[Diagnosis of invasion of tumor depth and surgical decision in gallbladder carcinoma].
Explore the source record for details and available documents.
Biliary Tract Surgical Procedures↗
Biomedical subjects
Kuniharu Yamamoto
Publications and source records attributed to Kuniharu Yamamoto.
[Low-dose cisplatin plus 5-fluorouracil with radiotherapy for unresectable upper and hilar bile duct carcinoma].
We report herein the value of a combined treatment modality for bile duct cancer (intraluminal brachytherapy: ILBT+extrabeam radiation therapy+chemotherapy+expandable metallic biliary stent), employed for cases in which excision of the upper and the hilar bile duct cancer was not possible. The combined treatment modality group did not attain a two-year survival rate according to the Kaplan Meier method. They were not able to surpass the treatment results of the excision group which ended in radical cure level of C. Moreover, with the combined modality treatment, the addition of radiation therapy significantly improved the cumulative survival rate. In conclusion, the first choice of treatment for the upper and the hilar bile duct cancer is excision, and it is necessary to thoroughly examine the possibility of excision. Additionally, to surpass the treatment results of the excision group that ended in a radical cure level of C, it is necessary to include radiation therapy and chemotherapy using new anti-cancer drugs in a combined treatment modality.
Antimetabolites, Antineoplastic↗
A novel adenovirus expressing human 4-1BB ligand enhances antitumor immunity.
4-1BB ligand (4-1BBL), a member of the tumor necrosis factor (TNF) superfamily, interacts with 4-1BB (CDw137) expressed on activated T cells and delivers a costimulatory signal for T cell activation and growth. Various studies have demonstrated a role for murine 4-1BB in immune function, but relatively few investigations of human 4-1BB have been conducted. Here we report on the construction of a recombinant E1/E3-deleted adenovirus encoding human 4-1BBL (Ad4-1BBL) and its stimulation of antitumor immunity. Ad4-1BBL was able to efficiently infect several human adenocarcinoma cell lines and induce 4-1BBL expression on the cell surface within 24 h, this enhancing the antitumor activity not only of lymphokine-activated killer cells with a T cell phenotype (T-LAK) but also naive peripheral blood mononuclear cells (PBMC). This antitumor activity with T-LAK cells was further enhanced by addition of bispecific antibody (BsAb; anti-MUC1xanti-CD3). Cocultivation of Ad4-1BBL-infected tumor cells with either T-LAK cells or PBMC resulted in significant elevation of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and granulocyte-macrophage colony-stimulating factor (GM-CSF) production. Furthermore, remarkable tumor growth inhibition was observed in cholangiocarcinoma-grafted severe combined immunodeficient (SCID) mice to which Ad4-1BBL and T-LAK cells were administered when tumor size exceeded 5 mm in diameter. These results provide strong evidence in support of the efficacy of adenovirally delivered 4-1BBL for genetic immunotherapy of cancer.
4-1BB Ligand↗
[Laparoscopic biliary surgery].
Laparoscopic cholecystectomy has become the standard treatment for patients with symptomatic gallbladder disease. However, there is a substantial proportion of patients in whom laparoscopic cholecystectomy cannot be successfully performed, and conversion to open surgery is required because of technical difficulties or complications. The incidence of bile duct injury has increased in laparoscopic cholecystectomy. Meticulous dissection and intraoperative cholangiography could significantly reduce the rate of that injury. Laparoscopic cholecystectomy for acute cholecystitis is still controversial because of surgical difficulty. In our experience, early laparoscopic cholecystectomy is a beneficial option for patients with acute cholecystitis, and it may even be safe in the acute stage. A better alternative for high-risk early operation and septic cases is percutaneous transhepatic gallbladder drainage. The coexistence of gallbladder cancer should be ruled out and preoperative diagnosis should be done carefully. Laparoscopic management of common bile duct (CBD) stones has many advantages. However it has been reported to be demanding and time-consuming to perform, which limits its widespread adoption. In our experience with 258 patients, laparoscopic CBD exploration was feasible for almost all CBD stones. The technical difficulties associated with laparoscopic CBD exploration could be overcome with the development of suitable equipment and increased expertise.
