Biomedical subjects

Hideomi Watanabe

Publications and source records attributed to Hideomi Watanabe.

At least 19 recordsLinked to original sources

PubMed2006

The autocrine motility factor (AMF) and AMF-receptor combination needs sugar chain recognition ability and interaction using the C-terminal region of AMF.

The autocrine motility factor (AMF) promotes cellular locomotion or invasion, and regulates tumor angiogenesis or ascites accumulation. These signals are triggered by binding between AMF and its receptor (AMFR), a glycoprotein on the cell surface. AMF has been identified as phosphohexose isomerase (PHI). Previous reports have suggested that the substrate-recognition of exo-PHI is significant for receptor binding. Crystallographic studies have shown that AMF consists of three domains, and that the substrate or inhibitor of PHI is stored between the large and small domains, corresponding to approximately residues 117-288. Here, site-directed mutagenesis was used to investigate 18 recombinant human AMF point mutants involving critical amino acid residues for substrate or enzyme inhibitor recognition or binding. Mutation of residues that interact with the phosphate group of the PHI substrate significantly reduced the cell motility-stimulating activity. Their binding capacities for AMFR were also lower than wild-type human AMF. Mutants that retained the enzymic activity showed the motility-stimulating effect and receptor binding and had sensitivity to a PHI inhibitor. Mutant AMFR lacking the N-sugar chain was expressed on the cell membrane but did not respond to AMF-stimulation, and N-glycosidase-treated AMFR did not compete with receptor binding of AMF. Furthermore, the AMF domains that contain the substrate storage domain and C-terminal region stimulate cell locomotion. These results suggest that the N-glyco side-chain of AMFR is a trigger and that interaction between the 117-C-terminal part of AMF and the extracellular core protein of AMFR is needed during AMF-AMFR interactions.

Cell Line, Tumor↗

PubMed2006

Autocrine motility factor/glucose-6-phosphate isomerase is a possible predictor of metastasis in bone and soft tissue tumours.

In order to assess the involvement of autocrine motility factor (AMF) in mesenchymal tumours, AMF protein and mRNA expression was analysed in tumours, tumour-like lesions, and other lesions of bone and soft tissue. Immunohistochemical analysis of 200 cases revealed positive staining in 72.5% of the cases, suggesting that AMF is a widely expressed protein. Chordoid, chondroid, and muscular tumours revealed higher immunoreactivity in both benign and malignant tumours. Immunoblotting analysis corroborated the results of immunohistochemistry. Generally, malignant tumours revealed higher expression of AMF than benign tumours of the same histopathological lineage, except for dermatofibroma/dermatofibrosarcoma protuberans. However, mRNA levels were not concordant with protein levels, and sarcomas that displayed higher mRNA and lower protein expression levels showed a trend for distant metastasis. In cultured cells, AMF was secreted and detected in conditioned culture medium. Furthermore, when proteasome inhibitors were added to cells in order to examine the changes in turnover rates, these compounds did not significantly alter the intracellular levels of AMF protein. On the basis of these overall findings, it is suggested that a particular subset of sarcomas secrete AMF, rather than degrading this protein at a higher turnover rate. This secreted AMF presumably enhances their cell motility through an autocrine effect and eventually causes increased metastatic potential. Collectively, AMF was observed in a wide spectrum of lesions of mesenchymal tissue, supporting the notion that it is involved in various cellular functions, including proliferation, differentiation, metabolism, and metastasis. In addition, higher expression of its mRNA may indicate higher levels of protein secretion and define a particularly aggressive group of tumours with high metastatic potential.

Bone Neoplasms↗

PubMed2006

AMF/G6PI induces differentiation of leukemic cells via an unknown receptor that differs from gp78.

Autocrine Motility Factor (AMF)/maturation factor (MF)/neuroleukin (NLK) is a multifunctional protein, which acts as a glucose 6-phosphate isomerase (G6PI) intracellularly. Exto-G6PI stimulates invasion and metastasis of tumor cells, neurotropic growth and differentiation of leukemic cells. The cell motility and proliferation receptor is known to be gp78 (78 kilo-Dalton glycoprotein), which has seven transmembrane domains in its N-terminal region, but the maturation factor receptor remains unclear. The human acute monocytic leukemia line does not express gp78 and its motile activity is not enhanced by AMF though it is well differentiated by AMF exposure. The forced expression of gp78 in leukemic cells recovered acceptable motile stimulation, concomitant with reduced differentiation ability. Two unknown proteins were detected by crosslinking between AMF and leukemic cells. The results of this report suggest that the receptor molecule for AMF/NLK/MF in leukemic differentiation is not gp78.

