bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characteristics of microRNAs from Bombyx mori
Authors: He Ping-an , Nie Zuoming , Chen Jianqing , Chen Jian , Lv Zhengbing , Sheng Qing , Zhou Songping , Gao Xiaolian , Kong Lingyin , Wu Xiangfu , Jin Yongfeng , Zhang Yaozhou 
Published: May 2008

Abstract

Background
MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression by targeting messenger RNAs (mRNAs) and causing mRNA cleavage or translation blockage. Of the 355 Arthropod miRNAs that have been identified, only 21 are B. mori miRNAs that were predicted computationally; of these, only let-7 has been confirmed by Northern blotting.

Results
Combining a computational method based on sequence homology searches with experimental identification based on microarray assays and Northern blotting, we identified 46 miRNAs, an additional 21 plausible miRNAs, and a novel small RNA in B. mori. The latter, bmo-miR-100-like, was identified using the known miRNA aga-miR-100 as a probe; bmo-miR-100-like was detected by microarray assay and Northern blotting, but its precursor sequences did not fold into a hairpin structure. Among these identified miRNAs, we found 12 pairs of miRNAs and miRNA*s. Northern blotting revealed that some B. mori miRNA genes were expressed only during specific stages, indicating that B. mori miRNA genes (e.g., bmo-miR-277) have developmentally regulated patterns of expression. We identified two miRNA gene clusters in the B. mori genome. bmo-miR-2b, which is found in the gene cluster bmo-miR-2a-1/bmo-miR-2a-1*/bmo-miR-2a-2/bmo-miR-2b/bmo-miR-13a*/bmo-miR-13b, encodes a newly identified member of the mir-2 family. Moreover, we found that methylation can increase the sensitivity of a DNA probe used to detect a miRNA by Northern blotting. Functional analysis revealed that 11 miRNAs may regulate 13 B. mori orthologs of the 25 known Drosophila miRNA-targeted genes according to the functional conservation. We predicted the binding sites on the 1671 3'UTR of B. mori genes; 547 targeted genes, including 986 target sites, were predicted. Of these target sites, 338 had perfect base pairing to the seed region of 43 miRNAs. From the predicted genes, 61 genes, each of them with multiple predicted target sites, should be considered excellent candidates for future functional studies. Biological classification of predicted miRNA targets showed that "binding", "catalytic activity" and "physiological process" were over-represented for the predicted genes.

Conclusion
Combining computational predictions with microarray assays, we identified 46 B. mori miRNAs, 13 of which were miRNA*s. We identified a novel small RNA and 21 plausible B. mori miRNAs that could not be located in the available B. mori genome, but which could be detected by microarray. Thirteen and 547 target genes were predicted according to the functional conservation and binding sites, respectively. Identification of miRNAs in B. mori, particularly those that are developmentally regulated, provides a foundation for subsequent functional studies.
Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker
Authors: Keam Bhumsuk , Im Seock-Ah , Han Sae-Won , Ham Hye Seon , Kim Min A , Oh Do-Youn , Lee Se-Hoon , Kim Jee Hyun , Kim Dong-Wan , Kim Tae-You , Heo Dae Seog , Kim Woo Ho , Bang Yung-Jue 
Published: May 2008

Abstract

Background
The objective of this study was to evaluate the efficacy and toxicity of infusional 5-fluorouracil (5-FU), folinic acid and oxaliplatin (modified FOLFOX-6) in patients with advanced gastric cancer (AGC), as first-line palliative combination chemotherapy. We also analyzed the predictive or prognostic value of germline polymorphisms of candidate genes associated with 5-FU and oxaliplatin.

Methods
Seventy-three patients were administered a 2 hour infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2) followed by a 46 hour continuous infusion of 5-FU (2,400 mg/m2). Genomic DNA from the patients' peripheral blood mononuclear cells was extracted. Ten polymorphisms within five genes were investigated including TS, GSTP, ERCC, XPD and XRCC.

