A short synthetic approach to the protected uracil 3′-epi-polyoxin C 20 has been developed. The stereoselective [3,3]-sigmatropic rearrangement of the corresponding 7-thiocyanato-α-d-xylo-hept-5-enfuranose 6 was employed as the key step to construct the C-5 stereocentre in 5-isothiocyanato-α-d-gluco-hept-6-enfuranose 8 and the formal synthesis of uracil 3′-epi-polyoxin C has been accomplished for the first time. This synthesis provides a facile method for multigram scale preparation and thus is useful for the research into the polyoxins’ structure–activity relationship and to search for more potent and effective anticandidal agents.

You have accessJournal of Urology1 Apr 2008IMMUNE MONITORING OF AN ALLOGENIC GENETICALLY- MODIFIED TUMOR CELL VACCINE (RCC-26/CD80/IL-2) IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA Alexander Buchner, Heike Pohla, Bernhard Frankenberger, Andrea Baur, Christian G Stief, Alfons Hofstetter, Ralph Oberneder, Juergen Kopp, Antonio Pezzutto, Thomas Blankenstein, and Dolores J Schendel Alexander BuchnerAlexander Buchner More articles by this author , Heike PohlaHeike Pohla More articles by this author , Bernhard FrankenbergerBernhard Frankenberger More articles by this author , Andrea BaurAndrea Baur More articles by this author , Christian G StiefChristian G Stief More articles by this author , Alfons HofstetterAlfons Hofstetter More articles by this author , Ralph ObernederRalph Oberneder More articles by this author , Juergen KoppJuergen Kopp More articles by this author , Antonio PezzuttoAntonio Pezzutto More articles by this author , Thomas BlankensteinThomas Blankenstein More articles by this author , and Dolores J SchendelDolores J Schendel More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(08)61208-2AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "IMMUNE MONITORING OF AN ALLOGENIC GENETICALLY- MODIFIED TUMOR CELL VACCINE (RCC-26/CD80/IL-2) IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA." The Journal of Urology, 179(4S), p. 412 © 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 179Issue 4SApril 2008Page: 412 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information Alexander Buchner More articles by this author Heike Pohla More articles by this author Bernhard Frankenberger More articles by this author Andrea Baur More articles by this author Christian G Stief More articles by this author Alfons Hofstetter More articles by this author Ralph Oberneder More articles by this author Juergen Kopp More articles by this author Antonio Pezzutto More articles by this author Thomas Blankenstein More articles by this author Dolores J Schendel More articles by this author Expand All Advertisement PDF downloadLoading ...

Aims: Pre-clinical studies showed that the allogeneic tumor cell line RCC-26 displayed natural immunogenic potential that was enhanced through expression of CD80 costimulatory molecules and secretion of interleukin-2. Here we report the study of RCC-26/CD80/IL-2 cells in a phase I vaccine trial of renal cell carcinoma patients with metastatic disease (mRCC). Fifteen patients of HLA-A*0201 allotype, with at least one metastatic lesion, were included. Irradiated vaccine cells were applied in increasing doses of 2.5, 10 and 40 x 106 cells over 22 weeks. Primary study parameters were safety and toxicity. Sequential blood samples were analyzed by interferon-gamma-ELISPOT assays to detect tumor antigen-associated (TAA) effector cells. Results: The vaccine was well tolerated and the designated vaccination course was completed in 9 of 15 patients. Neither vaccine-induced autoimmunity nor systemic side effects were observed. Delayed type hypersensitivity (DTH) skin reactions were detected in 11 of 12 evaluated patients and were particularly strong in patients with prolonged survival. In parallel, vaccine-induced immune responses against vaccine or over-expressed TAA were detected in 9 of 12 evaluated patients. No tumor regressions occurred according to RECIST criteria, however median time to progression was 5.3 months and median survival was 15.6 months, indicating substantial disease stabilization. Conclusions: Vaccine use was safe and feasible in mRCC. Clinical benefits were limited in these patients with advanced disease however immune monitoring revealed vaccine-induced responses against multiple TAA in the majority of study participants. These results suggest that this vaccine could be useful in combination therapies and/or minimal residual disease.

