イマチニブ ガ チョコウ シ チョウキ カンゼン カンカイ CR オ イジ シテ イル ショウチョウ GIST フクマク ハシュ サイハツ ノ 1レイ

We report the case of a patient with recurrent gastrointestinal stromal tumor （GIST） complicated with peritoneal dissemination who achieved long-term complete remission （CR） with imatinib mesylate therapy. A 64-year-old man was admitted to our hospital because of severe abdominal pain. Abdominal computed tomography （CT） showed free air and an intra-abdominal abscess. Perforation of the small intestine was diagnosed, and an emergency operation was performed. Two adjacent tumors （each,6cm in size）, one of which was ruptured, were found by laparotomy in the jejunum and as a peritoneal dissemination. Jejunojejunostomy with the two adjacent tumors was performed and as much of the disseminated tumors as possible were resected. Histopathological analysis indicated a high-risk GIST of the small intestine. Abdominal CT at 1.5 years after the initial operation showed multiple recurrent tumors due to peritoneal dissemination. The patient subsequently received imatinib mesylate therapy at 400mg/day, and 5 months later, abdominal CT showed no evidence of tumor recurrence. DNA analysis of the tumor revealed an exon 11 mutation in the c-kit gene. The patient continues to receive imatinib mesylate therapy （400mg/day）, and CR of the recurrent tumors has been maintained for 8 years and 7 months

チョウヘイソク オ キタシタ シキュウ ケイガン ショウチョウ テンイ ノ 1レイ

We report a patient of a metastatic small intestinal tumor from uterine cervical cancer. A 76 year-old woman admitted to our hospital because of dyspnea. She showed progressive acute renal failure with pulmonary edema. Abdominal CT showed an advanced uterine cervical tumor and bilateral hydronephrosis. She was treated with temporary hemodialysis and tube nephrostomy. 1 week after admission, she presented with severe nausea, vomiting and rapidly progressive abdominal distension. We diagnosed her as strangulated ileus of the small intestine and she underwent an emergency operation. Laparotomy revealed an isolated tumor of the ileum and dilatation of the proximal small intestine without peritoneal dissemination, and a partial resection of the ileum was performed. Histopathological findings showed that the tumor was composed of squamous cell carcinoma cells, indicating that it was metastasis from uterine cervical cancer. Metastatic small intestinal tumor from primary uterine cervical cancer is very rare. To our knowledge, only 5 cases have been reported in Japan, including the present case

Truncated SRSF3 regulates IL-8 production

Serine/arginine-rich splicing factor 3 (SRSF3) is a member of the SR protein family and plays wide-ranging roles in gene expression. The human SRSF3 gene generates two alternative splice transcripts, a major mRNA isoform (SRSF3-FL) encoding functional full-length protein and a premature termination codon (PTC)-containing isoform (SRSF3-PTC). The latter is degraded through nonsense-mediated mRNA decay (NMD). Treatment of a human colon cancer cell line (HCT116) with 100 μM sodium arsenite increased SRSF3-PTC mRNA levels without changing SRSF3-FL mRNA levels. A chemiluminescence-based NMD reporter assay system demonstrated that arsenite treatment inhibited NMD activity and increased SRSF3-PTC mRNA levels in the cytoplasm, facilitating translation of a truncated SRSF3 protein (SRSF3-TR) from SRSF3-PTC mRNA. SRSF3-TR lacked two-thirds of Arg/Ser-rich (RS) domain whose phosphorylation state is known to be crucial for subcellular distribution. SRSF3-FL was localized in the nucleus, while overexpressed SRSF3-TR was diffusely distributed in the cytoplasm and the nucleus. A part of SRSF3-TR was also associated with stress granules in the cytoplasm. Interestingly, treatment of HCT116 cells with a small interference RNA specifically targeting SRSF3-PTC mRNA significantly attenuated arsenite-stimulated induction of c-JUN protein, its binding activity to the AP-1 binding site (-126 to 120 bp) in the interleukin (IL)-8 gene promoter, and AP-1 promoter activity, resulting in significant reduction of arsenite-stimulated IL-8 production. Our results suggest that SRSF3-TR may function as a positive regulator of oxidative stress-initiated inflammatory responses in colon cancer cells

