bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of lymphangiogenesis in pharyngolaryngeal carcinoma patients
Authors: Garcia-Carracedo Darío , Rodrigo Juan Pablo , Astudillo Aurora , Nieto Carlos Suarez , Gonzalez Maria Victoria 
Published: August 2010

Abstract

Background
Lymphatic vessel spread is considered a major route for head and neck squamous cell carcinoma metastasis. Formation of new lymphatic vessels could facilitate the process, raising the malignant potential of these tumours. Recent identification of lymphatic markers allows the study of the lymphangiogenesis phenomenon. We searched for molecular events involved in the lymphangiogenic process that could have prognostic value in laryngeal/pharyngeal carcinoma patients.

Methods
104 paraffin-embedded pharyngeal/laryngeal tumour samples were studied. Immunohistochemical analysis of podoplanin and double immunofluorescence analysis of Ki-67 and D2-40 were performed. Lymph vessel density (inside the tumour mass, at its periphery or considered as a whole) and the presence of tumour emboli inside lymphatics were recorded. The proliferative state of endothelial lymphatic cells was evaluated.

Results
Lymphatic vessels were detected inside the tumour mass (75%) and in the surrounding tissue (80%); some of them in a proliferative state. Tumour emboli were detected in a high proportion of the cases (45%). Lymphatic vessel density was higher in the pharyngeal cases (p = 0.0029), in greater size (p = 0.039), more advanced stage primary tumours (p = 0.006) and in carcinomas of patients with affected nodes (p = 0.019). The presence of tumour emboli and a high global vessel density were indicators of poor prognosis (recorded as death from tumour) in the laryngeal group (p = 0.015 and p = 0.027, respectively), but notably not in the pharyngeal one. Interestingly, high global vessel density showed a negative prognostic value among pathologically staged N0 laryngeal carcinomas (p = 0.03).

Conclusions
The lymphangiogenic process correlated with aggressive tumour features (pN category, tumour size, tumour stage), but might play different roles in tumours arising from different anatomic sites.
Our results suggest that detection of tumour emboli and assessment of global vessel density using the D2-40 antibody, may be useful in the clinical practice, as predictors of reduced survival among pN0 laryngeal carcinoma patients.
Moisture-induced solid state instabilities in α-chymotrypsin and their reduction through chemical glycosylation
Authors: Flores-Fernández Giselle M , Pagán Miraida , Almenas Mariangely , Solá Ricardo J , Griebenow Kai 
Published: August 2010

Abstract

Background
Protein instability remains the main factor limiting the development of protein therapeutics. The fragile nature (structurally and chemically) of proteins makes them susceptible to detrimental events during processing, storage, and delivery. To overcome this, proteins are often formulated in the solid-state which combines superior stability properties with reduced operational costs. Nevertheless, solid protein pharmaceuticals can also suffer from instability problems due to moisture sorption. Chemical protein glycosylation has evolved into an important tool to overcome several instability issues associated with proteins. Herein, we employed chemical glycosylation to stabilize a solid-state protein formulation against moisture-induced deterioration in the lyophilized state.

Results
First, we investigated the consequences of moisture sorption on the stability and structural conformation of the model enzyme α-chymotrypsin (α-CT) under controlled humidity conditions. Results showed that α-CT aggregates and inactivates as a function of increased relative humidity (RH). Furthermore, α-CT loses its native secondary and tertiary structure rapidly at increasing RH. In addition, H/D exchange studies revealed that α-CT structural dynamics increased at increasing RH. The magnitude of the structural changes in tendency parallels the solid-state instability data (i.e., formation of buffer-insoluble aggregates, inactivation, and loss of native conformation upon reconstitution). To determine if these moisture-induced instability issues could be ameliorated by chemical glycosylation we proceeded to modify our model protein with chemically activated glycans of differing lengths (lactose and dextran (10 kDa)). The various glycoconjugates showed a marked decrease in aggregation and an increase in residual activity after incubation. These stabilization effects were found to be independent of the glycan size.