Results
The overall response rate (RR) was 43.8%. Median time to progression (TTP) and overall survival (OS) were 6.0 months and 12.6 months, respectively. Toxicities were generally tolerable and manageable. The RR was significantly higher in patients with a 6-bp deletion homozygote (-6 bp/-6 bp) in TS-3'UTR (55.0% vs. 30.3% in +6 bp/+6 bp or +6 bp/-6 bp, p = 0.034), and C/A or A/A in XPD156 (52.0% vs. 26.1% in C/C, p = 0.038). The -6 bp/-6 bp in TS-3'UTR was significantly associated with a prolonged TTP and OS. In a multivariate analysis, the 6-bp deletion in TS-3'UTR was identified as an independent prognostic marker of TTP (hazard ratio = 0.561, p = 0.032).

Conclusion
Modified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients. The 6-bp deletion in TS-3'UTR might be a candidate to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial.
Androgen receptor expresion in breast cancer: Relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors
Authors: Gonzalez Luis O , Corte Maria D , Vazquez Julio , Junquera Sara , Sanchez Rosario , Alvarez Ana C , Rodriguez Juan C , Lamelas Maria L , Vizoso Francisco J 
Published: May 2008

AbstractBackgroundIn the present study we analyze, in patients with breast cancer, the tumor expression of androgen receptors (AR), its relationship with clinicopathological characteristics and with the expression of several matrix metalloproteases (MMPs) and their inhibitors (TIMPs), as well as with prognosis.MethodsAn immunohistochemical study was performed using tissue microarrays and specific antibodies against AR, MMPs -1, -2, -7, -9, -11, -13, -14, and TIMPs -1, -2 and -3. More than 2,800 determinations on tumor specimens from 111 patients with primary invasive ductal carcinoma of the breast (52 with axillary lymph node metastases and 59 without them) and controls were performed. Staining results were categorized using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically.ResultsA total of 83 cases (74.8%) showed a positive immunostaining for AR, but with a wide variation in the staining score values. There were no significant associations between the total immunostaining scores for AR and any clinicopathological parameters. However, score values for MMP-1, -7 and -13, were significantly higher in AR-positive tumors than in AR-negative tumors. Likewise, when we considered the cellular type expressing each factor, we found that AR-positive tumors had a higher percentage of cases positive for MMP-1, -7, -11, and TIMP-2 in their malignant cells, as well as for MMP-1 in intratumoral fibroblasts. On the other hand, multivariate analysis demonstrated that patients with AR-positive tumors have a significant longer overall survival than those with AR-negative breast carcinomas (p= 0.03).ConclusionOur results confirm that AR are commonly expressed in breast cancer, and are correlated with the expression of some MMPs and TIMP-2. Although we found a specific value of AR expression to be a prognostic indicator in breast cancer, the functional role of AR in these neoplasms is still unclear and further data are needed in order to clarify their biological signification in breast cancer.
SOCS3 inhibiting migration of A549 cells correlates with PYK2 signaling in vitro
Authors: Zhang Siyang , Guo Dawei , Jiang Lili , Zhang Qingfu , Qiu Xueshan , Wang Enhua 
Published: May 2008

Abstract

Background
Suppressor of cytokine signaling 3 (SOCS3) is considered to inhibit cytokine responses and play a negative role in migration of various cells. Proline-rich tyrosine kinase 2 (PYK2) is a non-receptor kinase and has been found crucial to cell motility. However, little is known about whether SOCS3 could regulate PYK2 pro-migratory function in lung cancer.

Methods
The methylation status of SOCS3 was investigated in HBE and A549 cell lines by methylation-specific PCR. A549 cells were either treated with a demethylation agent 5-aza-2'-deoxycytidine or transfected with three SOCS3 mutants with various functional domains deleted. Besides, cells were pretreated with a proteasome inhibitor β-lactacystin where indicated. The effects of SOCS3 up-regulation on PYK2 expression, PYK2 and ERK1/2 phosphorylations were assessed by western blot using indicated antibodies. RT-PCR was used to estimate PYK2 mRNA levels. Transwell experiments were performed to evaluate cell migration.

