bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral Response to Chemotherapy in Endemic Burkitt Lymphoma
Authors: Tang Weihua , Harmon Paula , Gulley Margaret L. , Mwansambo Charles , Kazembe Peter N. , Martinson Francis , Wokocha Clifford , Kenney Shannon C. , Hoffman Irving , Sigel Carlie , Maygarden Susan , Hoffman Mariah , Shores Carol 
Published: March 2010

Abstract
Purpose: Some EBV-directed therapies are predicted to be effective only when lytic viral replication occurs. We studied whether cyclophosphamide chemotherapy induces EBV to switch from latent to lytic phases of infection in a series of EBV-associated Burkitt lymphomas.
Experimental Design: Children with first presentation of an expanding, solid maxillary or mandibular mass consistent with Burkitt lymphoma underwent fine-needle aspiration just prior to the initiation of cyclophosphamide therapy and again 1 to 5 days later. Aspirated cells were examined for latent and lytic EBV infection using in situ hybridization to EBV-encoded RNA (EBER), immunohistochemical analysis of the lytic EBV proteins BZLF1 and BMRF1, reverse transcription PCR targeting BZLF1 transcripts, and EBV viral load measurement by quantitative PCR.
Results: Among 21 lymphomas expressing EBER prior to chemotherapy, 9 of 10 still expressed EBER on day 1 after therapy whereas only 2 of 11 (18%) specimens still expressed EBER at days 3 to 5, implying that chemotherapy was fairly effective at eliminating latently infected cells. Neither of the lytic products, BZLF1 or BMRF1, were significantly upregulated at the posttherapy time points examined. However, EBV genomic copy number increased in 5 of 10 samples 1 day after treatment began, suggesting that viral replication occurs within the first 24 hours.
Conclusion: Cyclophosphamide may induce the lytic phase of EBV infection and is fairly effective in diminishing EBER-expressing tumor cells within 5 days. These findings provide the rationale for a trial testing synergistic tumor cell killing using cyclophosphamide with a drug like ganciclovir targeting lytically infected cells. Clin Cancer Res; 16(7); 2055–64. ©2010 AACR.
Sulforaphane Inhibits Constitutive and Interleukin-6–Induced Activation of Signal Transducer and Activator of Transcription 3 in Prostate Cancer Cells
Authors: Hahm Eun-Ryeong , Singh Shivendra V. 
Published: March 2010

Abstract
d,l-Sulforaphane (SFN), a synthetic analogue of broccoli-derived l-isomer, inhibits viability of human prostate cancer cells and prevents development of prostate cancer and distant site metastasis in a transgenic mouse model. However, the mechanism underlying the anticancer effect of SFN is not fully understood. We now show that SFN inhibits constitutive and interleukin-6 (IL-6)–inducible activation of signal transducer and activator of transcription 3 (STAT3), which is an oncogenic transcription factor activated in many human malignancies, including prostate cancer. Growth-suppressive concentrations of SFN (20 and 40 μmol/L) decreased constitutive (DU145 cells) and IL-6–induced (DU145 and LNCaP cells) phosphorylation of STAT3 (Tyr705) as well as its upstream regulator Janus-activated kinase 2 (Tyr1007/1008). Exposure of DU145 and LNCaP cells to SFN resulted in suppression of (a) IL-6–induced transcriptional activity of STAT3 as judged by luciferase reporter assay and (b) nuclear translocation of phospho-STAT3 as revealed by immunofluorescence microscopy. Levels of many STAT3-regulated gene products, including Bcl-2, cyclin D1, and survivin, were also reduced in SFN-treated cells. The IL-6–mediated activation of STAT3 conferred partial but marked protection against SFN-induced apoptosis as evidenced by cytoplasmic histone-associated DNA fragmentation and cleavage of poly(ADP-ribose) polymerase and procaspase-3. Furthermore, knockdown of STAT3 protein using small interfering RNA resulted in a modest yet statistically significant increase in SFN-induced apoptotic DNA fragmentation in DU145 cells. Suppression of STAT3 activation was also observed in cells treated with naturally occurring analogues of SFN. In conclusion, the present study indicates that inhibition of STAT3 partially contributes to the proapoptotic effect of SFN. Cancer Prev Res; 3(4); 484–94. ©2010 AACR.
Mast cell proteases: multifaceted regulators of inflammatory disease
Authors: Pejler Gunnar , Rönnberg Elin , Waern Ida , Wernersson Sara 
Published: March 2010

