bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two New Diterpenoid Lactams from Spiraea japonica var. ovalifolia
Authors: Liu Hai‐Yang , Ni Wei , Chen Chang‐Xiang , Di Ying‐Tong , Hao Xiao‐Jiang 
Published: June 2009

Abstractmagnified imageTwo new diterpenoid alkaloids, spiramilactams A (1) and B (2), were isolated from the basic fraction of a MeOH extract of whole plants of Spiraea japonica var. ovalifolia. Their structures were established on the basis of extensive spectroscopic and mass‐spectrometric analyses.
Lignans and a Sesquiterpene Glucoside from Carissa carandas Stem
Authors: Wangteeraprasert Ruchira , Likhitwitayawuid Kittisak 
Published: June 2009

Abstractmagnified imageTwo new compounds, the sesquiterpene glucoside carandoside (1) and (6S,7R,8R)‐7a‐[(β‐glucopyranosyl)oxy]lyoniresinol (2), were isolated from the stem of Carissa carandas, together with three known lignans. The structures of the isolated compounds were determined on the basis of spectroscopic evidence. Their DPPH free radical‐scavenging activities were also evaluated.
Oligonucleotide Analogues with Integrated Bases and Backbone. Part 21
Authors: Bogliotti Nicolas , Vasella Andrea 
Published: June 2009

Abstractmagnified imageGelation of organic solvents by the A*[s]U(*) dinucleosides 1 and 2 requires the formation of linear associates cross‐linked by H‐bonding involving either the nucleobase or HOCH2C(6/I). This is evidenced by the absence of gel formation of the N6‐methyladenosine analogue 5 of 1 and the dehydroxy analogue 4 of 2.
Ginkgo biloba: specificity of neuropsychological improvement—a selective review in search of differential effects
Authors: Kaschel Reiner 
Published: June 2009

AbstractExtracts of Ginkgo biloba are widely used for the treatment of cognitive impairment. Whereas reviews have focused on the question whether ginkgo is effective to enhance cognition in general, little is known about specificity of improvement. This might be crucial for future trials, thus enabling hypotheses about sensitive outcome measures. Therefore, this article summarizes such information, i.e. neuropsychological effects of chronic administration of ginkgo in healthy and cognitively impaired subjects of any age. Objective psychometric test results were considered if they reflected distinct cognitive functions from randomized controlled group‐studies (RCT). We reviewed 29 RCTs yielding 209 placebo‐drug comparisons of psychometric scores in four different cognitive domains comprising 14 sub‐functions. Whereas little specific information can be obtained from trials for treatment of dementia, a pattern of pharmacological actions on cognitive processes emerges here from studies for mild cognitive impairment (MCI), depression, multiple sclerosis and healthy young and elderly subjects. There is consistent evidence that chronic administration improves selective attention, some executive processes and long‐term memory for verbal and non‐verbal material. Further trials should be more comprehensive as there are few data available on some cognitive functions and psychometric flaws in the selection of tests and the interpretation of their results favouring predominantlyβ‐errors. Thus, though this pattern is encouraging it also asks for a cautious interpretation to date. Copyright © 2009 John Wiley & Sons, Ltd.
Oncogenic human papillomaviruses block expression of the B‐cell translocation gene‐2 tumor suppressor gene
Authors: Cullmann Claire , Hoppe‐Seyler Karin , Dymalla Susanne , Lohrey Claudia , Scheffner Martin , Dürst Matthias , Hoppe‐Seyler Felix 
Published: June 2009