Results
SOCS3 expression was found impaired in A549 cells and higher PYK2 activity was correlated with enhanced cell migration. We identified that SOCS3 was aberrantly methylated in the exon 2, and 5-aza-2'-deoxycytidine restored SOCS3 expression. Reactivation of SOCS3 attenuated PYK2 expression and phosphorylation, cell migration was inhibited as well. Transfection studies indicated that exogenous SOCS3 interacted with PYK2, and both the Src homology 2 (SH2) and the kinase inhibitory region (KIR) domains of SOCS3 contributed to PYK2 binding. Furthermore, SOCS3 was found to inhibit PYK2-associated ERK1/2 activity in A549 cells. SOCS3 possibly promoted degradation of PYK2 in a SOCS-box-dependent manner and interfered with PYK2-related signaling events, such as cell migration.

Conclusion
These data indicate that SOCS3 negatively regulates cell motility and decreased SOCS3 induced by methylation may confer a migration advantage to A549 cells. These results also suggest a negative role of SOCS3 in PYK2 signaling, and a previously unidentified regulatory mechanism for PYK2 function.
Associations between physical activity and depressive symptoms in women
Authors: Teychenne Megan , Ball Kylie , Salmon Jo 
Published: May 2008

Abstract

Background
The high prevalence of depression in women is an increasing public health concern. Although studies have found associations between physical activity (PA) and depression, little is known about the optimal domain, dose and social context of PA for reducing the risk of depression. This study aimed to investigate associations between specific components of PA (domain, dose and social context) and odds of depressive symptoms in women.

Methods
The sample included 1,501 women, aged 18–65. Analyses were performed using cross-sectional data collected from a mail-out survey in 2004. The survey included self-report measures of PA behaviours and depressive symptoms. Crude and adjusted (age, marital status and physical health) odds ratios (OR) and 95% confidence intervals (CI) were calculated for each component of PA and odds of depressive symptoms using logistic regression analyses.

Results
Those who reported more than 3.5 hours leisure-time PA per week had lower odds of depressive symptoms when compared to those who undertook less than this. No other domains of PA (eg. work-related, transport-related or domestic activity) were associated with odds of depressive symptoms. Odds of depressive symptoms were lower among women who reported more than 1.5 hours of moderate-intensity (OR = 0.67, CI = 0.45–0.98) or more than 1.75 hours vigorous-intensity (OR = 0.60, CI = 0.42–0.84) leisure-time PA per week. Being discouraged to be active by others was associated with higher odds of depressive symptoms (OR = 2.28, CI = 1.00–5.16), whilst being active with a family member was associated with lower odds of depressive symptoms (OR = 0.61, CI = 0.43–0.87).

Conclusion
Acknowledging the cross-sectional design, these findings suggest that the domain and social context of PA may be more important for mental health among women than simply the total dose of PA.
Interactions of biotic and abiotic environmental factors in an ectomycorrhizal symbiosis, and the potential for selection mosaics
Authors: Piculell Bridget J , Hoeksema Jason D , Thompson John N 
Published: May 2008

Abstract

Background

Geographic selection mosaics, in which species exert different evolutionary impacts on each other in different environments, may drive diversification in coevolving species. We studied the potential for geographic selection mosaics in plant-mycorrhizal interactions by testing whether the interaction between bishop pine (Pinus muricata D. Don) and one of its common ectomycorrhizal fungi (Rhizopogon occidentalis Zeller and Dodge) varies in outcome, when different combinations of plant and fungal genotypes are tested under a range of different abiotic and biotic conditions.

Results

We used a 2 × 2 × 2 × 2 factorial experiment to test the main and interactive effects of plant lineage (two maternal seed families), fungal lineage (two spore collections), soil type (lab mix or field soil), and non-mycorrhizal microbes (with or without) on the performance of plants and fungi. Ecological outcomes, as assessed by plant and fungal performance, varied widely across experimental environments, including interactions between plant or fungal lineages and soil environmental factors.

