Microbial Antigen-Presenting Extracellular Vesicles Derived from Genetically Modified Tumor Cells Promote Antitumor Activity of Dendritic Cells.

Tumor-derived extracellular vesicles (EVs), as tumor vaccines, carry tumor-associated antigens (TAAs), and were expected to transfer TAAs to antigen-presenting cells. However, treatment with tumor-derived EVs exhibited no obvious antitumor effect on the established tumors, likely due to their immuno-suppressive functions, and also to the poor immunogenicity of TAAs. In order to improve the immune stimulating properties, EVs expressing a highly immunogenic bacterial antigen, 6 kDa early secretory antigenic target (ESAT-6), from Mycobacterium tuberculosis were prepared by genetically modifying the parent tumor cells with a plasmid coding for ESAT-6.

Tumor Growth Suppression With Novel Intra-arterial Chemotherapy Using Epirubicin-entrapped Water-in-oil-in-water Emulsion .

Background/aim: A mixture of anticancer agents and iodized poppy seed oil (IPSO) has been widely used for intra-arterial chemotherapy of hepatocellular carcinoma. However, the anticancer agents can easily separate from IPSO, so the therapeutic potential is limited. We developed epirubicin-entrapped water-in-oil-in-water emulsion (WOW-Epi) using a double-membrane emulsification technique.

Bioadhesive and biodissolvable hydrogels consisting of water-swellable poly(acrylic acid)/poly(vinylpyrrolidone) complexes.

Films that can form bioadhesive hydrogels on wet biotissues absorbing blood or body fluids are useful for medical devices such as hemostats, adhesion barriers, wound dressings, and drug release devices. We focused on a hydrogen-bonding polymer complex consisting of poly(acrylic acid) (PAA) and poly(vinylpyrrolidone) (PVP). PAA is known as a tissue-adhesive polymer.

Selective boron delivery by intra-arterial injection of BSH-WOW emulsion in hepatic cancer model for neutron capture therapy.

Objective: Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a BSH-entrapped water-in-oil-in-water (WOW) emulsion, evaluated it as a selective boron carrier for the possible application of BNCT in hepatocellular carcinoma treatment.

Methods: We prepared the BSH-entrapped WOW emulsion using double emulsification technique and then evaluated the delivery efficacy by performing biodistribution experiment on VX-2 rabbit hepatic tumour model with comparison to iodized poppy-seed oil mix conventional emulsion.

Exosomes derived from tumor cells genetically modified to express Mycobacterium tuberculosis antigen: a novel vaccine for cancer therapy.

Objectives: To examine the potential of exosomes derived from the tumor cells, which had been genetically modified to express a Mycobacterium tuberculosis antigen, as a cancer vaccine aimed at overcoming the weak immunogenicity of tumor antigens.

Results: We transfected B16 melanoma cells with a plasmid encoding the M. tuberculosis antigen, early secretory antigenic target-6 (ESAT-6).

Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a (10)BSH-containing WOW emulsion.

A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the first patient in a pilot study of boron neutron capture therapy (BNCT) involving the selective intra-arterial infusion of a (10)BSH-containing water-in-oil-in-water emulsion ((10)BSH-WOW). The size of the tumorous region remained stable during the 3 months after the BNCT. No adverse effects of the BNCT were observed.

Feasibility evaluation of neutron capture therapy for hepatocellular carcinoma using selective enhancement of boron accumulation in tumour with intra-arterial administration of boron-entrapped water-in-oil-in-water emulsion.

Introduction: Hepatocellular carcinoma (HCC) is one of the most difficult to cure with surgery, chemotherapy, or other combinational therapies. In the treatment of HCC, only 30% patients can be operated due to complication of liver cirrhosis or multiple intrahepatic tumours. Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of (10)B atoms in tumour cells for effective tumour cell destruction by BNCT.

[Chemokine and chemokine receptor related to cancer metastasis].