AbstractHuman papillomavirus (HPV)‐induced carcinogenesis is critically dependent on the activities of the viral E6 and E7 oncogenes. Here, we demonstrate that expression of the putative tumor suppressor gene B‐cell translocation gene‐2 (BTG2) is reinduced in HPV16‐ and HPV18‐positive cancer cells on silencing of viral oncogene expression, indicating that BTG2 is repressed by oncogenic HPVs. Inhibition of BTG2 expression was mediated by the HPV E6 oncogene and occurred in a p53‐dependent manner. Luciferase reporter gene analyses revealed that BTG2 repression takes place at the transcriptional level and is dependent on the integrity of the major p53‐response element within the BTG2 promoter. Ectopic expression of BTG2 acted antiproliferative in cervical cancer cells. Tissue specimens commonly exhibited reduced BTG2 protein levels in HPV‐positive high‐grade lesions (CIN2/3) and cervical carcinomas, when compared with normal cervical epithelium. These findings identify the antiproliferative BTG2 gene as a novel cellular target blocked by the HPV E6 oncoprotein. © 2009 UICC
Reproductive factors and postmenopausal hormone use in relation to endometrial cancer risk in the Nurses' Health Study cohort 1976–2004
Authors: Karageorgi Stalo , Hankinson Susan E. , Kraft Peter , De Vivo Immaculata 
Published: June 2009

AbstractEndometrial cancer is a disease primarily driven by cumulative exposure to estrogen unopposed by progesterone. Reproductive factors associated with changes in endogenous hormone levels and use of exogenous hormones such as postmenopausal hormones influence the risk of disease. The authors used the Nurses' Health Study, comprised of 121,700 nurses, to assess the above associations. Over 28 years of follow‐up, 778 adenocarcinoma cases were diagnosed and 1,850,078 person‐years were accumulated. Cox proportional hazards models were used to estimate relative risks (RR) and 95% confidence intervals (CI). A late age at menarche decreased the risk independent of body mass index (BMI) (P‐trend = 0.02). A late age at menopause increased cancer risk (P‐trend = 0.0003). An advanced age at last birth reduced the risk (P‐trend < 0.0001), however, an inverse association with age at first birth and parity diminished after adjustment for age at last birth. Compared with never users, an increased risk was observed among long‐term (≥5 years) users of both estrogen (E) (RR = 7.67, 95% CI: 5.57, 10.57) and combined estrogen plus progesterone (E+P) (RR = 1.52, 95% CI: 1.03, 2.23). Normal‐weight (BMI < 25) women had the highest risk following E or E+P use (P‐interaction‐E = 0.0008, P‐interaction‐E+P = 0.02). The findings from this study underscore the importance of hormonal mechanisms in endometrial carcinogenesis.
Id‐1 promotes tumorigenicity and metastasis of human esophageal cancer cells through activation of PI3K/AKT signaling pathway
Authors: Li Bin , Tsao Sai Wah , Li Yuk Yin , Wang Xianghong , Ling Ming Tat , Wong Yong Chuan , He Qing Yu , Cheung Annie L.M. 
Published: June 2009

AbstractId‐1 (inhibitor of differentiation or DNA binding) is a helix‐loop‐helix protein that is overexpressed in many types of cancer including esophageal squamous cell carcinoma (ESCC). We previously reported that ectopic Id‐1 expression activates the phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (AKT) signaling pathway in human esophageal cancer cells. In this study, we confirmed a positive correlation between Id‐1 and phospho‐AKT (Ser473) expressions in ESCC cell lines, as well as in ESCC on a tissue microarray. To investigate the significance of Id‐1 in esophageal cancer progression, ESCC cells with stable ectopic Id‐1 expression were inoculated subcutaneously into the flank of nude mice and were found to form larger tumors that showed elevated Ki‐67 proliferation index and increased angiogenesis, as well as reduced apoptosis, compared with control cells expressing the empty vector.The Id‐1‐overexpressing cells also exhibited enhanced metastatic potential in the experimental metastasis assay. Treatment with the PI3K inhibitor LY294002 attenuated the tumor promotion effects of Id‐1, indicating that the effects were mediated by the PI3K/AKT signaling pathway. In addition, our in vitro experiments showed that ectopic Id‐1 expression altered the expression levels of markers associated with epithelial–mesenchymal transition and enhanced the migration ability of esophageal cancer cells. The Id‐1‐overexpressing ESCC cells also exhibited increased invasive potential, which was in part due to PI3K/AKT‐dependent modulation of matrix metalloproteinase‐9 expression. In conclusion, our results provide the first evidence that Id‐1 promotes tumorigenicity and metastasis of human esophageal cancer in vivo and that the PI3K inhibitor LY294002 can attenuate these effects. © 2009 UICC
Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression
Authors: Bhatia Kishor , Goedert James J. , Modali Rama , Preiss Liliana , Ayers Leona W. 
Published: June 2009