The sensitivity of the visual detection of diffuse multiple myeloma with unenhanced MRI is limited for low-grade or moderate infiltration, whereas the sensitivity for high grade infiltration is reliable. The specificity is high and the diagnostic confidence improves after application of contrast material with calculation of the percentage increase in signal intensity.

PURPOSE To determine the detection of diffuse bone marrow infiltration with MRI in comparison with histopathological findings. MATERIALS AND METHODS MRI was performed on 45 patients with histologically proven multiple myeloma and on 30 healthy individuals. Three experienced radiologists read separately Tl-weighted SE sequences, STIR sequences and the combination of Tl-weighted SE and STIR sequences of the spine. Additionally, Tl-weighted SE sequences were obtained after gadolinium administration and the percentage increase in signal intensity was calculated. Bone marrow histology was used as gold standard for assessing the grade of infiltration. A dichotomous decision (infiltration yes/no) was made when assessing the MRI examinations. RESULTS For the visual detection of diffuse infiltration, the best sensitivity was found with Tl-weighted SE sequences, achieving 71 % on average. The specificity was 89 %. The STIR sequences showed a sensitivity of 61 % and a specificity of 98 %, and the combination of Tl-weighted/STIR-sequences achieved a sensitivity of 65 % and a specificity of 94 %. In comparison with the histological findings, the sensitivity of the Tl-weighted sequences was 35 % for low-grade, 89 % for moderate and 100 % for high-grade infiltration. The application of contrast material with calculation of the percentage signal increase improved the detection by 7 %. CONCLUSION The sensitivity of the visual detection of diffuse multiple myeloma with unenhanced MRI is limited for low-grade or moderate infiltration, whereas the sensitivity for high grade infiltration is reliable. The specificity is high and the diagnostic confidence improves after application of contrast material with calculation of the percentage increase in signal intensity.

Ziele: Vergleich der visuellen Detektionsrate eines diffusen Plasmozytombefalls in Korrelation zur Histologie und verwendeten MRT-Sequenz. Methode: Es wurden MRT-Wirbelsäulenaufnahmen von 45 primär untherapierten Patienten mit histologisch gesichertem diffusem Plasmozytom und 30 gesunden Patienten untersucht. Zwei unabhängige Reader werteten ohne Kenntnis der klinischen Befunde T1 gewichtete-Sequenzen, STIR-Sequenzen sowie T1-/STIR-Aufnahmen in Kombination qualitativ aus. Der Goldstandard war die Knochenmarkshistologie, in der Infiltrationsgrad, Hämatopoese und Fettgehalt bestimmt wurden. Die Einteilung des histologischen Infiltrationsgrads erfolgte in mittelgradige Infiltration (<50 Vol%) und hochgradige Infiltration (>50%). Die visuelle Befundung erfolgte in 3 Kategorien: kein Befall, mittelgradiger, hochgradiger Befall und unentschieden. Ergebnis: Die Sensitivität bei der Befundung der T1-Aufnahmen lag für beide Reader im Mittel bei 89%, die Spezifität bei 77% (ppV=0,85; npV=0,83). Bei den STIR-Aufnahmen war die Sensitivität 80%, die Spezifität 82% (ppV=0,95; npV=0,77). Für die Kombination T1/STIR wurde eine Sensitivität von 83% bzw. Spezifität von 90% erreicht (ppF=0,92; npF=0,80). In 7 Fällen waren sie unentschieden. Der Infiltrationsgrad wurde im MRT bei geringem histologischem Befall zu 32% richtig bestimmt, bei hohem Befall zu 90%. Schlussfolgerung: Die Kombination von T1- und STIR-Aufnahmen als Standardsequenz zeigte eine hohe Sensitivität und Spezifität in der Detektion des diffusen Plasmozytoms. Das Ausmass des Infiltrationsgrads wird mit MRT jedoch nur bei hochgradigem Befall korrekt diagnostiziert.