AbstractMast cells (MCs) are currently receiving increased attention among the scientific community, largely because of the recent identification of crucial functions for MCs in a variety of disorders. However, it is in many cases not clear exactly how MCs contribute in the respective settings. MCs express extraordinarily high levels of a number of proteases of chymase, tryptase, and carboxypeptidase A type, and these are stored in high amounts as active enzymes in the MC secretory granules. Hence, MC degranulation leads to the massive release of fully active MC proteases, which probably have a major impact on any condition in which MC degranulation occurs. Indeed, the recent generation and evaluation of mouse strains lacking individual MC proteases have indicated crucial contributions of these to a number of different disorders. MC proteases may thus account for many of the effects ascribed to MCs and are currently emerging as promising candidates for treatment of MC-driven disease. In this review, we discuss these findings.
Akt regulates the expression of MafK, synaptotagmin I, and syntenin-1, which play roles in neuronal function
Authors: Ro Young-Tae , Jang Bo-Kwang , Shin Chan Young , Park Eui U , Kim Chul Geun , Yang Sung-Il 
Published: March 2010

AbstractBackgroundAkt regulates various cellular processes, including cell growth, survival, and metabolism. Recently, Akt's role in neurite outgrowth has also emerged. We thus aimed to identify neuronal function-related genes that are regulated by Akt.MethodsWe performed suppression subtractive hybridization on two previously established PC12 sublines, one of which overexpresses the wild-type (WT) form and the other, the dominant-negative (DN) form of Akt. These sublines respond differently to NGF's neuronal differentiation effect.ResultsA variety of genes was identified and could be classified into several functional groups, one of which was developmental processes. Two genes involved in neuronal differentiation and function were found in this group. v-Maf musculoaponeurotic fibrosarcoma oncogene homolog K (MafK) induces the neuronal differentiation of PC12 cells and immature telencephalon neurons, and synaptotagmin I (SytI) is essential for neurotransmitter release. Another gene,syntenin-1(Syn-1) was also recognized in the same functional group into whichMafKandSytIwere classified. Syn-1 has been reported to promote the formation of membrane varicosities in neurons. Quantitative reverse transcription polymerase chain reaction analyses show that the transcript levels of these three genes were lower in PC12 (WT-Akt) cells than in parental PC12 and PC12 (DN-Akt) cells. Furthermore, treatment of PC12 (WT-Akt) cells with an Akt inhibitor resulted in the increase of the expression of these genes and the improvement of neurite outgrowth. These results indicate that dominant-negative or pharmacological inhibition of Akt increases the expression ofMafK,SytI, andSyn-1genes. Using lentiviral shRNA to knock down endogenous Syn-1 expression, we demonstrated that Syn-1 promotes an increase in the numbers of neurites and branches.ConclusionsTaken together, these results indicate that Akt negatively regulates the expression ofMafK,SytI, andSyn-1genes that all participate in regulating neuronal integrity in some way or another.
Analysis of DNA strand-specific differential expression with high density tiling microarrays
Authors: Quintales Luis , Sánchez Mar , Antequera Francisco 
Published: March 2010

Abstract

Background
DNA microarray technology allows the analysis of genome structure and dynamics at genome-wide scale. Expression microarrays (EMA) contain probes for annotated open reading frames (ORF) and are widely used for the analysis of differential gene expression. By contrast, tiling microarrays (TMA) have a much higher probe density and provide unbiased genome-wide coverage. The purpose of this study was to develop a protocol to exploit the high resolution of TMAs for quantitative measurement of DNA strand-specific differential expression of annotated and non-annotated transcripts.

