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Biomedical subjects

Mika Watanabe

Publications and source records attributed to Mika Watanabe.

At least 19 recordsLinked to original sources

Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma.

PURPOSE: Nitroglycerin may improve the response to chemotherapy in advanced non-small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported. EXPERIMENTAL DESIGN: Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasma VEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb. RESULTS: The rates of immunoreactive cells for HIF-1alpha, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1alpha in tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma. CONCLUSIONS: Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasing VEGF and P-gp production via reduction of HIF-1alpha.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Spinal intramedullary metastasis of medulloblastoma at initial diagnosis.

CASE REPORT: Spinal magnetic resonance imaging of a 4-year-old boy with medulloblastoma at the initial presentation showed intramedullary lesion without enhancement effect and slight cord swelling from C-5 to T-1. After complete response to the initial therapy, this lesion recurred and slowly expanded. Cervical 11C-methionine-positron emission tomography could establish the diagnosis of intramedullary metastasis. CONCLUSION: Spinal intramedullary metastasis of medulloblastoma at initial diagnosis is extremely rare, but must be considered.

Antineoplastic Agents↗

Malignant astrocytic tumors: clinical importance of apparent diffusion coefficient in prediction of grade and prognosis.

PURPOSE: To retrospectively assess the apparent diffusion coefficient (ADC) for prediction of malignancy and prognosis of malignant astrocytic tumors. MATERIALS AND METHODS: The institutional review board approved this study and did not require patient informed consent. Findings from 37 consecutive patients (21 men, 16 women; mean age, 43 years) with pathologically proved malignant astrocytic tumors that included 22 glioblastomas (GBMs) and 15 anaplastic astrocytomas (AAs) were retrospectively evaluated. The minimum ADC value of each tumor was preoperatively determined from several regions of interest defined in the tumor, preferably with avoidance of cystic or necrotic components, on ADC maps derived from isotropic diffusion-weighted images. Surgical intervention, followed by radiation therapy, was undertaken in all cases according to hospital protocol. Immunohistologically, Ki-67 labeling index (LI), indicating cell proliferation, was also determined. The patients were classified into two groups, progressive and stable, according to the 2-year observation after the initial treatment. Correlation analysis (Pearson product moment correlation), Student t test, Welch test, receiver operating characteristic analysis, and Kaplan-Meier method with log-rank test were used for statistical evaluation. RESULTS: There was a significant negative correlation between minimum ADC and Ki-67 LI (r = -0.562, P < .001). The mean minimum ADC (0.834 x 10(-3) mm2 x sec(-1)) of GBM was significantly lower than that (1.06 x 10(-3) mm2 x sec(-1)) of AA (P < .001, Student t test). The mean minimum ADC (0.80 x 10(-3) mm2 x sec(-1)) of the progressive group was significantly lower than that (1.037 x 10(-3) mm2 x sec(-1)) of the stable group (P < .001). The cutoff value of 0.90 x 10(-3) mm2 x sec(-1) for minimum ADC for differentiation of patients with a favorable prognosis from those with a poor prognosis provided the best combination of sensitivity (79%) and specificity (81%) (receiver operating characteristic analysis). The significant difference in the prognosis between two groups classified by using this cutoff value of minimum ADC was noted (P = .002, log-rank test). CONCLUSION: The minimum ADC of malignant astrocytomas can provide additional information about their clinical malignancy related to posttreatment prognosis.

Adult↗

IL-17A promotes the growth of airway epithelial cells through ERK-dependent signaling pathway.

The effects of IL-17A on mucin production and growth of airway epithelial cells were examined. Histological and immunohistochemical analyses revealed that IL-17A increased the mucin production and number of tracheal epithelial cells in air-liquid interface cultures. The biological property of IL-17A to stimulate the mucin production by tracheal epithelial cells was determined using an ELISA. The mitogenic effect of IL-17A on tracheal epithelial cells was confirmed with Calcein-AM assay. The growth-stimulatory effect of IL-17A was dose-dependent and mediated via the ERK MAP kinase pathway. Inhibitors of MEK abrogated the mitogenic effect of IL-17A, whereas an inhibitor of p38 or JNK displayed no significant inhibitory effect. Moreover, relatively lower doses of IL-13 also significantly increased the growth of tracheal epithelial cells through a distinct signaling pathway from that of IL-17A. These findings provide the first evidence that IL-17A stimulates the growth of airway epithelial cells through the ERK MAP kinase pathway.

