Single-Molecule Co-Immunoprecipitation Reveals Functional Inheritance of EGFRs in Extracellular Vesicles.

Cancer cells actively release extracellular vesicles (EVs) as important carriers of cellular information to tumor microenvironments. Although the composition and quantity of the proteins contained in EVs are characterized, it remains unknown how these proteins in EVs are related to those in the original cells at the functional level. With epidermal growth factor receptor (EGFR) in lung adenocarcinoma cells as a model oncoprotein, it is studied how distinct types of EVs, microvesicles and exosomes, represent their original cells at the protein and protein-protein interaction (PPI) level. Using the recently developed single-molecule immunolabeling and co-immunoprecipitation schemes, the quantity and PPI strengths of EGFRs derived from EVs and the original lung adenocarcinoma cells are determined. It is found that the microvesicles exhibit higher correlations with the original cells than the exosomes in terms of the EGFR levels and their PPI patterns. In spite of these detailed differences between the microvesicles and exosomes, the EGFR PPI strengths measured for EVs generally show a tight correlation with those determined for the original cells. The results suggest that EGFRs contained in EVs closely reflect the cellular EGFR in terms of their downstream signaling capacity.

Associations between the standardized uptake value of (18)F-FDG PET/CT and the prognostic factors of invasive lobular carcinoma: in comparison with invasive ductal carcinoma.

BACKGROUND: The aims of this study were to evaluate the associations between the maximum standardized uptake value (SUVmax) and prognostic factors in invasive lobular carcinoma (ILC) and to compare these results with those in invasive ductal carcinoma (IDC). METHODS: The study included pathologically confirmed ILCs (n = 32) and IDCs (n = 73). We retrospectively evaluated the preoperative (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and measured the SUVmax. The pathologic results were reviewed regarding the size, histological type, histological grade, estrogen receptor (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and Ki-67 of the primary tumor. We also compared the associations between the SUVmax and prognostic factors. RESULTS: The mean SUVmax of the ILCs was significantly lower compared with that of the IDCs (P = 0.032). The SUVmax increased with tumor grade (P < 0.001) and was higher with ER negativity compared with ER positivity (P = 0.007) in IDC. The SUVmax was higher with EGFR positivity compared with EGFR negativity (P = 0.013) in IDC and higher with Ki-67 positivity compared with Ki-67 negativity in IDC and ILC (P < 0.001 and P = 0.002, respectively). The SUVmax was not significantly different regarding PR or HER2 for both tumor groups. The correlation between the tumor size and the SUVmax was demonstrated for IDCs (r = 0.57), but not for ILCs (r = 0.25). CONCLUSIONS: The SUVmax was significantly different according to the tumor grade, ER, EGFR, and Ki-67 for IDCs. The SUVmax exhibited a positive association with Ki-67 in ILC; however, it was not significantly different with other factors, which suggests that the role of (18)F-FDG PET/CT may be limited in ILC.

In vivo evaluation of carotid artery stents using multi-detector-row computed tomography angiography: comparison of 3 kernels.

OBJECTIVE: The objective of this study was to assess the lumen visibility of carotid artery stents using multi-detector-row computed tomography (MDCT) angiography; compare medium-smooth, medium-sharp, and sharp kernels; and correlate these results to those of digital subtraction angiography (DSA). METHODS: We retrospectively evaluated 52 stents from 51 patients who underwent 16- and 64-slice MDCT angiography. Lumen diameters were measured 3 times by 2 neuroradiologists, and artificial luminal narrowing was calculated. To assess detection of in-stent restenosis (>50%), 2 neuroradiologists evaluated all MDCT and DSA images. RESULTS: Excellent intraobserver and interobserver agreements were obtained for the lumen diameter measurements (P < 0.001). Lumen diameter visibility improved, and artificial luminal narrowing decreased from the medium-smooth kernel to the sharp kernel. Visual estimation of all CT angiography using the 3 kernels showed high accuracy for detection of in-stent restenosis (>50%), compared with DSA. CONCLUSIONS: Computed tomography angiography using a sharp kernel allows for more accurate assessment of lumen visibility after carotid artery stenting.

