Excessive generation of reactive oxygen species (ROS) is considered to play an important role in arsenic-induced carcinogenicity in the liver, lungs, and urinary bladder. However, little is known about the mechanism of ROS-based carcinogenicity, including where the ROS are generated, and which arsenic species are the most effective ROS inducers. In order to better understand the mechanism of arsenic toxicity, rat liver RLC-16 cells were exposed to arsenite (iAs(III)) and its intermediate metabolites [i.e., monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III))]. MMA(III) (IC(50) = 1 μM) was found to be the most toxic form, followed by DMA(III) (IC(50) = 2 μM) and iAs(III) (IC(50) = 18 μM). Following exposure to MMA(III), ROS were found to be generated primarily in the mitochondria. DMA(III) exposure resulted in ROS generation in other organelles, while no ROS generation was seen following exposures to low levels of iAs(III). This suggests the mechanisms of induction of ROS are different among the three arsenicals. The effects of iAs(III), MMA(III), and DMA(III) on activities of complexes I-IV in the electron transport chain (ETC) of rat liver submitochondrial particles and on the stimulation of ROS production in intact mitochondria were also studied. Activities of complexes II and IV were significantly inhibited by MMA(III), but only the activity of complexes II was inhibited by DMA(III). Incubation with iAs(III) had no inhibitory effects on any of the four complexes. Generation of ROS in intact mitochondria was significantly increased following incubation with MMA(III), while low levels of ROS generation were observed following incubation with DMA(III). ROS was not produced in mitochondria following exposure to iAs(III). The mechanism underlying cell death is different among As(III), MMA(III), and DMA(III), with mitochondria being one of the primary target organelles for MMA(III)-induced cytotoxicity.

Situs inversus totalis (SIT) is a relatively rare congenital anomaly, occurring at an incidence of 1 in 10 000-50 000 live births. Although there are some case reports of SIT with the presence of cancer, there are few reports on the relationship between SIT and cancer. However, the recent phylogenetic investigations of this condition suggest that this may be linked to the development and progression of cancer on the molecular level. The key elements are one of the intracellular motor proteins, the KIF3 complex, and the cell-adhesion factors N-cadherin and beta-catenin. We herein present the cases of advanced gastric cancer and lung cancer with SIT, and review the relationship between SIT and the development and progression of cancer.

Anastomosis with SST is preferred to that with hemi-DST to minimize postoperative complications.

Purpose: We evaluated the clinical importance, such as the occurrence of postoperative pancreatic fistula (POPF) or prognosis, of preoperative serum markers of chronic inflammation, nutrition, and immunity, as well as that of serum tumor markers after curative resection of pancreatic ductal adenocarcinomas (PDACs).Methods: Between 2006 and 2015, 43 patients with PDACs underwent curative resection at Tottori Prefectural Central Hospital. We analyzed which preoperative indicators (i.e., C-reactive protein/albumin ratio [CAR], neutrophil/lymphocyte ratio [NLR], prognostic nutritional index [PNI], carcinoembryonic antigen [CEA], and carbohydrate antigen 19-9 [CA 19-9]) were the most relevant risk factors for occurrence of POPF and poor patient survival.Results: POPF was detected in 8/43 (18.6%) patients. One patient died of pancreatic fistula at 2 months postoperatively. Among nine candidate factors (operative procedure, operation time, tumor stage, preoperative serum amylase, preoperative CAR, NLR, PNI, CEA, and CA 19-9), we did not identify any significant risk factor for the occurrence of POPF. The 5-year overall survival (OS) rate of the 43 patients was 22.4%, and the overall median survival time was 21 months. The multivariate OS analysis demonstrated that high CAR and low PNI were strong preoperative markers of poor prognosis independently of tumor stage.Conclusions: Preoperative CAR and PNI are useful prognostic markers for patients with operable PDACs.

The effects of hyperthermia (38-42 degrees C) on the metabolism of 5-fluorouracil (5-FU) were examined using Ehrlich tumour cells (E-cells) and Sarcoma-180 cells (S-180 cells) in vitro. A temperature-dependent elevation of the intracellular concentration of 5-FU was observed in both types of tumour cell after incubation with 5-FU. The levels of 5-fluorouridine (FUR) and 5-fluoro-2'-deoxyuridine (FdUR), which are active metabolites of 5-FU, increased significantly after treatment of cells with 5-FU and hyperthermia. The highest concentrations of these active metabolites were found when the cells were incubated at 39 degrees C. The levels of alpha-fluoro-beta-ureido-propionic acid (FUPA) and F-beta-alanine, which are inactive catabolic metabolites of 5-FU, also increased when the cells were incubated at 39 degrees C. The percentage inhibition of thymidilate synthetase (TS) activity remained high (about 60-70%) at 39 degrees C for 240 min. These results suggest that the optimal temperature for potentiating the intracellular metabolism of 5-FU, in terms of both activation and inactivation, is 39 degrees C in vitro.