Animals↗

PubMed2005

PET evaluation of fatty tumors in the extremity: possibility of using the standardized uptake value (SUV) to differentiate benign tumors from liposarcoma.

OBJECTIVE: The relative utility of various preoperative diagnostic imaging modalities, including PET (utilizing FDG and FMT), CT, and MR imaging, for evaluation of lipoma and liposarcoma, especially well-differentiated liposarcoma, was investigated. METHODS: Imaging findings in 32 patients with histopathologically documented lipoma, including one with fibrolipoma and one with angiolipoma, and 25 patients with liposarcomas whose subtypes included 10 well-differentiated, 10 myxoid, and 5 other types were reviewed retrospectively. Pre-operative imaging included FDG-PET (n = 44), FMT-PET (n = 21), CT (n = 25), and MR imaging (n = 53). RESULTS: Statistically significant imaging features of MR images favoring a diagnosis of liposarcoma involved lesions containing less than 75% fat (p < 0.001) as well as the presence of septa (p < 0.001). As compared with well-differentiated liposarcoma, benign lesions were differentiated significantly only by the presence of septa (p < 0.001), which also provided significant differentiation on CT (p < 0.05). The mean SUVs for malignant tumors were significantly higher than those for benign lesions in both FDG- and FMT-PET analyses (p < 0.0001, p = 0.0011, respectively). By using a cut-off value for FDG- and FMT-PET set at 0.81 and 1.0 respectively, which provided the highest accuracy, benign lesions were differentiated significantly from liposarcomas (p < 0.001, and p < 0.02). Furthermore, benign tumors and the three subtypes of liposarcoma were divided significantly into four biological grades by FDG- and FMT-accumulation rates (rho = 0.793, p < 0.0001; and rho = 0.745, p = 0.0009, respectively). A cut-off value of 0.81 for FDG-PET provided significant differentiation between benign lesions and well-differentiated liposarcoma (p < 0.01). CONCLUSIONS: The presence of septa on MR images differentiated lipomas from liposarcoma, even well-differentiated type. PET analysis, especially FDG-PET, quantitatively provided not only the differentiation but also the metabolic separation among subtypes of liposarcoma. Interpretation of the visual diagnostic modalities requires extensive experience and carries a risk of ignoring a critical portion of malignancy. PET metabolic imaging may be an objective and useful modality for evaluating adipose tissue tumors preoperatively.

Adult↗

PubMed2005

Pancreatic and gastric metastases of leiomyosarcoma arising in the left leg.

Pancreatic or gastric metastases from other primary malignancies are rare, especially from leiomyosarcoma. We report a case of leiomyosarcoma in the left lower leg with metastases to the pancreas and stomach. A 61-year-old man had liver cirrhosis caused by hepatitis C virus infection and was followed up by his primary physician. Two years before presentation at our hospital, he had undergone surgical resection of leiomyosarcoma in the left lower leg and systemic chemotherapy for multiple metastatic tumors in the lung. On admission, endoscopic examination and computed tomography were performed for a routine checkup to exclude esophageal varices and liver tumor. Although the patient had no specific symptoms, multiple gastric and pancreatic metastases were identified by endoscopy and computed tomography, respectively. In general, metastases to the pancreas and stomach are rare. We discuss the clinical and diagnostic findings of pancreatic and gastric metastases by reviewing previously reported cases.

Humans↗

PubMed2005

Remission induced by interferon alfa in a patient with massive osteolysis and extension of lymph-hemangiomatosis: a severe case of Gorham-Stout syndrome.