Cholecystectomy, Laparoscopic↗
Adenovirus expressing p27KIP1 induces apoptosis against cholangiocarcinoma cells by triggering Fas ligand on the cell surface.
BACKGROUND/AIMS: The prognosis of patients with cholangiocarcinoma is poor because of the difficulty of surgical curative resection. Therefore, other effective treatments must be developed especially those involving gene therapy. p27kip1, one of the cyclin-dependent kinase inhibitors, is known to limit proliferation of the cells. Our previous reports have shown that the overexpression of p27kip1 by a recombinant adenoviral vector expressing p27kip1 (Adp27) induces apoptosis. However, the mechanism of the Adp27-mediated apoptosis is not still resolved. Activation of the Fas pathway is one of the important gates for apoptosis. In this report, we examined whether p27kip1-induced apoptosis is closely related to the Fas/Fas ligand (FasL) system. RESULTS: After infection of Adp27, flow cytometric analysis showed that Fas ligand was expressed on the cell surface of cholangiocarcinoma cell lines (TFK-1). In spite of detecting the cell surface expression of Fas ligand, overexpression of p27kip1 increased no amount of Fas ligand in mRNA by quantitative RT-PCR and protein level by Western blot. In addition, the immunocytochemical analysis showed that Fas ligand was adequately stored within the cytosol of TFK-1 cells. More interestingly, Adp27-induced apoptosis was completely inhibited by the neutralizing antibody of Fas ligand (NOK-1). This result suggests that overexpression of p27kip1 may deliver Fas ligand to the cell surface and mainly utilizes the Fas pathway as a gate of apoptosis. CONCLUSIONS: This is the first report to prove that Adp27-mediated apoptosis utilizes the Fas pathway by delivering Fas ligand to the cell surface.
Adenoviridae↗
Adenovirus expressing mutant p27kip1 enhanced apoptosis against cholangiocarcinoma than adenovirus-p27kip1 wild type.
BACKGROUND/AIMS: The prognosis of cholangiocarcinoma is extremely poor despite the aggressive multidisciplinary cancer therapies that have been used clinically. Thus, it is imperative to develop new and effective treatments, such as gene therapy in order to treat this disease. p53 is the most common target for cancer gene therapy treatment. However, cholangiocarcinoma has a low frequency of p53 mutation, which makes this protein a poor candidate for gene therapy in this disease and another suitable gene therapy target must be found. p27kip1 is a universal cyclin-dependent kinase (CDK) inhibitor that blocks cell cycle progression and inhibits proliferation. Our previous reports have demonstrated the role of p27kip1 in the induction of apoptosis using a recombinant adenoviral vector expressing p27kip1 (Adp27) in several different human cancer cells. p27kip1 is regulated by two mechanisms composed of a ubiquitin-proteasome system and proteolytic processing system that requires the phosphorylation of p27kip1 on Thr-187 by the cyclinE/Cdk2 complex followed by proteolytic degradation. METHODOLOGY: In this study, we focused our aim on the degradation of p27kip1 protein mediated by a recombinant adenoviral expressing a mutant p27kip1 (Adp27-mt), which has a mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188 (ATGATC). RESULTS: We observed that the mutated p27kip1 markedly inhibited ubiquitination and the subsequent degradation of p27kip1 when compared to wild type p27kip1. Consequently, we found that mutated p27kip1 induced a stronger induction of apoptosis and cell growth inhibition than wild type p27kip1 in cholangiocarcinoma cell lines TFK-1 and HuCCT-1. Furthermore, we demonstrated that Adp27-mt mainly caused G2/M arrest in the cell cycle progression and a decreased cyclinB1 and Cdc2 protein where as Adp27-wt mediated a G1/S arrest at 48 hours after infection. CONCLUSIONS: In this study, we showed that adenoviral vector expression of mutant p27kip1 protein inhibited degradation by the ubiquitin-proteasome system and strongly induced apoptosis and cell growth inhibition compared to wild type p27kip1. Thus recombinant adenovirus expressing mutant p27kip1 may be potentially useful for gene therapy against cholangiocarcinoma.
Adenoviridae↗