bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melanoma-associated Chondroitin Sulfate Proteoglycan (MCSP)-targeted delivery of soluble TRAIL potently inhibits melanoma outgrowth in vitro and in vivo
Authors: de Bruyn Marco , Rybczynska Anna A , Wei Yunwei , Schwenkert Michael , Fey Georg H , Dierckx Rudi AJO , van Waarde Aren , Helfrich Wijnand , Bremer Edwin 
Published: November 2010

Abstract

Background
Advanced melanoma is characterized by a pronounced resistance to therapy leading to a limited patient survival of ~6 - 9 months. Here, we report on a novel bifunctional therapeutic fusion protein, designated anti-MCSP:TRAIL, that is comprised of a melanoma-associated chondroitin sulfate proteoglycan (MCSP)-specific antibody fragment (scFv) fused to soluble human TRAIL. MCSP is a well-established target for melanoma immunotherapy and has recently been shown to provide important tumorigenic signals to melanoma cells. TRAIL is a highly promising tumoricidal cytokine with no or minimal toxicity towards normal cells. Anti-MCSP:TRAIL was designed to 1. selectively accrete at the cell surface of MCSP-positive melanoma cells and inhibit MCSP tumorigenic signaling and 2. activate apoptotic TRAIL-signaling.

Results
Treatment of a panel of MCSP-positive melanoma cell lines with anti-MCSP:TRAIL induced TRAIL-mediated apoptotic cell death within 16 h. Of note, treatment with anti-MCSP:sTRAIL was also characterized by a rapid dephosphorylation of key proteins, such as FAK, implicated in MCSP-mediated malignant behavior. Importantly, anti-MCSP:TRAIL treatment already inhibited anchorage-independent growth by 50% at low picomolar concentrations, whereas > 100 fold higher concentrations of non-targeted TRAIL failed to reduce colony formation. Daily i.v. treatment with a low dose of anti-MCSP:TRAIL (0.14 mg/kg) resulted in a significant growth retardation of established A375 M xenografts. Anti-MCSP:TRAIL activity was further synergized by co-treatment with rimcazole, a σ-ligand currently in clinical trials for the treatment of various cancers.

Conclusions
Anti-MCSP:TRAIL has promising pre-clinical anti-melanoma activity that appears to result from combined inhibition of tumorigenic MCSP-signaling and concordant activation of TRAIL-apoptotic signaling. Anti-MCSP:TRAIL alone, or in combination with rimcazole, may be of potential value for the treatment of malignant melanoma.
Detection of carcinoembryonic antigen messenger RNA in blood using quantitative real-time reverse transcriptase-polymerase chain reaction to predict recurrence of gastric adenocarcinoma
Authors: Qiu Miao-zhen , Li Zhuang-hua , Zhou Zhi-wei , Li Yu-hong , Wang Zhi-qiang , Wang Feng-hua , Huang Peng , Aziz Fahad , Wang Dao-yuan , Xu Rui-hua 
Published: November 2010

Abstract

Background
The existence of circulating tumor cells (CTCs) in peripheral blood as an indicator of tumor recurrence has not been clearly established, particularly for gastric cancer patients. We conducted a retrospective analysis of the relationship between CTCs in peripheral blood at initial diagnosis and clinicopathologic findings in patients with gastric carcinoma.

Methods
Blood samples were obtained from 123 gastric carcinoma patients at initial diagnosis. mRNA was extracted and amplified for carcinoembryonic antigen (CEA) mRNA detection using real-time RT-PCR. Periodic 3-month follow-up examinations included serum CEA measurements and imaging.

Results
The minimum threshold for corrected CEA mRNA score [(CEA mRNA/GAPDH mRNA) × 106] was set at 100. Forty-five of 123 patients (36.6%) were positive for CEA mRNA expression. CEA mRNA expression significantly correlated with T stage and postoperative recurrence status (P = 0.001). Recurrent disease was found in 44 of 123 cases (35.8%), and 25 of these (56.8%) were positive for CEA mRNA. Of these patients, CEA mRNA was more sensitive than serum CEA in indicating recurrence. Three-year disease-free survival of patients positive for CEA mRNA was significantly poorer than of patients negative for CEA mRNA (P < 0.001). Only histological grade and CEA mRNA positivity were independent factors for disease-free survival using multivariate analysis.

