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BackgroundTransforming acidic coiled-coil containing protein 3 (TACC3) is expressed during the mitotic phase of nuclear division and regulates microtubules. Recently, high TACC3 expression in tumor cells of various cancers including soft tissue sarcoma has been reported. However, its role in

The etiology of rheumatoid arthritis (RA) is thought to involve dysfunction of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway; PD-1 negatively regulates autoimmunity by interacting with its ligand, PD-L1. We therefore investigated PD-1/PD-L1 expression in synovial tissue of patients with RA. We immunohistochemically stained synovial specimens from 51 patients with RA and assessed the association between PD-1/PD-L1 expression and rheumatoid factor (RF), the total count of infiltrating T cells, C-reactive protein (CRP), and Krenn’s synovitis score. PD-1 expression on infiltrating lymphocytes was detected in 34/51 RA cases (66.7%), while PD-1 expression was very mildly correlated only with the number of total infiltrating T cells (R2 = 0.1011, P = 0.0230). On the other hand, PD-L1 expression on synovial lining cells was observed in 37/51 RA cases (72.5%). Furthermore, a higher PD-L1 expression was significantly associated with RF positive state (P = 0.0454), and the correlations between PD-L1 expression and the number of infiltrating T cells (R2 = 0.5571, P

Autoimmune regulator (AIRE) is a transcription factor that is expressed in medullary thymic epithelial cells. It plays an essential role in central tolerance by eliminating self-reactive T cells. Recently, extrathymic AIRE-expressing cells have been revealed, which are associated with peripheral tolerance. Moreover, AIRE expression has been demonstrated in skin tumors and breast cancer. However, the expression of AIRE in osteosarcoma is unknown. We used immunohistochemistry to investigate AIRE expression in biopsy samples from 43 patients with conventional osteosarcoma and statistically analyzed the association between AIRE expression and clinicopathological characteristics. High AIRE expression was detected in 25 patients (58.1%), and significantly associated with the presence of lung metastasis (P = 0.014) and an increased number of forkhead box P3-positive tumor-infiltrating lymphocytes (regulatory T cells) (P = 0.014). The overall survival rate for all osteosarcoma patients with high AIRE expression was significantly shorter than that for those with low AIRE expression (P = 0.046). In a subgroup analysis of American Joint Committee on Cancer stage II patients who underwent complete surgical resection and conventional chemotherapy, the overall survival and metastasis-free survival rates were significantly shorter for patients with high AIRE expression than for those with low AIRE expression (P = 0.019 and P

Gene and protein abnormalities of anaplastic lymphoma kinase (ALK) play an important role in the pathogenesis of various cancers and serve as important therapeutic targets. We investigated ALK protein expression, phosphorylation, and genetic aberrations using fluorescence in situ hybridization (FISH) in 81 soft tissue tumor samples: inflammatory myofibroblastic tumor, n=1; alveolar soft part sarcoma, n=2; leiomyosarcoma, n=10; well-differentiated liposarcoma, n=7; pleomorphic liposarcoma, n=2; extraskeletal osteosarcoma, n=1; epithelioid sarcoma, n=1; synovial sarcoma, n=4; malignant peripheral nerve sheath tumor, n=4; undifferentiated pleomorphic sarcoma, n=19; rhabdomyosarcoma, n=6; myxofibrosarcoma, n=8; myxoid liposarcoma, n=11; fibrosarcoma, n=4; and desmoid-type fibromatosis, n=1. ALK protein expression, gene signal gain (without translocation), and phosphorylation were observed in 33/81 (40.7%), 55/81 (67.9%), and 30/81 (37.0%) tumor samples, respectively. ALK protein expression was statistically associated with phosphorylation, but not with gene signal gain. ALK phosphorylation-positive cases showed a statistically worse metastasis-free survival compared with phosphorylation-negative cases (P=0.0215). Particularly, metastasis of myxoid liposarcoma was associated with ALK phosphorylation (P=0.0019), but not with ALK protein expression or gene signal gain. However, the prognosis had no association with ALK protein expression, gene signal gain, or phosphorylation. ALK protein expression and phosphorylation play an important role in tumor biology and provide potential therapeutic targets for soft tissue tumors. Future research should focus on the oncogenic role and the efficacy of potential inhibitors of ALK.

