超常磁性体を用いたMRリンフォグラフィーによる口腔癌患者のセンチネルリンパ節同定

The purpose of this study was to examine the feasibility of interstitial MR lymphography using Superparamagnetic Iron Oxide (SPIO) to detect sentinel lymph nodes (SLNs) in head and neck cancer. For two patients with cT2N0 squamous cell carcinoma of the tongue, the submucosal injection of SPIO as well as sentinel lymph node navigation surgery (SLNNS) was performed before undergoing surgical treatment. SPIO was used for MR lymphography and Tc-99m phytate for SPECT. We compared the images by both modalities. Berlin blue stain was also performed postoperatively if SLNs had the uptake of SPIO. The lymph nodes with MR signal attenuation and those with hot spots were probed to be anatomically identical. All the lymph nodes detected as a SLN by a gamma-probe contained the blue granules from SPIO. These data suggest that SPIO can be a novel tracer for performing SLNNS and SLN biopsy in oral cancer patients with cN0 neck.博士（医学）・甲622号・平成26年3月17

Thymoma-associated Graft-versus-Host Disease-like Erythroderma

We report a 40-year-old woman with recurrent thymoma associated with myasthenia gravis, in whom an unusual form of erythroderma developed. A histological examination revealed a graft-versus-host disease (GVHD)-like reaction. After high-dose steroid therapy, the metastatic thymoma lesion in the abdominal cavity was reduced in size from 9.5 × 6 × 7.5 cm to 4 × 3 × 1 cm in diameter. Nevertheless, the GVHD-like erythroderma become aggravated, her condition worsened, and the patient finally suffered from respiratory failure and died of sepsis. A GVHD-like reaction may be a rare presentation of thymoma-associated immunological disorders such as myasthenia gravis or pure red cell aplasia. Herein, we discuss the present case and review pertinent reports of thymoma cases associated with GVHD

Malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart: a case report

A rare case is presented of a 61-year-old man with a malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart. The primary tumor originated in the right thigh in 1982. Since then, the patient has had repeated local recurrences in spite of repeated surgical treatment and adjuvant chemotherapy. He has developed previous metastases of the lung and heart. The patient died of cardiac involvement

Annexin A2-STAT3-Oncostatin M receptor axis drives phenotypic and mesenchymal changes in glioblastoma

Glioblastoma (GBM) is characterized by extensive tumor cell invasion, angiogenesis, and proliferation. We previously established subclones of GBM cells with distinct invasive phenotypes and identified annexin A2 (ANXA2) as an activator of angiogenesis and perivascular invasion. Here, we further explored the role of ANXA2 in regulating phenotypic transition in GBM. We identified oncostatin M receptor (OSMR) as a key ANXA2 target gene in GBM utilizing microarray analysis and hierarchical clustering analysis of the Ivy Glioblastoma Atlas Project and The Cancer Genome Atlas datasets. Overexpression of ANXA2 in GBM cells increased the expression of OSMR and phosphorylated signal transducer and activator of transcription 3 (STAT3) and enhanced cell invasion, angiogenesis, proliferation, and mesenchymal transition. Silencing of OSMR reversed the ANXA2-induced phenotype, and STAT3 knockdown reduced OSMR protein expression. Exposure of GBM cells to hypoxic conditions activated the ANXA2-STAT3-OSMR signaling axis. Mice bearing ANXA2-overexpressing GBM exhibited shorter survival times compared with control tumor-bearing mice, whereas OSMR knockdown increased the survival time and diminished ANXA2-mediated tumor invasion, angiogenesis, and growth. Further, we uncovered a significant relationship between ANXA2 and OSMR expression in clinical GBM specimens, and demonstrated their correlation with tumor histopathology and patient prognosis. Our results indicate that the ANXA2-STAT3-OSMR axis regulates malignant phenotypic changes and mesenchymal transition in GBM, suggesting that this axis is a promising therapeutic target to treat GBM aggressiveness

Comprehensive investigation of areae gastricae pattern in gastric corpus using magnifying narrow band imaging endoscopy in patients with chronic atrophic fundic gastritis.