Lymphangiosarcoma (LAS) may occur as a rare complication of primary lymphedema. A case of LAS in hereditary lymphedema of the lower extremity in a 36-year old female is reported. Despite of chemotherapy, local hyperthermia and later amputation of the extremity the patient died of progressive disease due to pulmonary metastasis. In respect to this case, the different therapeutic concepts, as reported in the literature, and their results are presented and discussed.

BACKGROUND. The goal of the current study was to assess the correlation between bone marrow histology and contrast enhancement in infiltrative diffuse myeloma.METHODS. Forty-four patients with homogeneous diffuse infiltration of bone marrow by multiple myeloma were examined using magnetic resonance imaging of the spine. The sequence protocol included T1-weighted spin-echo (pre- and post-gadolinium dimeglumine administration) and short-inversion time inversion recovery sequences. The percent increase in signal after intravenous gadolinium administration was calculated in bone marrow from patients with myeloma and from a control group of 86 patients who did not have bone marrow disease. Grade of infiltration with plasma cells, fat cell content, and hematopoietic marrow content were evaluated via histologic assessment of bone marrow, and microvessel density was evaluated via anti-CD34-positive immunostaining.RESULTS. increased microvessel density was observed in association with increasing plasma cell content (Kruskall-Wallis test: P < 0.0001). Contrast enhancement increased in a stepwise manner according to grade of microvessel density (Mann-Whitney U test: P < 0.05 and P < 0.001 for increases from low to intermediate and intermediate to high grade) and was significantly higher in patients with myeloma compared with control patients (Mann-Whitney U test: P < 0.001). A significant correlation also was found between histologic extent of tumor infiltration and contrast enhancement (Mann-Whitney U test: P < 0.0001). The mean level of contrast enhancement was 18% in the control group, 26% in patients with lowgrade infiltration, 49% in patients with intermediate-grade infiltration, and 90% in patients with high-grade infiltration. In addition, fat cell content was found to be inversely correlated with contrast enhancement (chi-square test: P < 0.01).CONCLUSIONS. As a consequence of increased microvessel density, decreased fat cell content, and increased cellularity, the presence of diffuse bone marrow infiltration in patients with multiple myeloma can be verified using gadolinium-enhanced magnetic resonance imaging. (C) 2004 American Cancer Society.

Bei mehr als 50% aller Patienten mit multiplem Myelom kommt es während des Krankheitsverlaufs zur pathologischen Fraktur. Mit 15% ist das multiple Myelom zudem der häufigste Tumor der Wirbelsäule, 8–10% der Patienten entwickeln neurologische Ausfälle bis hin zur Paraplegie. Entsprechend ist die operative Therapie des multiplen Myeloms eine im individuellen Krankheitsverlauf absolut relevante Maßnahme, wenngleich naturgemäß eine tatsächliche prognostische Beeinflussung der Erkrankung nur in den sehr seltenen Fällen des peripheren solitären Plasmozytoms stattfinden kann.

OBJECTIVE. The aim of our study was to compare the signal-to-noise ratio and the diagnostic accuracy of moving-table MR angiography of the peripheral arteries with body coil and dedicated phased array coil systems.SUBJECTS AND METHODS. Forty patients were examined with digital subtraction angiography and moving-table MR angiography with a 1.5-T MR imaging system either with a body coil (n = 20) or with a dedicated phased array coil (n = 20). The timing of contrast material was performed with real-time MR fluoroscopy.RESULTS. For the iliac artery, upper leg, and lower leg, the mean values for signal-to-noise ratios were 56, 51, and 17, respectively, for the body coil, and 54, 74, and 64, respectively, for the dedicated phased array coil. For the body coil, sensitivity and specificity in identifying stenosis greater than 50% and occlusions were 100% and 96%, respectively, for the iliac arteries, and 100% and 96%, respectively, for the upper leg. For the dedicated phased array coil, sensitivity and specificity for sis greater than 50% and occlusions were 100% and 96%, respectively, for the iliac arteries, and 100% and 98%, respectively, for the upper leg. Sensitivity and specificity were inferior for the body coil (88% and 85%) compared with the dedicated phased array coil (100% and 96%) in the lower leg. A significant difference of the mean values of contrast-to-noise ratio was found before and after subtraction for the dedicated phased array coil and body-coil techniques (Student's t test, p < 0.01).CONCLUSION. In comparison with the body coil, the dedicated peripheral phased array surface coil system improves signal-to-noise ratio for the upper and lower leg and diagnostic accuracy in the lower leg.

