OX40 ligand expressed by DCs costimulates NKT and CD4+ Th cell antitumor immunity in mice.

The exceptional immunostimulatory capacity of DCs makes them potential targets for investigation of cancer immunotherapeutics. We show here in mice that TNF-alpha-stimulated DC maturation was accompanied by increased expression of OX40 ligand (OX40L), the lack of which resulted in an inability of mature DCs to generate cellular antitumor immunity. Furthermore, intratumoral administration of DCs modified to express OX40L suppressed tumor growth through the generation of tumor-specific cytolytic T cell responses, which were mediated by CD4+ T cells and NKT cells.

Efficacy of preoperative radiotherapy to portal vein tumor thrombus in the main trunk or first branch in patients with hepatocellular carcinoma.

Background: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in the main trunk or the first branch is very poor.

Methods: Radiotherapy (RT) to PVTT was followed by hepatectomy within 2 weeks. The dose used was 30-36 Gy, in 10-12 fractions, for 15-20 days.

Feasibility study of single agent Cisplatin and concurrent radiotherapy in Japanese patients with squamous cell carcinoma of the head and neck: preliminary results.

Background: Concurrent chemoradiotherapy with the single agent cisplatin (CDDP + RT) has been recognized worldwide as the standard treatment for unresectable locally advanced SCCHN. The objective of this study was to clarify the feasibility of CDDP + RT in Japanese patients. Patients and methods Patients with unresectable squamous cell carcinoma of the head and neck were given single daily fractionated radiation (70 Gy at 2 Gy/day) and chemotherapy consisting of a 2 h infusion of CDDP 100 mg/m(2) on days 1, 22 and 43.

Study of compounds suppressing free radical generation from UV-exposed ketoprofen.

Ketoprofen [(RS)-2-(3-benzoylphenyl)propanoic acid] is widely used for the treatment of inflammatory diseases and musculoskeletal injury. However, there is concern regarding its potential for photosensitization as a side effect. Free radicals and active oxygen species generated from ketoprofen on exposure to ultraviolet (UV) light have been implicated in phototoxicity and photosensitization.

A human lung carcinoma cell line supports efficient measles virus growth and syncytium formation via a SLAM- and CD46-independent mechanism.

Measles virus (MV) propagates mainly in lymphoid organs throughout the body and produces syncytia by using signaling lymphocyte activation molecule (SLAM) as a receptor. MV also spreads in SLAM-negative epithelial tissues by unknown mechanisms. Ubiquitously expressed CD46 functions as another receptor for vaccine strains of MV but not for wild-type strains.

Influence of delayed tumor clearance on reliability of complete response rate in chemoradiotherapy for head and neck cancer.

Objective: The relationship was studied between the timing of assessment of complete response and ultimate cure rate in the chemoradiotherapy of advanced head and neck cancer.

Methods: A retrospective review was conducted regarding tumor responses at 4 weeks, 3 months, and 6 months after concomitant chemoradiotherapy using cisplatin and 5-FU for 70 patients with stage III/IV squamous cell carcinoma of the oropharynx, hypopharynx and supraglottic larynx. Predictive values of tumor responses at these three time points for survival and tumor control at 2 years were tested using the chi-square test.

Feasibility of oxaliplatin and infusional fluorouracil/leucovorin (FOLFOX4) for Japanese patients with unresectable metastatic colorectal cancer.

Background: A combination of oxaliplatin and infusional fluorouracil/leucovorin (FOLFOX4) is one of the standard regimens for palliative and adjuvant chemotherapy for colorectal cancer. However, the feasibility of FOLFOX4 for Japanese patients has not been determined. We conducted this prospective study to evaluate the feasibility of FOLFOX4.

Accelerated radiotherapy and larynx preservation in favorable-risk patients with T2 or worse hypopharyngeal cancer.

Objective: To evaluate the advantage of accelerated fractionation radiotherapy for patients with hypopharyngeal cancer requiring total laryngectomy.

Methods: Seventy patients with previously untreated, technically resectable hypopharyngeal cancer who received larynx-preserving treatment with radiotherapy between April 1992 and June 2004 were analyzed. No patients had previous history of other malignancy or poor performance status that would possibly affect the outcomes.