The relationship has become clear between the expression of chemokine/chemokine receptors on cancer cells and the invasion, metastasis and peritoneal dissemination. Many cancer cells express chemokine receptors which are not expressed on the surface of normal tissues. Recently, it has been reported that overexpression of CXCR4/CXCL12 is related with metastasis to lung, liver, lymph nodes and bone marrow, while the overexpression of CCR7/CCL21 is mainly related with lymph node metastasis.

Tumor growth suppression by adenovirus-mediated introduction of a cell-growth-suppressing gene tob in a pancreatic cancer model.

TOB (transducer of ErbB-2) is a tumor suppressor that interacts with protein-tyrosine kinase receptors, including ErbB-2. Introduction of the tob gene into NIH3T3 cells results in cell growth suppression. In this study, we evaluated the effect of tob expression in pancreatic cell lines (AsPC-1, BxPC-3, SOJ) and discuss the tumor-suppressing effects of adenoviral vector expressing tob cDNA.

Improvement of sensitivity to platinum compound with siRNA knockdown of upregulated genes in platinum complex-resistant ovarian cancer cells in vitro.

It is known that some cancers show platinum complex resistance and that others show platinum complex sensitivity among ovarian cancers. Oxaliplatin (cis-[oxalato[trans-l-1, 2-diamino-cyclohexane] platinum[II]]; l-OHP), an active anti-cancer agent consisting of platinum, inhibits RNA synthesis and results in cytostatic effects. We investigated the difference between an oxaliplatin-resistant ovarian cancer cell line, KFR, and an oxaliplatin-sensitive ovarian cancer cell line, KF-1, using DNA microarray analysis.

Application of drug delivery system to boron neutron capture therapy for cancer.

Background: Tumor cell destruction in boron neutron capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons ((10)B + (1)n --> (7)Li + (4)He (alpha) + 2.31 MeV (93.7 %)/2.

Highly efficient in vivo gene transfection by plasmid/PEI complexes coated by anionic PEG derivatives bearing carboxyl groups and RGD peptide.

A new class of an anionic poly (ethylene glycol) derivative, PEG-Suc, bearing 17.7 pairs of carboxylic acid-side chains was synthesized. PEG-Suc deposited onto the DNA/polyethyleneimine complexes without destroying them even at high dose ratio.

Effective anti-tumor activity of oxaliplatin encapsulated in transferrin-PEG-liposome.

Oxaliplatin (trans-L-diaminocyclohexane oxalatoplatinum, L-OHP) is a novel cisplatin derivative that can improve the side effects of cisplatin such as toxicity to the kidneys and peripheral nerve system. However, L-OHP is effective only when combined with 5-Fluorouracil (5-FU) and Leucovorin. The relatively low anti-tumor index of L-OHP alone is because low levels accumulate in tumor tissues due to high partitioning to erythrocytes in vivo.

Evaluation of neutron dosimetry on pancreatic cancer phantom model for application of intraoperative boron neutron-capture therapy.

Pancreatic cancer is one of the most difficult neoplasms to cure and there is a need for new combinated therapy. If sufficient boron compound can be targeted accurate to the tumour, Boron Neutron-Capture Therapy (BNCT) can be applied to pancreatic cancer. We administrated BNCT to a cancer with pancreatic cancer patient using intraoperative irradiation.

Gene transfer by DNA/mannosylated chitosan complexes into mouse peritoneal macrophages.

Chitosan is a biodegradable and biocompatible polymer and is useful as a non-viral vector for gene delivery. In order to deliver pDNA/chitosan complex into macrophages expressing a mannose receptor, mannose-modified chitosan (man-chitosan) was employed. The cellular uptake of pDNA/man-chitosan complexes through mannose recognition was then observed.

Combined immunocell therapy using activated lymphocytes and monocyte-derived dendritic cells for malignant melanoma.