Giant cell tumor with secondary aneurysmal bone cyst: a unique presentation with an ossified extraosseous soft tissue mass.

The authors describe a case of giant cell tumor (GCT) with secondary aneurysmal bone cyst (ABC) in a 44-year-old man with chronic, intermittent knee pain. A unique feature is the presentation of GCT with an ossified extraosseous soft tissue mass. Radiograph demonstrates a multiloculated lytic lesion in the distal meta-epiphyseal region of the femur with an adjacent extraosseous soft tissue mass. The soft tissue mass was partially ossified along its margin and internal septa. MRI demonstrates a multiloculated lesion in the distal femur with multiple fluid-fluid levels and cortical penetration of the lesion. Both the intraosseous lesion and extraosseous soft tissue mass have similar MR signal characteristics. At surgery, the intraosseous component was found to be contiguous with the extraosseous soft tissue mass through a cortical perforation. To the best of our knowledge, this is the first case report of GCT with aneurysmal bone cyst initially presenting with an extraosseous soft tissue mass.

Evaluation of middle cerebral artery stents using multidetector row CT angiography in vivo study: comparison of the three different kernels.

BACKGROUND: There are very few reports assessing middle cerebral artery (MCA) stents using multidetector computed tomography (MDCT). PURPOSE: To assess MCA stents using multidetector CT angiography (CTA) in vivo evaluation: the differences in the CTA results according to the three different kernels. MATERIAL AND METHODS: We retrospectively evaluated 27 MCA stents from 26 patients who underwent CTA with 16- and 64-slice MDCT after percutaneous transluminal angioplasty and stenting (PTAS). By CTA, using medium-smooth kernel (B30), medium-sharp kernel (B50), and sharp kernel (B60), the lumen diameter, artificial luminal narrowing (ALN), and subjective visibility score of the stented vessels were evaluated. The subjective visibility score ranged from 1 (poor quality) to 5 (excellent) using a five-point scale. RESULTS: There were excellent inter-observer agreements for the lumen diameter measurements (P < 0.001). The mean diameter of the stented vessels was 2.10 ± 0.31 mm on digital subtraction angiography (DSA), 0.93 ± 0.20 mm on CTA using B30, 1.18 ± 0.27 mm on CTA using B50, and 1.29 ± 0.29 mm on CTA using B60. The mean ALN was 55.7 ± 6.0% on CTA using B30, 43.8 ± 7.5% on CTA using B50, and 38.7 ± 8.3% on CTA using B60. CTA with higher kernels had a smaller ALN than images with smaller kernels. The median subjective visibility score on the CTA using B50 was 3, which was higher than for the other kernels. The differences in the lumen diameter, ALN, and the subjective visibility score of the stented vessels on CTA using the three different kernels was statistically significant (P < 0.001). CONCLUSION: The sharp kernel was better to assess the lumen diameter and ALN, but was inferior to the medium-sharp kernel for in-stent evaluation due to high image-to-noise. CTA with medium-sharp kernel showed good lumen visibility and acceptable ALN for MCA stents. This could therefore be a non-invasive, readily applicable clinical method for assessing MCA stent patency after stent placement.

Extratendinous migration of calcific tendinitis of the rotator cuff: imaging findings and clinical characteristics with temporal changes.