Results
We extensively filtered probes present in Affymetrix Genechip Yeast Genome 2.0 expression and GeneChip S. pombe 1.0FR tiling microarrays to generate custom Chip Description Files (CDF) in order to compare their efficiency. We experimentally tested the potential of our approach by measuring the differential expression of 4904 genes in the yeast Schizosaccharomyces pombe growing under conditions of oxidative stress. The results showed a Pearson correlation coefficient of 0.943 between both platforms, indicating that TMAs are as reliable as EMAs for quantitative expression analysis. A significant advantage of TMAs over EMAs is the possibility of detecting non-annotated transcripts generated only under specific physiological conditions. To take full advantage of this property, we have used a target-labelling protocol that preserves the original polarity of the transcripts and, therefore, allows the strand-specific differential expression of non-annotated transcripts to be determined. By using a segmentation algorithm prior to generating the corresponding custom CDFs, we identified and quantitatively measured the expression of 510 transcripts longer than 180 nucleotides and not overlapping previously annotated ORFs that were differentially expressed at least 2-fold under oxidative stress.

Conclusions
We show that the information derived from TMA hybridization can be processed simultaneously for high-resolution qualitative and quantitative analysis of the differential expression of well-characterized genes and of previously non-annotated and antisense transcripts. The consistency of the performance of TMA, their genome-wide coverage and adaptability to updated genome annotations, and the possibility of measuring strand-specific differential expression makes them a tool of choice for the analysis of gene expression in any organism for which TMA platforms are available.
Different methods for administering 17β-estradiol to ovariectomized rats result in opposite effects on ischemic brain damage
Authors: Strom Jakob O , Theodorsson Elvar , Holm Lovisa , Theodorsson Annette 
Published: March 2010

Abstract

Background
Numerous stroke studies have controversially shown estrogens to be either neuroprotective or neurodamaging. The discordant results observed in rat brain ischemia models may be a consequence of discrepancies in estrogen administration modes resulting in plasma concentration profiles far from those intended. To test this hypothesis we reproduced in detail and extended an earlier study from our lab using a different mode of 17β-estradiol administration; home-made silastic capsules instead of commercial slow-release 17β-estradiol pellets. Four groups of female rats (n = 12) were ovariectomized and administered 17β-estradiol or placebo via silastic capsules. All animals underwent MCAo fourteen days after ovariectomy and were sacrificed three days later.

Results
In contrast to our earlier results using the commercial pellets, the group receiving 17β-estradiol during the entire experiment had significantly smaller lesions than the group receiving placebo (mean ± SEM: 3.85 ± 0.70% versus 7.15 ± 0.27% of total slice area, respectively; p = 0.015). No significant neuroprotection was found when the 17β-estradiol was administered only during the two weeks before or the three days immediately after MCAo.

Conclusions
The results indicate that different estrogen treatment regimens result in diametrically different effects on cerebral ischemia. Thus the effects of estrogens on ischemic damage seem to be concentration-related, with a biphasic, or even more complex, dose-response relation. These findings have implications for the design of animal experiments and also have a bearing on the estrogen doses used for peri-menopausal hormone replacement therapy.
The AP-1 repressor protein, JDP2, potentiates hepatocellular carcinoma in mice
Authors: Bitton-Worms Keren , Pikarsky Eli , Aronheim Ami 
Published: March 2010

Abstract

Background
The AP-1 transcription factor plays a major role in cell proliferation, apoptosis, differentiation and developmental processes. AP-1 proteins are primarily considered to be oncogenic. Gene disruption studies placed c-Jun as an oncogene at the early stage of a mouse model of hepatocellular carcinoma. Mice lacking c-Jun display reduced number and size of hepatic tumors attributed to elevated p53 expression and increased apoptosis. This suggests that c-Jun inhibition may serve as a therapeutic target for liver cancer. The c-Jun dimerization protein 2, JDP2 is an AP-1 repressor protein that potently inhibits AP-1 transcription. On the other hand, the JDP2 locus was found at a recurring viral integration site in T-cell lymphoma. We sought to examine the potential of JDP2 to inhibit c-Jun/AP-1 oncogenic activity in mice. Towards this end, we generated a tetracycline inducible transgenic mouse expressing JDP2 specifically in the liver. We used diethylnitrosamine (DEN) injection to initiate liver cancer in mice and assessed the extent of liver cancer in JDP2-transgenic and wild type control mice by biochemical and molecular biology techniques.

Results
JDP2-transgenic mice display normal liver function. JDP2-transgenic mice displayed potentiation of liver cancer, higher mortality and increased number and size of tumors. The expression of JDP2 at the promotion stage was found to be the most critical for enhancing liver cancer severity.

