orabase and Liver-Neoplasms

To assess by prospective randomized controlled trial the feasibility and efficacy of using a bioresorbable hyaluronic acid/carboxymethylcellulose membrane (HA membrane) to prevent abdominal and perihepatic adhesions in metastatic colorectal cancer patients requiring 2-stage hepatectomy.. Two-stage hepatectomy offers the possibility of long-term survival to selected patients whose liver metastases cannot be removed in a single procedure. However, the second operation is made more difficult by adhesions arising from the first. HA membrane reduces adhesions in gynecologic and abdominal surgery but this is the first trial in hepatectomy.. Fifty-four candidates for 2-stage hepatectomy were randomized at the end of the first procedure to implantation of HA membrane (n = 41) or standard management (n = 13). Thirty patients from the membrane arm and 11 well-matched controls underwent the planned second hepatectomy.. Positioning of the HA membranes was feasible in all but one patient and did not increase complications associated with the first hepatectomy. At second hepatectomy, patients in the HA membrane arm required 33% less time than controls to achieve complete liver mobilization (median: 50 vs 75 minutes; primary endpoint). The risk of extensive adhesions was reduced in the HA membrane group (31% had grade 3-4 adhesions vs 55% in controls), as was adhesion severity (17% thick and hypervascular adhesions vs 46%). The proportion of patients with complications at second hepatectomy was higher in the control group (55% vs 23% in the HA membrane group, P = 0.07).. Use of 4 HA membranes at the end of first hepatectomy reduced the extent and severity of adhesions and facilitated the second hepatectomy in patients with liver metastases who required a 2-stage hepatectomy. A larger study to confirm these findings is warranted. (NCT01262417).

Topics: Absorbable Implants; Adult; Aged; Carboxymethylcellulose Sodium; Colorectal Neoplasms; Female; Hepatectomy; Humans; Hyaluronic Acid; Liver Neoplasms; Male; Membranes, Artificial; Middle Aged; Prospective Studies; Reoperation; Survival Rate; Tissue Adhesions; Treatment Outcome

The efficacy of treatment for advanced hepatocellular carcinoma (HCC) has remained limited. Polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) is a synthetic double-stranded RNA that serves as a viral mimic and induces an immune response. Intratumoral (IT) poly-ICLC injections can induce an autovaccination effect and prime the immune system, whereas intramuscular (IM) injection of poly-ICLC can attract and maintain tumor-specific cytotoxic T lymphocytes in tumors. We found that IT injection of poly-ICLC upregulated the expression of CD83 and CD86 on conventional type 1 dendritic cells in tumors. Combination therapy with IT followed by IM injections of poly-ICLC significantly inhibited tumor growth and increased the tumor-infiltrating CD8

Topics: Animals; Carboxymethylcellulose Sodium; Carcinoma, Hepatocellular; CD8-Positive T-Lymphocytes; Liver Neoplasms; Mice; Poly I-C; Polylysine; Vaccination

Curcumin is a more efficient polyphenol than many chemotherapeutics. It can inhibit many signaling pathways at the same time resulting in modulation and down regulation for many oncogenic activities, tumor suppressor genes, several transcription factors and their signaling pathways. However it is still not employed as a potential therapeutic tool for cancer treatment. This is due to its hydrophobicity, its hypersensitivity and its poor adsorption. Many trials have been applied for encapsulating curcumin as a delivery system thinking to save its biological benefits. In our recent work, encapsulated curcumin was successfully used to produce bio cross-linkers for mucoadhesive polymer forming multi branched or flower like shape. Moreover, this strategy is not used only to save its biological function, but also to provide a novel bio cross-linker for hydrogel system. This study was investigated by using scanning electron microscopy, FTIR, U-V Visible Spectroscopy. Encapsulated curcumin provides promising bio safe cross-linker for optimizing hydrogel system, since carboxymethyl cellulose raises its ability to penetrate mucus layer. Additionally, flow cytometry and cytotoxicity show ability of encapsulated curcumin to inhibit proliferation of liver cancer cells.