Calcium channel blockers (CCBs) decrease lower esophageal sphincter pressure,which may result in gastrointestinal disease.In a previous study,we observed an increased risk of gastrointestinal disease following treatment with CCBs in elderly patients.However,there have been few epidemiological studies in non-elderly patients to determine whether CCBs increase the risk of gastrointestinal disease.We hypothesized that there would be greater use of antisecretory drugs,such as H2-receptor antagonists and proton pump inhibitors (PPIs),among patients prescribed CCBs and to test this hypothesis,performed a dynamic retrospective cohort study from September 2005 to August 2008 at six community pharmacies in Nagasaki Prefecture,targeting patients aged< 55 y.Correlations between initiation of treatment with antisecretory drugs and maintenance therapy with PPIs were determined by the Cox proportional hazards model.The study included 86 patients on CCBs and 93 controls not on them.During the study period,12 patients on CCBs and 6 controls started to use antisecretory drugs,for which the hazard ratio was 4.02 (95% confidence interval 1.82-10.10,P

There is no established optimum treatment for malignant fibrous histiocytoma (MFH) at present, and few MFH cell lines are established. In the present study, we established new MFH cell lines, KHZ-MFH and SFT85-03, and investigated the JAK/STAT (Janus kinase/signal transducer and activator of transcription) signaling pathway. We found that MFH cells secreted high levels of IL-6 and that STAT3 was constitutively activated in these cells. The JAK2 kinase inhibitor, tyrphostin AG490, suppressed the growth of MFH cells and inhibited the secretion of IL-6. Furthermore, blockade of activated STAT3 by forced expression of a cytokine signaling repressor, SOCS3 gene as well as a dominant-negative STAT3 in these cells significantly suppressed their growth. These results indicated that an autocrine mechanism of the JAK/STAT3 signaling pathway could promote the growth of MFH cells and that this pathway could be a therapeutic target of MFH.

A 73-year-old woman with idiopathic pulmonary fibrosis (IPF) had an elevated serum CA19-9 level, but not KL-6. Her condition worsened and she subsequently died and this was associated with a rise in the serum KL-6 level. At autopsy, the lung showed a honeycomb appearance macroscopically and, microscopically, hyaline membrane formation was seen. Immunohistochemical staining revealed partial colocalization of KL-6 and CA19-9 to dilated bronchiolar cells. These features suggest that the mechanisms that cause the synthesis and release of CA19-9 and KL-6 from damaged lung tissue in IPF are likely to differ from those in diffuse alveolar damage. In addition, serum KL-6 levels may reflect the severity of disease more sensitively than CA19-9 levels.

Transforming acidic coiled-coil-containing protein 3 (TACC3), a microtubule regulator, is associated with various cancers. However, the relationship between TACC3 and soft tissue sarcomas (STS) remains unclear. We investigated the expression of TACC3 in 136 STS patient samples using immunohistochemical (IHC) staining, and the statistical associations between TACC3 expression and clinicopathological characteristics were evaluated. Additionally, the expression levels of the tumor suppressor p53 and of the cell proliferation marker Ki-67 were also assessed by IHC. High TACC3 expression was detected in 94/136 of STS cases (69.1%), and significantly correlated with higher grade according to the French Fédération Nationale des Centres de Lutte Contre le Cancer system (P

【背景】肝細胞癌に対する局所療法の一つとしてラジオ波焼灼療法(Radiofrequency ablation : RFA)は急速に普及しつつある.今回, 我々は当院におけるRFAの経験を報告し, その有用性と安全性を検討した.【対象】腫瘍径3cm以下, 腫瘍数3個以内の適応基準に合致しRFA治療が完遂し追跡可能であった肝細胞癌76症例, 117結節について検討した.【結果】平均観察期間10.0±6.0ヶ月で局所再発は117結節中11結節(9.4%)で, 異所再発は76症例中21例(27.6%)であった.死亡例は4例で死因は肝細胞癌が2例, 肝不全が1例, 脳出血が1例であった.主な合併症は疼痛, 発熱, 嘔気・嘔吐, 一過性の肝障害, 呼吸苦, 胆道系酵素の上昇や胸水であったが全て対症療法で対応可能であった.【結語】RFAは重篤な副作用が少なく, 肝細胞癌の局所制御性に優れた治療法であると考えられた.

