bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic prognostic factors in childhood atypical teratoid and rhabdoid tumor of the central nervous system
Authors: Dufour Christelle , Beaugrand Annick , Le Deley Marie Cécile , Bourdeaut Franck , André Nicolas , Leblond Pierre , Bertozzi Anne‐Isabelle , Frappaz Didier , Rialland Xavier , Fouyssac Fanny , Edan Christine , Grill Jacques , Quidot Marion , Varlet Pascale 
Published: December 2011

AbstractBACKGROUND:The objective of this study was to describe the clinical and pathologic features and to identify prognostic factors in patients with atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system (CNS).METHODS:Patients aged <18 years with newly diagnosed CNS AT/RT who were treated in France between 1998 and 2008 were retrospectively identified. The study included all patients who had a diagnosis of AT/RT confirmed by pathologic review, including immunostaining for INI 1, tumor protein 53 (p53), β‐catenin, claudin‐6, and Ki‐67 and analysis for SMARCB1/hSNF5/INI1 mutation.RESULTS:Fifty‐eight patients with confirmed AT/RT were eligible for the current analysis. The median age at diagnosis was 1.4 years (range, 14 days to 8.5 years). The site of the primary tumor was supratentorial in 26 patients, infratentorial in 28 patients and spinal in 4 patients. Loss of INI1 nuclear expression was observed in 49 of 50 evaluable tumors. Positive claudin‐6 was observed in 37 of 42 assessed tumors and, in 12 of those tumors, the staining was strong and diffuse. Positive nuclear immunoreactivity for β‐catenin was observed in 24 of 44 tumors, and P53 was overexpressed in 31 of 44 tumors. Primary adjuvant therapy included chemotherapy in 47 patients and radiotherapy in 16 patients. The median follow‐up was 58 months (range, 9‐125 months), and the median survival was 9 months. Multivariate analysis identified age <2 years (P = .01), metastasis at diagnosis (P = .03), and strong immunopositivity for claudin‐6 (P = .03) as prognostic factors for the risk of death.CONCLUSIONS:AT/RT tumors in children carry a dismal prognosis. Age <2 years, metastasis at diagnosis, and strong claudin‐6 positivity appeared to be independent prognostic factors for outcome. Cancer 2012. © 2011 American Cancer Society.
Prognostic factors in mucoepidermoid carcinoma of the salivary glands
Authors: McHugh Catherine H. , Roberts Dianna B. , El‐Naggar Adel K. , Hanna Ehab Y. , Garden Adam S. , Kies Merrill S. , Weber Randal S. , Kupferman Michael E. 
Published: December 2011

AbstractBACKGROUND:Mucoepidermoid carcinoma (MEC) is the most common malignancy of the major salivary glands. Prior reports noted histological grade and tumor stage as consistently important prognostic factors. This study reviewed the experience of patients with MEC at the University of Texas MD Anderson Cancer Center to determine the impact of clinical and pathologic findings on disease outcomes.METHODS:A retrospective clinical review was performed of patients with salivary gland MEC treated at a tertiary cancer center from 1990 to 2007.RESULTS:A total of 125 patients were included. The 5‐year overall survival and disease‐free survival of all patients were 79.3% and 76.5%, respectively. Patients with low‐ and intermediate‐grade disease had significantly better overall survival and disease‐free survival than patients with high‐grade disease, but no difference in survival rates was found between low‐ and intermediate‐grade disease. Pathologic results of positive lymph nodes, extracapsular lymph node spread, and perineural invasion were all found to be poor prognostic indicators. On multivariate analysis, advanced disease stage and perineural invasion were found to be the most significant prognostic factors.CONCLUSIONS:Patients with either low‐ or intermediate‐grade tumors uniformly have favorable local control and survival. High histological grade, advanced stage, perineural invasion, positive surgical margins, and submandibular location all portend for poor outcomes in MEC. Further advances in therapy are needed to improve outcomes for high‐grade and advanced‐stage disease. Cancer 2012. © 2011 American Cancer Society.
Fludarabine, cyclophosphamide, and rituximab in patients with advanced, untreated, indolent B‐cell nonfollicular lymphomas
Authors: Ferrario Andrea , Pulsoni Alessandro , Olivero Barbara , Rossi Giuseppe , Vitolo Umberto , Tedeschi Alessandra , Merli Francesco , Rigacci Luigi , Stelitano Caterina , Goldaniga Maria , Mannina Donato , Musto Pellegrino , Rossi Francesca , Gamba Enrica , Baldini Luca 
Published: December 2011