Conclusions
This study suggests that JDP2 expression may play a critical role in liver cancer development by potentiating the compensatory proliferative response and increased inflammation in the DEN liver cancer model.
Effects of prolonging administration gonadotropin on unexpectedly poor ovarian responders undergoing in vitro fertilization
Authors: Wei Zhaolian , Cheng Xianxia , Li Huirong , Cao Yunxia , Cong Lin , Zhou Ping , Li Jun 
Published: March 2010

Abstract

Background
There are still some patients who show poor response to ovarian stimulation prior to evidence of normal ovarian reserve in vitro fertilization. However, there are few studies about how to treat the unexpectedly ovarian poor responder in vitro fertilization. The main aim of this study evaluate the effect of prolonging administration follicle-stimulating hormone in woman with the unexpectedly ovarian poor responder in vitro fertilization on implantation rate, clinical pregnancy rate and live birth rate.

Methods
922 patients subjected to IVF were divided into two groups according to the predicted criterion of ovarian poor response. 116 patients predicted poor response received the short protocol (group C). The others received the long protocol, among the latter, there were 149 patients undergoing unexpectedly ovarian poor response (group B) and 657 patients exhibited normal ovarian response (group A). The doses of gonadotropin, duration of administration, implantation rate, clinical pregnancy rate and live birth rate were recorded among three groups.

Results
The implantation rate of embryo, clinic pregnancy rate and delivery rate are similar between the group A and group B, while there are significant differences between the doses of gonadotropins (35.1 +/- 8.9 ampules vs.53.0 +/- 15.9 ampules) and the duration of administration (15.3 +/- 3.6D vs. 9.8 +/- 2.6D) of these two groups. There are no significant differences about clinical pregnancy rate and live birth rate between group B and group C.

Conclusion
Prolonging administration gonadotropin on the unexpectedly poor ovarian responders does not lower live birth rate in vitro fertilization.
Radiation therapy of recurrent anal squamous cell carcinoma in-situ: a case report
Authors: Troicki Filip , Pappas Alexandros , Noone Robert , DeNittis Albert 
Published: March 2010

Abstract

Introduction
High-grade anal intraepithelial neoplasia, also referred to as anal squamous carcinoma in-situ, or Bowen's disease of the anus, make up less than 1% of all digestive system cancers in the United States. The treatment of choice is surgical resection with anal mapping. However, this disease often recurs or persists, requiring additional surgery for these patients. This can compromise the anal sphincter leading to leakage. In this case report, we discuss the efficacy of radiation therapy as a modality to treat post-excisional recurrent Bowen's disease, which may prevent sphincter compromise, leading to improved quality of life.

Case presentation
An 84-year-old Caucasian woman presented with post-excisional persistent/recurrent squamous cell carcinoma in-situ. The initial lesion measured 3 cm in diameter on the right lateral side of the anal margin. A standard surgery consisting of wide local excision with anal mapping was performed. The margins were clear and our patient was followed up. Our patient recurred with a 1.2 × 0.8 cm lesion on the left anal verge extending to the anal canal. A biopsy along with mapping was done, and 2 of the 17 mapping specimens were positive for carcinoma in-situ, one in the anal canal. Due to the location of the positive anal mapping, and in order to prevent sphincter compromise on re-excision, our patient was offered definitive radiation therapy. Two years after radiation therapy, our patient showed no signs of recurrent disease and had good sphincter control.

Conclusion
Although the main treatment modality for treating persistent/recurrent Bowen's disease is surgery, an alternative approach using external beam radiation for CIS may be enough to provide a cure for some patients with recurrent disease.
Global and unbiased detection of splice junctions from RNA-seq data
Authors: Ameur Adam , Wetterbom Anna , Feuk Lars , Gyllensten Ulf 
Published: March 2010

AbstractWe have developed a new strategy for de novo prediction of splice junctions in short-read RNA-seq data, suitable for detection of novel splicing events and chimeric transcripts. When tested on mouse RNA-seq data, >31,000 splice events were predicted, of which 88% bridged between two regions separated by ≤100 kb, and 74% connected two exons of the same RefSeq gene. Our method also reports genomic rearrangements such as insertions and deletions.
Diabetes Mellitus, Inflammation, Obesity: Proposed Treatment Pathways for Current and Future Therapies
Authors: Sonnett Travis E , Levien Terri L , Gates Brian J , Robinson Jennifer D , Campbell R Keith 
Published: March 2010