PURPOSE: The aim of this study was to analyze the imaging findings and clinical characteristics of extratendinous migration of calcific tendinitis of the shoulder with temporal changes. METHODS: Seventy-six patients with extratendinous calcific tendinitis of the shoulder diagnosed by ultrasonography (US) or magnetic resonance imaging (MRI) were enrolled in this retrospective study. Clinical symptoms and imaging findings (on radiography, US, and MRI) of extratendinous calcific tendinitis during an acute painful attack were analyzed. Temporal changes were analyzed in 28 patients before an acute attack and 40 patients after an acute attack. For comparison, 65 patients with intratendinous calcific tendinitis were included. RESULTS: Patients with extratendinous calcific tendinitis had a significantly higher average visual analogue scale (VAS) score (8.8±1.6) than the intratendinous group (6.4±2.2) (P<0.001). The fragmented type (80.5%) was the most common shape on US; sonographic black hole appearance (14.6%) and echogenic fluid (9.8%) were characteristic findings of intrabursal calcifications. In 28 patients with previous radiographs, radiographic type III (78.6%) was dominant and the location of calcific deposits changed (82.1%) during the acute painful attack, which was also perceivable in 12 patients with previous US or MRI. In follow-up radiographs of 40 patients, calcifications shrunk by more than 50% or became invisible in 82.5% of patients, with symptom improvement (VAS score, 8.9±1.5 to 1.9±1.2). Follow-up US and MRI of 16 patients also showed decreased size (56.3%) or disappearance (43.7%) of calcific deposits. CONCLUSION: Extratendinous calcific tendinitis has distinctive imaging features, the temporal changes of which correlate well with clinical symptoms.

Imaging of primary chest wall tumors with radiologic-pathologic correlation.

Neoplasms and tumorlike lesions that originate from chest wall tissues are uncommon compared with tumors in other parts of the body, and unfamiliarity with these disease entities can cause diagnostic difficulties for radiologists. Furthermore, the imaging features of many of these tumors are nonspecific, particularly those that are locally aggressive. However, a systematic approach based on patient age, clinical history, lesion location, and characteristic imaging findings often helps limit the differential diagnosis. Primary chest wall tumors can be classified as bone or soft-tissue tumors, with the latter being further classified into adipocytic tumors, vascular tumors, peripheral nerve sheath tumors, cutaneous lesions, fibroblastic-myofibroblastic tumors, and so-called fibrohistiocytic tumors, largely based on the 2002 World Health Organization classification. Within each category, it is possible to further limit the differential diagnosis with cross-sectional imaging. Information on specific features (eg, mineralization, fibrosis, hemosiderin deposits) and imaging patterns (eg, the "target sign" and "fascicular sign" seen in neurogenic tumors) can aid in making the diagnosis. Radiologists can achieve a sufficiently specific diagnosis of bone tumors and soft-tissue tumors if typical findings are present.

Periosteal autograft for articular cartilage defects in dogs: MR imaging and ultrasonography of the repair process.

BACKGROUND: Autologous periosteal grafting is used as treatment for cartilage defects. PURPOSE: To assess the role of MR imaging and ultrasonography in the evaluation of the post-graft repair process with imaging and histologic correlation. MATERIAL AND METHODS: Periosteal grafts obtained from the tibia of eight dogs were transplanted to the experimental cartilage defects in the femoral condyles (15 knees). The control group was comprised of three dogs (five knees). MR imaging using 4.7T and ultrasonography of the grafted specimens was performed at one, two, four, eight, and 16 weeks after transplantation. The animals were sacrificed at the time of imaging at the previously specified intervals. Histologic analysis with imaging correlation was subsequently performed. RESULTS: All specimens taken from one to 16 weeks demonstrated periosteal proliferation in the graft. At one week, experimental cartilage defects were no longer present on MR imaging. Area of high signal intensity (SI) in the defect was present which corresponded to hemorrhage, edema, and fibrosis on histology. At two, four, and eight weeks, all but two graft demonstrated heterogeneous high SI on T2-weighted image, consistent with immature cartilage. At 16 weeks, all grafts showed heterogeneous isointense to adjacent cartilage on all sequences, which corresponded to dominant mature cartilage. The repair tissue near the exposed subchondral bone revealed heterogeneous high SI on T2-weighted images. This corresponded to the fibrosis with vascular penetration and edema. In the control group, no cartilage repair was noted within cartilage defects. The serial MR features of the grafted area correlated well with the histologic findings. Serial sonographic findings were not sufficient to provide the regenerated cartilage maturity. CONCLUSION: MR imaging is capable of depicting the repair characteristics following periosteal grafting for articular cartilage defects. MR imaging may provide useful information in the assessment of the graft appearance with definite implications regarding the degree and success of incorporation.