Background: The beneficial effects of immunocell therapy, using either activated lymphocytes (ALs) or dendritic cells (DCs), in the treatment of melanoma has been demonstrated. DCs are professional antigen-presenting cells that induce cytotoxic T lymphocytes against tumor cells. DC therapy may be promising when combined with ALs.

Efficacy of immuno-cell therapy in patients with advanced pancreatic cancer.

Background: Patients with advanced pancreatic carcinoma have a risk of relapse after primary therapy, and the prognosis for these patients remains bleak. The effect of immuno-cell therapy in advanced pancreatic carcinoma, with or without other standard therapies, was examined.

Patients And Methods: Forty-six patients with advanced pancreatic carcinoma, undergoing immuno-cell treatment, were evaluated.

Preparation of antitumor oxaliplatin/cisplatin docking dinuclear platinum complex.

A new dinuclear docking Pt(II) complex, (cis-diammine) (l-1,2-cyclohexanediamine)(mu-dichloro)-diplatinum(II) oxalate was synthesized by reacting oxaliplatin(l-OHP, [Pt(oxalato)(L-dach)]), L-dach = 1R, 2R-cyclohexanediamine), with cisplatin (CDDP). Elemental analysis of the compound indicated that it was 1:1 molar ratio complex of oxaliplatin and cisplatin. A plausible chemical structure has been proposed as Cl(-) bridged dinuclear complex, judged from its yellow coloration and NMR spectral analysis.

A report of three patients treated with immunocell therapy with imatinib mesylate.

Background: Immunocell therapy has been applied to patients with refractory cancer in clinical trials or as an unconventional cancer therapy, however the efficacy is still limited. To improve this efficacy, a combination therapy may be beneficial. Molecularly-targeted therapy acts directly on neoplasm cells to suppress their growth without causing myelosuppression.

Intracellular targeting of sodium mercaptoundecahydrododecaborate (BSH) to solid tumors by transferrin-PEG liposomes, for boron neutron-capture therapy (BNCT).

The successful treatment of cancer by boron neutron-capture therapy (BNCT) requires the selective delivery of relatively high concentration of 10B compounds to malignant tumor tissue. This study focuses on a new tumor-targeting drug delivery system for BNCT that uses small (less than 200 nm in diameter), unilamellar mercaptoundecahydrododecaborate (BSH)-encapsulating, transferrin (TF)-conjugated polyethyleneglycol liposomes (TF-PEG liposomes). When TF-PEG liposomes were injected at a dose of 35 mg 10B/kg, we observed a prolonged residence time in the circulation and low uptake by the reticuloendothelial system (RES) in Colon 26 tumor-bearing mice, resulting in enhanced accumulation of 10B into the solid tumor tissue (e.

Accumulation of boron compounds to tumor with polyethylene-glycol binding liposome by using neutron capture autoradiography.

The cytotoxic effect of boron neutron capture therapy (BNCT) is due to a nuclear reaction between 10B and thermal neutrons. It is necessary to accumulate the 10B atoms to the tumor cells selectively for effective BNCT. In order to achieve an accurate measurement of 10B concentrations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of the sliced whole-body samples of tumor bearing mice using CR-39 plastic track detectors.

Cholesterol hepatolithiasis with peribiliary cysts.

A 78-year-old man was admitted to our clinic because of fatigue. Imaging modalities showed beaded stricture and dilation of the intrahepatic left segmental bile duct. Anomalous pancreatico-biliary ductal union and polycystic kidney disease were absent.

Advanced renal cell carcinoma treated with granulocyte-macrophage colony-stimulating factor gene therapy: a clinical course of the first Japanese experience.

A phase I study of granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor vaccine for patients with metastatic renal cell carcinoma (RCC) was initiated in 1998, as the first cancer gene therapy in Japan. The study is still ongoing, but the first patient is presented here as a case report. The patient was a 60-year-old man with Stage IV CRC with multiple lung metastases.