The treatment of massive osteolysis with lymphangioma and/or hemangioma (Gorham-Stout syndrome) has been controversial. The authors report on a patient with multiple massive osteolyses and extensive lymph-hemangiomatosis whose lesions were reduced by interferon alfa therapy. A 2-year-old girl had complained of left chylothorax. Thoracoscopy showed an increase in small lymphatic vessels in the chest wall. The chylothorax was improved by coagulation of the lymphatic vessels. Later, multiple massive osteolyses appeared in the left 11th and 12th ribs, the TH10-L3 vertebrae, and the right femur. There were also hemangiomas in the liver and spleen, a tumor lesion in the left lower chest wall, and hemangiomatous change on the skin surface of the left back. The left lung had only a minimal air content. After OK-432 was injected into the femur and chest wall lesions, the femur lesion disappeared. Then, as right chylothorax appeared, OK-432 was injected into the right pulmonary cavity. The chylothorax disappeared, but pericardial effusion appeared. After steroid pulse therapy, pericardial effusion disappeared. During these treatments, the 7th to 10th ribs disappeared from the x-ray and scoliosis developed. One month later, a cloudy fluid collection in the right lung was found on computed tomography. Interferon alfa and steroid pulse therapy were started. Interferon alfa (1,500,000 units) was subcutaneously administered daily for 2 months and was gradually reduced and maintained at 1,500,000 unit/wk. Steroids were also reduced and maintained at 5 mg/d of predonine. Later, the progress of osteolysis and the extension of lymph-hemangiomatosis stopped. Ten months later, hemangioma in the back disappeared, and the 7th to 10th ribs, which had disappeared, reappeared. The interferon alfa therapy was stopped 14 months after it was administered. The patient's condition has been stable for 10 months since then. At this time, computed tomography shows regression of the hemangiomatous lesion in the back. The authors clinically diagnosed the patient as having Gorham-Stout syndrome with extension of lymph-hemangiomatosis. Interferon alfa with or without steroid therapy should be a choice for patients with extension lesions.

Adrenal Cortex Hormones↗

PubMed2005

Clinical background and its relation to results of percutaneous needle biopsy of suspected bone metastasis under guidance with CT fluoroscopy.

PURPOSE: To investigate the clinical background of needle biopsy of suspected bone metastasis under guidance with CT fluoroscopy. PATIENTS AND METHODS: During a 3-year period (from April 2000 to March 2003), 103 needle biopsies on 101 lesions of 90 patients were performed for pathological evaluation of suspected bone metastasis. The clinical course of these patients prior to biopsy and its relation to the biopsy results were retrospectively reviewed. RESULTS: Sixty-two patients (69% of total cases) were referred for biopsy from orthopedic surgeons, and 51 of these patients consulted orthopedic surgeons on the initial presentation. Malignancy was pathologically proved in 47 (76%) of the 62 orthopedic patients, and in 19 (68%) of the 28 patients referred from other clinicians. Thirteen (21%) of the orthopedic patients had a history of malignancy, while 22 (78%) of the non-orthopedic patients were cancer patients. Metastasis was pathologically proved in 23 (66%) of the 35 patients with a history of malignancy, while malignancy was pathologically proved in 43 (78%) of the 55 patients without known malignancy. Diagnostic accuracy of the needle bone biopsy was 96%, and its complication rate was 0.7%. CONCLUSION: In the era of CT fluoroscopy, needle biopsy for suspected bone metastasis was most frequently requested for the patients who consulted orthopedic surgeons for the occurrence of local bone pain as the initial symptom of unknown malignancy. Frequency of malignancy proved by the biopsy in those patients was as high as that in the cancer patients referred from other clinicians.

Adolescent↗

PubMed2004

Overexpression of autocrine motility factor in metastatic tumor cells: possible association with augmented expression of KIF3A and GDI-beta.