Background:  Barium radiographic studies have suggested the importance of evaluating areae gastricae pattern for the diagnosis of gastritis. Significance of endoscopic appearance of areae gastricae in the diagnosis of chronic atrophic fundic gastritis (CAFG) was investigated by image-enhanced endoscopy. Materials and Methods:  Endoscopic images of the corpus lesser curvature were studied in 50 patients with CAFG. Extent of CAFG was evaluated with autofluorescence imaging endoscopy. The areae gastricae pattern was evaluated with 0.2% indigo carmine chromoendoscopy. Micro-mucosal structure was examined with magnifying chromoendoscopy and narrow band imaging. Results:  In patients with small extent of CAFG, polygonal areae gastricae separated by a narrow intervening part of areae gastricae was observed, whereas in patients with wide extent of CAFG, the size of the areae gastricae decreased and the width of the intervening part of areae gastricae increased (p < 0.001). Most areae gastricae showed a foveola-type micro-mucosal structure (82.7%), while intervening part of areae gastricae had a groove-type structure (98.0%, p < 0.001). Groove-type mucosa had a higher grade of atrophy (p < 0.001) and intestinal metaplasia (p < 0.001) compared with foveola type. Conclusions:  As extent of CAFG widened, multifocal groove-type mucosa that had high-grade atrophy and intestinal metaplasia developed among areae gastricae and increased along the intervening part of areae gastricae. Our observations facilitate our understanding of the development and progression of CAFG

Dynamics of rheumatoid joint

In the present communication the recent works done by the Rheumatism Research Group of Department of Orthopedic Surgery, Okayama University, are described. The principal findings may briefly be summarized as follows. 1. Pathohistological pictures of the synovial membrane are classified into six types. Among them, Fibrinoid type and Follicular-Fibrosis type are the representative ones of chronic rheumatoid arthritis. 2. For the evaluation of the systemic as well as the local activities in rheumatoid arthritis and for judging the therapeutic effect, some indices have been established. 3. Injection of steroid hormones into the local joints fails to give satisfactory results in advanced, chronic rheumatoid arthritis. In such instances the flushing of the joint with physiological saline solution is effective. 4. In the case of chronic rheumatoid arthritis where the inflammation of hand and phalangeal joints is marked, RA-test gives rapid and more intense reaction, and most of such cases are of Follicular-Fibrosis type. 5. When lymph follicles appearing in the synovial membrane are stained when methyl green pyronine, the arrangement of lymphoid cells and plasma cells becomes distinctly clear. By micro-autoradiographic observations it can be seen that ³H-thymindine injected into the joint cavity is mostly ingested by the lymphoid cells in lymph follicles. 6. In the observation by the fluorescent antibody method multinuclear leucocytes found in the joint fluid and in the peripheral blood react with 19S and 7S-gamma-globulins. 7. When the serum and the joint fluid of the patient with rheumatoid arthritis are fractionated, they separate into three peaks at 19S, 7S, and 4S. Both S. S. C. A.-test and L. F. T. tests reveal the peak at 19S. The serum of chronic hepatitis positive to RA-test and the serum of rheumatoid arthritis are found to react immunologically the same to anti-&#946;2 M globulin sheep serum. 8. When the reticulo-endothelial system of rat is blocked by 900,000 molecules of poly-vinyl-pyrroridon, the ability of antibody production is diminished. 9. Chemical synovectomy of injecting osmic acid is effective to FibrinoidCoating type. Its action mechanism lies in the complete cleaning of the surface of synovial membrane. 10. By radiating synovectomy with 193Au a fairly good result can be expected. 198Au is ingested by those cells in the surface layer of the synovial membrane and also by histiocytes in the synovial membrane. When 5 mc of 198Au are injected into the knee joint, a marked necrosis of the synovial membrane occurs. When 198Au is added to the ascites cells of rabbit during the tissue culture, in the concentration of over 14 &#956;C degeneration of these cells can be recognized. 11. From the examination results of prognosis on those 25 cases with 41 rheumatoid knee joints after surgical synovectomy, it is considered that this method is indicated for Follicular-Fibrosis type. Ones with rheumatoid knee joint of Fibrinoid-Coating type gold sol treatment should be resorted to. In the cases of hand joints, surgical synovectemy is to be recommended at a relatively early stage.</p