Conclusions
CEA mRNA copy number in peripheral blood at initial diagnosis was significantly associated with disease recurrence in gastric adenocarcinoma patients. Real-time RT-PCR detection of CEA mRNA levels at initial diagnosis appears to be a promising predictor for disease recurrence in gastric adenocarcinoma patients.
Human TOP1 residues implicated in species specificity of HIV-1 infection are required for interaction with BTBD2, and RNAi of BTBD2 in old world monkey and human cells increases permissiveness to HIV-1 infection
Authors: Khurana Bharat , Zhuang Lei , Moitra Prasun K , Stantchev Tzanko S , Broder Christopher C , Cutler Mary Lou , D'Arpa Peter 
Published: November 2010

Abstract

Background
Host determinants of HIV-1 viral tropism include factors from producer cells that affect the efficiency of productive infection and factors in target cells that block infection after viral entry. TRIM5α restricts HIV-1 infection at an early post-entry step through a mechanism associated with rapid disassembly of the retroviral capsid. Topoisomerase I (TOP1) appears to play a role in HIV-1 viral tropism by incorporating into or otherwise modulating virions affecting the efficiency of a post-entry step, as the expression of human TOP1 in African Green Monkey (AGM) virion-producing cells increased the infectivity of progeny virions by five-fold. This infectivity enhancement required human TOP1 residues 236 and 237 as their replacement with the AGM counterpart residues abolished the infectivity enhancement. Our previous studies showed that TOP1 interacts with BTBD1 and BTBD2, two proteins which co-localize with the TRIM5α splice variant TRIM5δ in cytoplasmic bodies. Because BTBD1 and BTBD2 interact with one HIV-1 viral tropism factor, TOP1, and co-localize with a splice variant of another, we investigated the potential involvement of BTBD1 and BTBD2 in HIV-1 restriction.

Results
We show that the interaction of BTBD1 and BTBD2 with TOP1 requires hu-TOP1 residues 236 and 237, the same residues required to enhance the infectivity of progeny virions when hu-TOP1 is expressed in AGM producer cells. Additionally, interference with the expression of BTBD2 in AGM and human 293T target cells increased their permissiveness to HIV-1 infection two- to three-fold.

Conclusions
These results do not exclude the possibility that BTBD2 may modestly restrict HIV-1 infection via colocation with TRIM5 variants in cytoplasmic bodies.
Molecular characterization of two distinct monopartite begomoviruses infecting tomato in india
Authors: Pandey Prerna , Mukhopadhya Subhra , Naqvi Afsar R , Mukherjee Sunil K , Shekhawat Gyan S , Choudhury Nirupam R 
Published: November 2010

Abstract

Background

Tomato leaf curl viruses, which are the members of the genus Begomovirus, have emerged as devastating pathogens worldwide causing huge economic losses and threatening production of crops like cassava, cotton, grain legumes and vegetables. Even though the ToLCV isolates from Northern India have been shown to possess bipartite genome (designated as DNA A and DNA B), those from Australia, Taiwan and Southern India have a single genomic component (DNA A). We describe here the genetic diversity of two isolates of monopartite Tomato leaf curl virus infecting tomato in two extreme regions (North and South) of Indian subcontinent.

Results
The rolling circle amplification (RCA) products obtained from symptomatic samples were digested, cloned and sequenced. The complete DNA sequence of two Tomato leaf curl virus isolates identified as ToLCV-CTM (India, New Delhi, 2005) and ToLCVK3/K5 (India, Kerala, 2008) are reported here. These isolates had the characteristic features of Begomovirus genome organization with six conserved open reading frames (ORFs). The ToLCV-K3 and ToLCV-K5 isolates may be the strains of the same virus since they show sequence homology of 97% over their entire genome. This, according to the guidelines established by the ICTV Geminiviridae Study-Group is higher than threshold (92%) for delineation of different viral variants and hence single, average value has been assigned for all their analyses presented here. The ToLCV-CTM and ToLCV-K3/K5 viruses were found to be monopartite, as neither DNA-B component nor betasatellite associated with begomovirus species, were detected. The complete nucleotide sequence of DNA-A genome of CTM exhibited highest sequence homology (88%) to Croton yellow vein mosaic virus (AJ507777), and of isolates K3/K5 (88.5%) to Tomato leaf curl Pakistan virus (DQ116884). This is less than the threshold value for demarcation of species in the genus Begomovirus.

