitoneally with different concentrations of PVP-I (0-312.5 µg/mouse), cisplatin (40 mg/kg) or 5'-FU (30 mg/kg) or left untreated. In vitro, the studies demonstrated the antiproliferative and significant apoptosis-inducing effects of PVP-I in a dose- and time-dependent manner. In vivo, PVP-I significantly repressed the growth of H22 and CT26 cells in Balb/c mice compared to controls. To explore the mechanism of the antitumor effect of PVP-I, the superoxide dismutase (SOD) activity of ascites extracted from a mouse model and the supernatant of CT26 cells was detected by an SOD kit. The activity of SOD was significantly inhibited in the experimental groups. Taken together, our data suggest that PVP-I exhibits a strong inhibitory effect on tumor growth in colon cancer (CT26) and hepatoma (H22) resulting from apoptosis, both in vitro and in vivo, suggesting a new potential therapeutic approach after tumor excision surgery to colon cancer and hepatoma.

The influence of membrane molecular weight cutoff on a novel bioartificial liver.

Given the xenogeneic immune reaction relevant to the molecular weight cutoff of the membrane of a bioartificial liver (BAL) system, we investigated the influence of membrane molecular weight cutoff in our BAL system in this study. Acute liver failure in beagles was induced by d-galactosamine administration. Eight beagles were divided into two groups by the membrane molecular weight cutoff of the plasma component separator. Group 1 beagles were treated with BAL containing 200 kDa retention rating membrane. Group 2 beagles were treated with BAL containing 1200 kDa retention rating membrane. Each group underwent two 6-h BAL treatments that were performed on day 1 and day 21. The hemodynamic and hematologic response, humoral immune responses, and cytotoxic immune response to BAL therapy were studied before and after treatments. All beagles remained hemodynamically and hematologically stable during BAL treatments. BAL treatment was associated with a significant decline in levels of complement; however, a longer time of level maintenance was observed in Group 2. Group 2 beagles experienced a significant increase in levels of IgG and IgM after two BAL treatments. Significant levels of canine proteins were detected in BAL medium from Group 2; only trace levels of canine proteins were detected in BAL medium from Group 1. The posttreatment viability of co-culture cells in Group 2 was lower compared with Group 1, and the viability of co-culture cells after treatments was associated with deposition of canine proteins on the cells. Xenogeneic immune response was influenced by membrane molecular weight cutoff in the BAL.

Effects of membrane molecular weight cutoff on performance of a novel bioartificial liver.

Immunoisolation using semipermeable membranes has been incorporated into bioartificial liver (BAL) devices to separate cellular components of the recipient's immune system from the cells within the BAL device. This study was designed to explore the influence of membrane molecular weight cutoff on performance of the multilayer radial-flow BAL using porcine hepatocytes cocultured with mesenchymal stem cells. In this study, healthy beagles underwent 6-h treatment with a BAL containing membrane with 200 kDa retention rating or 1200 kDa retention rating. Functional markers of BAL performance were monitored before and after treatment, as well as cytotoxic immune response to BAL therapy. The results showed that hepatocyte performance levels such as albumin secretion, urea synthesis, and viability were all significantly higher in 200 kDa retention rating group compared with the 1200 kDa retention rating group after treatment (P < 0.05). Significant levels of canine proteins were detected in BAL medium from the 1200 kDa retention rating group. Fluorescence microscopy further verified that heavy deposition of canine IgG, IgM, and complement (C3) on coculture cells was obtained after BAL treatment in the 1200 kDa retention rating group. However, only trace deposits of canine immunoproteins were observed on coculture cells obtained from BAL in the 200 kDa retention rating group. Small membrane molecular weight cutoff of the BAL could reduce the transfer of xenoreactive antibodies into the BAL medium and improve the performance of the BAL.