AbstractBACKGROUND:Indolent nonfollicular non‐Hodgkin B‐cell lymphomas (INFLs) are clonal mature B‐cell proliferations for which treatment has not been defined to date.METHODS:In this phase 2 study of patients with advanced INFL, the authors evaluated the efficacy and safety of first‐line rituximab, fludarabine, and cyclophosphamide (FCR) as induction immunochemotherapy (rituximab 375 mg/m2 intravenously on day 1 of each cycle and on days 1 and 14 of cycles 4 and 5; fludarabine 25 mg/m2 intravenously on days 2‐4, cyclophosphamide 250 mg/m2 intravenously on Days 2‐4) every 28 days for 6 cycles followed by a maintenance phase with 4 infusions of rituximab (375 mg/m2 intravenously on day 1) every 2 months for responders.RESULTS:Forty‐seven patients were enrolled. Among 46 evaluable patients (28 men; median age, 59 years), 19 were diagnosed with lymphoplasmacytic lymphoma, 21 were diagnosed with small lymphocytic lymphoma, and 6 were diagnosed with nodal marginal zone lymphoma. The overall response rate after maintenance was 89.1% with a 67.4% complete remission (CR) rate (CR/unconfirmed CR) and a 21.7% partial response rate. After a median follow‐up of 40.9 months, the failure‐free survival and progression‐free survival rates both were 90.1%, and the overall survival rate was 97.4%. The main toxicity was hematologic, and related grade 3 and 4 neutropenia was observed in 55.3% of patients.CONCLUSIONS:FCR induction therapy followed by a short maintenance phase is a highly effective regimen with acceptable toxicity. Cancer 2012. © 2011 American Cancer Society.
The prognostic significance of lymphovascular invasion in invasive breast carcinoma
Authors: Rakha Emad A. , Martin Stewart , Lee Andrew H. S. , Morgan David , Pharoah Paul D. P. , Hodi Zsolt , MacMillan Douglas , Ellis Ian O. 
Published: December 2011

AbstractBACKGROUND:Although lymphovascular invasion (LVI) has been associated with a poor outcome in patients with breast cancer, it is not included in most internationally recognized staging systems, including the American Joint Committee on Cancer tumor, lymph node, metastasis (TNM) classification. This is mainly because it remains unclear whether the presence of LVI is an independent, high‐risk criterion in clinically relevant staging subgroups.METHODS:The current study was based on a large and well characterized consecutive series of patients who had operable (pathologic T1 [pT1]‐pT2, pathologic N0 [pN0]‐pN3, M0) breast cancer (3812 informative cases) who were treated according to standard protocols at a single institution and who had long‐term follow‐up to assess the prognostic value of definite LVI in clinically and molecularly relevant staging subgroups.RESULTS:LVI was strongly associated with both breast cancer‐specific survival (BCSS) and distant metastasis‐free survival (DMFS) in the entire series and in different subgroups. Multivariate analyses identified LVI as an independent predictor of both BCSS and DMFS in patients with operable breast cancer overall; in the TNM clinical subgroups pT1a‐pT1c/pN0 and pT2/pN0; and in the molecular classes estrogen receptor (ER)‐positive, ER‐negative, human epidermal growth factor 2 [HER2]‐negative, and triple‐negative. In patients who had lymph node‐negative tumors, LVI could be used as a high‐risk criterion providing survival disadvantage equivalent to that provided by 1 or 2 involved lymph nodes (pN0 to pN1) and to that provided by 1 size category (pT1 to pT2). The use of immunohistochemistry for detecting an endothelial‐specific marker contributed to the prognostic significance of LVI when applied to routine LVI negative/possible cases.CONCLUSIONS:LVI provided a strong predictor of outcome in patients with invasive breast cancer and should be incorporated into breast cancer staging systems. Cancer 2012. © 2011 American Cancer Society.
Predicting survival in women with breast cancer and brain metastasis
Authors: Marko Nicholas F. , Xu Zhiyuan , Gao Tianming , Kattan Michael W. , Weil Robert J. 
Published: December 2011