An essential nutrient selenium has been reported to be a potential cancer preventive and inhibitory agent, although no exact mechanism has yet been proposed. Since little is known about the anti-proliferative effect of selenium on osteosarcoma, this issue was addressed in the present study in vitro using three osteosarcoma cell lines, and in vivo using an osteosarcoma transplantable to nude mice. Selenium inhibited the tumor growth in vitro and morphological changes indicative of apoptosis were demonstrated. Osteosarcomas in nude mice were inhibited in growth by selenium with no cytotoxic change in normal tissues. The findings suggested that selenium may offer a novel therapeutic modality for osteosarcoma.

The histological grade of chondrosarcoma correlates well with their clinical behavior and with the patient's survival duration. We have previously demonstrated that p21 was expressed in the hypertrophic chondrocytes of the growth plate. To assess the relationship of p21 (waf1/cip1) to cell differentiation in chondrosarcoma, we examined the p21 expression in 14 cases of chondrosarcoma immunohistochemically and the induction of p21 by insulin-like growth factor-I (IGF-I) during cell differentiation in SW1353 chondrosarcoma cells. p21 immunoreactivity was seen in well-differentiated chondrosarcoma cells and was mutually exclusive with MIB1 reactivity in grade-1 chondrosarcoma. In vitro, the proteoglycan synthesis of SW1353 cells was increased by IGF-I in a dose-dependent manner. However, cell proliferation was not markedly stimulated. Overexpressions of p21 mRNA and p21 protein in SW1353 cells were induced by IGF-I 100 ng/ml. Our results suggested that the p21 expression was directly related to tumor differentiation and that the p21 expression was an important mediator for IGF-I in chondrosarcoma cells.

STUDY DESIGN A case report. OBJECTIVES To illustrate a rare case of synovial sarcoma arising within a peripheral nerve. SUMMARY OF BACKGROUND DATA A synovial sarcoma arising within a peripheral nerve is very unusual. Only five cases of primary synovial sarcoma within a peripheral nerve have been reported. This is the first case with involvement of the nerve root. The authors diagnosed the tumor arising within the S1 nerve root as synovial sarcoma using cytogenetic analysis that detected the chimeric SYT/SSX gene. METHODS In addition to the immunohistochemical study, a reverse transcription-polymerase chain reaction (RT-PCR) assay was conducted for the SYT-SS10 fusion gene using archival formalin-fixed paraffin-embedded tumor specimens. RESULTS Computed tomography scan, magnetic resonance imaging performed before surgery, and the intraoperative findings showed that the tumor was embedded within the S1 nerve root. Although the histologic findings were suggestive of a malignant peripheral nerve sheath tumor, the results of the cytologic study confirmed its diagnosis of synovial sarcoma. CONCLUSION Primary intraneural synovial sarcoma, although rare, must be distinguished from malignant peripheral nerve sheath tumor. The molecular assay of the detection of the SYT/SSX fusion gene is useful to make a definite diagnosis of monophasic synovial sarcoma.

