Search

In order to analyze the effects of inorganic phosphate (Pi) on the energy metabolism of suspen­sion-cultured cells of Catharanthus roseus, short-term changes in levels of glycolytic metabolites were monitored after the addition of 1.25 mм Pi to cultures of cells previously cultured in a Pi-free Murashige-Skoog medium for 24 h. The levels of all phosphorylated intermediates of glycolysis examined were found to increase after addition of Pi. The most striking increases were observed in levels of glucose-6-phosphate and fructose-6-phosphate which rose to approximately 8 (after 30 min) and 15 times (after 120 min) their initial values. The levels of ATP and pyrophosphate doubled during the first 30 min of incubation. In contrast, the level of pyruvate decreased significantly during the initial 30 min and then began to increase again for the next 90 min. The short­ term effects of Pi on the rates of synthesis of proteins and RNA were estimated from the rates of incorporation of 14C-labelled amino acids and uridine into the macromolecules. No appreciable stimulation of the synthesis of proteins and RNA was induced by Pi within 120 min after the addition of Pi. Possible mechanisms are discussed that may be involved in the changes in metabo­lism initiated by the addition of Pi to the cultures.

1975年から1982年までの間, 国立療養所近畿中央病院で入院加療を受けた肺小細胞癌144例における7例の5年生存例について検討した.男性3例女性4例で, 全て限局型であり, 多剤併用化学療法及び放射線療法により, 早期に安全寛解を得, その後再発をみていない.予後因子として進展度, PS, 治療効果が生存に有意に寄与していた.多剤併用化学療法及び放射線療法により, 早期に完全寛解に導入する事が長期生存例を得る為に重要であると考えられた

Summary Background In approximately the year 2000, the results of a number of important studies of non-small-cell lung cancer (NSCLC) were published. Methods Between July 1992 and December 2003, 223 patients with NSCLC aged ≥70 years received chemotherapy alone as their initial treatment at the National Cancer Center Hospital East. These patients were divided into 2 groups: those that began treatment between 1992 and 1999 (group A) and between 2000 and 2003 (group B). The details of chemotherapy regimens and outcomes were compared. Results In group A, 83% of patients received platinum-based chemotherapy, two-thirds of these regimens comprised platinum plus second-generation combination chemotherapy. In contrast, although 55% of patients received platinum-based chemotherapy in group B, 41% of patients received non-platinum-based chemotherapy. Among patients in group B, performance status was significantly associated with the selection of platinum-based or non-platinum-based chemotherapy; age was marginally associated with this selection. Median survival time (MST), 1-year survival rate, and 2-year survival rate were 6.7 months, 14%, and 7%, respectively, in group A, and 8.1 months, 35%, and 20% in group B (p = 0.0109). Multivariate analysis revealed that clinical stage and administration of salvage chemotherapy were independent prognostic factors. Conclusions In and after the year 2000, chemotherapy regimens changed greatly and survival of elderly patients significantly improved in our institute, and this improvement appears to be attributable mostly to the effect of salvage chemotherapy. These results suggest that even elderly patients should be offered salvage chemotherapy regardless of age, if possible.

Purpose In a comparative phase 3 study involving 1114 Japanese patients receiving highly emetogenic chemotherapy (HEC), palonosetron (PALO) was found to be superior to granisetron (GRA) for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in the delayed phase. This post hoc analysis of the phase 3 study evaluated the efficacy of PALO for the control of nausea. Methods The proportion of patients without nausea was assessed at 24-h intervals during the acute phase (0–24 h), delayed phase (24–120 h), and overall (0–120 h). No nausea rates were also evaluated by sex, type of chemotherapy (cisplatin or doxorubicin/epirubicin plus cyclophosphamide [AC/EC]), and age (

