bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis and management of retroperitoneal ancient schwannomas
Authors: Choudry Haroon A , Nikfarjam Mehrdad , Liang John J , Kimchi Eric T , Conter Robert , Gusani Niraj J , Staveley-O'Carroll Kevin F 
Published: February 2009

Abstract

Background
Ancient schwannomas are degenerate peripheral nerve sheath tumors that very rarely occur in the retroperitoneum. They generally reach large proportions before producing symptoms due to mass effect. We describe three cases of retroperitoneal ancient schwannomas and discuss the diagnosis and management of these tumors.

Case presentations
Three female patients with retroperitoneal ancient schwannomas were reviewed. One patient presented with several weeks of upper abdominal pain and lower chest discomfort, whereas back pain and leg pain with associated weakness were predominant symptoms in the remaining two. Abdominal imaging findings demonstrated heterogeneous masses in the retroperitoneum with demarcated margins, concerning for malignancy. The patients successfully had radical excision of their tumors. Histological examination showed encapsulated tumors that displayed alternating areas of dense cellularity and areas of myxoid matrix consistent with a diagnosis of ancient schwannoma.

Conclusion
A diagnosis of ancient schwannoma should be entertained for any heterogeneous, well encapsulated mass in the retroperitoneum. In these cases less radical surgical resection should be considered as malignant transformation of these tumors is extremely rare and recurrence is uncommon following excision.
Evaluation of day one embryo quality and IVF outcome – a comparison of two scoring systems
Authors: Brezinova Jana , Oborna Ivana , Svobodova Magda , Fingerova Helena 
Published: February 2009

Abstract

Background
The aim of our retrospective study was to compare the clinical usefulness of two non-invasive embryo scoring systems based either on a simplified pronuclear morphology of the zygote or on early cleavage rate, as well as their combination, for the selection of embryos with the best implantation potential in embryo transfer (ET).

Methods
Over a period of five years, the quality of 2708 embryos from 364 IVF cycles in women under the age of 39 years was assessed using these scoring systems in a university assisted reproduction centre. ET was always performed on day 3 of cultivation. The outcome of ETs of 702 embryos scored in the respective systems or their combination was retrospectively analyzed in terms of biochemical (bPR) and clinical pregnancy rates (cPR) and implantation rate (IR). Mann-Whitney U test and t-test for differences between relative values were used, p < 0.05 was considered statistically significant.

Results
There was no difference in outcome parameters in 109 cycles where only Pattern "0" zygotes, according to our simplified pronuclear morphology classification, were transferred and 140 cycles where only "other" pattern zygotes were transferred, regardless of their cleavage rate. On the contrary, significantly greater cPR and IR (p = 0.003 and p = 0.006, respectively) were achieved in 120 cycles where only early cleavage (EC) embryos were transferred compared with 152 cycles where only non early cleavage (NEC) embryos were transferred regardless of their pronuclear morphology. The best outcome in terms of cPR (56%) and IR (43%) was found in 50 cycles when Pattern "0" and EC embryos only were used for transfer.

Conclusion
The results indicate that early cleavage is a better independent marker of implantation potential than zygote morphology. The best outcome can be achieved if both embryo scoring systems are used jointly and the embryo is classified as EC and Pattern "0".
Issues associated with assessing nuclear localization of N-terminally unphosphorylated β-catenin with monoclonal antibody 8E7
Authors: Maher Meghan T , Flozak Annette S , Hartsell Alyssa M , Russell Susan , Beri Rohinee , Peled Ofra N , Gottardi Cara J 
Published: February 2009

Abstract

Background
β-catenin is a dual function adhesion/transcriptional co-activator protein, and both functions are critical for normal tissue homeostasis. Since the transcriptional functions of β-catenin are more often implicated in various disease processes, there is much interest in the development and use of reagents to interrogate spatial and temporal evidence of β-catenin nuclear signaling in cells and tissues. An important study demonstrated that the signaling form of β-catenin is specifically unphosphorylated at residues S37 and T41, and suggested that this form exhibits a propensity for cytosolic/nuclear accumulation relative to the total pool of β-catenin.

Results
We show that monoclonal antibody, 8E7, which recognizes the signaling form of β-catenin specifically unphosphorylated at S37 and T41 (Active B-Catenin, ABC), also cross-reacts with a widely expressed, variably accessible nuclear antigen that is not β-catenin. In cell types commonly used to study Wnt activation, this non-specific nuclear staining can be robust, obscuring the ABC signal. Definitive detection of nuclear localized ABC can be confirmed through an ability of classical cadherins to sequester ABC to cell junctions. In tissues, milder antigen retrieval methods can reduce the accessibility of mAb 8E7 to this cross-reacting nuclear antigen.