AbstractBACKGROUND:Brain metastases (BMs) are a common occurrence in patients with breast cancer, and accurately predicting survival in these patients is critical to appropriate management. A survival nomogram for breast cancer patients with BM was constructed, and its performance is compared to current predictive models of survival.METHODS:A Cox proportional hazards regression with a nomogram representation was used to model survival in a population of 261 women with breast cancer and BMs treated from 1999 to 2008. The model was validated internally by 10‐fold cross‐validation and bootstrapping, and concordance (c) indices were calculated. The predictive performance of the nomogram described here is compared to current prognostic models, including recursive partitioning analysis, graded prognostic assessment, and diagnosis‐specific graded prognostic assessment.RESULTS:The c‐index for the model described here was 0.67. It outperformed recursive partitioning analysis, graded prognostic assessment, and diagnosis‐specific graded prognostic assessment, based on c‐index comparisons.CONCLUSIONS:The nomogram described here outperformed current strategies for survival prediction in breast cancer patients with BMs. Two additional advantages of this nomogram are its ability to predict individualized, 1‐, 3‐, and 5‐year survival for novel patients and its straightforward representations of the relative effects of each of 9 covariates on neurologic survival. This represents a potentially valuable alternative to current models of survival prediction in this patient population. Cancer 2012. © 2011 American Cancer Society.
NRAS mutation status is an independent prognostic factor in metastatic melanoma
Authors: Jakob John A. , Bassett Roland L. , Ng Chaan S. , Curry Jonathan L. , Joseph Richard W. , Alvarado Gladys C. , Rohlfs Michelle L. , Richard Jessie , Gershenwald Jeffrey E. , Kim Kevin B. , Lazar Alexander J. , Hwu Patrick , Davies Michael A. 
Published: December 2011

AbstractBACKGROUND:There is a need for improved prognostic markers in melanoma. In this study, the authors tested the prognostic significance and clinicopathologic correlations of v‐raf murine sarcoma viral oncogene homolog B1 (BRAF) and neuroblastoma RAS viral (v‐ras) oncogene homolog (NRAS) mutations in patients with metastatic melanoma.METHODS:Clinical and pathologic data were collected retrospectively on melanoma patients who were clinically tested for BRAF (exon 15) and NRAS (exons 1 and 2) mutations at The University of Texas M. D. Anderson Cancer Center. Analyses were performed to identify significant associations of mutations with tumor and patient characteristics and with survival from the diagnosis of stage IV disease.RESULTS:The genotypes of the full cohort (n = 677) were 47% BRAF mutation, 20% NRAS mutation, and 32% wild‐type for BRAF and NRAS (“WT”). Tumor mutation status was associated (P = .008) with the risk of central nervous system involvement at the diagnosis of stage IV disease, with a higher prevalence observed in BRAF‐mutant (24%) and NRAS‐mutant (23%) patients than in WT patients (12%). Among patients with nonuveal melanoma who underwent mutation testing within 6 months of stage IV diagnosis (n = 313), patients with NRAS mutations had a median survival of 8.2 months from stage IV diagnosis, which was shorter than the median survival of WT patients (15.1 months; P = .004). Multivariate analysis of this population incorporating age, sex, metastases (M1) category, serum lactate dehydrogenase level, and mutation status confirmed that NRAS mutations are associated independently with decreased overall survival (vs WT; P = .005; hazard ratio, 2.05).CONCLUSIONS:Patients with BRAF or NRAS mutations were more likely than WT patients to have central nervous system involvement at the time they were diagnosed with distant metastatic disease. NRAS mutation status was identified as an independent predictor of shorter survival after a diagnosis of stage IV melanoma. Cancer 2012. © 2011 American Cancer Society.
A comparison of the demographics, clinical features, and survival of patients with adenoid cystic carcinoma of major and minor salivary glands versus less common sites within the Surveillance, Epidemiology, and End Results registry
Authors: Li Nan , Xu Li , Zhao Hui , El‐Naggar Adel K. , Sturgis Erich M. 
Published: December 2011