Summary The activities of two isoenzymes of 6-phosphogluconate dehydrogenase from suspension-cultured cells of Catharanthus roseus were not inhibited by 10 μM fructose-2,6-bisphosphate, which has been reported to be a potent inhibitor of 6-phosphogluconate dehydrogenase from castor beans. Slight inhibition was observed when the concentration of this compound was increased to 1 mM. However, this concentration of fructose-2,6-bisphosphate is more than 100 times higher than the estimated concentration in vivo. The activity of the isoenzymes of 6-phosphogluconate dehydrogenase from Catharanthus roseus was inhibited competitively by glucose- 1,6-bisphosphate. The Ki values of two isoenzymes were 190 μM and 175 μM, respectively. These data suggest that inhibition of 6-phosphogluconate dehydrogenase by fructose-2,6bisphosphate is not of great importance in the regulation of the pentose phosphate pathway in Catharanthus roseus cells in vivo .

The arginase activity in peripheral erythrocytes from individuals of various age groups was studied. The mean arginase activity was highest in the neonates, but there was no statistically significant difference between the infants and children or adults. There was no difference in the enzyme activities of males and females. A comparison was made between arginase activities in blood specimens obtained by venipuncture and those collected in capillary tubes, which revealed a high correlation. This method permits measurement of arginase activity in small amounts (approximately 250 μl) of blood, which renders determination of the enzyme activity easily applicable to neonates.

Arqininemia is a rare inborn error of ureagenesis due to a deficiency of arginase activity (Terheggen et al., 1969; Terheggen, et al., 1970a; Terheggen et al., 1970b; Terheggen et al., 1975; Cederbaum et al., 1976; Snyderman et al., 1977; Cederbaum et al., 1977; Michels and Beaudet, 1978; Snyderman et al., 1979). Despite the apparent defect in enzyme activity, hyperammonemia is only intermittently observed in this disease, unlike other enzymopathies of the urea cycle. Increase in orotic acid excretion is also another biochemical characteristic of this disease (Snyderman et al., 1977; Bachmann and Colombo, 1980). However, the mechanisms of hy-perammonemia and orotic aciduria have not been thoroughly explained. The purpose of this communication is to describe clinical features at 2 hours of testing. Concentration of arginine was elevated also in cerebrospinal fluid (1.91 mg/dl, normal range; 0.15–0.55 mg/dl), orotic aciduria.

Background Non-small-cell lung cancers (NSCLCs) harboring translocations in anaplastic lymphoma kinase (ALK) are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib. Case presentation We describe a case of post-operative local recurrence of lung adenocarcinoma in an 81 year-old male. He underwent radiation and received chemotherapy with docetaxel, but neither treatment regimen was effective. Following identification of ALK rearrangements, crizotinib treatment was initiated. After treatment with crizotinib for 5 days, adverse events including acute renal failure (grade 2/CTCAE ver4.0) and congestive heart failure (grade 3) occurred. Crizotinib modified treatment was required. Half dose of crizotinib treatment could not control tumor progression. Ultimately, crizotinib was administrated at a dose of 250 mg twice daily every 3 day dosing for 13 months with maintenance of the anti-tumor effect. Conclusion This is the first case report that skip schedule was more effective than dose reduction daily in crizotinib administration for ALK rearranged NSCLC patient with severe adverse events.