MRI of chondromyxoid fibroma.

BACKGROUND: Chondromyxoid fibroma is a rare benign primary bone tumor of cartilage. Despite a characteristic radiographic appearance, chondromyxoid fibroma with atypical radiographic findings may mimic more common tumors. PURPOSE: To describe the MR findings of chondromyxoid fibroma. MATERIAL AND METHODS: MR images of 19 histopathologically confirmed chondromyxoid fibromas were retrospectively analyzed for signal intensity, periosteal reaction, adjacent abnormal bone marrow and soft tissue signal, and patterns of contrast enhancement. RESULTS: All cases of chondromyxoid fibroma showed hypointense to intermediate signal intensity and internal hyperintense foci were observed in seven (37%) cases on T1-weighted images. On T2-weighted images, all lesions were hyperintense: peripheral intermediate signal band with central hyperintense signal in 11 (58%) of 19 lesions, whereas diffusely hyperintense with heterogeneous pattern in eight (42%). Periosteal reaction was observed in 11 (58%) of 19 cases. Adjacent abnormal bone marrow or soft tissue signal was observed in 12 (63%) or 14 (74%) of 19 cases, respectively. On contrast-enhanced T1-weighted images, peripheral nodular enhancement was observed in 69% (11/16) and diffuse contrast enhancement was observed in 31% (5/16) with homogeneous (n = 3) or heterogeneous (n = 2) patterns. Among the cases with peripheral nodular enhancement, the peripheral nodular enhancing portion generally corresponded to the peripheral intermediate signal band on T2-weighted images, although the peripheral enhancement was not as wide as a band of intermediate signal intensity. On the other hand, the central non-enhancing portion generally corresponded to the central hyperintense signal intensity on T2-weighted images. CONCLUSION: The helpful features of chondromyxoid fibroma are the peripheral intermediate signal band and central hyperintense signal on T2-weighted images, generally corresponding to the peripheral nodular enhancement and central non-enhancing portion on contrast-enhanced T1-weighted images, respectively.

Emphasis on the MR imaging findings of brown tumor: a report of five cases.

OBJECTIVE: Brown tumors are focal reactive osteolytic lesions that are encountered in patients with primary or secondary hyperparathyroidism, and these tumors have nonspecific magnetic resonance (MR) imaging findings. However, there are only a few reports on MR imaging of brown tumors. The purpose of this study is to describe the spectrum of MR imaging findings of brown tumors. MATERIALS AND METHODS: The MR imaging features of five patients with clinical and pathological evidence of brown tumor were retrospectively reviewed by two radiologists. The patients had primary hyperparathyroidism, which was confirmed as parathyroid adenoma (n = 2) and parathyroid carcinoma (n = 3). The MR images were evaluated for the presence of solid or cystic portions, the signal intensity of the lesions, the contrast enhancement pattern and the presence of cortex destruction and fluid-fluid levels. RESULTS: Twelve bone lesions were detected on the MR images of five patients; three lesions in two patients, four lesions in one patient, and one lesion in two patients. The tumor was solid in three lesions, mixed solid and cystic in four, and cystic in five. All the solid lesions were accompanied by mixed lesions. Discontinuity of the cortex and adjacent soft-tissue enhancement were seen in all the solid lesions. Fluid-fluid levels were seen in two cases within the cystic component of the mixed lesions and cystic lesions. CONCLUSIONS: The five patients with brown tumor demonstrated a wide spectrum of MR imaging findings. There are few lesions that are osteolytic on the radiographs and that show a short T2 on MR imaging, such as brown tumor. Multiple cystic or mixed lesions are the expected findings of brown tumors.