Conclusion
These findings reveal that interpretation of nuclear, signaling active β-catenin using monoclonal antibody 8E7 should be considered judiciously, and in conjunction with independent methods.

Reviewers
This article was reviewed by Frank J. T. Staal (nominated by Rachel Gerstein), Jyoti M. Sen (nominated by Avinash Bhandoola) and Manabu Sugai.
Fgf receptor 3 activation promotes selective growth and expansion of occipitotemporal cortex
Authors: Thomson Rachel E , Kind Peter C , Graham Nicholas A , Etherson Michelle L , Kennedy John , Fernandes Ana C , Marques Catia S , Hevner Robert F , Iwata Tomoko 
Published: February 2009

Abstract
Background
Fibroblast growth factors (Fgfs) are important regulators of cerebral cortex development. Fgf2, Fgf8 and Fgf17 promote growth and specification of rostromedial (frontoparietal) cortical areas. Recently, the function of Fgf15 in antagonizing Fgf8 in the rostral signaling center was also reported. However, regulation of caudal area formation by Fgf signaling remains unknown.

Results
In mutant mice with constitutive activation of Fgf receptor 3 (Fgfr3) in the forebrain, surface area of the caudolateral cortex was markedly expanded at early postnatal stage, while rostromedial surface area remained normal. Cortical thickness was also increased in caudal regions. The expression domain and levels of Fgf8, as well as overall patterning, were unchanged. In contrast, the changes in caudolateral surface area were associated with accelerated cell cycle in early stages of neurogenesis without an alteration of cell cycle exit. Moreover, a marked overproduction of intermediate neuronal progenitors was observed in later stages, indicating prolongation of neurogenesis.

Conclusion
Activation of Fgfr3 selectively promotes growth of caudolateral (occipitotemporal) cortex. These observations support the 'radial unit' and 'radial amplification' hypotheses and may explain premature sulcation of the occipitotemporal cortex in thanatophoric dysplasia, a human FGFR3 disorder. Together with previous work, this study suggests that formation of rostral and caudal areas are differentially regulated by Fgf signaling in the cerebral cortex.
Currarino's syndrome misinterpreted as Hirschsprung's disease for 17 years: a case report
Authors: Saberi Hooshang , Habibi Zohreh , Adhami Amin 
Published: February 2009

Abstract

Background
Currarino's syndrome is an autosomal dominant hereditary disease known by the triad of anorectal stenosis, anterior sacral defect, and a presacral mass that is most often an anterior sacral meningocele. Actually this syndrome could remain asymptomatic in many instances, but symptomatic patients might present with constipation as the sole manifestation of the Currarino's syndrome among the other wide spectrum of manifestations.

Case presentation
An 18-year old woman was diagnosed with a late-recognized Currarino syndrome, presented by a longstanding constipation which had been wrongly diagnosed and treated as Hirschsprung's disease since early childhood.

Conclusion
Long-lasting constipation could imply to neural tube anomaly such as anterior sacral meningocele with or without association to Currarino's syndrome.
Subcutaneous emphysema, pneumomediastinum and pneumoperitoneum after unsuccessful ERCP: a case report
Authors: Alexiou Konstantinos , Sakellaridis Timothy , Sikalias Nikolaos , Karanikas Ioannis , Economou Nikolaos , Antsaklis Giorgios 
Published: February 2009

AbstractBackgroundThe presence of subcutaneous emphysema, pneumomediastinum and pneumoperitoneum simultaneously is a rare complication of upper gastrointestinal endoscopy that usually indicates free perforation to the peritoneal cavity or the retroperitoneal space.Case presentationWe report an unusual case of a self-limited subcutaneous emphysema, pneumomediastinum and pneumoperitoneum following an unsuccessful ERCP for removal of a common bile duct stone.ConclusionThere was no radiological evidence of peritoneal or retroperitoneal perforation. This complication is distinct from pneumomediastinum and pneumoperitoneum due to perforation, and must be recognized, because it is benign and needs no surgical or radiological intervention.
Gene expression profiling of the tumor microenvironment during breast cancer progression
Authors: Ma Xiao-Jun , Dahiya Sonika , Richardson Elizabeth , Erlander Mark , Sgroi Dennis C 
Published: February 2009

Abstract
Introduction
The importance of the tumor microenvironment in breast cancer has been increasingly recognized. Critical molecular changes in the tumor stroma accompanying cancer progression, however, remain largely unknown. We conducted a comparative analysis of global gene expression changes in the stromal and epithelial compartments during breast cancer progression from normal to preinvasive to invasive ductal carcinoma.