Autocrine motility factor (AMF), which is identical to phosphohexose isomerase (PHI)/glucose-6-phosphate isomerase (GPI), a ubiquitous enzyme essential for glycolysis, neuroleukin (NLK), a neurotrophic growth factor, and maturation factor (MF) mediating the differentiation of human myeloid cells, enhances the motility and metastatic ability of tumor cells. AMF/PHI activity is elevated in the serum or urine in patients with malignant tumors. Here, we constructed an amf/phi/nlk/mf gene using adenovirus vector and transfected into two tumor cell lines. Overexpression of AMF/PHI/NLK/MF enhanced AMF secretion into the culture media in both tumor cell lines. However, upregulation of motility and metastatic ability was found only in metastatic fibrosarcoma cells expressing an AMF receptor, gp78, and was not found in gp78-undetectable osteosarcoma cells. Thus, not only serum AMF activity but also gp78-expression in tumor cells may be required for metastasis-related motility induction. With the use of microarray analyses, we detected two augmented genes, rho GDP dissociation inhibitor beta and kinesin motor 3A, as well as AMF itself. The RNA message and protein expression of these two molecules was confirmed to be upregulated, suggesting a possible association with AMF-induced signaling for cell motility and metastasis.

Adenoviridae↗

PubMed2003

Reconstruction with autologous pasteurized whole knee joint I: experimental study in a rabbit model.

Hyperthermia-treated bone has been used for skeletal reconstruction after resection of malignant bone tumors, and more favorable results have been seen after pasteurization than after autoclaving or boiling. Pasteurization destroys malignant cells while preserving the bone-inducing property. All previous experimental models have studied replantation of bone segments, but reconstruction of joints is more important clinically. We studied the effects of extracorporeal hyperthermia on the reintegration of autologous whole knee joint grafts over a period of 16 weeks in a rabbit model. The whole knee joint was resected from 32 animals, heat-treated at 65 degrees C for 30 min, and replanted. In the control group, resection and replantation were performed without heat treatment. Reintegration was assessed by macroscopic analysis, histology, histochemistry, and radiography. Reintegration of the pasteurized group showed excellent remodeling during the 16 weeks, similar to the control groups. Responses to the pasteurization and the subsequent reintegration of cartilage, menisci, and ligaments were similar at 4, 8, 12, and 16 weeks with no significant difference between the two groups, although cartilage degradation seemed to occur earlier in the study group than in the control group. These results suggest that pasteurization may be superior to other cell-lethal treatments for autotransplantation of the whole joint currently available.

Animals↗

PubMed2003

Reconstruction with autologous pasteurized whole knee joint II: application for osteosarcoma of the proximal tibia.

Reconstruction of the knee joint for osteosarcoma of the proximal tibia is a formidable challenge. Here we present two patients whose knees were reconstructed with autologous grafts of whole-knee joint treated by extracorporeal pasteurization. Incorporation at the junction between host and pasteurized bone was evident. On the other hand, direct reattachment of the patellar tendon to the pasteurized tibia was not successful in case 1. In case 2, in contrast, the patella was divided followed by successful reconstruction at the osseous site. Avoiding reattachment of pasteurized ligamentous structure is recommended. The operation protocol is not ideal but so far may be superior to other reconstruction procedures because there are many fundamental complications such as low long-term survival of a massive prosthesis and the lethal risk of transfection (e.g. human immunodeficiency virus); moreover, immunological responses of the allograft can be avoided.

Adolescent↗

PubMed2003

FDG-PET for evaluating musculoskeletal tumors: a review.

Positron-emission tomography (PET) can provide an in vivo method for evaluating metabolism and physiology in normal and diseased tissues. Clinical trials with [(18)F]2-deoxy-2-fluoro- d-glucose (FDG), the most commonly used radiolabeled tracer for PET imaging, have demonstrated increased accumulation of FDG in several cancer tissues. In this article, we introduce the basic principles of FDG-PET and review current knowledge about FDG-PET for evaluating musculoskeletal tumors. Recent reports and our own experience suggest that FDG-PET cannot be a screening method for differential diagnosis between benign and malignant musculoskeletal lesions, including many neoplasms originating from different tissues altogether. FDG-PET might not accurately reflect the malignant potential of musculoskeletal tumors, but rather might implicate cellular components included in the lesions. A high accumulation of FDG can be observed in histiocytic, fibroblastic, and some neurogenic lesions, regardless of whether they are benign or malignant. More specific uses of FDG-PET, such as grading, staging, and monitoring of musculoskeletal sarcomas, should be considered for each tumor of a different histologic subtype.

Bone Neoplasms↗

PubMed2003

The relation between static and dynamic knee stability after ACL reconstruction.