Conclusion
K3/K5 and CTM are considered to be novel isolates of Tomato leaf curl virus. Sequence analyses and phylogenetic study indicate that these two ToLCV isolates might have evolved by recombination between viruses related to two or more viral ancestors. The existence of different ToLCV isolates having high genome diversity in India poses a threat to the tomato production in the Asian continent.
Hypofractionated radiotherapy after conservative surgery for breast cancer: analysis of acute and late toxicity
Authors: Deantonio Letizia , Gambaro Giuseppina , Beldì Debora , Masini Laura , Tunesi Sara , Magnani Corrado , Krengli Marco 
Published: November 2010

Abstract

Background
A variety of hypofractionated radiotherapy schedules has been proposed after breast conserving surgery in the attempt to shorten the overall treatment time. The aim of the present study is to assess acute and late toxicity of using daily fractionation of 2.25 Gy to a total dose of 45 Gy to the whole breast in a mono-institutional series.

Methods
Eighty-five women with early breast cancer were assigned to receive 45 Gy followed by a boost to the tumour bed. Early and late toxicity were scored according to the Radiation Therapy Oncology Group criteria. For comparison, a group of 70 patients with similar characteristics and treated with conventional fractionation of 2 Gy to a total dose of 50 Gy in 25 fractions followed by a boost, was retrospectively selected.

Results
Overall median treatment duration was 29 days for hypofractionated radiotherapy and 37 days for conventional radiotherapy. Early reactions were observed in 72/85 (85%) patients treated with hypofractionation and in 67/70 (96%) patients treated with conventional fractionation (p = 0.01). Late toxicity was observed in 8 patients (10%) in the hypofractionation group and in 10 patients (15%) in the conventional fractionation group, respectively (p = 0.4).

Conclusions
The hypofractionated schedule delivering 45 Gy in 20 fractions shortened the overall treatment time by 1 week with a reduction of skin acute toxicity and no increase of late effects compared to the conventional fractionation. Our results support the implementation of hypofractionated schedules in clinical practice.
Transarticular screw fixation for atlantoaxial instability - modified Magerl's technique in 38 patients
Authors: Bahadur Raj , Goyal Tarun , Dhatt Saravdeep S , Tripathy Sujit K 
Published: November 2010

Abstract

Background
Symptomatic atlantoaxial instability needs stabilization of the atlantoaxial joint. Among the various techniques described in literature for the fixation of atlantoaxial joint, Magerl's technique of transarticular screw fixation remains the gold standard. Traditionally this technique combines placement of transarticular screws and posterior wiring construct. The aim of this study is to evaluate clinical and radiological outcomes in subjects of atlantoaxial instability who were operated using transarticular screws and iliac crest bone graft, without the use of sublaminar wiring (a modification of Magerl's technique).

Methods
We evaluated retrospectively 38 subjects with atlantoaxial instability who were operated at our institute using transarticular screw fixation. The subjects were followed up for pain, fusion rates, neurological status and radiographic outcomes. Final outcome was graded both subjectively and objectively, using the scoring system given by Grob et al.

Results
Instability in 34 subjects was secondary to trauma, in 3 due to rheumatoid arthritis and 1 had tuberculosis. Neurological deficit was present in 17 subjects. Most common presenting symptom was neck pain, present in 35 of the 38 subjects.
Postoperatively residual neck and occipital pain was present in 8 subjects. Neurological deficit persisted in only 7 subjects. Vertebral artery injury was seen in 3 subjects. None of these subjects had any sign of neurological deficit or vertebral insufficiency. Three cases had nonunion. At the latest follow up, subjectively, 24 subjects had good result, 6 had fair and 8 had bad result. On objective grading, 24 had good result, 11 had fair and 3 had bad result. The mean follow up duration was 41 months.

