Relevance of DT-diaphorase activity to mitomycin C (MMC) efficacy on human cancer cells: Differences in in vitro and in vivo systems

Using 4 human cancer cell lines, 4 tumors xenografted into nude mice, and 11 fresh tumor specimens removed at surgery, we investigated the relevance of NAD(P)H:quinone oxidoreductase (DT-diaphorase, DTD) activity (nmoles/min/mg protein) to mitomycin C (MMC)-induced cytotoxicity. In culture cell lines, KB cells had significantly higher levels of DTD activity (8260) than PH101 (1934), SH101 (1805) or K562 (1796), and the highest sensitivity to MMC. In contrast, the higher the DTD activity of xenografts, the greater their resistance to MMC, while the inhibition rate of relative tumor growth for MMC, as evaluated by the NCI protocol, was highest in SH-6, high in CH-5, lower in CH-4 and lowest in EH-6. The investigation using 11 fresh tumor specimens also showed an inverse relationship between IC⁵⁰ values after a 30-min MMC treatment, as evaluated by ATP assay and DTD activities. Moreover, a non-toxic DTD inhibitor, dicoumarol (DIC), or flavin adenine dinucleotide (FAD), suppressed the efficacy of MMC in culture cells, but enhanced it in xenografts. Thus, we suggest that DTD may play an important role in MMC-induced cytotoxicity but MMC metabolism by DTD in solid tumors may differ from that in culture cells.     

Brefeldin A Blocks the Cytotoxicity of T Cell Receptor α/β and γ/δ Cytotoxic T Lymphocyte Clones Reacting against Human Autologous Cancer Cells

We studied the effector mechanism of T cell receptor (TCR) α/β - and γ/δ -type cytotoxic T lymphocyte (CTL) clones that react with human autologous tumor cells. Treatment of tumor cells with a fungal antibacterial reagent, brefeldin A (BFA), resulted in the inhibition of cytotoxicity of an autologous tumor (HST-2)-specific CD8⁺ TCR α/β -type CTL, TcHST-2. Other anti-metabolites such as chloroquine, cycloheximide and colchicine did not affect the cytotoxicity. The cell-surface antigen expression, including MHC class I molecules, was not influenced by BFA treatment. Furthermore, BFA did not influence the cytotoxicity of lymphokine-activated killer cells and natural killer cells. Since BFA blocks the transport of peptides from endoplasmic reticulum to the Golgi apparatus, the above data suggest that BFA could affect washing out of the peptide fragments from the MHC class I groove. Consequently, target tumor cells were protected from killing by CTL, Moreover, we obtained a CD4⁻, 8⁻, TCR γ/δ -type (Vδ1⁺) CTL clone, TcHOT, that reacts against an autologous ovarial carcinoma, HOT. BFA could also inhibit this cytotoxicity, and it is likely that different presenting molecules other than MHC class I proteins participate in the cytotoxicity of this TCR gm/δ - type CTL. These studies suggest that both TCR α/β - and γ/δ -type CTL may require antigenic peptides that are most likely derived from the BFA-sensitive, intracellular endogenous target proteins.     

The Japan Society of Coloproctology

The Japan Society of Proctology was inaugurated in 1940 by a number of proctologists in the hope of confirming the independence of their special field of medicine. Originally, it was a small society, consisting mainly of proctologists in practice. Afterward, the scope of the specialty was enlarged, so the name of the society changed to the Japan Society of Coloproctology in 1967. The number of members increased steadily after the 1970s because of the remarkable increase of colorectal lesions in Japan and the rapid progress of coloproctology in the world. The number of societal members reached 5,000 in 1994. Annual meetings of the Society have been held regularly ever since, and the 50th meeting was commemorated in Tokyo in 1995. Also, regular journals of the Society have been issued since its establishment. In addition, the Society has supported many international and domestic societies and has collaborated with them.     

Safety and feasibility of laparoscopic gastrectomy for gastric cancer patients with a history of abdominal surgery

Purpose

To assess the safety and feasibility of laparoscopic gastrectomy (LG) for gastric cancer patients with a history of abdominal surgery (HAS).

Methods

This retrospective study analyzed data collected from gastric cancer patients with HAS, who underwent LG between 2004 and 2015. We compared the clinicopathological features that correlated with conversion to open surgery and the development of severe postoperative complications (Clavien–Dindo classification of grade III or higher).

Results

Of the 41 patients identified, 6 (14.6%) required conversion to open surgery. The incidence of conversion to open surgery was associated with a history of lower gastrointestinal tract surgery (p?=?0.009), attempted laparoscopic total gastrectomy (p?=?0.002), and excessive blood loss (p?<?0.001). Severe postoperative complications developed in six patients (14.6%). Although the development of complications was associated with high postoperative serum C-reactive protein, the type of past abdominal surgery was not significantly correlated with severe complications.

Conclusions

LG was feasible for gastric cancer patients with a HAS, but for those with a history of lower abdominal surgery or those who require total gastrectomy, surgeons should carefully consider the indications for LG.