Conclusion

These results show the potential for selection mosaics in plant-mycorrhizal interactions, and indicate that these interactions are likely to coevolve in different ways in different environments, even when initially the genotypes of the interacting species are the same across all environments. Hence, selection mosaics may be equally as effective as genetic differences among populations in driving divergent coevolution among populations of interacting species.
DREAM is reduced in synovial fibroblasts of patients with chronic arthritic pain: is it a suitable target for peripheral pain management?
Authors: Reisch Nataša , Engler Andrea , Aeschlimann André , Simmen Beat R , Michel Beat A , Gay Renate E , Gay Steffen , Sprott Haiko 
Published: May 2008

AbstractIntroductionThe endogenous pain-relieving system depends in part on the regulation of nociceptive signals through binding of opioids to the corresponding opioid receptor. Interfering with the trans-repression effect of downstream regulatory element antagonist modulator (DREAM) on the transcription of the opioid dynorphin-encoding prodynorphin (pdyn) gene might enhance pain relief in the periphery.MethodsExpression levels were measured in osteoarthritis (OA) synovial fibroblast-like cells (SFLCs) (n = 8) and in peripheral blood mononuclear cells (PBMCs) from OA patients (n = 53) and healthy controls (n = 26) by real-time polymerase chain reaction. Lysed OA SFLCs were analyzed by immunoprecipitation. Translation of DREAM mRNA was inhibited by small interfering RNAs (siRNAs). Expressions of DREAM,pdyn, andc-fosmRNAs were measured at 24, 48, and 72 hours after transfection.ResultsThe expression of DREAM mRNA was shown in both healthy and OA SFLCs as well as PBMCs. Inhibiting transcription using siRNAs led to a marked reduction in DREAM expression after 24, 48, and 72 hours. However, no significant changes inc-fosandpdynexpression occurred. In addition, DREAM mRNA expression was significantly reduced in OA patients with chronic pain (pain intensity as measured by a visual analog scale scale of greater than 40), but nopdynexpression was detectable.ConclusionTo our knowledge, this is the first report showing the expression of DREAM in SFLCs and PBMCs on the mRNA level. However, DREAM protein was not detectable. Since repression ofpdyntranscription persists after inhibiting DREAM translation, DREAM appears to play no functional role in the kappa opioid receptor system in OA SFLCs. Therefore, our data suggest that DREAM appears not to qualify as a target in peripheral pain management.
Racial Differences in Clinical Outcomes From Metastatic Breast Cancer: A Pooled Analysis of CALGB 9342 and 9840—Cancer and Leukemia Group B
Authors: Polite Blase N. , Cirrincione Constance , Fleming Gini F. , Berry Donald A. , Seidman Andrew , Muss Hyman , Norton Larry , Shapiro Charles , Bakri Kamal , Marcom Kelly , Lake Diana , Schwartz Joel H. , Hudis Clifford , Winer Eric P. 
Published: May 2008

Purpose African American women are more likely to be diagnosed with metastatic breast cancer at the time of presentation than whites, and have shorter survival once diagnosed. This study examines racial differences in clinical outcomes in the setting of two large cooperative group randomized clinical trials. Patients and Methods The study cohort consisted of 787 white (80%) and 195 African American (20%) patients with metastatic breast cancer enrolled in two successive Cancer and Leukemia Group B (CALGB) trials using taxanes in the metastatic setting. Differences in overall survival (OS), response incidence, and time to treatment failure (TTF) were examined by race. In addition, differences in the incidence of baseline and treatment-related toxicities were examined. Results With 779 deaths (166 African Americans and 613 whites), median OS was 14.3 months for African Americans and 18.75 months for whites (hazard ratio [HR] = 1.37; 95% CI, 1.15 to 1.63). When adjusted for prognostic factors, African Americans had a 24% increase in the hazard of death compared with whites (HR = 1.24; 95% CI, 1.02 to 1.51). No significant differences in TTF or overall response to therapy were seen. No clinically significant toxicity differences were seen. Conclusion African Americans with metastatic breast cancer have an increased hazard of death compared with whites despite the receipt of similar per-protocol treatment, but experience no differences in TTF or overall response to therapy. We hypothesize that more direct and robust measures of comorbidities, and perhaps other factors such as receipt of subsequent therapy could help further explain the observed survival difference.
Safety of Fertility Preservation by Ovarian Stimulation With Letrozole and Gonadotropins in Patients With Breast Cancer: A Prospective Controlled Study
Authors: Azim Amr A. , Costantini-Ferrando Maria , Oktay Kutluk 
Published: May 2008