Conclusion
Water sorption leads to aggregation, inactivation, and structural changes of α-CT as has been similarly shown to occur for many other proteins. These instabilities correlate with an increase in protein structural dynamics as a result of moisture exposure. In this work, we present a novel methodology to stabilize proteins against structural perturbations in the solid-state since chemical glycosylation was effective in decreasing and/or preventing the traditionally observed moisture-induced aggregation and inactivation. It is suggested that the stabilization provided by these chemically attached glycans comes from the steric hindrance that the sugars conveys on the protein surface therefore preventing the interaction of the protein internal electrostatics with that of the water molecules and thus reducing the protein structural dynamics upon moisture exposure.
In silico evaluation of a control system and algorithm for automated insulin infusion in the ICU setting
Authors: Ortiz José L , Guarini Marcelo W , Borzone Gisella R , Olmos Pablo R 
Published: August 2010

Abstract

Background
It is known that tight control of glucose in the Intensive Care Unit reduces morbidity and mortality not only in diabetic patients but also in those non-diabetics who become transiently hyperglycemic. Taking advantage of a recently marketed subcutaneous glucose sensor we designed an Automatic Insulin Infusion System (AIIS) for inpatient treatment, and tested its stability under simulated clinical conditions.

Methods
The system included: reference glucose, glucose sensor, insulin and glucose infusion controllers and emergency infusion logic. We carried out computer simulations using Matlab/Simulink®, in both common and worst-case conditions.

Results
The system was capable of controlling glucose levels without entering in a phase of catastrophic instability, even under severe simulated challenges. Care was taken to include in all simulations the 5-10 minute delay of the subcutaneous glucose signal when compared to the real-time serum glucose signal, a well-known characteristic of all subcutaneous glucose sensors.

Conclusions
When tested in-Silico, a commercially available subcutaneous glucose sensor allowed the stable functioning of a proportional-derivative Automatic Insulin Infusion System, which was able to maintain glucose within acceptable limits when using a well-established glucose response model simulating a patient. Testing of the system in vivo using animal models is now warranted.
Leukocyte oxygen radical production determines disease severity in the recurrent Guillain-Barré syndrome
Authors: Mossberg Natalia , Andersen Oluf , Nordin Magnus , Nilsson Staffan , Svedhem Åke , Bergström Tomas , Hellstrand Kristoffer , Movitz Charlotta 
Published: August 2010

AbstractBackgroundThe recurrent Guillain-Barré syndrome (RGBS) is characterized by at least two GBS episodes with intervening remission. In a previous study of monophasic GBS, we reported that the magnitude of oxygen radical production ("respiratory burst") in peripheral blood leukocytes was inversely correlated to disease severity. The present study sought to establish a similar correlation in patients with RGBS.MethodsOxygen radical production in leukocytes was induced by formyl-Met-Leu-Phe (fMLF), Trp-Lys-Tyr-Met-Val-Met-NH2(WKYMVM), or phorbol myristate acetate (PMA) and assessed by quantifying superoxide anion formed by the leukocyte NADPH oxidase.ResultsDisease severity, assessed using the MRC score, was negatively correlated to superoxide anion production triggered by fMLF or WKYMVM (p = 0.001 and 0.002, respectively; n = 10). Superoxide anion production also was significantly lower in RGBS patients with incomplete recovery after stimulation with fMLF (p = 0.004) or WKYMVM (p = 0.003).ConclusionWe conclude that a lower respiratory burst in leukocytes is strongly associated with a severe course of RGBS.
A novel cell-free mitochondrial fusion assay amenable for high-throughput screenings of fusion modulators
Authors: Schauss Astrid C , Huang Huiyan , Choi Seok-Yong , Xu Liqun , Soubeyrand Sébastien , Bilodeau Patricia , Zunino Rodolfo , Rippstein Peter , Frohman Michael A , McBride Heidi M 
Published: August 2010

Abstract

Background
Mitochondria are highly dynamic organelles whose morphology and position within the cell is tightly coupled to metabolic function. There is a limited list of essential proteins that regulate mitochondrial morphology and the mechanisms that govern mitochondrial dynamics are poorly understood. However, recent evidence indicates that the core machinery that governs mitochondrial dynamics is linked within complex intracellular signalling cascades, including apoptotic pathways, cell cycle transitions and nuclear factor kappa B activation. Given the emerging importance of mitochondrial plasticity in cell signalling pathways and metabolism, it is essential that we develop tools to quantitatively analyse the processes of fission and fusion. In terms of mitochondrial fusion, the field currently relies upon on semi-quantitative assays which, even under optimal conditions, are labour-intensive, low-throughput and require complex imaging techniques.