     

Orthopedic,ophthalmic, and psychiatric diseases primarily affect activity limitation for Japanese males and females: Based on the Comprehensive Survey of Living Conditions

Background

Healthy life expectancy (HLE) is used as one of the primary objectives of fundamental health promotion plans and social development plans. Activity limitation is used to calculate HLE, but little study has been done to identify determinants of activity limitation in order to extend HLE. The purpose of this study is to identify diseases and injuries that commonly lead to activity limitation to prioritize countermeasures against activity limitation.

Radiorespirometric study of glucose metabolism in liver-damaged rats

Changes in glucose metabolism in rats during feeding with 3-methyl-4-(dimethylamino)azobenzene(3-Me-DAB) were investigated by radiorespirometry with ¹⁴C-labelled carbohydrates as substrates, in relation to the levels of liver glycolytic enzyme activities.Rats were fed on 0.06% 3-Me-DAB for 7 weeks. Radiorespirometry was carried out by the IP administration of [U-¹⁴C]glucose 2.5 Ci or [1-¹⁴C]acetate 2.0 Ci weekly during the experimental period.In the analysis of the radiorespirometric pattern obtained with [U-¹⁴C]glucose, the peak time (PT) was markedly shortened at week 4. At week 6 of 3-Me-DAB feeding, the peak height (PH) and yield value (YV) both increased significantly with concomitant shortening of PT. The duration of the activation in radiorespirometric parameters was paralleled reasonably well by that of glycolytic enzyme activity; the activation of liver glucose-6-phosphate dehydrogenase (G-6-PDH) shortens PT, while the activation of the tricarboxylic acid (TCA) cycle increases YV.This study showed that the radiorespirometric pattern reflected glucose metabolism in the liver well. In conclusion, radiorespirometric analysis with ¹⁴C-labelled glucose as a substrate may be useful for the clinical diagnosis of liver diseases.     

Comparison of DNA synthesis in white and brown adipose tissue in rats with ventromedial hypothalamic lesions

Ventromedial hypothalamic (VMH) lesions cause excessive fat accumulation in white adipose tissue (WAT), and brown adipose tissue (BAT); however, little information is available on whether or not cell proliferation occurs in WAT and BAT after VMH lesioning. In this study, we determined the DNA content and thymidine incorporation in unilateral parametrial WAT and interscapular BAT 0, 1, 3, and 7 days after VMH lesioning, and examined the mechanism of increased DNA content in WAT. In rats with VMH lesions, the weight of WAT and BAT had increased significantly at 7 days, and the DNA content and thymidine incorporation of WAT had increased significantly at 3 days and continued to increase for up to 7 days, while those of BAT did not increase for as long as 7 days after VMH lesioning. Restricted food intake according to the pair-feeding method partially inhibited the increased DNA content in WAT. The increased DNA content in WAT was mostly restored but not completely by the administration of anti-insulin antibody, and by administration of propranolol, a -adrenergic blocker. The results demonstrated that VMH lesions induced DNA synthesis in WAT early after VMH lesioning, but did not induce DNA synthesis in BAT, and suggested that either hyperinsulinemia or a -adrenergic receptor mechanism or both may be responsible for the increased DNA content in WAT.     

In vitro binding of 67Ga to isolated rat liver cells

In order to understand the mechanism of the accumulation of gallium citrate (Ga-67) in normal liver, an in vitro investigation system was developed using isolated rat liver cells, and various basal factors relating to ⁶⁷Ga binding to normal rat liver cells were studied. In this study, the values of ⁶⁷Ga binding to the liver cells increased in parallel with the number of cells; however, binding was hardly affected by higher doses of ⁶⁷Ga. The binding of ⁶⁷Ga to the cells was inhibited by the presence of ethylenediaminetetraacetate (EDTA) and citrate. Phosphate and bicarbonate (10^-2 M) slightly inhibited ⁶⁷Ga binding to the cells. The binding of ⁶⁷Ga to the cells increased as the pH was decreased. These results suggest that ⁶⁷Ga binding to normal rat liver cells may occur in free gallium. Moreover, the utilization of isolated rat liver cells is useful for understanding the ⁶⁷Ga accumulation mechanism in normal liver.     

Focus of tricholemmal differentiation (tricholemmal carcinoma) within Bowen's disease/carcinoma

Bowen's disease (BD)/carcinoma is a type of squamous cell carcinoma of the skin, however, the possibility of adnexal differentiation (the development of sebaceous carcinoma or porocarcinoma) occurring in BD/carcinoma has been suggested. We herein describe a case of BD with superficial invasive carcinoma, which showed a clear cell focus, demonstrating tricholemmal differentiation. This clear cell focus showed the following findings: primarily composed of clear cells, somewhat columnar clear cells aligned in a palisade along a discernible basement membrane, tricholemmal keratinization and glycogen contained within the cells. In addition, the immunohistochemical profile in this clear cell focus, namely, negative staining for cytokeratin (CK)1 and positive staining for CK17 and calretinin in the inner cells of the neoplastic lobule, corresponded to that of the outer root sheath cells. This case suggested that adnexal differentiation can rarely occur within true BD/carcinoma, although adnexal carcinomas are commonly associated with a simple bowenoid change.