It is essential for terminal chondrocytes to die before the conversion of calcified cartilage to bone. We have previously demonstrated that apoptosis occurred in the terminal hypertrophic chondrocyte of the growth plate. However, the essential mechanism by which the differentiation of chondrocytes is regulated has not yet been characterized. The purpose of this study was to investigate the mechanism for regulating chondrocyte differentiation. We focused on PTHrP and p21 which regulated the differentiation of chondrocytes and investigated how these factors interacted with each other in chondrocyte differentiation in the growth plate. PTHrP was strongly positive on immunostaining at the interface between the proliferating and the upper zone of the hypertrophic chondrocytes, whereas p21 was negative. On the other hand, p21 was positive in the lower zone of hypertrophic chondrocytes. Furthermore, PTHrP up-regulated the cell proliferation and down-regulated the expression of the p21 messengers in SW-1353 chondrosarcoma cells. These findings indicated that PTHrP might be a negative regulator for p21 in the differentiation of chondrocytes.

Giant-cell tumor is predominantly a benign condition, but it can evolve into a malignant tumor or metastasize to the lung. Transformation of benign giant-cell tumor into sarcoma is relatively common after radiation therapy. We report here a case of a patient who had local recurrence seven years after marginal resection and radiation therapy for a giant-cell tumor of the sacrum. One years after initial operation, the patient returned to us because of a lump in the lower abdomen, and re-resection of the tumor and radiation therapy (50Gy) were performed. Microscopic examination showed the typical feature of benign giant-cell tumor. Seven years after the radiation therapy, low back pain developed gradually and a computerized tomography showed a huge tumor of the pelvic space. Histological features of the tumor indicated malignant transformation into fibrosarcoma.

We report a case of dedifferentiated leiomyosarcoma. The patient was a 56 year-old man. The tumor was local recurrence in the right greater pectoral muscle after radiotherapy and chemotherapy. Tumor showed typical moderately leiomyosarcoma with dedifferentiated component. This component was revealed as pleomorphic malignant fibrous histiocytoma as a result of immunohistochemistry. These results indicated dedifferentiated components derive from loose muscle features due to dedifferentiation. We diagnosed this case as dedifferentiated leiomyosarcoma.

過去7年間に新たに多発性骨髄腫と診断された19例について調査した．男性9例，女性10例，年齢は33～88歳であった．腰痛を有するものは12例，初発症状として腰痛を認めたものは9例であった．診断までに整形外科受診を行っていた症例は11例で，整形外科受診が診断の契機となった症例は4例にすぎなかった．診断の契機としては，15例が血液検査異常，特に血清蛋白の高値8例，貧血7例，蛋白分画異常7例であった．また，整形外科受診時の診断名は6例が脊椎圧迫骨折，3例が変形性脊椎症などであった．MRIを施行した15例中，多発性骨髄腫の所見を認めるものは7例であった．多発性骨髄腫の多くが腰痛を有し，初発症状として腰痛を認め，整形外科受診を行う可能性が高いことがわかった．頑固な腰痛・増強する腰痛や付随症状を有する腰痛に対しては血液検査，尿検査，MRIの精査が必要であると思われた．

We describe a rare case of pleomorphic type of malignant fibrous histiocytoma (MFH) in the buttock that presented a systemic involvement. The case was of a 58-year-old woman presenting hepatic dysfunction and inflammatory reactions including fever, positive C-reactive protein (CRP), an elevated erythrocyte sedimentation rate, and high levels of platelets and ferritin. The fever of 3 months duration subsided on the first postoperative day. The MFH resection also brought rapid normalization in CRP, platelets, and leukocytes. The local and systemic productions of cytokines induced by this tumor were evaluated. In vivo and in vitro production of interleukin (IL)-6, IL-1beta, and tumor necrosis factor alpha by tumor cells were measured using enzyme-linked immunosorbent assay. Blood samples taken preoperatively, tumor tissues, and the primary culture medium showed extraordinarily high IL-6 levels. The plasma IL-6 level was normalized postoperatively. Immunohistochemistry showed the positivity of tumor cells for IL-6. The IL-6 produced by the tumor was concluded to have been responsible for the systemic illness.