Purpose Because of the accompanying increase in estrogen levels, safety of performing in vitro fertilization (IVF) in women with breast cancer is unknown. Our goal was to determine the effect of controlled ovarian stimulation (COS) using a combination of letrozole with standard fertility medications on disease-free survival in women undergoing embryo or oocyte cryopreservation before adjuvant chemotherapy. Patients and Methods A total of 215 women with breast cancer were prospectively evaluated for fertility preservation before adjuvant chemotherapy. Of those, 79 elected to undergo COS with letrozole and gonadotropins for embryo or oocyte cryopreservation. The remaining 136 patients underwent no fertility-preserving procedure and served as controls. Results Study and control groups were similar at enrollment except for a trend for higher estrogen-receptor positivity in the COS group (P = .08). Time between surgery and chemotherapy was longer for IVF patients (45.08 v 33.46 days; P < .01). Peak estradiol levels ranged from 58.4 to 1,166 pg/mL (mean, 405.94 ± 256.64 pg/mL or 1,486.76 ± 942.13 pmol/L) in COS patients. The median follow-up after chemotherapy was 23.4 months (range, 7.5 to 63.6 months) in the COS group and 33.05 months (range, 4.5 to 63.6) in the control group. The hazard ratio for recurrence after IVF was 0.56 (95% CI, 0.17 to 1.9), and the survival was not compromised compared with controls (P = .36). Conclusion Ovarian stimulation with gonadotropins and letrozole for the purpose of fertility preservation is unlikely to cause substantially increased recurrence risk. Further research, including longer-term follow-up is needed to confirm these findings.
Guidelines for the Management of Pediatric and Adult Tumor Lysis Syndrome: An Evidence-Based Review
Authors: Coiffier Bertrand , Altman Arnold , Pui Ching-Hon , Younes Anas , Cairo Mitchell S. 
Published: May 2008

Purpose Tumor lysis syndrome (TLS) has recently been subclassified into either laboratory TLS or clinical TLS, and a grading system has been established. Standardized guidelines, however, are needed to aid in the stratification of patients according to risk and to establish prophylaxis and treatment recommendations for patients at risk or with established TLS. Methods A panel of experts in pediatric and adult hematologic malignancies and TLS was assembled to develop recommendations and guidelines for TLS based on clinical evidence and standards of care. A review of relevant literature was also used. Results New guidelines are presented regarding the prevention and management of patients at risk of developing TLS. The best management of TLS is prevention. Prevention strategies include hydration and prophylactic rasburicase in high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk patients, and close monitoring for low-risk patients. Primary management of established TLS involves similar recommendations, with the addition of aggressive hydration and diuresis, plus allopurinol or rasburicase for hyperuricemia. Alkalinization is not recommended. Although guidelines for rasburicase use in adults are provided, this agent is currently only approved for use in pediatric patients in the United States. Conclusion The potential severity of complications resulting from TLS requires measures for prevention in high-risk patients and prompts treatment in the event that symptoms arise. Recognition of risk factors, monitoring of at-risk patients, and appropriate interventions are the key to preventing or managing TLS. These guidelines should assist in the prevention of TLS and improve the management of patients with established TLS.
Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non–Small-Cell Lung Cancer
Authors: Scagliotti Giorgio Vittorio , Parikh Purvish , von Pawel Joachim , Biesma Bonne , Vansteenkiste Johan , Manegold Christian , Serwatowski Piotr , Gatzemeier Ulrich , Digumarti Raghunadharao , Zukin Mauro , Lee Jin S. , Mellemgaard Anders , Park Keunchil , Patil Shehkar , Rolski Janusz , Goksel Tuncay , de Marinis Filippo , Simms Lorinda , Sugarman Katherine P. , Gandara David 
Published: May 2008

PurposeCisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non–small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting.Patients and MethodsThis noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2on day 1 and gemcitabine 1,250 mg/m2on days 1 and 8 (n = 863) or cisplatin 75 mg/m2and pemetrexed 500 mg/m2on day 1 (n = 862) every 3 weeks for up to six cycles.ResultsOverall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P ≤ .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common.ConclusionIn advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.