Topics: Carboxymethylcellulose Sodium; Curcumin; Drug Carriers; Humans; Liver Neoplasms; Nanoparticles

Perihepatic adhesions induced by hepatectomy make the subsequent repeat hepatectomy technically demanding. The aim of this study was to verify the effect of hyaluronic acid/carboxymethyl cellulose-based bioresorbable membrane (HA membrane) in preventing posthepatectomy adhesion formation by focusing on the ease of the adhesiolysis in subsequent hepatectomy for recurrent tumors.. A total of 201 patients who underwent hepatectomy using HA membrane were prospectively followed-up for 3 years. Thirty of the 201 patients underwent a repeat hepatectomy for recurrence. The operative data of 85 cases of repeat hepatectomy, the primary hepatectomy of which had been performed without the use of HA membrane, served as the historical control data. The primary endpoint was the time interval between the skin incision and the start of hepatic parenchymal transection (the preparation time) including adhesiolysis. Secondary endpoints were blood loss during the operation, incidence of postoperative complications, and the biochemical data.. The median preparation time (183 vs. 228 min; p = 0.027) and total operation time (374 vs. 439 min; p = 0.041) were significantly shorter in the HA membrane group than in the control group.. Use of HA membranes during hepatectomy enabled significant shortening of the adhesiolysis time during the sequential hepatectomy performed for recurrent tumors.

Topics: Absorbable Implants; Adult; Aged; Aged, 80 and over; Biocompatible Materials; Carboxymethylcellulose Sodium; Cohort Studies; Hepatectomy; Hospitals, University; Humans; Hyaluronic Acid; Liver Neoplasms; Membranes, Artificial; Middle Aged; Postoperative Complications; Prognosis; Prospective Studies; Reference Values; Statistics, Nonparametric; Tissue Adhesions; Treatment Outcome

Hepatocellular carcinoma (HCC) is associated with high mortality and the current therapy for advanced HCC, Sorafenib, offers limited survival benefits. Here we assessed whether combining the TLR3 agonist: lysine-stabilized polyinosinic-polycytidylic-acid (poly-ICLC) with Sorafenib could enhance tumor control in HCC. Combinatorial therapy with poly-ICLC and Sorafenib increased apoptosis and reduced proliferation of HCC cell lines in vitro, in association with impaired phosphorylation of AKT, MEK and ERK. In vivo, the combinatorial treatment enhanced control of tumor growth in two mouse models: one transplanted with Hepa 1-6 cells, and the other with liver tumors induced using the Sleeping beauty transposon. Tumor cell apoptosis and host immune responses in the tumor microenvironment were enhanced. Particularly, the activation of local NK cells, T cells, macrophages and dendritic cells was enhanced. Decreased expression of the inhibitory signaling molecules PD-1 and PD-L1 was observed in tumor-infiltrating CD8+ T cells and tumor cells, respectively. Tumor infiltration by monocytic-myeloid derived suppressor cells (Mo-MDSC) was also reduced indicating the reversion of the immunosuppressive tumor microenvironment. Our data demonstrated that the combinatorial therapy with poly-ICLC and Sorafenib enhances tumor control and local immune response hence providing a rationale for future clinical studies.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Carboxymethylcellulose Sodium; Carcinoma, Hepatocellular; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cell Proliferation; Cell Survival; Disease Progression; Extracellular Signal-Regulated MAP Kinases; Humans; Immune System; Immunosuppressive Agents; Liver Neoplasms; Male; MAP Kinase Kinase Kinases; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Niacinamide; Phenylurea Compounds; Phosphorylation; Poly I-C; Polylysine; Proto-Oncogene Proteins c-akt; Signal Transduction; Sorafenib; Toll-Like Receptor 3

We report herein the development of a smart magnetic nanoparticle-aptamer probe, or theranostic nanoprobe, which can be used for targeted imaging and as a drug carrier for hepatocellular carcinoma treatment. The theranostic nanoprobe combines the delivery potential of a non-toxic cellulose derivative polymer, specific capability of cancer-specific molecule (DNA-based EpCAM aptamer) and the imaging capability of magnetic iron oxide nanoparticles. Our proof-of-concept design demonstrates efficient in vitro MR imaging of the cancer cells, and enhanced delivery of an anticancer drug into the cancer cells with comparable treatment efficacy.

