Aim The aim is to report the long‐term outcomes of preoperative cisplatin and fluorouracil plus docetaxel (DCF) vs Adriamycin (ACF) for resectable esophageal squamous cell carcinoma (ESCC). Previously, this trial showed that DCF is associated with prolonged recurrence‐free survival (RFS). Methods Patients were randomly assigned to two cycles of ACF (35 mg/m2 of Adriamycin, 70 mg/m2 of cisplatin intravenously on day 1, and 700 mg/m2 of fluorouracil infusion for 7 days) every 4 weeks or DCF (70 mg/m2 of docetaxel, 70 mg/m2 of cisplatin intravenously on day 1, and 700 mg/m2 of fluorouracil infusion for 5 days) every 3 weeks, followed by surgery. The primary endpoint was RFS. The secondary endpoint was overall survival (OS). Results Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, 162 of whom were eligible and randomly assigned to the two groups. The median follow‐up for surviving patients was 69.8 months. The 5‐year RFS was significantly better in the DCF group than in the ACF group (59.9% vs 40.7%, hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.35‐0.86; P = .009) and the 5‐year OS was significantly better in the DCF group than in the ACF group (63.5% vs 49.4%, HR, 0.61; 95% CI, 0.38‐0.96; P = .03). The benefit of DCF chemotherapy on survival was significantly greater in the subgroups with more advanced clinical T and N stage. Conclusions Cisplatin and fluorouracil plus docetaxel are associated with better RFS and OS than ACF in resectable ESCC patients.

This study demonstrated that biweekly administration of 150 mg/m(2) irinotecan was feasible for patients with MBC treated previously with anthracyclines or taxanes.

Classical Hodgkin lymphoma (CHL) is a B-cell neoplasm characterized by Hodgkin and Reed-Sternberg (HRS) cells. Its prevalence exhibits a bimodal pattern of peaking in young adults and the elderly. There is an association with Epstein-Barr virus (EBV) infection in about 50% of cases of CHL of the elderly, and the outcome of these patients is unfavorable. It is not well known how the latent infection of EBV is involved in the pathophysiology of CHL of the elderly. To address this issue, we examined the tumor microenvironment (TME) and the expression of molecules related to EBV infection in HRS cells in 10 EBV-positive CHL and 7 EBV-negative CHL patients older than 50 years. In EBV-positive CHL, we found an increased population of FOXP3(+) cells, while that of granzyme B(+) cells was reduced, compared with those in EBV-negative CHL. The expression of inhibitory chemokine CCL20 was increased in EBV-positive HRS cells compared with that in EBV-negative HRS cells. In addition, despite increased expression of a pattern recognition receptor, RIG-I, in intracellular innate immunity, there was no evidence of interferon regulatory factor 3 activation or interferon-ß induction in EBV-positive HRS cells in CHL of the elderly. The disease recurred frequently (50%) in EBV-positive CHL. The current study thus suggests the possibility that the latent infection of EBV alters the expression of chemokines and the innate immunity response in HRS cells and modulates TME to an immunosuppressive state, which may account for the unfavorable disease course in CHL of the elderly.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma, and initial or predominant presentation in the lungs is uncommon. The synchronous occurrence of IVLBCL and malignant tumors is less frequent, and no such reports have described pulmonary presentations. We report a rare case of pulmonary IVLBCL accompanying lung cancer and interstitial lesions. A 73-year-old man with a history of pneumonia underwent a follow-up examination. Computed tomography revealed diffuse, bilateral ground-glass opacities (GGO) with a partial solid mass. Histologically, the mass consisted of adenocarcinoma. However, two other types of interstitial lesions were scattered throughout the resected lung: 1) peribronchovascular thickening with the aggregation of macrophages and anthracosis, and 2) alveolar septal thickening in the centrilobular area with atypical CD20-positive large cells in the capillaries. These two types of lesions were not mixed. Computed tomography and positron emission tomography demonstrated no other organ involvement. The patient was considered to have the synchronous occurrence of pulmonary IVLBCL and lung cancer (adenocarcinoma). After R-CHOP therapy, GGO on CT disappeared. Lung cancer often accompanies benign background lesions, and the combination of these lesions with lung cancer may make it difficult to detect the presence of pulmonary IVLBCL. However, the histological distribution pattern of IVLBCL may be a clue to the correct diagnosis.

To understand the mechanism by which Epstein-Barr virus (EBV) is activated in Akata cells by cross-linking of surface immunoglobulin, the interaction between mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and EBV activation was investigated. Immunoblotting using an anti-phosphoMAPK antibody (Ab) revealed that anti-IgG Ab induced rapid phosphorylation of MAPK in the cells. The phosphorylation was inhibited by MAPK/ERK kinase specific inhibitor, PD98059. The expressions of the EBV immediate early BZLF1 mRNA and its protein product ZEBRA, and early antigen were also inhibited by the inhibitor. These results indicate that MAPK is involved in the pathways of EBV activation.

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In order to understand mechanistic relationships between signaling pathways regulating mitogen-activated protein kinase (MAPK) phosphorylation and Epstein-Barr virus (EBV) reactivation, we compared MAPK phosphorylation, and EBV reactivation and latency in Burkitt's lymphoma cell lines (BLCLs) versus B lymphoblastoid cell lines (LCLs). EBV was reactivated in the BLCLs Akata and Raji, and in a LCL OB-R33 cells after cross-linking surface immunoglobulin (sIg) with anti-Ig. After stimulation with anti-Ig, MAPK phosphorylation was strongly induced in all BLCLs and in a few LCLs, but not in other LCLs. MAPK was constitutively phosphorylated in most LCLs but not in BLCLs. Expression of EBNA2 and LMP1, and LMP2A was analyzed with both immunoblotting and RT-PCR. EBNA2 and LMP1 were expressed in most LCLs and in some BLCLs. LMP2A was expressed in all BLCLs and LCLs except Namalwa cells. To test the hypothesis that LMPI induces constitutive MAPK phosphorylation, the LMP1 expression vector was transfected into Akata cells. MAPK phosphorylation was not induced in such transfected cells. Our results indicate that BLCLs and LCLs respectively have distinct MAPK phosphorylation patterns, and that induction of MAPK phosphorylation correlates with EBV reactivation in a few cell lines but not in most of the tested cell lines.

Overcoming apoptosis resistance to chemotherapy and radiation may lead to a reduction in gastric cancer death. We hypothesize that the apoptotic machinery in gastric cancer cells is dependent upon specific cellular conditions. In the course of our study of the expression of apoptosis-related genes in human gastric cancer cell lines, we have identified a cDNA clone which predicts an alternative form of caspase-9. The caspase-9 variant, which we designated as caspase-9 beta, retained a truncated structure of native caspase-9 without its catalytic domain and was expressed in seven cell lines from human gastric cancer. Among the cell lines examined, MKN-28 cells, which exhibited the most resistance against apoptotic stimuli, expressed the highest level of caspase-9 beta. The induction of apoptosis by staurosporine or actinomycin D was markedly suppressed in caspase-9 beta-transfected HeLa cells. These results are consistent with our hypothesis that the caspase-9 beta may be an endogenous dominant-negative molecule which attenuates apoptotic activity in human gastric cancer cells.