We present five patients with acute traumatic hemarthrosis of the knee who also had hemorrhage within the bone marrow around the knee detected by magnetic resonance imaging. No additional bony, ligamentous, meniscal or osteochondral injuries were evident from clinical examination, initial and repeated plain radiographs, or magnetic resonance imaging. The main symptoms were sharply localized pain and tenderness of the contused area. When hemarthrosis was demonstrated at the first office visit, three cases had fat droplets in the blood. Two patients with hemarthrosis of the knee undergoing arthroscopy showed no obvious lesions of intra-articular structures. Instead they showed congestion of the joint capsule located in accordance with the traumatic episode. Magnetic resonance imaging demonstrated marrow abnormalities as diffusely low and high signal intensity areas in T1-weighted and T2-weighted images, respectively, in locations consistent with the traumatic episode and the symptoms. These disappeared within an average of 13 weeks (range in 4 cases, 12 to 16 weeks). These findings were considered diagnostic of bone contusion. Symptom duration was about 2 weeks in all cases. In conclusion the clinician should consider the possibility of coexisting bone contusion in cases of acute traumatic hemarthrosis of the knee with no evidence of bone or intra-articular lesions on clinical examination and conventional radiographs.

This article reports a case of osteoid osteoma of the proximal humerus. A 22-year-old man had pain in the right shoulder for 18 months after a traffic accident. We found a small sclerotic change in the proximal humerus on X-ray images and typical nidus on CT in his first visit to our hospital. The tumor was removed and the pain in the shoulder disappeared completely after operation. He underwent arthroscopic surgery for the pain at another hospital one year ago, but the cause of the pain was not identified. We reviewed X-ray images which were taken 18 months ago at that hospital. The images did not show any marked changes. Osteoid osteoma of the proximal humerus is rare but we should consider the diagnosis of osteoid osteoma for patients with severe and long-term pain in the shoulder.

Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is extremely rare, and the etiology of disease is not fully understood. We present herein the case of a primary hepatic MALT lymphoma with Helicobacter pylori and hepatitis C virus infection. A 71-year-old male was admitted to our institution to undergo a precise evaluation of a hepatic tumor incidentally detected during a computed tomography (CT) scan for chest examination. Dynamic CT showed faint enhancement during the arterial phase. The gadoxetate disodium-enhanced magnetic resonance imaging showed a hyper-intensity on the arterial phase and low intensity during the late and hepatocyte phases. Liver biopsy specimen showed small to intermediate size atypical lymphocytes with positive CD20 immunohistochemical staining. It was finally diagnosed as primary hepatic MALT lymphoma. FDG-PET/CT showed faintly increased uptake with a maximum standardized uptake value of 4.6, and did not show other pathological uptake. We present the rare case of primary hepatic MALT lymphoma and discussed the etiology of this disease.

Extra-abdominal desmoid tumors preferentially affect the shoulders, arms, backs, buttocks, and thighs of young adults. Multicentric occurrence is rather rare but seems to be another distinctive feature of extra-abdominal desmoid tumors. In this article we report a rare case of multicentric extra-abdominal desmoid tumors arising in bilateral lower limbs.

Purpose There is a growing body of evidence supporting the use of hyaluronan (HA) for treatment of injured tendons, although the mechanism of the healing effect has not yet been clarified. We therefore investigated the effects of HA on the proliferation and migration of tendon fibroblasts derived from rabbit flexor tendon epitenon and endotenon. Methods From explanted rabbit intrasynovial flexor tendons (n = 5), we cultured tendon fibroblasts derived from the epitenon and endotenon. CD44 expression on the tendon fibroblasts was detected by flow cytometric analysis. Various concentrations of HA (0.1–5.0 mg/mL) were added to monolayer-cultured tendon fibroblasts. We evaluated cell proliferation by recording changes in cell number, and measured cell migration by wound-healing assay. Results Flow cytometric analysis detected CD44 expression on the tendon fibroblasts. Treatment with HA at various concentrations notably and dose dependently inhibited cell proliferation and promoted cell migration. Conclusions Hyaluronan modulates the proliferation and migration of rabbit fibroblasts derived from the flexor tendon epitenon and endotenon.