Aged↗

New trends of immunohistochemistry for making differential diagnosis of breast lesions.

Immunohistochemistry is widely used for pathological diagnosis of breast lesions. Other than hormone receptors and HER2/neu analysis for primary breast carcinomas, several markers may be useful for differential diagnoses, although in limited situations. To decide the malignant potential of intraductal proliferative lesions, analysis for the staining pattern of cytokeratins may be a good reference. Most ductal carcinoma in situ cases are diffusely positive for luminal cell markers (CK8, CK18, CK19), but negative for basal cell markers (CK5/6 and CK14). However, usual ductal hyperplasia may show the mosaic staining patterns for any of these markers, which may indicate a heterogeneous cell population in benign lesions. Myoepithelial markers (alpha-SMA, myosin, calponin, p63, CD10) are almost consistently positive for benign papillomas but they do not completely distinguish intraductal papillary carcinomas. Preservation of myoepithelial layer is the diagnostic key when looking at benign sclerosing lesions, including carcinoma with pseudoinvasive structures. E-cadherin is mostly positive for ductal carcinomas but negative for lobular carcinomas. Some of the lobular carcinomas are positive for 34betaE12, but they are consistently negative for CK5/6. Comparison with histopathological findings of hematoxylin and eosin is essential to make proper diagnosis in the individual case.

Biomarkers, Tumor↗

Subcutaneous granuloma annulare in a child's palm: a case report.

We present a rare case of subcutaneous lesions arising in the palm of a 4-year-old girl. Histologic examination of the biopsy specimens showed granulomatous inflammation with focal necrobiosis, which was consistent with subcutaneous granuloma annulare. Subcutaneous granuloma annulare is a self-limited disease and treatment is not required, although recurrence and/or multiple lesions are frequent.

Biopsy↗

Acute pancreatitis due to pancreatic arteriovenous malformation: 2 case reports and review of the literature.

Pancreatic arteriovenous malformation (AVM) is a relatively rare disease. Based on our literature search, 51 cases of pancreatic AVM have been reported since 1968. The gastrointestinal bleeding is the most common presenting symptom (24/51 cases [47%]). There were only 6 cases of pancreatitis in these cases. We describe 2 cases of acute pancretitis with pancreatic AVM. The patients who were diagnosed with acute pancreatitis were admitted to our hospital. Pancreatitis was considered to be caused by pancreatic AVM by some modalities of diagnostic imaging. The respective pancreatic AVM lesions of patients were resected to prevent the recurrence of pancreatitis. They are asymptomatic after the surgery. Pancreatic AVM is thought to be the one of the reasons for acute pancreatitis.

Acute Disease↗

Osteosarcoma arising from giant cell tumor of bone ten years after primary surgery: a case report and review of the literature.

Giant cell tumor of the bone (GCT) is a relatively uncommon tumor. It is characterized by the presence of multinucleated giant cells. GCT is a primary benign tumor but may evolve into a malignant tumor, usually after irradiation. We report a rare case of osteosarcoma arising ten years after the primary surgery for GCT without radiation. A 45-year-old woman presented with severe right knee pain after suffering contusion. Roentgenogram revealed a bone tumor in the lateral femoral condyle of the right knee. Histopathological examination demonstrated the features of GCT, and treatment consisted of curettage and bone grafting. Four months after the operation, multiple lung metastases of GCT occurred, which were treated by partial lobectomy. Ten years after the primary treatment, severe knee pain recurred. Roentgenogram and magnetic resonance imaging (MRI) demonstrated a destructive lesion in the lateral condyle of the right knee. Histopathological examination demonstrated a lacy pattern of osteoids and abnormal mitoses in the aggregated atypical mononuclear cells, indicating osteosarcoma. Despite above-knee amputation and chemotherapy, scapular and lung metastases developed and the patient died five months after above knee amputation. One may question whether the primary GCT contained some malignant cells. However, given the aggressiveness of the malignant tumor, this is unlikely. The recurrence of pain and aggravation of bone destruction many years after the primary treatment suggest malignant transformation of GCT.