Topics: Antigens, Neoplasm; Antimetabolites, Antineoplastic; Aptamers, Nucleotide; Carboxymethylcellulose Sodium; Carcinoma, Hepatocellular; Cell Adhesion Molecules; Cell Survival; Doxorubicin; Epithelial Cell Adhesion Molecule; Ferric Compounds; Hep G2 Cells; Humans; Liver Neoplasms; Magnetic Phenomena; Magnetic Resonance Imaging; Metal Nanoparticles

Topics: Adult; Aged; Carboxymethylcellulose Sodium; Carcinoma, Hepatocellular; Dextrans; Drug Combinations; Embolization, Therapeutic; Female; Gelatin Sponge, Absorbable; Humans; Iodamide; Iodized Oil; Iron; Liver; Liver Neoplasms; Male; Middle Aged

Topics: Analysis of Variance; Carboxymethylcellulose Sodium; Carcinoma, Hepatocellular; Dextrans; Drug Combinations; Embolization, Therapeutic; Gelatin Sponge, Absorbable; Humans; Iodamide; Iodobenzoates; Iron; Liver Neoplasms; Methylcellulose; Prognosis

Topics: Animals; Biological Products; Carboxymethylcellulose Sodium; Carcinoma, Hepatocellular; Catheterization; Dextrans; Drug Combinations; Embolization, Therapeutic; Gelatin Sponge, Absorbable; Hepatic Artery; Humans; Iodamide; Iodized Oil; Iron; Liver Neoplasms; Liver Neoplasms, Experimental; Male; Middle Aged; Picibanil; Rabbits

Ferromagnetic microembolization (FME) was applied to patients with hepatoma, using iron microspheres (30-50 mu), suspended in aqueous polysaccharide solution; dextran 40 (12%), sodium carboxymethyl-cellulose (2%) in saline solution. Hepatic arterial infusion of this agent was performed under external magnetic control to confine iron microspheres within the target organs. The therapeutic effect of this procedure on 44 patients with hepatoma was evaluated in relation to the stages of the disease, showing excellent, improved survival terms; survival rates calculated by Kaplan-Meier's method for patients with stage I to III hepatomas were 80% (1 year), 50% (2 years) and 30% (3 years). In order to extend the therapeutic effect of this procedure further, polysaccharide solution was also utilized as a carrier of anti-cancer agents. Serologic and histologic data in experimental animals showed evidence of prolonged release of Mitomycin from polysaccharide solution admixed, indicating its potential use as a method of chemo-embolization. In addition to this, we have also been developing the induction heating of the magnetic microspheres, introduced into the lesion by means of FME, to heat the lesion selectively. The procedure is still in the experimental phase. However, recent results strongly suggest the possibility of its clinical use. In conclusion, we consider FME to be one of the most reliable and potentially valuable methods for extending the capability of multidisciplinary treatment of hepatoma.

Topics: Animals; Antineoplastic Agents; Carboxymethylcellulose Sodium; Carcinoma, Hepatocellular; Dextrans; Drug Combinations; Embolization, Therapeutic; Humans; Hyperthermia, Induced; Iodamide; Iron; Liver Neoplasms; Liver Neoplasms, Experimental; Magnetics; Microspheres; Rabbits

Topics: Carboxymethylcellulose Sodium; Carcinoma, Hepatocellular; Dextrans; Drug Combinations; Embolization, Therapeutic; Humans; Iodamide; Iron; Liver Neoplasms; Microspheres

Topics: Animals; Carboxymethylcellulose Sodium; Dextrans; Drug Combinations; Embolization, Therapeutic; Humans; Iodamide; Iodobenzoates; Iron; Kidney Neoplasms; Liver Neoplasms; Magnetics; Male; Methylcellulose; Middle Aged; Rabbits