[A Case of a Gastrointestinal Stromal Tumor of the Stomach with Lymph Node Metastasis].

A 87-year-old female was pointed out wall thickness in the upper part of gastric body for examination of anemia. The mass had a contrast effect, some of it protruded outside the wall, and the surrounding lymph nodes were enlarged. Upper endoscopy showed irregular ulcerative lesion with submucosal volume from posterior wall to the greater curvature in the upper part of gastric body. Biopsy was performed, and GIST of stomach was diagnosed. Surgery was performed for the GIST of the stomach. During open surgery, invasion of pancreatic tail was observed, therefore proximal gastrectomy with D1 lymph node dissection and distal pancreatectomy were performed. Pathologically, the tumor measured 95×78×65 mm with mitotic figures(38/50 high-power fields). Immunohistochemical analysis revealed that tumor cells expressed positive results for c-kit, α-SMA and CD34, and negative results for S-100 and desmin on the basis of the histology and immunostaining profile, the tumor was diagnosed as a GIST. The patient was classed as high risk according to Fletcher's risk classification. Tumor invades pancreatic tail, and lymph node metastasis was observed. She was discharged on the postoperative day 27 and alive without tumor recurrence at 6 months after surgery, not undergoing adjuvant chemotherapy.

[A Case of Resection of Leiomyosarcoma Suspected to Originate from the Right Ovarian Vein].

We present a 58-year-old female patient who underwent resection of a leiomyosarcoma arising from the right ovarian vein. She was referred to our hospital because of lower abdominal pain that had been present for 1 month prior to the visit. Ultrasound examination revealed a well-defined, smooth, lobulated, highly vascular mass(57 mm)adjacent to the distal portion of the duodenum. Contrast-enhanced computed tomography revealed the contrast enhancement mass (60 mm)located surround the right ovarian vein. In abdominal magnetic resonance image examination, the mass exhibited isointense signal on T1-weighted images, high signal on T2-weighted images, and restricted diffusion on diffusion- weighted images. We suspected primary leiomyosarcoma of the ovarian vein and proceeded with surgical intervention. On intraoperative findings, the mass was in contact with the duodenum and the inferior vena cava but dissection was easily achieved. We excised the mass together with the right ovarian vein. Pathological findings showed the mass was composed of proliferating spindle-shaped cells arranged in bundles. Some areas showed polygonal nuclear atypia and abnormal mitotic figures. Additional immunostaining showed positive for α-SMA, caldesmon, calponin, and negative for desmin, CD34, CKA1/AE3, S100. Based on the intraoperative findings, we diagnosed it as leiomyosarcoma arising of the right ovarian vein.

[A Case of Intussusception Caused by Ascending Colon Cancer That Underwent Elective Surgery without Repositioning].

An 81-year-old man visited his previous doctor with complaints of fever, vomiting, and diarrhea, and was transferred to our hospital on the 8th day after being admitted to the hospital for further treatment for a mass in the right side of his abdomen on CT. At the time of transfer, a fist-sized mass was palpable in the right side of the abdomen, but there was no tenderness, and blood tests showed that the white blood cell count was 10,700/µL and CRP 1.36 mg/dL, indicating a mild increase in inflammatory reaction. Contrast-enhanced CT showed an 8-cm diameter mass in the ascending colon with a stratified structure, and an antegrade intussusception with the mass as the advanced part. No intestinal obstruction was showed, and the contrast effect on the wall of the intestinal wall of the intussusception was favorable. Since the intussusception was already present on the previous CT scan, and since the patient also had severe aortic stenosis and a cardiothoracic examination was necessary, we decided on an elective operation. During the waiting period, lower gastrointestinal endoscopy revealed a type 1 tumor in the ascending colon, and biopsy revealed a highly differentiated tubular adenocarcinoma. The scope was not passed through to the oral side, and endoscopic repositioning was difficult. On the 19th day(12th day of admission), right hemicolectomy of the colon with D3 lymphadenectomy was performed. Since the descending duodenal wall was partially retracted into the area of the duplication, a partial resection of the duodenal wall was also performed, and the specimen was removed without releasing the duplication. Histopathologically, the tumor was diagnosed a 9.5×5.7 cm type 1 tumor with pT3, pN0, cM0, pStage Ⅱa(9th edition). The patient was discharged on the 9th postoperative day with good postoperative course.