Bone Neoplasms↗

Chondrosarcoma of the ring finger: a case report and review of the literature.

Enchondromas are the most common benign cartilaginous bone tumors arising in the medullary cavity of the small bones of the hand. In contrast, chondrosarcomas, commonly occurring in the pelvis and proximal femur and humerus, are very uncommon at this site. We report an unusual case of chondrosarcoma arising in the ring finger proximal phalanx with its radiological and histological features and reviewed the literature. The patient was an 80-year-old man whose chief complaint was swelling and pain for seven years. The findings of cortical irregular thickening by plain radiography and computed tomography and soft tissue extension by magnetic resonance imaging suggested the tumor was chondrosarcoma rather than a common enchondroma. Thorough curettage and artificial bone grafting was performed because of the age of the patient, his senile dementia and the strong desire of the patient and his family. Histological examination revealed that the tumor was composed of polygonal cells with eosinophilic cytoplasm proliferating in the chondromatous matrix with partially myxoid changes. Nuclear irregularity, binucleated cells, bone permeation and encasement were observed and the tumor was diagnosed as grade 2 chondrosarcoma. The tumor recurred five months after surgery. Amputation of the ring finger including the distal part of the 4th metacarpal was performed. At two years after surgery, the patient was free from recurrence or lung metastasis. In conclusion, details of radiological as well as pathological findings are essential for differential diagnosis between benign enchondroma and chondrosarcoma in the hand. Chondrosarcoma of the hand requires a prompt and more radical treatment than enchondroma. Wide excision is recommended to avoid local recurrence or metastasis.

Aged, 80 and over↗

Osteosarcoma in a patient with neurofibromatosis type 1: a case report and review of the literature.

Neurofibromatosis type 1 (NF1) or von Recklinghausen's disease is a genetic disease generally characterized by café-au-lait spots and neurofibromas. Malignant tumors of the nervous system, such as malignant schwannomas, gliomas, or astrocytomas, have been well known to coexist with neurofibromatosis. However, occurrence of malignant tumors unrelated to the nervous system is rare. We report an unusual case of a 29-year-old NF1 female suffering from malignant peripheral nerve sheath tumor (MPNST) that eventually developed osteosarcoma in the proximal femur. Osteosarcoma is the most common high-grade malignant bone tumor in which the neoplastic cells produce osteoid. At 23 and 24 years old, she underwent excision of MPNST in the left posterior thigh. No osteosarcomatous portion was identified in these specimens. The patient underwent postoperative chemotherapy. At 29, left proximal thigh pain and swelling appeared. Computed tomography demonstrated cortical bone destruction in the left proximal femur where MPNST occurred. Magnetic resonance imaging revealed extraskeletal growth of the tumor. Bone scintigraphy demonstrated increased uptake in the left proximal femur. Hip disarticulation was performed. The removed tumor was composed of highly anaplastic cells. Lace-like irregular osteoid formation was observed among the tumor cells. MPNST component was totally absent. The tumor was diagnosed as osteoblastic type osteosarcoma. Two months after disarticulation the patient died of bilateral pulmonary metastasis. The correlation between the histogenesis of osteosarcoma and the genetic abnormality in NF1 patients has not been elucidated, but the finding of osteosarcomatous transformation in this case suggests the divergent cellular differentiation to mesenchymal malignant tumors of neuroectodermal tissue in NF1 patients.

Adult↗

Serum antibody against granulocyte/macrophage colony-stimulating factor and KL-6 in idiopathic pulmonary alveolar proteinosis.

Here we describe a case of idiopathic pulmonary alveolar proteinosis (I-PAP), in which anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) antibody and high level of KL-6 were found in the serum. Anti-GM-CSF antibody is responsible for I-PAP, and KL-6 is a serum marker for the activity of diffuse interstitial lung disease. A 38-year-old woman, who had no symptoms, was found to have an abnormal shadow on chest radiograph 5 years previously at a health check up. Chest radiograph showed a patchy shadow in the left lower lung field. Thoracoscopic biopsy was performed because the shadow had gradually expanded during the 5 years. Histological examination revealed proteinous material filling the alveoli and positive staining by the PAS method, suggesting PAP. Anti-GM-CSF antibody and a high level of KL-6 were detected in the serum at the time of diagnosis. Three years later, the shadow disappeared spontaneously. During this period, the level of KL-6 dramatically decreased, although that of GM-CSF antibody remained unchanged. The present case suggests that the serum level of the anti-GM-CSF antibody represents a useful marker for the diagnosis but not for follow-up of the clinical course. On the contrary, KL-6 is an excellent marker for the assessment of the clinical course of I-PAP.