The purpose of this prospective study was to quantify and compare the amount of anterior tibial translation (ATT) occurring in ACL-reconstructed knees during both a static passive Lachman test and an isokinetic knee extension exercise, pre- and postoperatively. Stress-radiography combined with an electrogoniometer system was applied to 49 knees before and after ACL reconstruction. The Lysholm score was calculated and subjective evaluation assessed before operation and at follow-up. Both measurement methods confirmed a significant decrease of ATT after surgery. Side-to-side differences in ATT were seen in the passive Lachman test postoperatively, and were not found during isokinetic extension from 90 degrees to 0 degree. There was no significant correlation between static passive stability and the functional knee score at follow-up. In addition, the patients with a more than 3 mm side-to-side difference in the passive Lachman test after surgery, showed less than a 1 mm side-to-side difference during isokinetic exercise at a flexion angle of 20 degrees. These results suggest that ACL reconstruction improves ATT in both tests, but the side-to-side difference is greater with the static Lachman test.

Adolescent↗

PubMed2002

Case report of a Cushing's syndrome patient with multiple pathologic fractures during pregnancy.

We describe a case of multiple pathologic fractures in a woman with Cushing's syndrome during pregnancy. Pathologic fractures were seen in the pubic and ischial bones and in T12 and L1 of the vertebral body. These findings, accompanied by easy fatigue, amenorrhea without nursing, psychological disorder, and premature birth, were retrospectively compatible with those of Cushing's syndrome, not pregnancy-associated osteoporosis. After adrenalectomy, the pain in her groin and back ceased. Plain radiographs showed healing of the fractures and increased mineralization. This case demonstrates the need to be alert to the possible presence of metabolic bone disease, including Cushing's syndrome, when we encounter multiple pathologic fractures with osteoporosis in young patients, even if the patient is pregnant.

Adrenalectomy↗

PubMed2002

Atypical growth plate closure: a possible chronic Salter and Harris Type V injury.

Salter-Harris Type V epiphyseal injury is relatively uncommon. The authors present a case involving the proximal tibia diagnosed both by radiologic and histologic findings. The findings suggest that Salter-Harris Type V injury can be a possible outcome when the disappearance of the physeal plate is reported in a patient who has great physical activity in childhood, even if the patient has suffered from no major injury.

Adolescent↗

PubMed2002

Pirarubicin-based versus doxorubicin-based osteosarcoma chemotherapy.

OBJECTIVE: To conduct a retrospective evaluation of tetrahydropyranyladriamycin (PIR)-based combination chemotherapy for osteosarcomas in comparison with doxorubicin (DOX)-based regimens to determine differences in response and toxicities between DOX- and PIR-containing regimens. METHODS: Toxicities and response rates of the 2 anthracyclines given as combination chemotherapy were assessed in patients with osteosarcoma, with 19 patients receiving PIR-based and 11 receiving DOX-based regimens. RESULTS: The survival of osteosarcoma patients treated with PIR was significantly better than that with DOX (p = 0.023) based on 2-year follow-up. Adverse effects such as mucositis and diarrhea were also less pronounced in the PIR cohort. CONCLUSIONS: PIR-based combination chemotherapy might be a useful and safe chemotherapeutic strategy for osteosarcomas compared with DOX regimens. Further assessment is necessary to confirm the safety and efficacy of this treatment.

Adolescent↗

PubMedDate not supplied

Positron emission tomography imaging of musculoskeletal tumors in the shoulder girdle.

The shoulder girdle presents unique features for the preoperative planning of musculoskeletal tumors. This is the first trial to evaluate positron emission tomography (PET) analysis for preoperative planning in shoulder girdle tumors. Fifty-two patients were examined with fluorine 18 fluoro-2-deoxy-D-glucose (FDG)-PET and/or alpha-methyltyrosine (FMT)-PET. Imaging findings were visually inspected in conjunction with computed tomography and/or magnetic resonance imaging, and standardized uptake values (SUVs) were generated. FDG-PET may be useful for the detection of malignant tumors and screening for metastatic spread, with the qualitative assessment of heterogeneous biologic activity providing a correct approach for biopsy. The mean SUVs for malignant tumors were significantly higher than those for benign lesions. However, a useful cutoff SUV was not found in either FDG- or FMT-PET for differentiating malignant from benign tumors from receiver operating characteristic curve analysis. SUVs on FDG- and FMT-PET may merely be limited to differentiating malignant from benign tumors in the shoulder girdle.

