as histopathological risk factors for late neck recurrence in clinical N0 early oral tongue carcinoma.

The MR imaging findings in mucinous carcinomas include dynamic curves of the gradually enhancing type and a very high signal intensity on T2-weighted images compared with other histologic types of invasive ductal carcinoma. These findings appear to be useful for diagnosis.

Background and purpose: We investigated clinical outcomes of proton beam concurrent chemoradiotherapy (CCRT) for unresectable, locally advanced pancreatic cancer (LAPC) patients. Materials and methods: Records from 42 unresectable LAPC patients (21 male and 21 female, 39-83 years old) with IIB/III clinical staging of 1/41 treated by proton beam CCRT were retrospectively reviewed. Twelve patients received a conventional 50 Gray equivalents (GyE) in 25 fractions protocol and 30 others received a higher dose protocol of 54.0-67.5 GyE in 25-33 fractions. Gemcitabine or S-1 (Tegafur, Gimeracil and Oteracil) was used concurrently. Toxicity, overall survival (OS) and local control (LC) were examined. Results: Acute adverse events of grades 1, 2, 3 and 4 were found in 4, 15, 17 and 2 patients, respectively. All grade 3 and 4 events were hematologic. Late adverse events of grades 1 and 2 were found in 3 and 2 patients, respectively. No late adverse effects of grade 3 or higher were observed. The 1-year/2-year OS rates from the start of CCRT were 77.8/50.8% with median survival time (MST) of 25.6 months. The 1year/2-year LC rate from CCRT start was 83.3/78.9% with a median time to local recurrence of more than 36 months. Total irradiation dose was the only significant factor in univariate analyses of OS and LC (p = 0.015 and 0.023, respectively). Conclusion: Proton beam CCRT lengthened survival periods compared to previous photon CCRT data and higher dose irradiation prolonged LC and OS for unresectable LAPC patients. Proton beam therapy is therefore safe and effective in these cases.

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It is thought that heavy-ion radiation therapy is a promising modality of cancer therapy that can deliver higher biological effects on tumors than conventional X-ray radiation therapy, and may also conserve the function of normal organs because of its excellent dose distribution.(1) Recently, excellent clinical results were reported in the treatment of lung cancer, prostate cancer, cancer of the head and neck, and malignant tumors of bone and soft tissue.(2) Heavy-ion has high linear energy transfer (LET) with increased relative biological effectiveness (RBE). However, the possible mechanism of increasing cell killing in heavyion therapy is not fully understood. Previous studies have demonstrated that the induction of cell killing of non-irradiated cells by adjacent cells that are directly irradiated by heavy-ions is considered to play an important role in radiation-induced cell death, not only in tumors but also in normal organs. This phenomenon is termed the "bystander effect", and was reported by Nagasawa and Little in 1992.(3) They reported that increased sister chromatid exchanges were observed in more than 30% of cells when less than 1% of the nuclei of cultured cells were actually traversed by an α-particle in Chinese hamster ovary cells. It has been proposed that the mediating mechanism involves secreted soluble factors, (4)(5)(6) an increase in oxidative stress,plasma membrane-bound lipid rafts, (8) and gap junctional intracellular communication (GJIC). (4,7,(9)(10)(11)(12)(13) Gap junctions are membrane channels that connect the cytoplasm of cells and allow direct exchange of small molecules and ions between adjacent cells. GJIC is essential for the maintenance of tissue homeostasis and proliferation and the regulation of embryonic development and differentiation, and it plays a key role in induction of the bystander effect. (14)(15)(16)(17) Here, bystander killing of cells by heavy-ion irradiation was investigated, focusing on the involvement of GJIC on cell survival, to clarify the underlying mechanisms of the bystander effect in a human lung cancer cell line in vitro. Materials and MethodsCell cultures. A549 (a human lung cancer cell line with wild-type p53) was obtained from the Cell Resource Center for Biomedical Research at the Institute of Development, Aging and Cancer, Tohoku University, Japan. Cells were cultured in RPMI-1640 medium (Immuno-Biological Laboratories, Takasaki, Japan) supplemented with 10% fetal calf serum (PAA Laboratories, Pasching, Austria). Two days prior to irradiation experiments, 5 × 10 5 and 5 × 10 4 cells were inoculated into a specially designed 35-mm microbeam dish that was constructed as previously described, (18) to prepare confluent cultures and sparsely populated cultures, respectively. Unless otherwise described, all cell cultures were maintained at 37°C in a humidified atmosphere of 5% CO 2 in air. The size of the cell nucleus and the whole cells was determined to be 14.6 ± 4.3 and 106 ± 24.9 μm 2 , respectively. Drug treatment. Prior to irradiation, cells were p...