Background: Despite the progression of therapeutic approaches, a high frequency of recurrence is what determines the long-term prognosis of patients with hepatocellular carcinoma (HCC). In this study, the chemopreventive effects of vitamin K2 on the recurrence and survival of patients with HCC after curative therapy were evaluated. Methods: Sixty patients who were diagnosed to be free of HCC after radiofrequency ablation therapy or surgery were randomly assigned to either the vitamin K2 group (n = 30 patients) or the control group (n = 30 patients). All patients were positive for the hepatitis C virus (HCV) antibody and hepatitis B surface antigen positive patients were excluded from this study. Patients in the vitamin K2 group received an oral dose of menatetrenone at 45 mg per day. Disease recurrence and the survival rates were analyzed in patients with HCC. Results: The cumulative recurrence-free rates in the vitamin K2 group were 92.3% at 12 months, 48.6% at 24 months and 38.8% at 36 months; and those in the control group were 71.7%, 35.9% and 9.9%, respectively (P = 0.045). The cumulative survival rates in the vitamin K2 group were 100% at 12 months, 95.0% at 24 months and 77.5% at 36 months; and those in the control group were 95.8%, 90.2% and 66.4%, respectively (P = 0.70). Conclusions: Vitamin K2 may have a suppressive effect on the recurrence of HCC and a beneficial effect on tumor recurrence. However, there was no significant difference in the survival rates. The chemopreventive effects of vitamin K2 are not sufficient. The development of a further regimen such as combination therapy is required.

A 69-year-old man developed an episode of severe community-acquired pneumonia 9 months after resection of aspergilloma. Although Aspergillus fumigatus was also isolated in the pleural cavity, it did not invade the remaining lung parenchyma. The patient developed progressive bilateral pneumonia leading to death from respiratory failure. Burkholderia cepacia was considered as prime pathogen, as it was repeatedly cultured from sputum and tracheal secretions, as well as the autopsy lung. B. cepacia is resistant to most antibiotics, and seldom causes pneumonia in patients without cystic fibrosis or chronic granulomatous disease. The precise reason that this apparently immunocompetent patient developed B. cepacia pneumonia remains unknown.

Study design A case report. Objectives To illustrate a rare case of histologically confirmed solitary bone cyst involving the spinous process of C7. Summary of background data A solitary bone cyst involving the spine is very unusual. Although four cases of a solitary bone cyst in the spine have been reported in the literature, the current authors have been able to find only one case of solitary bone cyst in the spinous process. All four patients reported in the literature were over 30 years of age. The patient in the current case was a 13-year-old girl with no history of trauma. Methods Radiographs and a computed tomography scan of the cervical spine were performed before the operation, as was a histologic examination to make a diagnosis of the lesion. Results The intraoperative findings from examination of the stagnant fluid within the lesion and the histologic examination indicated the diagnosis of a solitary bone cyst. Conclusions A solitary bone cyst in the spine is rare, especially in the young. An osteolytic lesion in the spinous process of the spine tends to be diagnosed as an osteoblastoma or as a giant cell tumor of the bone. A solitary bone cyst of the spine, although rare, must be considered as a differential diagnosis.

Fas/APO-1 (or CD95) is a 45-kDa cell surface glycoprotein that transduces cellular death signals for apoptosis upon cross-linking with the Fas ligand, which is experimentally replaced by anti-Fas antibodies. We examined the Fas expression at the protein and mRNA levels, and susceptibility to anti-Fas-mediated apoptosis, in 14 osteosarcoma cell lines. Ten of 14 ostesarcoma cell lines constitutively expressed detectable levels of Fas on the cell surface with positive cell rates ranging from 10.2 to 72.4%. Four other cell lines expressed Fas almost exclusively in the cytoplasm. An antibody against Fas was able to induce Fas-mediated cell death only in two cell lines with high levels of surface Fas. In the presence of the protein synthesis inhibitor cyclohexamide, antibody to Fas led to an induction of apoptosis in ten of the osteosarcoma cell lines antibody-concentration dependently. These data suggest that Fas is a potential protein related to apoptosis in osteosarcomas when the sensitizing activity of cyclohexamide on anti-Fas-mediated cytotoxicity was exerted.