AbstractMerkel cell polyomavirus (MCPyV) was recently discovered in Merkel cell carcinoma (MCC), a clinically and pathologically heterogeneous malignancy of dermal neuroendocrine cells. To investigate this heterogeneity, we developed a tissue microarray (TMA) to characterize immunohistochemical staining of candidate tumor cell proteins and a quantitative PCR assay to detect MCPyV and measure viral loads. MCPyV was detected in 19 of 23 (74%) primary MCC tumors, but 8 of these had less than 1 viral copy per 300 cells. Viral abundance of 0.06–1.2 viral copies/cell was directly related to presence of retinoblastoma gene product (pRb) and terminal deoxyribonucleotidyl transferase (TdT) by immunohistochemical staining (p ≤ 0.003). Higher viral abundance tumors tended to be associated with less p53 expression, younger age at diagnosis and longer survival (p ≤ 0.08). These data suggest that MCC may arise through different oncogenic pathways, including ones independent of pRb and MCPyV.
Cancer risk among patients with cystic fibrosis and their first‐degree relatives
Authors: Johannesson Marie , Askling Johan , Montgomery Scott M. , Ekbom Anders , Bahmanyar Shahram 
Published: June 2009

AbstractPatients with cystic fibrosis (CF) are at increased risk of some cancers. Little is known about the cancer risks among carriers heterozygous for the CF mutation and it is hypothesized this may be associated with reduced cancer risk. Using Swedish general population‐based registers, we identified 884 patients with CF from 1968 to 2003 and 3,033 of their first‐degree relatives The subjects were followed from birth of index persons or 1958, whichever came later, until death, emigration or 2003, whichever came first. Cancer risks were compared with the general Swedish population using standardized incidence ratios (SIR) with 95% confidence intervals (CI). Patients, followed for an average of 21 years, were at a higher overall risk of cancer. Some 26 cancer diagnoses, after excluding multiple diagnoses of nonmelanoma skin cancer in one man, produced an overall SIR of 3.2 (95% CI 2.1–4.6). We found statistically significantly increased risks for kidney, thyroid, endocrine, lymphoma and nonmelanoma skin cancer. There was no modification of cancer risk among parents and siblings, with an average of 21 years of follow‐up. This study did not identify a heterozygote advantage for CF gene mutations in relation to cancer risk. © 2009 UICC
Active MMP‐2 effectively identifies the presence of colorectal cancer
Authors: Murnane Mary Jo , Cai Jinguo , Shuja Sania , McAneny David , Klepeis Veronica , Willett John B. 
Published: June 2009