Breeding a hybrid larch in Hokkaido, northern Japan

Japanese larch (Larix kaempferi) is an important afforestation species in the boreal temperate zone. However, this species is sensitive to vole (Myodes rufocanus bedfordiae) gnawing and shoot blight disease by Botryosphaeria laricina. We developed the hybrid larch (L. gmelinii var. japonica × L. kaempferi) to overcome these problems. In addition to improving the resistance to vole gnawing and shoot blight disease, this hybrid showed high wood density and carbon accumulation ability, calculated with DBH, tree height, wood density, and tree number/ha. Wood density is inherited equally from the female and male parents, and growth traits are mainly inherited from the male parent. The hybrid larch exhibited a high Young’s modulus and its expected use was for medium and high-rise buildings. Hybridization rates were higher (84.2 – 94.1%) in a single maternal clone seed orchard compared to a multi-clone female and male seed orchard. We propagated nursery stocks of high carbon accumulating females (named “Clean-larch”) by rooted cutting with hybridized seedlings produced in a single maternal clone seed orchard. The hybrid larch is susceptible to Armillaria root rot. A research task left for the future is to find the optimum method for selecting the planting area for hybrid larch and Japanese larch

Nitrogen loading increases the ozone sensitivity of larch seedlings with higher sensitivity to nitrogen loading

Larch (Larix sp.) tree is a critical species for the future afforestation in Northeast Asia. The impacts of elevated concentrations of ground-level ozone (O₃) and nitrogen (N) deposition are raising concerns. However, knowledge of the combined effects of elevated O₃ and N loading are still limited. We investigated whether nitrogen loading mitigates the negative impacts of ozone on two larch species: the Japanese larch (L. kaempferi) and its hybrid larch F₁ (L. gmelinii var. japonica x L. kaempferi) or not. We used open-top cambers and compared responses of the larch seedlings. Results showed the N loading mitigated the negative effects of O₃ on Japanese larch. However, in hybrid larch F₁, N loading did not mitigate O₃-induced inhibition of growth and photosynthetic capacity. Mitigation effect of N loading on negative O₃ impacts may vary between the two Larix spp., Hybrid larch F₁ could be more affected by the combined effects of O₃ and N loading due to its higher growth response to N loading. Elevated O₃ also reduced leaf nitrogen/phosphorus (N/P) ratio by elevated O₃, with significant effects in hybrid larch F₁, particularly under N loading. In the present study, leaf N/P ratio was utilized to validate the hypothesis that a positive effect of N loading may be observed if O₃ does not induce P limitation in Larix spp. We demonstrated a potential leaf N/P ratio function, which could reflect responses to O₃ and N loading in hybrid larch F₁

Effects of nitrogen loading under low and high phosphorus conditions on above- and below-ground growth of hybrid larch F1 seedlings

Under present environmental conditions, hybrid larch F-1 (Larix gmelinii var. japonica x Larix kaempferi) is a promising afforestation species as it has a high growth rate and tolerance against grazing damage, disease and cold. However, the input of nitrogen (N) to forests due to the increase of anthropogenic N is causing imbalances of N compared to other nutrients, especially phosphorus (P), thus affecting the root growth of healthy seedlings. However, knowledge on how different N and P conditions affect F-1 root growth is still limited. In this study, various N (3 levels) and P (no addition and addition) conditions were imposed to investigate the effect of N loading on larch F-1 seedlings under different P conditions. Needle N: P ratio, aboveground growth, belowground growth as well as fine root production were measured. The results showed that needle N: P ratio was higher under low P loading, and aboveground growth of seedlings increased with N loading at both low and high P conditions. Relative fine root production was decreased by N loading. On the other hand, fine root to total dry proportion was increased by N loading at no P addition, suggesting that limited P availability could increase fine root production. Total root proportion to total dry mass was decreased by N loading at both P conditions. We concluded that N loading has different effects on above-and below-ground growth of larch F-1 and its effects may also differ according to P conditions, indicating that both N and P conditions should be carefully considered when planting hybrid larch F-1

Stem and crown growth of Japanese larch and its hybrid F₁ grown in two soils and exposed to two free-air O₃ regimes