Results
In order to overcome these technical limitations, we have developed a new, highly quantitative cell-free assay for mitochondrial fusion in mammalian cells. This assay system has allowed us to establish the energetic requirements for mitochondrial fusion. In addition, our data reveal a dependence on active protein phosphorylation for mitochondrial fusion, confirming emerging evidence that mitochondrial fusion is tightly integrated within the global cellular response to signaling events. Indeed, we have shown that cytosol derived from cells stimulated with different triggers either enhance or inhibit the cell-free fusion reaction.

Conclusions
The adaptation of this system to high-throughput analysis will provide an unprecedented opportunity to identify and characterize novel regulatory factors. In addition, it provides a framework for a detailed mechanistic analysis of the process of mitochondrial fusion and the various axis of regulation that impinge upon this process in a wide range of cellular conditions.
See Commentary: http://www.biomedcentral.com/1741-7007/8/99
Molecular characterization of partial fusion gene and C-terminus extension length of haemagglutinin-neuraminidase gene of recently isolated Newcastle disease virus isolates in Malaysia
Authors: Berhanu Ayalew , Ideris Aini , Omar Abdul R , Bejo Mohd Hair 
Published: August 2010

Abstract

Background
Newcastle disease (ND), caused by Newcastle disease virus (NDV), is a highly contagious disease of birds and has been one of the major causes of economic losses in the poultry industry. Despite routine vaccination programs, sporadic cases have occasionally occurred in the country and remain a constant threat to commercial poultry. Hence, the present study was aimed to characterize NDV isolates obtained from clinical cases in various locations of Malaysia between 2004 and 2007 based on sequence and phylogenetic analysis of partial F gene and C-terminus extension length of HN gene.

Results
The coding region of eleven NDV isolates fusion (F) gene and carboxyl terminal region of haemagglutinin-neuraminidase (HN) gene including extensions were amplified by reverse transcriptase PCR and directly sequenced. All the isolates have shown to have non-synonymous to synonymous base substitution rate ranging between 0.081 - 0.264 demonstrating presence of negative selection. Analysis based on F gene showed the characterized isolates possess three different types of protease cleavage site motifs; namely 112RRQKRF117, 112RRRKRF117 and 112GRQGRL117 and appear to show maximum identities with isolates in the region such as cockatoo/14698/90 (Indonesia), Ch/2000 (China), local isolate AF2240 indicating the high similarity of isolates circulating in the South East Asian countries. Meanwhile, one of the isolates resembles commonly used lentogenic vaccine strains. On further characterization of the HN gene, Malaysian isolates had C-terminus extensions of 0, 6 and 11 amino acids. Analysis of the phylogenetic tree revealed that the existence of three genetic groups; namely, genotype II, VII and VIII.

Conclusions
The study concluded that the occurrence of three types of NDV genotypes and presence of varied carboxyl terminus extension lengths among Malaysian isolates incriminated for sporadic cases.
Anti-HCV reactive volunteer blood donors distribution character and genotypes switch in Xi'an, China
Authors: Yue Qiao-hong , Zhang Xian-qing , Shang Yu , Chen Yao-zhen , Sun Wen-li , Su Min-quan , Mu Shi-jie , Hao Xiao-ke , Hu Xing-bin 
Published: August 2010

Abstract
HCV is prevailed in the world as well as in China. Blood transfusion is one of the most common transmission pathways of this pathogen. Although data of HCV infection character were reported during the past years, anti-HCV reactive profile of China donors was not fully clear yet. Furthermore, infection progress was found related to the HCV genotype. Different genotype led to different efficacy when interferon was introduced into HCV therapy. Here we provided character data of HCV infection in China blood donors from the year of 2000 to 2009. The infection rate in local donors was lower than general population and descended from 0.80% to 0.40% or so in recent years. About 83% HCV strains were categorized into genotypes 1b and 2a. But 1b subtype cases climbed and 2a subtype cases decreased. The current study threw more light on HCV infection of blood donors in China, at least in the Northern region.
HER2 and Chromosome 17 Effect on Patient Outcome in the N9831 Adjuvant Trastuzumab Trial
Authors: Perez Edith A. , Reinholz Monica M. , Hillman David W. , Tenner Kathleen S. , Schroeder Matthew J. , Davidson Nancy E. , Martino Silvana , Sledge George W. , Harris Lyndsay N. , Gralow Julie R. , Dueck Amylou C. , Ketterling Rhett P. , Ingle James N. , Lingle Wilma L. , Kaufman Peter A. , Visscher Daniel W. , Jenkins Robert B. 
Published: August 2010