AbstractFully active MMP‐2 is expressed at such low levels in human tissues that studies often fail to confirm its value as a cancer marker despite strong associations with malignancy. Our study utilized careful extraction, accurate activity measurements, standardization to purified controls and a new statistical metric to determine whether active MMP‐2 is an effective indicator of colorectal cancer compared to pro‐MMP‐2 or pro‐MMP‐9. MMP‐2 and MMP‐9 activities were analyzed in matched normal and cancer samples from 269 patients by gelatin zymography, computer‐assisted image analysis, serial dilutions of strong samples and standardization to controls. An index of effect size was designed for comparative evaluation of active MMP‐2, pro‐MMP‐2 and pro‐MMP‐9 activities. For each gelatinase, mean activity and protein levels/mg soluble protein in normal mucosa and colorectal cancer were calculated for the first time with respect to commercial standards. Active MMP‐2 activity, detected in 99% of colorectal cancers, was higher in 95% of cancers (on average 10‐fold) than in normal mucosa. Levels of pro‐MMP‐2 and pro‐MMP‐9, but not active MMP‐9, activities were also significantly higher in cancers versus normal. However, active MMP‐2 activity provided the most effective test for the presence of cancer (p < 0.0.0001) with an effect size statistically significantly larger than for either pro‐MMP‐2 or pro‐MMP‐9. Receiver operating characteristic (ROC) curves demonstrated that a cut‐off for active MMP‐2 of >44 SDU activity/mg soluble protein (>180 pg/mg), which is three times mean normal levels, would permit detection of colorectal cancer with an estimated sensitivity of 84% and estimated specificity of 93%. © 2009 UICC
KLF4‐dependent, PPARγ‐induced expression of GPA33 in colon cancer cell lines
Authors: Rageul Julie , Mottier Stéphanie , Jarry Anne , Shah Yatrik , Théoleyre Sandrine , Masson Damien , Gonzalez Frank J. , Laboisse Christian L. , Denis Marc G. 
Published: June 2009

AbstractThe glycoprotein A33 (GPA33) is a colon cancer antigen. Phase I trials with131I and125I monoclonal antibody A33 in colon carcinoma patients showed excellent localization to colorectal cancer and some evidence of tumor response. Using DNA microarrays, we have identified theGPA33gene as a target of PPARγ in HT29‐Cl.16E colon cancer cells. Treatment of HT29‐Cl.16E, Caco2, SW1116 and LS174T colon cancer cells with the PPARγ agonist GW7845 induced a 2‐ to 6‐fold increase in GPA33 mRNA as determined by real‐time PCR. This induction was also found in HT29‐Cl.16E cells treated with rosiglitazone and ciglitazone and was prevented by cotreatment with the PPARγ antagonist GW9662, indicating that this regulation was PPARγ dependent. No canonical PPAR responsive element was found in theGPA33promoter. We therefore analyzed the expression of transcription factors involved in GPA33 expression. CDXl, CDX2 and KLF5 expression was not modified by PPARγ activation. By contrast, a significant increase in KLF4 was seen, both at mRNA and protein levels. Furthermore, chromatin immunoprecipitation studies demonstrated that an increased amount of KLF4 protein was bound to theGPA33promoter in cells treated with rosiglitazone. Finally, downregulation of KLF4 expression by siRNA reduced rosiglitazone‐induced GPA33 expression. This indicates that PPARγ activation induces KLF4 expression, which in turn increases GPA33 expression. We also demonstrate that PPARγ activation leads to increased (p21WAF1/Cip1and keratin 19) or decreased (cyclin D1) expression of known KLF4 targets, suggesting that KLF4 is a nodal player in a network of PPARγ‐regulated genes. © 2009 UICC
BRCA1 modulates malignant cell behavior, the expression of survivin and chemosensitivity in human breast cancer cells
Authors: Promkan Moltira , Liu Guangming , Patmasiriwat Pimpicha , Chakrabarty Subhas 
Published: June 2009