Establishment of an antibody specific for cancer-associated haptoglobin: a possible implication of clinical investigation

We previously found that the serum level of fucosylated haptoglobin (Fuc-Hpt) was significantly increased in pancreatic cancer patients. To delineate the mechanism underlying this increase and develop a simple detection method, we set out to generate a monoclonal antibody (mAb) specific for Fuc-Hpt. After multiple screenings by enzyme-linked immunosorbent assay (ELISA), a 10-7G mAb was identified as being highly specific for Fuc-Hpt generated in a cell line as well as for Hpt derived from a pancreatic cancer patient. As a result from affinity chromatography with 10-7G mAb, followed by lectin blot and mass spectrometry analyses, it was found that 10-7G mAb predominantly recognized both Fuc-Hpt and prohaptoglobin (proHpt), which was also fucosylated. In immunohistochemical analyses, hepatocytes surrounding metastasized cancer cells were stained by the 10-7G mAb, but neither the original cancer cells themselves nor normal hepatocytes exhibited positive staining, suggesting that metastasized cancer cells promote Fuc-Hpt production in adjacent hepatocytes. Serum level of Fuc-Hpt determined with newly developed ELISA system using the 10-7G mAb, was increased in patients of pancreatic and colorectal cancer. Interestingly, dramatic increases in Fuc-Hpt levels were observed at the stage IV of colorectal cancer. These results indicate that the 10-7G mAb developed is a promising antibody which recognizes Fuc-Hpt and could be a useful diagnostic tool for detecting liver metastasis of cancer.This study was performed as a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Ministry of Education, Culture, Sports, Science and Technology of Japan and was supported by JSPS KAKENHI Grant Number JP16H05226

Differentiated glioblastoma cells accelerate tumor progression by shaping the tumor microenvironment via CCN1-mediated macrophage infiltration

Glioblastoma (GBM) is the most lethal primary brain tumor characterized by significant cellular heterogeneity, namely tumor cells, including GBM stem-like cells (GSCs) and differentiated GBM cells (DGCs), and non-tumor cells such as endothelial cells, vascular pericytes, macrophages, and other types of immune cells. GSCs are essential to drive tumor progression, whereas the biological roles of DGCs are largely unknown. In this study, we focused on the roles of DGCs in the tumor microenvironment. To this end, we extracted DGC-specific signature genes from transcriptomic profiles of matched pairs of in vitro GSC and DGC models. By evaluating the DGC signature using single cell data, we confirmed the presence of cell subpopulations emulated by in vitro culture models within a primary tumor. The DGC signature was correlated with the mesenchymal subtype and a poor prognosis in large GBM cohorts such as The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project. In silico signaling pathway analysis suggested a role of DGCs in macrophage infiltration. Consistent with in silico findings, in vitro DGC models promoted macrophage migration. In vivo, coimplantation of DGCs and GSCs reduced the survival of tumor xenograft-bearing mice and increased macrophage infiltration into tumor tissue compared with transplantation of GSCs alone. DGCs exhibited a significant increase in YAP/TAZ/TEAD activity compared with GSCs. CCN1, a transcriptional target of YAP/TAZ, was selected from the DGC signature as a candidate secreted protein involved in macrophage recruitment. In fact, CCN1 was secreted abundantly from DGCs, but not GSCs. DGCs promoted macrophage migration in vitro and macrophage infiltration into tumor tissue in vivo through secretion of CCN1. Collectively, these results demonstrate that DGCs contribute to GSC-dependent tumor progression by shaping a mesenchymal microenvironment via CCN1-mediated macrophage infiltration. This study provides new insight into the complex GBM microenvironment consisting of heterogeneous cells