[A Case Report of Gastric Cancer Excised after Neoadjuvant Chemotherapy and Long-Term Survival Achieved after NivolumabAdministration for Peritoneal Dissemination].

The patient was a 64-year-old man with Type 3 advanced cancer in the upper body of the stomach. The preoperative tumor marker value of CA19-9 was abnormally high, but there was no proof of distant metastasis or peritoneal dissemination. The first operation was an exploratory laparotomy due to direct tumor invasion to the pancreas. Systemic chemotherapy was performed for tumor reduction. First, S-1 plus cisplatin therapy was administered for 4 courses but discontinued because of renal dysfunction and thrombocytopenia. In the second-line therapy, ramucirumabplus paclitaxel therapy was administered for 7 courses. Since the tumor invasion to the pancreas turned to be clear based on a CT scan, total gastrectomy with regional lymphadenectomy was performed. However, 5 months after surgery, a single nodule appeared in the upper abdomen that was suspected to be peritoneal dissemination. Nivolumab therapy was administered for 16 months without tumor enlargement or any adverse effect. Recently, there has been a marked development in chemotherapy for gastric cancer. Unresectable cases became operable after the administration of appropriate chemotherapy. In our case, nivolumab therapy had no adverse effect. However, serious adverse effects have been reported by several authors which suggests that regular examinations for interstitial pneumonia, hypothyroidism, and other adverse effects are important.

Development of Extranodal NK/T-cell Lymphoma Nasal Type in Cerebrum Following Epstein-Barr Virus-positive Uveitis.

A 74-year-old woman developed bilateral uveitis with high Epstein-Barr virus (EBV) DNA load in the vitreous fluid without lymphoma cells. Four years after the onset, T2-weighted contrast-enhanced MRI revealed hyperintense lesions in the right occipital and parietal lobe. A biopsy resulted in the diagnosis of extranodal NK/T-cell lymphoma nasal type (ENKL). The repeat region of LMP1, an EBV gene, detected in the brain lesion was identical to that detected in the vitreous fluid. ENKL of the central nervous system is quite rare, and the pathogenesis has not been determined. The lymphoma in this case might have been closely associated with the EBV-positive uveitis.

DNA damage-induced apoptosis and genetic background of the host: host-specific signaling enhancers of apoptosis.

Radiation therapy, inducing DNA damage, is one of the most effective tools for treatments of human cancers, but the effectiveness of the therapy is largely depending on the host specific conditions. Recently genetic constitution has proven to be important for apoptosis-induction responding to DNA damage. Regarding the host-specific manner of responses against DNA-damage in animal model, we have reported that infection with Friend leukemia virus (FLV) enhances the DNA damage-induced apoptosis in hematopoietic cells derived from C3H but DBA/2 mice. Furthermore, p53 or ATM knockout mice of C3H background and DNA-PK-deficient C3H SCID mice did not show the enhanced apoptosis by FLV. Recently, we could show that this host-specific apoptosis was mediated by the kinase activity of DNA-PK in association with FLV env-coding protein, gp70. Interestingly, two host proteins, acinus and MCM2, were also associated with DNA-PK and gp70 and were host-specifically overexpressed in C3H-derived cells. Our data suggest that gp70 enhances cellular DNA damage-induced signaling in association with host-specific cellular proteins, including acinus and MCM2, resulting in the activation of DNA-PK to phosphorylate P53. By introducing gp70/acinus/MCM2-associated pathways into tumor cells, cancer therapy with DNA damage-inducing agents might become much more effective. Our aim is to develop a novel form of targeted therapy that can be combined with other treatment modalities, such as radiotherapy and chemotherapy, using the host-specific regulatory mechanisms of apoptotic enhancement.

Benzene risk estimation using radiation equivalent coefficients.

We estimated benzene risk using a novel framework of risk assessment that employed the measurement of radiation dose equivalents to benzene metabolites and a PBPK model. The highest risks for 1 microg/m(3) and 3.2 mg/m(3) life time exposure of benzene estimated with a linear regression were 5.4 x 10(-7) and 1.3 x 10(-3), respectively. Even though these estimates were based on in vitro chromosome aberration test data, they were about one-sixth to one-fourteenth that from other studies and represent a fairly good estimate by using radiation equivalent coefficient as an "internal standard."