Studying the Effects of Inositol Pyrophosphates in an In Vitro Vesicle-Vesicle Fusion Assay.

In a recent in vitro vesicle fusion study in which we monitored the fusion of reconstituted SNARE and synaptotagmin-containing proteoliposomes, we discovered that inositol pyrophosphate (5-IP7) is a potent inhibitor of neuronal exocytosis. We found that the inhibitory effect of 5-IP7, which is 10 times more potent than those of IP6 and 1-IP7, requires direct interaction with synaptotagmin. Here, we provide a detailed protocol for proteoliposome preparation and bulk observation of proteoliposome fusion based on FRET signals.

MR imaging manifestations of skin tumors.

In this study, we evaluated MR imaging findings of skin tumors and categorized them into four types: (1) discrete mass lesions of the dermis and epidermis, (2) mass lesions of the subcutis with or without abutment to the skin, (3) diffuse or localized skin thickening without a true mass, and (4) a skin mass with bone destruction. The categorization of MR images may be useful in the differential diagnosis of skin tumors.

Polyvinyl alcohol embolization adjuvant to oily chemoembolization in advanced hepatocellular carcinoma with arterioportal shunts.

OBJECTIVE: To assess the feasibility and safety of polyvinyl alcohol (PVA) embolization adjuvant to transarterial oily chemoembolization (P-TACE) in advanced hepatocellular carcinoma (HCC) with arterioportal shunts (APS). MATERIALS AND METHODS: Nineteen patients who underwent PVA embolization for APS before a routine chemoembolization (TACE) procedure were retrospectively reviewed. 10 of these 19 patients underwent follow-up TACE or P-TACE after P-TACE (Group A), but nine patients underwent only initial P-TACE because of progression of HCC and/or underlying liver cirrhosis (Group B). Hepatic function tests, APS grades, and portal flow directions were evaluated before and after P-TACE sessions. Complications after procedures and survival days were also evaluated. RESULTS: In group A, APS grade was improved in eight patients and five of six patients with hepatofugal flow showed restored hepatopetal flow postoperatively. No immediate complication was developed in either group. Transient hepatic insufficiency developed in eight (42.1%) of 19 patients after P-TACE, and seven (87.5%) of these eight recovered within two weeks under conservative care. The mean and median survival time all study subjects was 280 days and 162 days. CONCLUSION: P-TACE is feasible and safe in advanced HCC patients with APS.

Retroperitoneal malignant mesenchymoma: a case of mesenchymal mixed tumor with osteosarcoma, leiomyosarcoma, liposarcoma and fibrosarcoma.

Malignant mesenchymoma is an interesting but very rare tumor in which malignant differentiation has occurred twice or more. We report a case of retroperitoneal malignant mesenchymoma consisting of osteosarcoma, leiomyosarcoma, liposarcoma and fibrosarcoma. Abdominal CT showed a large retroperitoneal mass with two separate and distinct parts, namely an area of prominent calcification and one of clearly enhancing solid components. The mass contained histologically distinct tumorous components with no histologic admixure at the interfaces. The densely calcified nodule corresponded to osteosarcoma, and the noncalcified clearly enhancing nodules to leiomyosarcoma, liposarcoma and fibrosarcoma.

Airway obstruction in rheumatoid arthritis: CT manifestations, correlated with pulmonary function testing.

In the present study, the signs of airflow obstruction on inspiratory and expiratory CT scans in 45 patients with rheumatoid arthritis were investigated. Radiologic findings were evaluated and correlated with the clinical data, which included rheumatoid factors and pulmonary function tests results. A lung biopsy was performed in five patients. The pattern of CT findings was as follows: infiltrative (n=15), obstructive (n=12), mixed (infiltrative and obstructive; n=10), other complicating diseases (n=7), and normal (n=1). The rheumatologic factor between patients with bronchial wall thickenings and patients without thickenings was significantly different (p=0.009). The forced expiratory flow rate between 25% and 75% of the vital capacity (FEF(25-75%)) was significantly more reduced in patients with interlobular septal thickenings than in patients without these thickenings. The patients with mosaic attenuation had significantly lower mean values of FEF(25-75% ) (p=0.001) and a lower peak expiratory flow (p=0.003) than patients without mosaic attenuation. On expiratory scans, the mean air-trapping score was 21%. These air-trapping scores were found to be well correlated with FEV1/FVC (r=0.230, p=0.0452), and FEF25-75% (r=-0.63, p= 0.05). It is widely known that a relatively higher percentage of mosaic attenuation with air-trapping and a good correlation between these and functional values contribute to the detection of early airway obstruction in patients with rheumatoid arthritis, and even in patients with infiltrative lung disease only.