Methods
We combined laser capture microdissection and gene expression microarrays to analyze 14 patient-matched normal epithelium, normal stroma, tumor epithelium and tumor-associated stroma specimens. Differential gene expression and gene ontology analyses were performed.

Results
Tumor-associated stroma undergoes extensive gene expression changes during cancer progression, to a similar extent as that seen in the malignant epithelium. Highly upregulated genes in the tumor-associated stroma include constituents of the extracellular matrix and matrix metalloproteases, and cell-cycle-related genes. Decreased expression of cytoplasmic ribosomal proteins and increased expression of mitochondrial ribosomal proteins were observed in both the tumor epithelium and the stroma. The transition from preinvasive to invasive growth was accompanied by increased expression of several matrix metalloproteases (MMP2, MMP11 and MMP14). Furthermore, as observed in malignant epithelium, a gene expression signature of histological tumor grade also exists in the stroma, with high-grade tumors associated with increased expression of genes involved in immune response.

Conclusions
Our results suggest that the tumor microenvironment participates in tumorigenesis even before tumor cells invade into stroma, and that it may play important roles in the transition from preinvasive to invasive growth. The immune cells in the tumor stroma may be exploited by the malignant epithelial cells in high-grade tumors for aggressive invasive growth.
Migration inhibitory factor (MIF) released by macrophages upon recognition of immune complexes is critical to inflammation in Arthus reaction
Authors: Paiva Claudia N , Arras Rosa H , Magalhães Elisabeth S , Alves Letícia S , Lessa Luiz Paulo , Silva Maria Helena , Ejzemberg Regina , Canetti Cláudio , Bozza Marcelo T 
Published: February 2009

AbstractDeposition of immune complexes (IC) triggers FcγR-dependent inflammation, leading to tissue damage in rheumatoid arthritis, systemic lupus erythematous, immune glomerulonephritis, and several immune vasculitides. Evidences support a role for macrophage migration inhibitory factor (MIF) in a number of inflammatory diseases, but the triggering of its secretion and its physiopathological role upon IC deposition remain elusive. Herein, we show that human macrophages secreted MIF after IC recognition, which in turn controlled the secretion of TNF. Macrophages from Mif−/− mice produced smaller amounts of TNF when stimulated with IgG-opsonized erythrocytes than wild-type (WT) cells. Using passive reverse Arthus reaction in the peritoneum and lungs as a model for IC-induced inflammation, we demonstrated that Mif−/− mice had a milder response, observed by reduced neutrophil recruitment, vascular leakage, and secretion of TNF, MIP-2, and keratinocyte-derived chemokine compared with WT controls. Adoptive transfer of alveolar macrophages from WT to Mif−/− mice rescued pulmonary neutrophil recruitment and TNF production upon passive reverse Arthus reaction. Our study indicates that Arthus inflammatory reaction is largely dependent on MIF and poses macrophages as a source of the MIF released upon IC recognition. These results give experimental support to the proposition that blockade of MIF might constitute an adjunctive, therapeutic approach to IC disease.
Three Immunomarker Support Vector Machines–Based Prognostic Classifiers for Stage IB Non–Small-Cell Lung Cancer
Authors: Zhu Zhi-Hua , Sun Bing-Yu , Ma Yun , Shao Jian-Yong , Long Hao , Zhang Xu , Fu Jian-Hua , Zhang Lan-Jun , Su Xiao-Dong , Wu Qiu-Liang , Ling Peng , Chen Ming , Xie Ze-Ming , Hu Yi , Rong Tie-Hua 
Published: February 2009