International Ocean Discovery Program (IODP) Expedition 361 drilled six sites on the southeast African margin and in the Indian-Atlantic ocean gateway, southwest Indian Ocean, from 30 January to 31 March 2016. In total, 5175 m of core was recovered, with an average recovery of 102%, during 29.7 days of on-site operations. The sites, situated in the Mozambique Channel at locations directly influenced by discharge from the Zambezi and Limpopo River catchments, the Natal Valley, the Agulhas Plateau, and Cape Basin, were targeted to reconstruct the history of the greater Agulhas Current system over the past ∼5 my. The Agulhas Current is the strongest western boundary current in the Southern Hemisphere, transporting some 70 Sv of warm, saline surface water from the tropical Indian Ocean along the East African margin to the tip of Africa. Exchanges of heat and moisture with the atmosphere influence southern African climates, including individual weather systems such as extratropical cyclone formation in the region and rainfall patterns. Recent ocean model and paleoceanographic data further point at a potential role of the Agulhas Current in controlling the strength and mode of the Atlantic Meridional Overturning Circulation (AMOC) during the Late Pleistocene. Spillage of saline Agulhas water into the South Atlantic stimulates buoyancy anomalies that act as control mechanisms on the basin-wide AMOC, with implications for convective activity in the North Atlantic and global climate change. The main objectives of the expedition were to establish the sensitivity of the Agulhas Current to climatic changes during the Pliocene-Pleistocene, to determine the dynamics of the Indian-Atlantic gateway circulation during this time, to examine the connection of the Agulhas leakage and AMOC, and to address the influence of the Agulhas Current on African terrestrial climates and coincidences with human evolution. Additionally, the expedition set out to fulfill the needs of the Ancillary Project Letter, consisting of high-resolution interstitial water samples that will constrain the temperature and salinity profiles of the ocean during the Last Glacial Maximum. The expedition made major strides toward fulfilling each of these objectives. The recovered sequences allowed generation of complete spliced stratigraphic sections that span from 0 to between ∼0.13 and 7 Ma. This sediment will provide decadal- to millennial-scale climatic records that will allow answering the paleoceanographic and paleoclimatic questions set out in the drilling proposal.

Background Mammalian target of rapamycin (mTOR) inhibitors have anti-tumor effects against renal cell carcinoma, pancreatic neuroendocrine cancer and breast cancer. In this study, we analyzed the antitumor effects of mTOR inhibitors in small cell lung cancer (SCLC) cells and sought to clarify the mechanism of resistance to mTOR inhibitors. Methods We analyzed the antitumor effects of three mTOR inhibitors including everolimus in 7 SCLC cell lines by MTS assay. Gene-chip analysis, receptor tyrosine kinases (RTK) array and Western blotting analysis were performed to identify molecules associated with resistance to everolimus. Results Only SBC5 cells showed sensitivity to everolimus by MTS assay. We established two everolimus resistant-SBC5 cell lines (SBC5 R1 and SBC5 R10) by continuous exposure to increasing concentrations of everolimus stepwise. SPP1 and MYC were overexpressed in both SBC5 R1 and SBC5 R10 by gene-chip analysis. High expression levels of eukaryotic translation initiation factor 4E (eIF4E) were observed in 5 everolimus-resistant SCLC cells and SBC5 R10 cells by Western blotting. MYC siRNA reduced eIF4E phosphorylation in SBC5 cells, suggesting that MYC directly activates eIF4E by an mTOR-independent bypass pathway. Importantly, after reduction of MYC or eIF4E by siRNAs, the SBC5 parent and two SBC5-resistant cells displayed increased sensitivity to everolimus relative to the siRNA controls. Conclusion These findings suggest that eIF4E has been shown to be an important factor in the resistance to everolimus in SCLC cells. Furthermore, a link between MYC and mTOR-independent eIF4E contribute to the resistance to everolimus in SCLC cells. Control of the MYC-eIF4E axis may be a novel therapeutic strategy for everolimus action in SCLC.

Background Lung adenocarcinoma patients with EGFR gene mutations have shown a dramatic response to gefitinib. However, drug resistance eventually emerges which limits the mean duration of response. With that in view, we examined the correlations between MET gene status as assessed by fluorescence in situ hybridization (FISH) with overall survival (OS) and progression-free survival (PFS) in adenocarcinoma patients with EGFR gene mutations who had received gefitinib therapy. Methods We evaluated 35 lung cancer samples with EGFR mutation from adenocarcinoma patients who had received gefitinib. Gene copy numbers (GCNs) and amplification of MET gene before gefitinib therapy was examined by FISH. MET protein expression was also evaluated by immunohistochemistry (IHC). Results FISH assessment showed that of the 35 adenocarcinoma samples, 10 patients (29%) exhibited high polysomy (5 copies≦mean MET per cell) and 1 patient (3%) exhibited amplification (2≦MET gene (red)/CEP7q (green) per cell). IHC evaluation of MET protein expression could not confirm MET high polysomy status. The Eleven patients with MET FISH positivity had significantly shorter progression-free survival (PFS) and overall survival (OS) than the 24 patients who were MET FISH-negative (PFS: p = 0.001 and OS: p = 0.03). Median PFS and OS with MET FISH-positivity were 7.6 months and 16.8 months, respectively, whereas PFS and OS with MET FISH-negativity were 15.9 months and 33.0 months, respectively. Univariate analysis revealed that MET FISH-positivity was the most significant independent factor associated with a high risk of progression and death (hazard ratio, 3.83 (p = 0.0008) and 2.25 (p = 0.03), respectively). Conclusions Using FISH analysis to detect high polysomy and amplification of MET gene may be useful in predicting shortened PFS and OS after Gefitinib treatment in lung adenocarcinoma. The correlation between MET gene status and clinical outcomes for EGFR-TKI should be further evaluated using large scale samples.