AbstractBACKGROUND:The scientific literature to date lacks population‐based studies on the demographics, clinical features, and survival of patients with adenoid cystic carcinoma (ACC) of different anatomic sites.METHODS:The authors identified 5349 patients who had ACC of the major salivary glands (N = 1850), minor salivary glands (N = 2077), breast (N = 696), skin (N = 291), lung and bronchus (N = 203), female genital system (N = 132), and eye and orbit (N = 100) from the Surveillance, Epidemiology, and End Results (SEER) registry. Differences in demographics, clinical features, and survival of patients were assessed.RESULTS:ACC of the eye and orbit was associated with younger age at presentation (mean age,49.9 years). ACC of the skin or breast tended to present with less aggressive prognostic features, whereas ACC of the lung and bronchus or eye and orbit tended to present with more aggressive prognostic features. In a multivariate survival analysis of patients who presented with localized disease, patients with ACC of the breast (hazard ratio [HR], 0.40) or skin (HR, 0.40) had a significantly lower risk death than patients with ACC of the major salivary glands; whereas patients with ACC of the lung and bronchus (HR, 3.72) or the eye and orbit (HR, 3.67) had a significantly higher risk. For patients who presented with regional disease, the only clear prognostic difference in multivariate analysis was that patients with ACC of skin fared significantly better.CONCLUSIONS:The demographics and clinical features of patients with ACC differ by disease site. The current results indicated that site may be an important predictor of survival for patients who present with localized disease but is less important for patients who present with regional disease. Cancer 2012. © 2011 American Cancer Society.
A phase 2 trial of combination therapy with thalidomide, arsenic trioxide, dexamethasone, and ascorbic acid (TADA) in patients with overlap myelodysplastic/myeloproliferative neoplasms (MDS/MPN) or primary myelofibrosis (PMF)
Authors: Bejanyan Nelli , Tiu Ramon V. , Raza Azra , Jankowska Ania , Kalaycio Matt , Advani Anjali , Chan Josephine , Saunthararajah Yogen , Mooney Lindsey , Maciejewski Jaroslaw P. , Sekeres Mikkael A. 
Published: December 2011

AbstractBACKGROUND.Primary myelofibrosis (PMF) and overlap myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are clonal hematopoietic disorders that share similar clinical features and molecular abnormalities, such as the Janus kinase 2 (JAK2) valine to phenylalanine mutation at codon 617 (V617F) and the tet methylcytosine dioxygenase 2 (TET2) mutation. There are limited therapeutic options available for these diseases, and single agents have only modest efficacy. In this phase 2 study, the authors combined multiple active agents (thalidomide, arsenic trioxide, dexamethasone, and ascorbic acid [TADA]) to treat patients with these disorders.METHODS.This multicenter trial was conducted from January 2005 to July 2007. The primary endpoint was to evaluate the efficacy of TADA therapy. Patients received the combination for one 12‐week cycle followed by maintenance thalidomide for an additional 3 months. Response was assessed using International Working Group criteria.RESULTS.Among 28 enrolled patients, the median age was 66.5 years; 15 patients had MDS/MPN‐unclassifiable, 8 patients had chronic myelomonocytic leukemia type 1, and 5 patients had PMF. Approximately 60% of the patients had normal cytogenetics. The JAK2V617F mutation was detected in 5 of 14 tested patients, and TET2 mutations were detected in 2 of 8 tested patients. Almost half of the patients had splenomegaly. With a median on‐study follow‐up of 5.7 months, 21 patients (75%) completed the entire 12‐week course of therapy, and 6 patients (29%) responded to TADA. With a median extended follow‐up of 24.1 months for 15 evaluable patients, the median progression‐free survival was 14.4 months, and the median overall survival was 21.4 months.CONCLUSIONS.The TADA regimen yielded clinical responses in patients with PMF and MDS/MPN. To the authors' knowledge, this study represents the first trial targeting this patient population. The results indicated that it is reasonable to incorporate multiple novel agents in the treatment of these rare diseases. Cancer 2012. © 2011 American Cancer Society.
Postnatal development of the amygdala: A stereological study in macaque monkeys
Authors: Chareyron Loïc J. , Lavenex Pamela Banta , Amaral David G. , Lavenex Pierre 
Published: December 2011

AbstractAbnormal development of the amygdala has been linked to several neurodevelopmental disorders, including schizophrenia and autism. However, the postnatal development of the amygdala is not easily explored at the cellular level in humans. Here we performed a stereological analysis of the macaque monkey amygdala in order to characterize the cellular changes underlying its normal structural development in primates. The lateral, basal, and accessory basal nuclei exhibited the same developmental pattern, with a large increase in volume between birth and 3 months of age, followed by slower growth continuing beyond 1 year of age. In contrast, the medial nucleus was near adult size at birth. At birth, the volume of the central nucleus was half of the adult value; this nucleus exhibited significant growth even after 1 year of age. Neither neuronal soma size, nor neuron or astrocyte numbers changed during postnatal development. In contrast, oligodendrocyte numbers increased substantially, in parallel with an increase in amygdala volume, after 3 months of age. At birth, the paralaminar nucleus contained a large pool of immature neurons that gradually developed into mature neurons, leading to a late increase in the volume of this nucleus. Our findings revealed that distinct amygdala nuclei exhibit different developmental profiles and that the amygdala is not fully mature for some time postnatally. We identified different periods during which pathogenic factors might lead to the abnormal development of distinct amygdala circuits, which may contribute to different human neurodevelopmental disorders associated with alterations of amygdala structure and functions. J. Comp. Neurol. 520:1965–1984, 2012. © 2011 Wiley Periodicals, Inc.
A critical look at the microalgae biodiesel
Authors: Petkov Georgi , Ivanova Albena , Iliev Ivan , Vaseva Irina 
Published: December 2011