Purpose Approximately 30% of patients with stage IB non–small-cell lung cancer (NSCLC) die within 5 years after surgery. Current staging methods are inadequate for predicting the prognosis of this particular subgroup. This study identifies prognostic markers for NSCLC. Patients and Methods We used computer-generated random numbers to study 148 paraffin-embedded specimens for immunohistochemical analysis. We studied gene expression in paraffin-embedded specimens of lung cancer tissue from 73 randomly selected patients with stage IB NSCLC who had undergone radical surgical resection and evaluated the association between the level of expression and survival. We used support vector machines (SVM)–based methods to develop three immunomarker-SVM–based prognostic classifiers for stage IB NSCLC. For validation, we used randomly assigned specimens from 75 other patients. Results We devised three immunomarker-SVM–based prognostic classifiers, including SVM1, SVM2, and SVM3, to refine prognosis of stage IB NSCLC successfully. The SVM1 model integrates age, cancer cell type, and five markers, including CD34MVD, EMA, p21ras, p21WAF1, and tissue inhibitors of metalloproteinases (TIMP) –2. The SVM2 model integrates age, cancer cell type, and 19 markers, including BCL2, caspase-9, CD34MVD, low-molecular-weight cytokeratin, high-molecular-weight cytokeratin, cyclo-oxygenase-2, EMA, HER2, matrix metalloproteinases (MMP) –2, MMP-9, p16, p21ras, p21WAF1, p27kip1, p53, TIMP-1, TIMP-2, vascular endothelial growth factor (VEGF), and β-catenin. The SVM3 model consists of SVM1 and SVM2. The three models were independent predictors of overall survival. We validated the classifiers with data from an independent cohort of 75 patients with stage IB NSCLC. Conclusion The three immunomarker-SVM–based prognostic characteristics are closely associated with overall survival among patients with stage IB NSCLC.
Prediction ofBRCAMutations Using the BRCAPRO Model in Clinic-Based African American, Hispanic, and Other Minority Families in the United States
Authors: Huo Dezheng , Senie Ruby T. , Daly Mary , Buys Saundra S. , Cummings Shelly , Ogutha Jacqueline , Hope Kisha , Olopade Olufunmilayo I. 
Published: February 2009

PurposeBRCAPRO, a BRCA mutation carrier prediction model, was developed on the basis of studies in individuals of Ashkenazi Jewish and European ancestry. We evaluated the performance of the BRCAPRO model among clinic-based minority families. We also assessed the clinical utility of mutation status of probands (the first individual tested in a family) in the recommendation of BRCA mutation testing for other at-risk family members.Patients and MethodsA total of 292 minority families with at least one member who was tested for BRCA mutations were identified through the Breast Cancer Family Registry and the University of Chicago. Using the BRCAPRO model, the predicted likelihood of carrying BRCA mutations was generated. Area under the receiver operating characteristic curves (AUCs) were calculated.ResultsThere were 104 African American, 130 Hispanic, 37 Asian-American, and 21 other minority families. The AUC was 0.748 (95% CI, 0.672 to 0.823) for all minorities combined. There was a statistically nonsignificant trend for BRCAPRO to perform better in Hispanic families than in other minority families. After taking into account the mutation status of probands, BRCAPRO performance in additional tested family members was improved: the AUC increased from 0.760 to 0.902.ConclusionThe findings support the use of BRCAPRO in pretest BRCA mutation prediction among minority families in clinical settings, but there is room for improvement in ethnic groups other than Hispanics. Knowledge of the mutation status of the proband provides additional predictive value, which may guide genetic counselors in recommending BRCA testing of additional relatives when a proband has tested negative.
Long-Term Survival of Patients With Glioblastoma Treated With Radiotherapy and Lomustine Plus Temozolomide
Authors: Glas Martin , Happold Caroline , Rieger Johannes , Wiewrodt Dorothee , Bähr Oliver , Steinbach Joachim P. , Wick Wolfgang , Kortmann Rolf-Dieter , Reifenberger Guido , Weller Michael , Herrlinger Ulrich 
Published: February 2009