Although the presence of nodal disease is prognostic in thymic malignancy, the significance of the extent of nodal disease has yet to be defined. Lymph node dissection has not been routinely performed, and there is currently no node map defined for thymic malignancy. To establish a universal language for reporting as well as characterize the staging of this disease more accurately, an empiric node map is proposed here. This was developed using prior classification systems, series reporting specifics of nodal involvement, anatomical studies of lymphatic drainage, and preexisting node maps of the chest as defined by the International Association for the Study of Lung Cancer and the neck as defined by the American Academy of OtolaryngologyHead and Neck Surgery and the American Society for Head and Neck Surgery. The development of this node map was a joint effort by the International Thymic Malignancy Interest Group and the Thymic Domain of the IASLC Staging and Prognostic Factors Committee. It was reviewed and subsequently approved by the members of ITMIG. This map will be used as an adjunct to define node staging as part of a universal stage classification for thymic malignancy. As more data are gathered using definitions set forth by this node map, a revision may be undertaken in the future.

An advanced method of determination of hydrogen peroxide in foods has been investigated.Hydrogen peroxide in sample was extracted with two times volume of methanol. 1ml of the extract containing hydrogen peroxide was transferred into a 20ml of test tube, and 3ml of distilled water and catalase solution (2, 000 I. U.) were added to the extract in the test tube and warmed for 15min at 37°C to produce the formaldehyde quantitatively. Then 1ml of 0.4% 3-methyl-2-benzothiazolone hydrazone hydrochloride solution was added into the test tube and warmed again for 25min at 37°C, and 5ml of 0.2% ferric nitrate solution was added, then the test tube was allowed to stand for 5min at room temperature for complete development of the color. The reaction mixture was diluted to 20ml with acetone. The absorbance of the solution was determined at 635nm of the wave length.Under the condition described above, it was found that the hydrogen peroxide in some kind of food could be determined with recovery 97-107% and variation coefficient of about 5%.

An improved method for quantitative determination of bromate in bread and fish paste products was established.A sample was homogenized with distilled water and made up to 200ml after centrifugation. The supernatant was filtered and n-butanol-ethanol (2:1) mixture was added to 10ml of the filtrate. The mixture was allowed to stand for 10min then centrifuged to remove the precipitate. DEAE-Sephadex A-25 suspension and acetic acid were added to the supernatant, and the mixture was stirred for 5min. After centrifugation, the supernatant was subjected to the same procedure with DEAE-Sephadex A-25 suspension. The DEAE-Sephadex A-25 was mixed with ethanol, and rinsed twice with ethanol, 5.0% acetic acid and distilled water. The solid was packed in a chromatocolumn, and bromate was eluted with 30ml of 30% potassium chloride solution. Two ml of 4×10-3M styrene monomer solution (washed with 1% sodium hydroxide solution before use), 1ml of 0.01M potassium bromide solution and 1ml of sulfuric acid were added to the effluent, and the whole was shaken vigorously. Styrene bromo derivative was extracted with 2ml of n-hexane, and bromate was determined by ECD-GC.In this method, it was found that bromate in foods could be determined with a recovery of 80-92.3% and a variation coefficient of 6.2-2.6%. The detection limit was 0.01μg/g.