PURPOSE:To evaluate early changes in musculoskeletal soft-tissue sarcomas under neoadjuvant chemotherapy combined with regional hyperthermia (RHT).PATIENTS AND METHODS:Nineteen consecutive patients with high-grade soft-tissue sarcomas of the musculoskeletal system were treated with neoadjuvant chemotherapy combined with RHT. Patients were imaged, using a high field MR-scanner, before onset of therapy, immediately after one and after four cycles of therapy. The images were evaluated for volume reduction and development of tumour necrosis. In addition, side effects such as surrounding soft-tissue oedema, bleeding and muscle or bone marrow necrosis were analysed.RESULTS:Tumour volume reduction was significant after the completion of neoadjuvant therapy (mean 49%, range 5-91%; (p < 0.001). Extent of tumour necrosis was also significantly different before (mean 22%) and after therapy (mean 58%, p < 0.001). Three patients showed strong tumour necrosis already after one cycle of treatment. Tumour volume reduction was not associated with the extent of pre-existing necrosis or necrosis development. The extent of tumour volume before start of therapy did not affect volume reduction or necrosis induction after therapy. Reduction of tumour oedema was significant after therapy (p < 0.001). No side effects were observed during thermochemotherapy.CONCLUSION:Neoadjuvant chemotherapy combined with RHT resulted in significant tumour volume reduction and induction of tumour necrosis, which can be detected early and monitored closely with MRI.

Fragestellung: Sakrale Ermüdungsfrakturen bei Osteoporose – gerade beim älteren Menschen nicht selten – werden oft, da röntgenologisch nicht immer nachweisbar, als Lumboischialgie verkannt und unzureichend therapiert. Anhand von 13 Fälle möchten wir Klinik, Radiologie und Verlauf der Frakturen darstellen.

Diffusion-weighted imaging allows for measurement of tissue microstructure and reflects the random motion of water protons. It provides a new method to study bone marrow and bone marrow alterations on the basis of altered water-proton mobility in various diseases. Different diffusion-weighted methods have proved to be capable of differentiating between benign edema and tumorous involvement of bone marrow. It is especially useful for the distinction of acute benign osteoporotic and malignant vertebral compression fractures. Diagnosis is based on the contrast to normal bone marrow. Hypo- or isointensity reflects acute benign collapse, whereas hyperintensity is indicative of the tumorous nature of a fracture. Apparent diffusion coefficients (ADC) are significantly lower in metastatic disease than in bone marrow edema. Furthermore, bone marrow cellularity can be estimated by ADC measurements. Diffusion-weighted imaging might be helpful for monitoring response to therapy in metastatic disease.

The theory behind diffusion-weighted imaging (DWI) in the spinal cord is reviewed with an emphasis on applications for spinal cord injury (SPI). Current animal research, mostly related to SPI, also is discussed. Computer simulations designed to elucidate the histologic correlates behind measured apparent diffusion coefficient values are reviewed and followed by an update on clinical use of spinal cord DWI.

Purpose: To evaluate the diagnosic accuracy of a diffusion-weigthed, steady-state free precession (SSFP) sequence for the differentiation of acute benign osteoporotic and neoplastic vertebral compression fractures. Methods: 85 patients with 102 vertebral compression fractures were examined with MR imaging using a spine array surface coil (Siemens, Vision, 1.5 Tesla). The following sequences were performed in sagittal orientation: T-1-weighted spin echo (SE), short-tau inversion recovery (STIR) and a diffusion-weighted SSFP sequence (TR = 25 msec, diffusion pulse length 5 = 3 msec). The SSFP images were evaluated qualitatively on a 5-grade scale from strongly hypointense to strongly hyperintense. Quantitative analysis was performed with region of interest measurements (ROI) and calculation of a bone marrow ratio. Results: 60 fractures were due to osteoporosis and 42 fractures were caused by malignancy. "Hyperintensity" in a vertebral fracture on a SSFP sequence provided a sensitivity of 100 % and a specificity of 93 %. The positive predictive value was 91 %, the negative predictive value was 100 %. Quantitative analysis of the bone marrow ratio showed a statistically significant difference between the osteporosis and the tumor group (p < 0.001). The mean value for the osteoporotic fractures was - 0.32 (SD 0.33) and + 2.07 (SD 1.37) for the tumor group. Conclusion: The SSFP sequence provides a high accuracy in the differentiation of benign osteoporotic and neoplastic vertebral compression fractures.