Adolescent↗

PubMedDate not supplied

Evaluation of hemangioma by positron emission tomography: role in a multimodality approach.

PURPOSE: The relative utility of various preoperative diagnostic imaging modalities for the evaluation of hemangioma of the extremities, including positron emission tomography (PET) (using 18F-fluoro-2-deoxy-D-glucose [FDG] and fluorine-18 alpha-methyltyrosine [FMT]), computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA), was investigated. METHODS: Imaging findings in 16 patients with 16 histopathologically documented hemangiomas of the extremities were retrospectively reviewed. Preoperative imaging included: FDG-PET (n = 16), FMT-PET (n = 12), MRI (n =16), CT (n =11), and DSA (n =14). RESULTS: All 16 lesions examined by PET with FDG and/or FMT showed accumulation. The standardized uptake values (SUVs) for FDG-PET for the 16 examined tumors ranged from 0.7 to 1.67; for FMT-PET, they ranged from 0.14 to 1.00. The SUVs with both tracers indicated the benign nature of the tumor. Computed tomography demonstrated variable attenuation and phleboliths in two patients. The MRI signal characteristics were relatively consistent: heterogeneous signals were slightly higher than those of skeletal muscle on T1-weighted images and brighter than those of subcutaneous fat on T2-weighted images. The pooling and cotton-wool staining depicted in DSA was found to be significantly correlated with FDG accumulation, suggesting that localized blood retention-induced ischemia may accelerate anaerobic glycolysis, which leads to high FDG uptake. CONCLUSION: Although plain radiography, CT, MRI, and angiography may provide anatomic extent and be pathognomonic, FDG-PET and FMT-PET may be the most reliable among the studied imaging modalities for differentiating benign hemangiomas from other soft tissue tumors, especially malignant neoplasms.

Adolescent↗

PubMedDate not supplied

Carbon-11 choline positron emission tomography in musculoskeletal tumors: comparison with fluorine-18 fluorodeoxyglucose positron emission tomography.

PURPOSE: Recently, a new positron emission tomography (PET) tracer, carbon-11 choline, has been introduced in oncology investigations, but the role of choline PET in musculoskeletal tumor evaluation has not been previously examined. This is the first trial to investigate the utility of choline PET in evaluating musculoskeletal tumors in comparison with fluorine-18 fluoro-2-deoxy-D-glucose (FDG) PET. METHOD: Thirty-three patients were examined with both choline PET and FDG PET, of which standardized uptake values (SUVs) were used for evaluation of the lesions. To decide the appropriate cutoff value and compare the two PET studies, receiver operating characteristic curve analysis was used. The binomial test was used for comparison of sensitivities between choline PET and FDG PET. RESULTS: A significant correlation (r = 0.537, P = 0.0013) between choline and FDG SUVs was noted for all lesions (n = 33). Mean SUVs for malignant tumors were significantly higher than those for benign lesions in both choline PET and FDG PET. Using a cutoff value of 2.7 for choline SUVs, the sensitivity for correctly diagnosing malignancy was 92.3% (12/13) with a specificity of 90.0% (18/20), resulting in an accuracy rate of 90.9%. With use of a cutoff value of 3.3 for SUVs in FDG PET, the sensitivity was 84.6% (11/13) with a specificity of 80.0% (16/20), resulting in an accuracy rate of 81.8%. The receiver operating characteristic curves of two analyses showed that the mean area under the curve value of choline PET (0.9577 +/- 0.041) was significantly greater (P = 0.0488) than that of FDG PET (0.8192 +/- 0.0806). There was no significant difference in sensitivity and specificity between choline PET and FDG PET analysis using either the binomial test (P = 0.4531) or McNemar test (P = 0.371). CONCLUSION: Choline PET analysis may not be inferior to FDG PET analysis for differentiating malignant from benign musculoskeletal tumors. The advantages of choline PET were shorter examination time and little retention in the bladder; therefore, this modality may be useful for preoperative planning for musculoskeletal tumors, especially for lesions around the hip joints.

Adolescent↗