Purpose To evaluate long-term survival in a prospective series of patients newly diagnosed with glioblastoma and treated with a combination of lomustine (CCNU), temozolomide (TMZ), and radiotherapy. Patients and Methods Thirty-nine patients received radiotherapy of the tumor site only (60 Gy) and CCNU/TMZ chemotherapy (n = 31 received standard-dose CCNU, 100 mg/m2 on day 1 and TMZ 100 mg/m2/d on days 2 to 6; n = 8 received intensified-dose CCNU 110 mg/m2 on day 1 and TMZ 150 mg/m2 on days 2 to 6) for up to six courses. Results In the whole cohort, the median overall survival (mOS) was 23.1 months; 47.4% survived for 2 years, and 18.5% survived for 4 years. After a median follow-up of 41.5 months, mOS had not been reached in the intensified group and was significantly higher than in the standard group (22.6 months; P = .024). In the intensified group, four of eight patients survived for at least 56 months, two of them without recurrence. O6-methylguanine–DNA methyltransferase (MGMT) gene promotor methylation in the tumor tissue was associated with significantly longer mOS (methylated, 34.3 months v nonmethylated, 12.5 months). A multivariate Cox proportional hazard model revealed MGMT status (methylated v nonmethylated; relative risk [RR] of death, 0.43; P = .003) and chemotherapy dose (intensified v standard; RR, 0.37; P = .012) as independent prognostic factors. WHO grade 4 hematoxicity was observed more frequently in the intensified group (57% v 16%). Conclusion The combination of radiotherapy, CCNU, and TMZ yielded promising long-term survival data in patients with newly diagnosed glioblastoma. Intensification of CCNU/TMZ chemotherapy may add an additional survival benefit, albeit with greater acute toxicity.
Recurrence Pattern After Temozolomide Concomitant With and Adjuvant to Radiotherapy in Newly Diagnosed Patients With Glioblastoma: Correlation With MGMT Promoter Methylation Status
Authors: Brandes Alba A. , Tosoni Alicia , Franceschi Enrico , Sotti Guido , Frezza Giampiero , Amistà Pietro , Morandi Luca , Spagnolli Federica , Ermani Mario 
Published: February 2009

Purpose The aim of the present study was to evaluate factors predicting the recurrence pattern after the administration of temozolomide (TMZ), initially concurrent with radiotherapy (RT) and subsequently as maintenance therapy, which has become standard treatment for patients with newly diagnosed glioblastoma (GBM). Patients and Methods Ninety-five patients with newly diagnosed GBM were treated with RT plus TMZ (75 mg/m2/d) followed by maintenance TMZ cycles (150 to 200 mg/m2 for 5 days every 28 days). Assessable MGMT methylation status and magnetic resonance imaging follow-up were mandatory in all cases. Results After a median follow-up of 18.9 months (range, 6.6 to 44.8 months), 79 patients (83%) had recurrence: inside the RT field in 57 patients (72.2%), outside in 17 patients (21.5%), and at RT margin in five patients (6.3%). MGMT status was correlated with the site of recurrence, which occurred inside, or at the margin of, the RT field in 51 patients (85%) with MGMT unmethylated status and in 11 patients (57.9%) with MGMT methylated status (P = .01). Recurrences outside the RT field occurred after a longer time interval than those inside the RT field (14.9 v 9.2 months, P = .02). Conclusion After the administration of TMZ concomitant with and adjuvant to RT in patients with GBM, the pattern of, and time to, recurrence are strictly correlated with MGMT methylation status.
Outcome of Deferred Initial Therapy in Mantle-Cell Lymphoma
Authors: Martin Peter , Chadburn Amy , Christos Paul , Weil Karen , Furman Richard R. , Ruan Jia , Elstrom Rebecca , Niesvizky Ruben , Ely Scott , DiLiberto Maurizio , Melnick Ari , Knowles Daniel M. , Chen-Kiang Selina , Coleman Morton , Leonard John P. 
Published: February 2009

Purpose Treatment of mantle-cell lymphoma (MCL) is nonstandardized, though patients are commonly treated immediately at diagnosis. Because data on observation, or “watch and wait,” have not been previously reported, we analyzed the outcome of deferred initial therapy. Patients and Methods Inclusion criteria in this retrospective analysis were a diagnosis of MCL between 1997 and 2007 and known date of first treatment. Hospital and research charts were reviewed for prognostic and treatment-related information. Date of death was derived from hospital records and confirmed using an online Social Security death index. Results Of 97 patients with MCL evaluated at Weill Cornell Medical Center, 31 patients (32%) were observed for more than 3 months before initial systemic therapy, with median time to treatment for the observation group of 12 months (range, 4 to 128 months). The observation group (median follow-up, 55 months) had a median age of 58 years (range, 40 to 81 years). Prognostic factors in assessable patients included advanced stage (III/IV) in 75%, elevated lactate dehydrogenase in 25%, and intermediate- or high-risk Mantle Cell International Prognostic Index in 54%. Better performance status and lower-risk standard International Prognostic Index scores were more commonly present in those undergoing observation. Although time to treatment did not predict overall survival in a multivariate analysis, the survival profile of the observation group was statistically superior to that of the early treatment group (not reached v 64 months, P = .004). Conclusion In selected asymptomatic patients with MCL, deferred initial treatment (“watch and wait”) is an acceptable management approach.