AbstractThe quantitative production of microalgae oil is often overestimated. The cost of the salts invested in the production of 1 kg algal diesel approximates the actual price of 1 kg mineral diesel. Total sum of electrical energy expenses for production of biodiesel from microalgae is several‐fold higher than the energy income from combustion of the same quantity. The biological value of cultivated microalgae as food is much higher than as fuel. An opinion is shared that money ought to be invested in microalgal biomass production as a food additive, forage, and pharmaceuticals. The aim is to prevent making too hasty steps and investments in microalgal biodiesel.
3‐Alkenyl‐2‐silyloxyindoles: An Enabling, Yet Understated Progeny of Vinylogous Carbon Nucleophiles
Authors: Rassu Gloria , Zambrano Vincenzo , Tanca Rossella , Sartori Andrea , Battistini Lucia , Zanardi Franca , Curti Claudio , Casiraghi Giovanni 
Published: December 2011

AbstractWe introduce novel 3‐alkenyl‐2‐silyloxyindole nucleophiles and demonstrate their utility by developing an unprecedented vinylogous Mukaiyama‐type aldol reaction with aromatic aldehydes. This reaction displays excellent levels of γ‐site selectivity and diastereoselectivity and delivers valuable hydroxylated oxindoles bearing a substituted exocyclic double bond at the C‐3 position. A preliminary trial of an asymmetric, catalytic version was conducted, and it showed promising enantioselectivity for the desired vinylogous aldol products.
The Synthesis of Long‐Chain α‐Alkyl‐β‐Hydroxy Esters Using Allylic Halides in a Fráter–Seebach Alkylation
Authors: Khan Ashna A. , Chee Stephanie H. , Stocker Bridget L. , Timmer Mattie S. M. 
Published: December 2011

AbstractThe Fráter–Seebach alkylation is a highly efficient means to diastereoselectively introduce α‐substituents to chiral β‐hydroxy esters, however, the yields of reactions in which longer chain alkyl halides are used can be disappointing. To provide a more robust protocol for the alkylation of β‐hydroxy esters, we prepared a variety of long‐chain allylic iodides with the view that the greater reactivity of the allylic system would lead to enhanced efficiency. Indeed, for all substrates studied, the yield of the α‐alkylation was greatly improved for the unsaturated allylic halides compared to their analogous saturated counterparts. Our methodology thus provides an improved means by which to access a variety of important lipophilic compounds such as mycolic acids, which are found on the cell wall of M. tuberculosis.
Profiling of Endo H‐released serum N‐glycans using CE‐LIF and MALDI‐TOF‐MS – Application to rheumatoid arthritis
Authors: Frisch Elena , Kaup Matthias , Egerer Karl , Weimann Andreas , Tauber Rudolf , Berger Markus , Blanchard Véronique 
Published: December 2011

AbstractHigh‐mannose and hybrid‐type N‐glycans are present in human serum glycoproteins in low abundance but have recently been described to play an important role in immune responses. It is therefore important to find a strategy to selectively analyze their structures in the context of health and disease in order to understand their impact on disease mechanisms. We report here the characterization of high‐mannose and hybrid‐type N‐glycans in total human serum. To this end, N‐glycans were released using Endo‐β‐N‐acetylglucosaminidase H (Endo H) and analyzed by CE‐LIF and MALDI‐TOF‐MS. We found that the high‐mannose structures Man5–9GlcNAc1 represented the majority of the pool. The monoglucosylated structure Glc1Man9GlcNAc1 as well as four hybrid structures could be identified. Then, we compared the Endo H‐released serum glycome of patients suffering from rheumatoid arthritis with healthy controls as mannose‐binding lectin deficiency (MBL) and modulation of α‐mannosidase activity were previously associated with this disease. Interestingly, we observed that both high‐mannose and hybrid structures were fairly constant, suggesting that circulating MBL and α‐mannosidase may not affect significantly the levels of serum glycoproteins carrying these glycans.