MR findings of the osteofibrous dysplasia.

OBJECTIVE: The aim of this study was to describe MR findings of osteofibrous dysplasia. MATERIALS AND METHODS: MR images of 24 pathologically proven osteofibrous dysplasia cases were retrospectively analyzed for a signal intensity of the lesion, presence of intralesional fat signal, internal hypointense band, multilocular appearance, cortical expansion, intramedullary extension, cystic area, cortical breakage and extraosseous extension, abnormal signal from the adjacent bone marrow and soft tissue and patterns of contrast enhancement. RESULTS: All cases of osteofibrous dysplasia exhibited intermediate signal intensity on T1-weighted images. On T2-weighted images, 20 and 4 cases exhibited heterogeneously intermediate and high signal intensity, respectively. Intralesional fat was identified in 12% of the cases. Internal low-signal bands and multilocular appearance were observed in 91%. Cortical expansion was present in 58%. Intramedullary extension was present in all cases, and an entire intramedullary replacement was observed in 33%. Cortical breakage (n = 3) and extraosseous mass formation (n = 1) were observed in cases with pathologic fractures only. A cystic area was observed in one case. Among 21 cases without a pathologic fracture, abnormal signal intensity in the surrounding bone marrow and adjacent soft tissue was observed in 43% and 48%, respectively. All cases exhibited diffuse contrast enhancement. CONCLUSION: Osteofibrous dysplasia exhibited diverse imaging features ranging from lesions confined to the cortex to more aggressive lesions with complete intramedullary involvement or perilesional marrow edema.

MR differentiation of low-grade chondrosarcoma from enchondroma.

PURPOSE: To evaluate magnetic resonance (MR) imaging for the discrimination between low-grade chondrosarcoma and enchondroma. MATERIALS AND METHODS: MR images of 34 patients who were confirmed with low-grade chondrosarcoma or enchondroma were retrospectively reviewed. After review of medical records, MR findings in 18 patients with low-grade chondrosarcoma and 16 patients with enchondroma were compared. MR images were retrospectively reviewed for the lesion location (central or eccentric; epiphysis, metaphysic, or diaphysis), margin, contour, mineralized matrix, endosteal scalloping, cortical expansion, cortical destruction, soft tissue mass formation, and periosteal reaction. Signal intensity, the patterns of contrast enhancement (unilocular or multilobular), soft tissue mass, and adjacent abnormal bone marrow and soft tissue signal were also reviewed. Statistical analysis was performed with chi-square test. RESULTS: The patients with low-grade chondrosarcoma had a significantly higher incidence of MR findings (P<.05): predominantly intermediate signal on T1-weighted images [72% (13/18) in low-grade chondrosarcoma vs. 25% (4/16) in enchondroma], multilocular appearance on contrast-enhanced T1-weighted images [83% (15/18) vs. 44% (7/16)], cortical destruction [33% (6/18) vs. 0% (0/16)], a soft tissue mass [28% (5/18) vs. 0% (0/16)], adjacent bone marrow and soft tissue abnormal signal [22% (4/18) vs. 0% (0/16)], and an involvement of the epiphysis or flat bone [56% (10/18) vs. 19% (3/16)]. CONCLUSION: MR imaging shows helpful features for differentiating low-grade chondrosarcoma from enchondroma.