AbstractBRCA1 is a multifunctional tumor‐suppressive protein. Many functional aspects of BRCA1 are not fully understood. We used a shRNA approach to probe the function of BRCA1 in human breast cancer cells. Knocking down BRCA1 expression by shRNA in the wild‐type BRCA1 human breast cancer MCF‐7 and MDA‐MB‐231 cells resulted in an increase in cell proliferation, anchorage‐independent growth, cell migration, invasion and a loss of p21/Waf1 and p27Kip1 expression. In BRCA1 knocked‐down cells, the expression of survivin was significantly up regulated with a concurrent decrease in cellular sensitivity to paclitaxel. We also found that cells harboring endogenous mutant or defective BRCA1 (MDA‐MB‐436 and HCC1937) were highly proliferative and expressed a relatively low level of p21/Waf1 and p27Kip1 by comparison to wild‐type BRCA1 cells. Cells harboring mutated BRCA1 also expressed a high level of survivin and were relatively resistant to paclitaxel by comparison to wild‐type cells. Increase resistance to paclitaxel was due to an increase in the expression of survivin in both the BRCA1 knocked‐down and mutant BRCA1 cells because knocking down survivin expression by siRNA restored sensitivity to paclitaxel. We conclude that BRCA1 down‐modulates the malignant behavior of breast cancer cells, promotes the expression of p21/Waf1, p27Kip1 and inhibits the expression of survivin. Moreover, loss of BRCA1 expression or function leads to an increase in survivin expression and a reduction in chemosensitivity to paclitaxel. © 2009 UICC
Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival
Authors: Greither Thomas , Grochola Lukasz F. , Udelnow Andrej , Lautenschläger Christine , Würl Peter , Taubert Helge 
Published: June 2009

AbstractPancreatic cancer is the eighth most common cancer and has an overall 5‐year survival rate lower than 10%. Because of their ability to regulate gene expression, microRNAs can act as oncogenes or tumor‐suppressor genes and so have garnered interest as possible prognostic and therapeutic markers during the last decade. However, the prognostic value of microRNA expression in pancreatic cancer has not been thoroughly investigated. We measured the levels of miR‐155, miR‐203, miR‐210, miR‐216, miR‐217 and miR‐222 by quantitative RT‐PCR in a cohort of 56 microdissected pancreatic ductal adenocarcinomas (PDAC). These microRNAs were chosen as they had previously been shown to be differentially expressed in pancreatic tumors compared to normal tissues. The possible association of microRNA expression and patients' survival was examined using multivariate Cox's regression hazard analyses. Interestingly, significant correlations between elevated microRNA expression and overall survival were observed for miR‐155 (RR = 2.50; p = 0.005), miR‐203 (RR = 2.21; p = 0.017), miR‐210 (RR = 2.48; p = 0.005) and miR‐222 (RR = 2.05; p = 0.035). Furthermore, tumors from patients demonstrating elevated expression levels of all 4 microRNAs possessed a 6.2‐fold increased risk of tumor‐related death compared to patients whose tumors showed a lower expression of these microRNAs. This study provides the first evidence for an oncogenic activity of miR‐155, miR‐203, miR‐210 and miR‐222 in the development of pancreatic cancer as has been reported for other tumor types. Furthermore, the putative target genes for these microRNAs suggest a complex signaling network that can affect PDAC tumorigenesis and tumor progression.
Timp‐2 binding with cellular MT1‐MMP stimulates invasion‐promoting MEK/ERK signaling in cancer cells
Authors: Sounni Nor Eddine , Rozanov Dmitri V. , Remacle Albert G. , Golubkov Vladislav S. , Noel Agnes , Strongin Alex Y. 
Published: June 2009

AbstractBoth invasion‐promoting MT1‐MMP and its physiological inhibitorTIMP‐2 play a significant role in tumorigenesis and are identified in the most aggressive cancers. Despite its antiproteolytic effects in vitro, clinical data suggest that TIMP‐2 expression is positively associated with tumor recurrence, thus emphasizing the wide‐ranging role of TIMP‐2 in malignancies. To shed light on this role of TIMP‐2, we report that low concentrations of TIMP‐2, by interacting with MT1‐MMP (a specific membrane receptor of TIMP‐2), induce the MEK/ERK signaling cascade in fibrosarcoma HT1080 cells which express MT1‐MMP naturally. TIMP‐2 binding with cell surface‐associated MT1‐MMP stimulates phosphorylation of MEK1/2, which is upstream of ERK1/2, and the ERK1/2 substrate p90RSK. Consistent with volumes of literature, we confirmed that the activation of ERK stimulated cell migration. Both the transcriptional silencing of MT1‐MMP and the inhibition of MEK1/2 reversed the signaling effects of TIMP‐2/MT1‐MMP while the active site‐targeting MMP inhibitor GM6001 did not. Our data suggest that both the interactions of TIMP‐2 with MT1‐MMP, which activate the pro‐migratory ERK signaling cascade,and the conventional inhibition of MT1‐MMP's catalytic activity by TIMP‐2, play a role in the invasion‐promoting function of MT1‐MMP. The TIMP‐2‐induced stimulation of ERK signaling in cancer cells explains the direct, as opposed to the inverse, association of TIMP‐2 expression with poor prognosis in cancer.
Hexabromocyclododecane decreases the lytic function and ATP levels of human natural killer cells
Authors: Hinkson Natasha C. , Whalen Margaret M. 
Published: June 2009