Purpose We examined associations between tumor characteristics (human epidermal growth factor receptor 2 [HER2] protein expression, HER2 gene and chromosome 17 copy number, hormone receptor status) and disease-free survival (DFS) of patients in the N9831 adjuvant trastuzumab trial. Patients and Methods All patients (N = 1,888) underwent chemotherapy with doxorubicin and cyclophosphamide, followed by weekly paclitaxel with or without concurrent trastuzumab. HER2 status was determined by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) at a central laboratory, Mayo Clinic, Rochester, MN. Patients with conflicting local positive HER2 expression results but normal central laboratory testing were included in the analyses (n = 103). Results Patients with HER2-positive tumors (IHC 3+, FISH HER2/centromere 17 ratio ≥ 2.0, or both) benefited from trastuzumab, with hazard ratios (HRs) of 0.46, 0.49, and 0.45, respectively (all P < .0001). Patients with HER2-amplified tumors with polysomic (p17) or normal (n17) chromosome 17 copy number also benefited from trastuzumab, with HRs of 0.52 and 0.37, respectively (P < .006). Patients who received chemotherapy alone and had HER2-amplified and p17 tumors had a longer DFS than those who had n17 (78% v 68%; P = .04), irrespective of hormone receptor status or tumor grade. Patients with HER2-normal tumors by central testing (n = 103) seemed to benefit from trastuzumab, but the difference was not statistically significant (HR, 0.51; P = .14). Patients with hormone receptor–positive or –negative tumors benefited from the addition of trastuzumab, with HRs of 0.42 (P = .005) and 0.60 (P = .0001), respectively. Conclusion These results confirm that IHC or FISH HER2 testing is appropriate for patient selection for adjuvant trastuzumab therapy. Trastuzumab benefit seemed independent of HER2/centromere 17 ratio and chromosome 17 copy number.
Long-Term Follow-Up of Patients With Follicular Lymphoma Receiving Single-Agent Rituximab at Two Different Schedules in Trial SAKK 35/98
Authors: Martinelli Giovanni , Hsu Schmitz Shu-Fang , Utiger Urs , Cerny Thomas , Hess Urs , Bassi Simona , Okkinga Emmie , Stupp Roger , Stahel Rolf , Heizmann Marc , Vorobiof Daniel , Lohri Andreas , Dietrich Pierre-Yves , Zucca Emanuele , Ghielmini Michele 
Published: August 2010

Purpose We report the long-term results of a randomized clinical trial comparing induction therapy with once per week for 4 weeks single-agent rituximab alone versus induction followed by 4 cycles of maintenance therapy every 2 months in patients with follicular lymphoma. Patients and Methods Patients (prior chemotherapy 138; chemotherapy-naive 64) received single-agent rituximab and if nonprogressive, were randomly assigned to no further treatment (observation) or four additional doses of rituximab given at 2-month intervals (prolonged exposure). Results At a median follow-up of 9.5 years and with all living patients having been observed for at least 5 years, the median event-free survival (EFS) was 13 months for the observation and 24 months for the prolonged exposure arm (P < .001). In the observation arm, patients without events at 8 years were 5%, while in the prolonged exposure arm they were 27%. Of previously untreated patients receiving prolonged treatment after responding to rituximab induction, at 8 years 45% were still without event. The only favorable prognostic factor for EFS in a multivariate Cox regression was the prolonged rituximab schedule (hazard ratio, 0.59; 95% CI, 0.39 to 0.88; P = .009), whereas being chemotherapy naive, presenting with stage lower than IV, and showing a VV phenotype at position 158 of the Fc-gamma RIIIA receptor were not of independent prognostic value. No long-term toxicity potentially due to rituximab was observed. Conclusion An important proportion of patients experienced long-term remission after prolonged exposure to rituximab, particularly if they had no prior treatment and responded to rituximab induction.
In Situ Vaccination With a TLR9 Agonist Induces Systemic Lymphoma Regression: A Phase I/II Study
Authors: Brody Joshua D. , Ai Weiyun Z. , Czerwinski Debra K. , Torchia James A. , Levy Mia , Advani Ranjana H. , Kim Youn H. , Hoppe Richard T. , Knox Susan J. , Shin Lewis K. , Wapnir Irene , Tibshirani Robert J. , Levy Ronald 
Published: August 2010