Conclusions
Transarticular screw fixation is an excellent technique for fusion of the atlantoaxial complex. It provides highest fusion rates, and is particularly important in subjects at risk for nonunion. Omitting the posterior wiring construct that has been used along with the bone graft in the traditional Magerl' s technique achieves equally good fusion rates and is an important modification, thereby avoiding the complications of sublaminar wire passage.
Biodetoxification of toxins generated from lignocellulose pretreatment using a newly isolated fungus, Amorphotheca resinae ZN1, and the consequent ethanol fermentation
Authors: Zhang Jian , Zhu Zhinan , Wang Xiaofeng , Wang Nan , Wang Wei , Bao Jie 
Published: November 2010

AbstractBackgroundDegradation of the toxic compounds generated in the harsh pretreatment of lignocellulose is an inevitable step in reducing the toxin level for conducting practical enzymatic hydrolysis and ethanol fermentation processes. Various detoxification methods have been tried and many negative outcomes were found using these methods, such as the massive freshwater usage and wastewater generation, loss of the fine lignocellulose particles and fermentative sugars and incomplete removal of inhibitors. An alternate method, biodetoxification, which degrades the toxins as part of their normal metabolism, was considered a promising option for the removal of toxins without causing the above problems.ResultsA kerosene fungus strain,Amorphotheca resinaeZN1, was isolated from the microbial community growing on the pretreated corn stover material. The degradation of the toxins as well as the lignocelluloses-derived sugars was characterized in different ways, and the results show thatA. resinaeZN1 utilized each of these toxins and sugars as the sole carbon sources efficiently and grew quickly on the toxins. It was found that the solid-state culture ofA. resinaeZN1 on various pretreated lignocellulose feedstocks such as corn stover, wheat straw, rice straw, cotton stalk and rape straw degraded all kinds of toxins quickly and efficiently. The consequent simultaneous saccharification and ethanol fermentation was performed at the 30% (wt/wt) solid loading of the detoxified lignocellulosic feedstocks without a sterilization step, and the ethanol titer in the fermentation broth reached above 40 g/L using food crop residues as feedstocks.ConclusionsThe advantages of the present biodetoxification byA. resinaeZN1 over the known detoxification methods include zero energy input, zero wastewater generation, complete toxin degradation, processing on solid pretreated material, no need for sterilization and a wide lignocellulose feedstock spectrum. These advantages make it possible for industrial applications with fast and efficient biodetoxification to remove toxins generated during intensive lignocellulose pretreatment.
Sox10- Venus mice: a new tool for real-time labeling of neural crest lineage cells and oligodendrocytes
Authors: Shibata Shinsuke , Yasuda Akimasa , Renault-Mihara Francois , Suyama Satoshi , Katoh Hiroyuki , Inoue Takayoshi , Inoue Yukiko U , Nagoshi Narihito , Sato Momoka , Nakamura Masaya , Akazawa Chihiro , Okano Hideyuki 
Published: November 2010

AbstractBackgroundWhile several mouse strains have recently been developed for tracing neural crest or oligodendrocyte lineages, each strain has inherent limitations. The connection between humanSOX10mutations and neural crest cell pathogenesis led us to focus on theSox10gene, which is critical for neural crest development. We generatedSox10-Venus BAC transgenic mice to monitor Sox10 expression in both normal development and in pathological processes.ResultsTissue fluorescence distinguished neural crest progeny cells and oligodendrocytes in theSox10-Venus mouse embryo. Immunohistochemical analysis confirmed that Venus expression was restricted to cells expressing endogenous Sox10. Time-lapse imaging of various tissues inSox10-Venus mice demonstrated that Venus expression could be visualized at the single-cell levelin vivodue to the intense, focused Venus fluorescence. In the adultSox10-Venus mouse, several types of mature and immature oligodendrocytes along with Schwann cells were clearly labeled with Venus, both before and after spinal cord injury.ConclusionsIn the newly-developedSox10-Venus transgenic mouse, Venus fluorescence faithfully mirrors endogenous Sox10 expression and allows forin vivoimaging of live cells at the single-cell level. ThisSox10-Venus mouse will thus be a useful tool for studying neural crest cells or oligodendrocytes, both in development and in pathological processes.
Targeted therapy in lymphoma
Authors: Johnston Patrick B , Yuan RuiRong , Cavalli Franco , Witzig Thomas E 
Published: November 2010