Ozone (O3) pollution and soil infertility may negatively affect boreal forests across the Northern Hemisphere. Impacts to economically and ecologically important larches (Larix sp., Pinacaeae) are particularly concerning. Using a free air O3 enrichment (FACE) system, we investigated the effect of 2-year elevated O3 exposure (approximate to 66 nmol mol-1)) on Japanese larch (L. kaempferi) and its hybrid larch F1 (L. gmelinii var. japonica x L. kaempferi) planted directly into either fertile brown forest soil (BF) or BF mixed with infertile volcanic ash soil (VA). Overall, photosynthetic pigmentation and the growth performance of the stem and crown were reduced in both taxa exposed to elevated O3. Furthermore, hybrid larch, in both O3 treatments, performed better than Japanese larch. This finding contradicts findings of prior experiments with potential experimental artifacts of O3 exposure facilities and root restrictions. Elevated O3 also disproportionately inhibited stem diameter growth and caused an imbalance in chlorophylls a/b and chlorophyll/carotenoid ratios. Hybrid and Japanese larches grown in BF and VA had a significantly lower drop of stem diameter over the run of stem height (from base to top) when exposed to elevated O-3, compared to ambient O3. This finding indicates altered stem shape under elevated O3. Among 11 response variables, there were no significant interactions between O3 treatment and taxa. There was also no significant interaction of soil condition and taxa, suggesting that the two larches shared a similar response to O3 and soil type. Understanding the performance of hybrid larch in relation to its parent species has ramifications for breeding success in a soil-degraded and O3-polluted environment

Effect of nitrogen load on growth and photosynthesis of seedlings of the hybrid larch F1 (Larix gmelinii var. japonica×L. kaempferi) grown on serpentine soil

We studied the growth and photosynthesis of the hybrid larch F1 (Larix gmelinii var. japonica × L. kaempferi) grown on serpentine soil and the effects of soil N load, to determine the performance of this species as reforestation material in serpentine regions. We prepared 16 experimental plots (2 m × 4 m each), eight on serpentine and eight on brown forest soil, and planted one-year-old cutting seedlings of the hybrid larch F1 in each plot, in May 2007. Ammonium sulfate was supplied to half of the plots of each soil type in 2008 and 2009, at a load of 47 kg N ha−1 year−1. Although the growth and photosynthetic capacity of hybrid larch F1 seedlings in the serpentine soil were limited, the rate of growth in serpentine soil was greater than that of Sakhalin spruce (Picea glehnii) that is dominant species in serpentine regions. There was significant interaction between soil type and N load for the growth and photosynthetic parameters. The N load adversely affected growth and photosynthetic parameters in the serpentine soil, while improved them in brown forest soil. Although the growth rate of hybrid larch F1 without N loading showed high potential as an afforestation species in serpentine region, increasing deposition of N might be a threat to the growth and photosynthesis of the hybrid larch F1 in serpentine soil

Growth and photosynthetic traits of hybrid larch F1 (Larix gmelinii var. japonica x L. kaempferi) under elevated CO2 concentration with low nutrient availability

The hybrid larch F1 (Larix gmelinii var. japonica x Larix kaempferi) is considered as one of the most important tree species not only for timber production but also as an afforestation material for severe conditions such as infertile soil. To predict the ability of hybrid larch F1 as an afforestation material under potential climates in the future, it is important to understand the response of hybrid larch F1 to elevated CO2 concentration ([CO2]) under low nutrient availability. Three-year-old seedlings of hybrid larch F1 were grown under two different levels of [CO2], 360 (ambient) and 720 μmol mol^[-1] (elevated), in combination with two different levels of nitrogen (N) supply (0 and 30 kg ha^[-1]) for one growing season. Elevated [CO2] reduced the maximum rates of carboxylation and electron transport in the needles. Net photosynthetic rates at growth [CO2] (i.e., 360 and 720 μmol mol^[-1] for ambient and elevated treatment, respectively) did not differ between the two CO2 treatments. Reductions in the N content and the N use efficiency to perform photosynthetic functions owing to the deficiency of nutrients other than N, such as P and K, and/or increase of cell wall mass were considered as the factors of photosynthetic down-regulation under elevated [CO2], whereas stomatal closure little affected the photosynthetic down-regulation. Although we observed strong down-regulation of photosynthesis, the dry matter increase of hybrid larch F1 seedlings was enhanced under elevated [CO2]. This is mainly attributable to the increase in the amount of needles with increasing the number of sylleptic branches. These results suggest that elevated CO2 may increase growth of hybrid larch F1 even under low nutrient availability, and that this increase may be regulated by both changes in crown architecture and in needle photosynthesis, which is mainly affected by not stomatal limitation but by biochemical limitation