[A Case of Ascending Colon Cancer with a Tumor Thrombus in the Superior Mesenteric Vein].

The progression of intravenous tumor thrombus in colorectal cancer is rare and reports on its resection are limited. This study reports a case of ascending colon cancer with a tumor thrombus in the superior mesenteric vein(SMV). A 44-year-old woman was admitted to our hospital for right, lower abdominal pain. Dynamic CT revealed an enhanced mass in the ascending colon and a tumor thrombus in the SMV. She was diagnosed with ascending colon cancer and an SMV tumor thrombus. An extended right hemicolectomy was performed. The SMV tumor thrombus extended from the gastrocolic trunk (GCT)to the right gastroepiploic vein and the anterior superior pancreaticoduodenal vein. To remove the tumor thrombus, a wedge-shaped incision was made through the SMV. Pathological examination showed a moderately differentiated adenocarcinoma of the ascending colon with extra-regional lymph node metastasis(No. 6)and intrapancreatic venous invasion. The pathological staging was pT4b, pN0, pM1a, pStage Ⅳa(Japanese Classification 9th edition). The patient was discharged on day 13 postoperatively. After discharge, 14 courses of mFOLFOX6 plus bevacizumab chemotherapy were administered. The patient is currently alive with no recurrence 15 months postoperatively.

A fluorescent calix[4]arene with naphthalene units at the upper rim exhibits long fluorescence emission lifetime without fluorescence quenching.

We synthesised a new compound with four naphthyl groups in the upper rims of calix[4]arene (1). Compared to the monomer unit, compound 1 has redshifted absorption and fluorescence, together with high fluorescence quantum yield and long fluorescence lifetime, which is extremely rare because long fluorescence lifetime emission tends to reduce the quantum yield. Single-crystal X-ray analysis and quantum calculations in the S1 state revealed π-π through-space interactions between naphthalene rings.

[A Resected Case of Intussusception Due to Undifferentiated Carcinoma of the Colon].

An 89-year-old woman was pointed out to have anemia for a routine blood examination by her family doctor and was referred to our gastroenterological department for further examination. Colonoscopy showed a type Ⅰ tumor in the transverse colon and insertion of fiber across the tumor was difficult. On contrast enema using gastrographin, a crab's claw-like appearance was found. CT after contrast enema revealed a tumor, 5 cm in diameter with pseudokidney sign near the hepatic flexure of the transverse colon. Pathological examination of biopsy specimen proved the tumor to be a poorly differentiated adenocarcinoma. Thus, she was diagnosed with intussusception due to transverse colon cancer and we performed partial resection of the transverse colon without regional lymphadenectomy. Final pathological diagnosis of the tumor was undifferentiated carcinoma and tumor stage was pT3pN0cM0, pStage Ⅱa. She was discharged 13 days after surgery and alive without tumor recurrence at 7 months after surgery, not undergoing adjuvant chemotherapy.

Vitamin D receptor in osteoblasts is a negative regulator of bone mass control.