AbstractThis study investigates the effect of hexabromocyclododecane (HBCD) on the lytic function of human natural killer (NK) cells and on ATP levels in NK cells. NK cells are capable of lysing tumor cells, virally infected cells, and antibody‐coated cells. HBCD is a brominated cyclic alkane used primarily as an additive flame retardant. If HBCD interferes with NK cell function, this could increase risk of tumor development and/or viral infection. NK cells were exposed to various concentrations of HBCD for 24 and 48 h and 6 days before determining lytic function and ATP levels. ATP levels and lytic function were also determined in NK cells that were exposed to HBCD for 1 h followed by 24 and 48 h, and 6 days in HBCD‐free media. The results indicated that exposure of NK cells to 10 µm HBCD for 24 h causes a very significant decrease in both NK cell lytic function and ATP levels (93.5 and 90.5%, respectively). Exposure of NK cells to 10 µm HBCD for 1 h followed by 24 h in HBCD‐free media showed a progressive and persistent loss of lytic function (89.3%) as well as a decrease in ATP levels (46.1%). The results indicate that HBCD exposures decreased lytic function as well as ATP levels. However, a decrease in lytic function was not necessarily accompanied by a similar decrease in ATP. Importantly, these results also indicate that a brief (1 h) exposure to HBCD causes a progressive loss of lytic function over a 6 day period. Copyright © 2009 John Wiley & Sons, Ltd.
AM–FM techniques in the analysis of optical coherence tomography signals
Authors: Pitris Costas , Kartakoullis Andreas , Bousi Evgenia 
Published: June 2009

AbstractThe subtle tissue changes associated with the early stages of malignancies, such as cancer, are not clearly discernible even at the current, improved, resolution of optical coherence tomography (OCT) systems. However, these changes directly affect the spectral content of the OCT image that contains information regarding these unresolvable features. Spectral analysis of OCT signals has recently been shown to provide additional information, resulting in improved contrast, directly related to scatterer size changes. Amplitude modulation–frequency modulation (AM–FM) analysis, a fast and accurate technique for the estimation of the instantaneous frequency, phase, and amplitude of a signal, can also be applied to OCT images to extract scatterer‐size information. The proposed technique could make available an extremely valuable tool for the investigation of disease characteristics that now remain below the resolution of OCT and could significantly improve the technology's diagnostic capabilities. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Successful weaning after plasma exchange for polyneuropathy related to POEMS syndrome
Authors: Wu Shang‐Gin , Kuo Ping‐Hung , Yang Pan‐Chyr 
Published: June 2009

AbstractRespiratory failure due to polyneuropathy associated with POEMS syndrome (Polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) is unusual. In this report, we describe a 47‐year‐old male patient with polyneuropathy related to POEMS syndrome who suffered from hypercapnic respiratory failure due to progressive weakness of the respiratory muscles. His respiratory muscle strength significantly improved after plasma exchange and was extubated successfully. To our knowledge, this is the first case of POEMS syndrome with aggressive polyneuropathy that was successful treated by plasma exchange and our experience provides insight regarding the optimal management of such patients. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.