Purpose Combining tumor antigens with an immunostimulant can induce the immune system to specifically eliminate cancer cells. Generally, this combination is accomplished in an ex vivo, customized manner. In a preclinical lymphoma model, intratumoral injection of a Toll-like receptor 9 (TLR9) agonist induced systemic antitumor immunity and cured large, disseminated tumors. Patients and Methods We treated 15 patients with low-grade B-cell lymphoma using low-dose radiotherapy to a single tumor site and—at that same site—injected the C-G enriched, synthetic oligodeoxynucleotide (also referred to as CpG) TLR9 agonist PF-3512676. Clinical responses were assessed at distant, untreated tumor sites. Immune responses were evaluated by measuring T-cell activation after in vitro restimulation with autologous tumor cells. Results This in situ vaccination maneuver was well-tolerated with only grade 1 to 2 local or systemic reactions and no treatment-limiting adverse events. One patient had a complete clinical response, three others had partial responses, and two patients had stable but continually regressing disease for periods significantly longer than that achieved with prior therapies. Vaccination induced tumor-reactive memory CD8 T cells. Some patients' tumors were able to induce a suppressive, regulatory phenotype in autologous T cells in vitro; these patients tended to have a shorter time to disease progression. One clinically responding patient received a second course of vaccination after relapse resulting in a second, more rapid clinical response. Conclusion In situ tumor vaccination with a TLR9 agonist induces systemic antilymphoma clinical responses. This maneuver is clinically feasible and does not require the production of a customized vaccine product.
Continental Divide? The Attitudes of US and Canadian Oncologists on the Costs, Cost-Effectiveness, and Health Policies Associated With New Cancer Drugs
Authors: Berry Scott R. , Bell Chaim M. , Ubel Peter A. , Evans William K. , Nadler Eric , Strevel Elizabeth L. , Neumann Peter J. 
Published: August 2010

Purpose Oncologists in the United States and Canada work in different health care systems, but physicians in both countries face challenges posed by the rising costs of cancer drugs. We compared their attitudes regarding the costs and cost-effectiveness of medications and related health policy. Methods Survey responses of a random sample of 1,355 United States and 238 Canadian medical oncologists (all outside of Québec) were compared. Results Response rate was 59%. More US oncologists (67% v 52%; P < .001) favor access to effective treatments regardless of cost, while more Canadians favor access to effective treatments only if they are cost-effective (75% v 58%; P < .001). Most (84% US, 80% Canadian) oncologists state that patient out-of-pocket costs influence their treatment recommendations, but less than half the respondents always or frequently discuss the costs of treatments with their patients. The majority of oncologists favor more use of cost-effectiveness data in coverage decisions (80% US, 69% Canadian; P = .004), but fewer than half the oncologists in both countries feel well equipped to use cost-effectiveness information. Majorities of oncologists favor government price controls (57% US, 68% Canadian; P = .01), but less than half favor more cost-sharing by patients (29% US, 41% Canadian; P = .004). Oncologists in both countries prefer to have physicians and nonprofit agencies determine whether drugs provide good value. Conclusion Oncologists in the United States and Canada generally have similar attitudes regarding cancer drug costs, cost-effectiveness, and associated policies, despite practicing in different health care systems. The results support providing education to help oncologists in both countries use cost-effectiveness information and discuss drug costs with their patients.
International Myeloma Working Group Consensus Statement Regarding the Current Status of Allogeneic Stem-Cell Transplantation for Multiple Myeloma
Authors: Lokhorst Henk , Einsele Hermann , Vesole David , Bruno Benedetto , Miguel Jesus San , Pérez-Simon Jose A. , Kröger Nicolaus , Moreau Philippe , Gahrton Gosta , Gasparetto Cristina , Giralt Sergio , Bensinger William 
Published: August 2010

Purpose To define consensus statement regarding allogeneic stem-cell transplantation (Allo-SCT) as a treatment option for multiple myeloma (MM) on behalf of International Myeloma Working Group. Patients and Methods In this review, results from prospective and retrospective studies of Allo-SCT in MM are summarized. Results Although the introduction of reduced-intensity conditioning (RIC) has lowered the high treatment-related mortality associated with myeloablative conditioning, convincing evidence is lacking that Allo-RIC improves the survival compared with autologous stem-cell transplantation. Conclusion New strategies are necessary to make Allo-SCT safer and more effective for patients with MM. Until this is achieved, Allo-RIC in myeloma should only be recommended in the context of clinical trials.