In this retrospective study, the effect of surgical therapy on a series of 70 patients with breast cancer who were surgically treated for metastasis of the bone was evaluated. At presentation, 19 patients had one osseous lesion, 19 patients had multiple bone lesions, and 32 patients had additional visceral involvement. The surgical procedures included 60 palliative procedures, six radical resections, and four biopsies. In 14 surviving patients, the mean observation period was 35.6 +/- 40.1 months. Of the six patients with radically resected solitary bone lesions, five patients had systemic progression of the disease develop. Of the 19 patients with presumably solitary bone lesions, five currently are free of tumor. Of the 19 patients with multiple bone lesions and initially no visceral tumor spread, only two are alive. Of the 32 patients with additional visceral metastases at surgery, four are alive with the disease. For the entire group, the survival rate was 59% after 1 year, 36% after 2 years, 13% after 5 years, and 7% after 10 years. The only two independent factors that were associated with survival were the extent of the disease and the duration of symptoms from bone metastasis. These findings suggest that in orthopaedic surgery in patients with bone metastases secondary to breast cancer, wide resection is not likely to be necessary. Patients with solitary bone lesions have a 39% chance of living 5 years.

Two cases of bone involvement by a malignant lymphoma are described. The first patient suffered from primary, polyostotic non-Hodgkin's lymphoma of lymphoblastic histology, a rare clinical picture according to literature data. The second patient had mediastinal Hodgkin's lymphoma of the nodular sclerosing type with a unique secondary localization in the femoral bone, that led to the final diagnosis.The diagnostic and therapeutical approach of bone lymphoma is discussed.

This study evaluated the prognostic value of a three‐grade staging system of spinal involvement using magnetic resonance imaging (MRI) in patients with multiple myeloma and determined its usefulness as an independent parameter in the staging system of Durie and Salmon.

PURPOSE: To evaluate the occurrence, location, and shape of the fluid sign in acute osteoporotic and neoplastic vertebral compression fractures at magnetic resonance (MR) imaging.MATERIALS AND METHODS: The study group comprised 87 consecutive patients with acute vertebral compression fractures due to osteoporotic (n = 52) or neoplastic (n = 35) infiltration. The MR imaging protocol included nonenhanced T1-weighted spin-echo and short inversion time inversion-recovery sequences and a 1.5-T system. Readers blinded to the outcome documented the occurrence, shape, and location of the fluid sign with consensus. The fluid sign was correlated with the cause age, and severity of the fracture. The diagnosis was confirmed with surgery, follow-up MR imaging, clinical follow-up, or unequivocal imaging findings. Wilcoxon and chi(2) tests were used to assess significance.RESULTS: In fractured vertebral bodies, the fluid sign was adjacent to the fractured end plates and exhibited signal intensity isointense to that of cerebrospinal fluid. The fluid sign was linear (n = 16), triangular (n = 5), or focal (n = 2) and was significantly associated with osteoporotic fractures (21 [40%] of 52; P < .001). The fluid sign occurred in two (6%) of 35 neoplastic compression fractures. Histologic examination demonstrated osteonecrosis, edema, and fibrosis at the site of the fluid sign. There was a tendency toward older fractures exhibiting the fluid sign, but this relationship was not significant (P > .05). In osteoporotic fractures, the fluid sign was significantly associated with fracture severity (P < .05).CONCLUSION: The fluid sign is featured in acute vertebral compression fractures that show bone marrow edema. It can be an additional sign of osteoporosis and rarely occurs in metastatic fractures. (C) RSNA, 2002.