Altered interaction of the matrix protein with the cytoplasmic tail of hemagglutinin modulates measles virus growth by affecting virus assembly and cell-cell fusion.

Clinical isolates of measles virus (MV) use signaling lymphocyte activation molecule (SLAM) as a cellular receptor, whereas vaccine and laboratory strains may utilize the ubiquitously expressed CD46 as an additional receptor. MVs also infect, albeit inefficiently, SLAM(-) cells, via a SLAM- and CD46-independent pathway. Our previous study with recombinant chimeric viruses revealed that not only the receptor-binding hemagglutinin (H) but also the matrix (M) protein of the Edmonston vaccine strain can confer on an MV clinical isolate the ability to grow well in SLAM(-) Vero cells.

A phase I dose-escalation study of ZD6474 in Japanese patients with solid, malignant tumors.

Introduction: ZD6474 (vandetanib) is an orally available inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor, and RET receptor tyrosine kinase activity. This study assessed the safety and tolerability of escalating doses of ZD6474 in Japanese patients with solid, malignant tumors.

Methods: Adult patients with solid tumors refractory to standard therapy received a once-daily oral dose of ZD6474 (100-400 mg) in 28-day cycles, until disease progression or unacceptable toxicity was observed.

Peritoneal fluids from patients with certain gynecologic tumor contain elevated levels of bioactive lysophospholipase D activity.

Levels of lysophosphatidic acid (LPA), an important phospholipid mediator, in serum and ascitic fluid from ovarian cancer patients were shown to be higher than those from healthy women and from patients with other type of cancer, respectively. Although LPA in human serum seems mainly to be generated by lysophospholipase D (lysoPLD), the source and pathway for LPA in the ascitic fluid remain still obscure. In this study, we examined whether lysoPLD activity producing bioactive LPA in human peritoneal fluid was significantly elevated under pathological statuses.

Geranylgeranylacetone inhibits ovarian cancer progression in vitro and in vivo.

Geranylgeranylacetone (GGA), an isoprenoid compound, is an anti-ulcer drug developed in Japan. In our previous study, GGA was shown to inhibit ovarian cancer invasion by attenuating Rho activation [K. Hashimoto, K.

Alendronate suppresses tumor angiogenesis by inhibiting Rho activation of endothelial cells.

We previously reported that alendronate inhibits intraperitoneal dissemination in an in vivo ovarian cancer model. Recently, nitrogen-containing bisphosphonates have been reported to have antiangiogenic activities. In this study, alendronate inhibited human umbilical vein endothelial cell (HUVEC) migration and capillary-like structure formation in vitro.

[The palliative care in the clinical oncology].

With the development of the medical oncology, the progress of the diagnosis and the treatment for cancer patients have provided the improvement of overall survival rates. Furthermore, the importance of the palliative care, which give the relief of the pain and maintain or improve quality of life in cancer patients, has become to be recognized recently. Because the palliative care aims to provide the cancer patients and families with the relief of "total pain", which means the complex etiology of pain, including its physical, emotional, social, economic, and spiritual components, it has been adapted not only at the terminally period but also at the beginning of the cancer treatment.

Involvement of nuclear factor-kB activation through RhoA/Rho-kinase pathway in LPS-induced IL-8 production in human cervical stromal cells.

Interleukin-8 (IL-8) is a chemokine that recruits and activates neutrophils in stromal tissue and plays an essential role in cervical ripening. Nuclear factor-kB (NF-kB) is known to be important for the up-regulation of IL-8 gene expression. We examined the molecular mechanisms responsible for NF-kB activation in IL-8 production in cervical stromal cells.

Multiple amino acid substitutions in hemagglutinin are necessary for wild-type measles virus to acquire the ability to use receptor CD46 efficiently.

Measles virus (MV) possesses two envelope glycoproteins, namely, the receptor-binding hemagglutinin (H) and fusion proteins. Wild-type MV strains isolated in B-lymphoid cell lines use signaling lymphocyte activation molecule (SLAM), but not CD46, as a cellular receptor, whereas MV vaccine strains of the Edmonston lineage use both SLAM and CD46 as receptors. Studies have shown that the residue at position 481 of the H protein is critical in determining the use of CD46 as a receptor.