The physiological and beneficial actions of vitamin D in bone health have been experimentally and clinically proven in mammals. The active form of vitamin D [1α,25(OH)(2)D(3)] binds and activates its specific nuclear receptor, the vitamin D receptor (VDR). Activated VDR prevents the release of calcium from its storage in bone to serum by stimulating intestinal calcium absorption and renal reabsorption. However, the direct action of VDR in bone tissue is poorly understood because serum Ca(2+) homeostasis is maintained through tightly regulated ion transport by the kidney, intestine, and bone. In addition, conventional genetic approaches using VDR knockout (VDR-KO, VDR(-/-)) mice could not identify VDR action in bone because of the animals' systemic defects in calcium metabolism. In this study, we report that systemic VDR heterozygous KO (VDR(+/L-)) mice generated with the Cre/loxP system as well as conventional VDR heterozygotes (VDR(+/-)) showed increased bone mass in radiological assessments. Because mineral metabolism parameters were unaltered in both types of mice, these bone phenotypes imply that skeletal VDR plays a role in bone mass regulation. To confirm this assumption, osteoblast-specific VDR-KO (VDR(ΔOb/ΔOb)) mice were generated with 2.3 kb α1(I)-collagen promoter-Cre transgenic mice. They showed a bone mass increase without any dysregulation of mineral metabolism. Although bone formation parameters were not affected in bone histomorphometry, bone resorption was obviously reduced in VDR(ΔOb/ΔOb) mice because of decreased expression of receptor activator of nuclear factor kappa-B ligand (an essential molecule in osteoclastogenesis) in VDR(ΔOb/ΔOb) osteoblasts. These findings establish that VDR in osteoblasts is a negative regulator of bone mass control.

Purification and identification of estrogen receptor alpha co-regulators in osteoclasts.

Mature osteoclasts are multinuclear, macrophage-like cells derived from hematopoietic stem cells in the bone marrow. Several transcription factors regulating osteoclast differentiation have been identified. However, the molecular basis of transcriptional regulation in osteoclasts at epigenetic levels is largely unknown. In fact, no osteoclast-specific transcriptional co-regulators have been characterized. Recently, selective ablation of estrogen receptor alpha (ERalpha) in mature osteoclasts derived from female mice (ERalpha(Deltaoc/Deltaoc)) exhibited trabecular bone loss due to induced apoptosis via upregulated expression of Fas ligand mRNA. In general, the component composition of the ERalpha-associated co-activator complex and its expression levels are distinct among tissues. However, ERalpha transcriptional co-regulators in mature osteoclasts remain unclear. In the present study, we achieved large-scale cultivation of mature, multinucleated osteoclasts and established a purification system for ERalpha-associated proteins. In addition to co-regulators previously found in other ERalpha target cells, several unexpected factors were found such as CAP-H. The mRNA expression level of CAP-H was high during osteoclast differentiation. These results demonstrate the existence of osteoclast-specific transcriptional co-regulators supporting ERalpha function.

Double PHD fingers protein DPF2 recognizes acetylated histones and suppresses the function of estrogen-related receptor alpha through histone deacetylase 1.

Estrogen-related receptor alpha (ERRalpha) is a member of the nuclear receptor superfamily and regulates many physiological functions, including mitochondrial biogenesis and lipid metabolism. ERRalpha enhances the transactivation function without endogenous ligand by associating with coactivators such as peroxisome proliferator-activated receptor gamma coactivator 1 alpha and beta (PGC-1alpha and -beta) and members of the steroid receptor coactivator family. However, the molecular mechanism by which the transactivation function of ERRalpha is converted from a repressive state to an active state is poorly understood. Here we used biochemical purification techniques to identify ERRalpha-associated proteins in HeLa cells stably expressing ERRalpha. Interestingly, we found that double PHD fingers protein DPF2/BAF45d suppressed PGC-1alpha-dependent transactivation of ERRalpha by recognizing acetylated histone H3 and associating with HDAC1. DPF2 directly bound to ERRalpha and suppressed the transactivation function of nuclear receptors such as androgen receptor. DPF2 was recruited to ERR target gene promoters in myoblast cells, and knockdown of DPF2 derepressed the level of mRNA expressed by target genes of ERRalpha. These results show that DPF2 acts as a nuclear receptor-selective co-repressor for ERRalpha by associating with both acetylated histone H3 and HDAC1.