Adult↗

A classic adamantinoma arising from osteofibrous dysplasia-like adamantinoma in the lower leg: a case report and review of the literature.

Adamantinoma is known as a low-grade malignant biphasic tumor. Classic adamantinoma is in general characterized by admixture of both epithelial and osteofibrous components that are associated with various proportions and differentiation patterns. Osteofibrous dysplasia (OFD) is a self-limited benign fibro-osseous lesion of bone during infancy and childhood. OFD-like adamantinoma is characterized by predominance of osteofibrous tissues, in which small groups of epithelial cells are only detected by careful search or immunohistochemistry. There have been controversies as to the potential correlation among OFD, OFD-like adamantinoma and classic adamantinoma. We report an unusual case of adamantinoma arising in the tibia, with an extensive review of the literature. The present findings suggest a direct correlation between OFD-like adamantinoma and classic adamantinoma. At the age of 12 years, the tibial biopsy lesion was diagnosed as OFD. At the age of 23, the lesion became larger and more destructive on x-ray films. The biopsy lesion was diagnosed as classic adamantinoma. Wide excision was performed. The primary lesion was retrospectively diagnosed as OFD-like adamantinoma because of presence of keratin-positive epithelial cells within the stroma. At five years after surgery, the patient was free from recurrence or metastasis. The retrospective histological findings of OFD-like adamantinoma in the original biopsy and of a classic adamantinoma in all sections of the later resection specimen raised the possibility of an unusual progression of OFD-like adamantinoma to a classic adamantinoma. The present case and the literature review suggest that an OFD-like adamantinoma may be a precursor lesion of classic adamantinoma. Therefore, the possibility of progression of OFD-like adamantinoma to a classic adamantinoma should be kept in mind, particularly when the destructive changes are seen radiologically.

Adamantinoma↗

Establishment and characterization of a clonal human extraskeletal Ewing's sarcoma cell line, EES1.

Ewing's sarcoma, a small round cell sarcoma arising in soft tissue as well as the bone, is one of the most malignant tumors in children and young adults. Few established cell lines of extraskeletal Ewing's sarcoma (EES) have been reported, which made it difficult to examine the biological features of EES. Therefore, we have established a new clonal cell line of EES. We report its morphological characters, results of chromosomal and immunohistochemical analysis. A piece of tumor obtained from the 18-year-old female patient with EES was xenografted in a nude mouse. In vitro subcultured cells were then obtained from this xenograft. A clonal cell line was subsequently established by limiting dilution and designated EES1. EES1 cells had a doubling time of 24 hours. In the xenografted tumor, the cells expressed vimentin, CD99 (MIC2), neuron specific enolase (NSE) and cytokeratin. The original tumor cells also expressed vimentin, CD 99, and NSE, but was negative for cytokeratin. The morphological and immunohistochemical features of this cell line established, except for cytokeratin expression, were consistent with those of the primary tumor. Cytogenetic analysis of EES1 revealed chromosomal translocation of t(11; 12)(q24;ql2). The chimeric fusion of the Ewing's sarcoma gene in band 22q12 with the Friend leukemia virus integration-1 gene in band 11q24 was also demonstrated. Fluorescence in situ hybridization further confirmed the presence of translocation involving the Ewing's sarcoma gene in both the primary tumor and EES1 cells. In conclusion, we have established a human EES cell line EES1, which will provide a useful model for studying various aspects of human EES.

Adolescent↗

Penetrating atheroma in cervical carotid artery stenosis.