AbstractDiscovery of new treatments for lymphoma that prolong survival and are less toxic than currently available agents represents an urgent unmet need. We now have a better understanding of the molecular pathogenesis of lymphoma, such as aberrant signal transduction pathways, which have led to the discovery and development of targeted therapeutics. The ubiquitin-proteasome and the Akt/mammalian target of rapamycin (mTOR) pathways are examples of pathological mechanisms that are being targeted in drug development efforts. Bortezomib (a small molecule protease inhibitor) and the mTOR inhibitors temsirolimus, everolimus, and ridaforolimus are some of the targeted therapies currently being studied in the treatment of aggressive, relapsed/refractory lymphoma. This review will discuss the rationale for and summarize the reported findings of initial and ongoing investigations of mTOR inhibitors and other small molecule targeted therapies in the treatment of lymphoma.
Expression and clinicopathological significance of Mel-18 and Bmi-1 mRNA in gastric carcinoma
Authors: Lu You-Wei , Li Jin , Guo Wei-Jian 
Published: November 2010

Abstract

Background
The Polycomb group (PcG) genes are a class of regulators responsible for maintaining homeotic gene expression throughout cell division. PcG expression is deregulated in some types of human cancer. Both Bmi-1 and Mel-18 are of the key PcG proteins. We investigate the expression and clinicopathological roles of Mel-18 and Bmi-1 mRNA in gastric cancer.

Methods
The expression of Mel-18 and Bmi-1 in a series of 71 gastric cancer tissues and paired normal mucosal tissues distant from the tumorous lesion was assayed by quantitative real time RT-PCR. The correlation between Mel-18 and Bmi-1 mRNA expression, and between Mel-18 or Bmi-1 mRNA level and clinicopathological characteristics were analyzed.

Results
Expression of Mel-18 and Bmi-1 genes was variably detected, but overexpression of Bmi-1 mRNA and decreased expression of Mel-18 mRNA were the most frequent alteration. In addition, the expression of Bmi-1 and Mel-18 mRNA inversely correlates in gastric tumors. Moreover, a significant positive correlation between Bmi-1 overexpression and tumor size, depth of invasion, or lymph node metastasis, and a significant negative correlation between Mel-18 low-expression with lymph node metastasis or the clinical stage were observed.

Conclusion
Our data suggest that Mel-18 and Bmi-1 may play crucial but opposite roles in gastric cancer. Decreased Mel-18 and increased Bmi-1 mRNA expression was associated with the carcinogenesis and progression of gastric cancer. It is possible to list Bmi-1 and Mel-18 as biomarkers for predicting the prognosis of gastric cancer.
Diagnosis of carotid arterial injury in major trauma using a modification of Memphis criteria
Authors: Ciapetti Marco , Circelli Alessandro , Zagli Giovanni , Migliaccio Maria Luisa , Spina Rosario , Alessi Alessandro , Acquafresca Manlio , Bartolini Marco , Peris Adriano 
Published: November 2010

Abstract

Background
Incidence of Blunt Cerebrovascular Injuries (BCVI) after head injury has been reported as 0.5-1% of all admissions for blunt trauma, with a high stroke and mortality rate. The purpose of this study is to evaluate if a modification of Memphis criteria could improve the rate of BCVI diagnosis.

Methods
Trauma patients consecutively admitted to Intensive Care Unit (ICU) from Jan 2008 to Oct 2009 were considered for the study. Memphis criteria comprehend: basilar skull fracture with involvement of the carotid canal, cervical spine fracture, neurological exam not explained by brain imaging, Horner's syndrome, LeFort II-III fractures, and neck soft tissue injury. As single criteria modification, we included all patients with petrous bone fracture, even without carotid canal involvement. In all patients at risk of BCVI, 64-slice angio-CT-scans was performed.

Results
During the study period, 266 patients were admitted to the ICU for blunt major trauma. Among them, 162 presented traumatic brain injury or cervical spine fracture. In accordance with the proposed modified-Memphis criteria, 53 patients showed risk factors for BCVI compared to 45 using the original Memphis criteria. Among the 53 patients, 6 resulted as having carotid lesions (2.2% of all blunt major traumas; one patient more than when using Memphis criteria). Anticoagulant therapy with low molecular weight heparin was administered in all patients. No stroke or hemorrhagic complications occurred. Clinical examination at 6-months showed no central neurological deficit.

Conclusion
A modification of a single criteria of Memphis screening protocol might permit the identification of a higher percentage of BCVI. Limited by sample size, this study needs to be validated.