Analysis of Kawasaki disease showing elevated antibody titres of Yersinia pseudotuberculosis.

Aim: To elucidate a clinical difference between patients with Kawasaki disease documented with Yersinia pseudotuberculosis infection and patients with Kawasaki disease without Yersinia pseudotuberculosis infection.

Patients And Methods: From January 1985 to July 2004, 452 patients were diagnosed with Kawasaki disease. Forty-two patients had elevated antibody titres of Yersinia pseudotuberculosis and/or positive stool culture (Yersinia-positive group).

Prospective study of positron emission tomography for evaluation of the activity of lapatinib, a dual inhibitor of the ErbB1 and ErbB2 tyrosine kinases, in patients with advanced tumors.

Background: To evaluate the role of FDG-PET in assessing anti-tumor efficacy of molecular targeted drugs, we prospectively performed FDG-PET and CT for response evaluation in patients treated with lapatinib, a dual inhibitor of ErbB1 and ErbB2 tyrosine kinases.

Methods: Lapatinib was given orally once a day at doses ranging from 1200 to 1800 mg in a phase I study. CT and FDG-PET were performed before treatment, and at 1, 2 and 3 months after the initiation of the treatment and every 2 months thereafter.

[Concurrent chemoradiotherapy (CRT) with S-1 and cisplatin (CDDP) in patients (pts) with locally advanced head and neck cancer (HNC)].

The standard care for unresectable locally advanced head and neck cancer (HNC) is concurrent chemoradiotherapy (CRT). Although there is no standard regimen of CRT, a platinum-based regimen has shown a better survival benefit than other regimens. The control arm in a randomized trial for unresectable locally advanced HNC is radiotherapy concurrent with CDDP (100 mg/m2, every 3 weeks), which has been considered to be too toxic for clinical practice in Western countries and has required frequent dose modifications.

A LINE-type retrotransposon active in meristem stem cells causes heritable transpositions in the sweet potato genome.

We isolated a LINE-type retrotransposon, LIb, which showed high transposition activity in sweet potato callus. A copy transposed in the callus was 6303 bp in length and showed key features of a LINE element. Apparently full-length copies sharing the 5' UTR sequence with the 6303-bp copy increased dramatically in the callus as several original copies in the sweet potato genome.

Preliminary report of treatment with oral contraceptive pills for intermenstrual vaginal bleeding secondary to a cesarean section scar.

Uterine scar has been reported as a possible cause of intermenstrual bleeding in women with previous cesareans. We evaluated the effectiveness of combined hormonal therapy (estrogen and progesterone tablets containing 0.5 mg of norgestrel and 0.

Generation of measles virus with a segmented RNA genome.

Viruses classified in the order Mononegavirales have a single nonsegmented RNA molecule as the genome and employ similar strategies for genome replication and gene expression. Infectious particles of Measles virus (MeV), a member of the family Paramyxoviridae in the order Mononegavirales, with two or three RNA genome segments (2 seg- or 3 seg-MeV) were generated using a highly efficient reverse genetics system. All RNA segments of the viruses were designed to have authentic 3' and 5' self-complementary termini, similar to those of negative-stranded RNA viruses that intrinsically have multiple RNA genome segments.

Effect of protein kinase Cbeta inhibitor on Ca2+ homeostasis in diabetic sensory neurons.

To elucidate the direct effect of selective protein kinase Cbeta inhibitor LY333531 on diabetic sensory neurons, we examined intracellular Ca(2+) concentration in isolated rat dorsal root ganglion neurons using the fluorescent Ca(2+) indicator fura-2. The duration of calcium transients induced by high (50 mM) extracellular K in small diabetic dorsal root ganglion neurons was significantly prolonged compared with that in control neurons. This prolonged intracellular Ca concentration elevation in diabetic neurons was normalized rapidly and reversibly by LY333531 in a dose-dependent manner, and the effect of LY333531 was completely abolished by pretreating the neurons with mitochondrial calcium uniporter inhibitor, Ruthenium 360.