A 61-year-old male presented with left hand motor weakness associated with cerebral infarction in the right frontal lobe. Right common carotid angiography demonstrated a 66% stenosis and carotid duplex scan demonstrated intermediate echogenic plaque, indicating typical carotid plaque. Carotid endarterectomy was performed 22 weeks after the ischemic onset. During exposure of the carotid artery, a soft and yellowish mass (5 x 5 mm) was observed in the lateral wall of the carotid bulbus, which was not covered with adventitia but with thin connective tissue. The mass was removed en-bloc with a small part of the surrounding arterial wall combined with ordinary endarterectomy. The artery was closed with a collagen-impregnated polyester patch graft (Hemashield patch) to maintain adequate arterial lumen. Histological examination of the removed plaque confirmed that atheroma had protruded from the intima through the media as well as the adventitia and formed an extra-arterial mass. Such a case requires great care to dissect the carotid artery to prevent premature disintegration of the atheroma.

Atherosclerosis↗

[A case of advanced colon cancer with metastases to both para-aortic lymph nodes and cervical vertebrae effectively treated by TS-1 therapy].

The patient was a 68-year-old woman who had cecal cancer with para-aortic lymph node metastases. Ileocecal resection was performed palliatively. Since metastasis to cervical vertebrae was detected after the operation, she received radiation therapy of 14 Gy to improve neck pain. Chemotherapy with TS-1 (80 mg/day) was started on an outpatient basis (4 weeks administration followed by a 2-week drug-free period). After 4 courses of this chemotherapy, metastases to both para-aortic lymph nodes and cervical vertebrae were remarkably reduced on CT and PET. Throughout the period of treatment, there was no adverse effect and this treatment has been maintained. In conclusion, this case seems significant from the viewpoint of achieving a partial response to TS-1 and maintaining a high quality of life. Moreover,we identified the presence of TS and DPD using an immunohistochemical staining technique. The primary tumor was positive for DPD stain test and negative for TS stain test. It was suggested that this cancer especially would respond to TS-1 chemotherapy.

Adenocarcinoma↗

Spinal hamartoma associated with spinal dysraphism.

OBJECTS: The aims of the study were (1) to review the pathological findings of spinal lipomatous masses associated with congenital spinal dysraphism and (2) to discuss the pathological diagnosis. METHODS: The pathological records of 47 patients at our institution were reviewed, and three illustrative cases were presented. CONCLUSION: Spinal tumorous lesions associated with spinal dysraphism have been traditionally described as lipoma since they are composed mostly of fatty tissue. However, they are different from lipomas arising in other part of the body in that they often contain various tissues of ecto- and mesodermal origin. In our study, we detected such heterotopic components in 24 out of 47 cases. Although they are also similar to teratoma, it is generally accepted that they are malformative lesions which lack neoplastic potential. We therefore should diagnose them as hamartoma rather than lipoma or teratoma.

Child↗

IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis.

In this study, we examined the biological action of IL-17 on human non-small cell lung cancer (NSCLC). Although IL-17 had no direct effect on the in vitro growth rate of NSCLC, IL-17 selectively augmented the secretion of an array of angiogenic CXC chemokines, including CXCL1, CXCL5, CXCL6, and CXCL8 but not angiostatic chemokines, by three different NSCLC lines. Endothelial cell chemotactic activity (as a measure of net angiogenic potential) was increased in response to conditioned medium from NSCLC stimulated with IL-17 compared with those from unstimulated NSCLC. Enhanced chemotactic activity was suppressed by neutralizing mAb(s) to CXCL1, CXCL5, and CXCL8 or to CXCR-2 but not to vascular endothelial growth factor-A. Transfection with IL-17 into NSCLC had no effect on the in vitro growth, whereas IL-17 transfectants grew more rapidly compared with controls when transplanted in SCID mice. This IL-17-elicited enhancement of NSCLC growth was associated with increased tumor vascularity. Moreover, treatment with anti-mouse CXCR-2-neutralizing Ab significantly attenuated the growth of both neomycin phosphotransferase gene-transfected and IL-17-transfected NSCLC tumors in SCID mice. A potential role for IL-17 in modulation of the human NSCLC phenotype was supported by the findings that, in primary NSCLC tissues, IL-17 expression was frequently detected in accumulating and infiltrating inflammatory cells and that high levels of IL-17 expression were associated with increased tumor vascularity. These results demonstrate that IL-17 increases the net angiogenic activity and in vivo growth of NSCLC via promoting CXCR-2-dependent angiogenesis and suggest that targeting CXCR-2 signaling may be a novel promising strategy to treat patients with NSCLC.

Animals↗