Objective To review the pathophysiology, pharmacology, and current or future therapies under study for use in treating diabetes mellitus, inflammation associated with diabetes mellitus, and/or obesity related to diabetes mellitus, through 1 of 4 investigational pathways: adiponectin, ghrelin, resveratrol, or leptin. Data sources A literature search using MEDLINE (1966–December 12, 2009), PubMed (1950–December 12, 2009), Science Direct (1994–December 12, 2009), and International Pharmaceutical Abstracts (1970–December 12, 2009) was performed using the terms adiponectin, ghrelin, resveratrol, leptin, inflammation, obesity, and diabetes mellitus. English-language, original research, and review articles were examined, and citations from these articles were assessed as well. Study selection and data extraction Clinical studies and in vitro studies were included in addition to any Phase 1, 2, or 3 clinical trials. Data synthesis Mechanistic pathways regarding adiponectin, ghrelin, resveratrol, and leptin are of interest as future treatment options for diabetes mellitus. Each of these pathways has produced significant in vitro and in vivo clinical data warranting further research as a possible treatment pathway for diabetes-related inflammation and/or obesity reduction. While research is still underway to determine the exact effects these pathways have on metabolic function, current data suggest that each of these compounds may be of interest for future therapies. Conclusions While several pathways under investigation may offer additional benefits in the treatment of diabetes mellitus and associated impairments, further investigation is necessary for both investigational and approved therapies to ensure that the impact in new pathways does not increase risks to patient safety and outcomes.
Ubiquitin fragments: their known biological activities and putative roles
Authors: Pasikowski Paweł , Cydzik Marzena , Kluczyk Alicja , Stefanowicz Piotr , Szewczuk Zbigniew 
Published: March 2010

AbstractUbiquitin (Ub) is involved in many key processes of cell biology. Identification of compounds that could interfere in the ubiquitination process is of importance. It could be expected that peptides derived from the Ub-binding regions might be able to interact with Ub receptors themselves and modify an ability of the Ub receptors interactions. This review summarizes current knowledge about known Ub-derived peptides and discusses putative activity of unexplored Ub fragments. Among identified biologically active Ub-derived peptides, its decapeptide fragment of the LEDGRTLSDY sequence was found to exhibit strong immunosuppressive effects on the cellular and humoral immune responses, comparable to that of cyclosporine. Some of the Ub fragments possess strong antibacterial and antifungal potency. In the search for new peptides that could interfere in the interaction of Ub with other proteins, we investigated the pentapeptide Ub sequences present in non-ubiquitin proteins. Based on examination of the Swiss-Prot database, we postulated that sequences of some Ub fragments often exist in other protein molecules. However, some of those motives are represented more frequently than others and could be involved in regulation of cellular processes related to Ub.
Structure and molecular evolution of multicopper blue proteins
Authors: Komori Hirofumi , Higuchi Yoshiki 
Published: March 2010

AbstractThe multicopper blue protein family, which contains cupredoxin-like domains as a structural unit, is one of the most diverse groups of proteins. This protein family is divided into two functionally different types of enzymes: multicopper oxidase and nitrite reductase. Multicopper oxidase catalyzes the oxidation of the substrate and then reduces dioxygen. The structures of many multicopper oxidases are already known, and until recently they were classified into two main groups: the three- and six-domain types. Both function as monomers and have three spectroscopically different copper sites: Types I (blue), II, and III (tri-nuclear). Nitrite reductase is a closely related protein that contains Types I and II (mono-nuclear) coppers but reduces nitrite instead of dioxygen. Nitrite reductase, which consists of two domains, forms a homotrimer. Multicopper oxidase and nitrite reductase share similar structural architectures and also contain Type I copper. Therefore, it is proposed that they have a common ancestor protein. Recently, some two-domain type multicopper oxidases have been found and their crystal structures have been determined. They have a trimeric quaternary structure and contain an active site at the molecular interface such as nitrite reductase. These results support previous hypotheses and provide an insight into the molecular evolution of multicopper blue proteins.