bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signaling pathways mediating a selective induction of nitric oxide synthase II by tumor necrosis factor alpha in nerve growth factor-responsive cells
Authors: Thomas Michael S , Zhang WenRu , Jordan Paivi M , Saragovi H Uri , Taglialatela Giulio 
Published: September 2005

AbstractBackgroundInflammation and oxidative stress play a critical role in neurodegeneration associated with acute and chronic insults of the nervous system. Notably, affected neurons are often responsive to and dependent on trophic factors such as nerve growth factor (NGF). We previously showed in NGF-responsive PC12 cells that tumor necrosis factor alpha (TNFα) and NGF synergistically induce the expression of the free-radical producing enzyme inducible nitric oxide synthase (iNOS). We proposed that NGF-responsive neurons might be selectively exposed to iNOS-mediated oxidative damage as a consequence of elevated TNFα levels. With the aim of identifying possible therapeutic targets, in the present study we investigated the signaling pathways involved in NGF/TNFα-promoted iNOS induction.MethodsWestern blotting, RT-PCR, transcription factor-specific reporter gene systems, mutant cells lacking the low affinity p75NTR NGF receptor and transfections of TNFα/NGF chimeric receptors were used to investigate signalling events associated with NGF/TNFα-promoted iNOS induction in PC12 cells.ResultsOur results show that iNOS expression resulting from NGF/TNFα combined treatment can be elicited in PC12 cells. Mutant PC12 cells lacking p75NTR did not respond, suggesting that p75NTR is required to mediate iNOS expression. Furthermore, cells transfected with chimeric TNFα/NGF receptors demonstrated that the simultaneous presence of both p75NTR and TrkA signaling is necessary to synergize with TNFα to mediate iNOS expression. Lastly, our data show that NGF/TNFα-promoted iNOS induction requires activation of the transcription factor nuclear factor kappa B (NF-κB).ConclusionCollectively, ourin vitromodel suggests that cells bearing both the high and low affinity NGF receptors may display increased sensitivity to TNFα in terms of iNOS expression and therefore be selectively at risk during acute (e.g. neurotrauma) or chronic (e.g. neurodegenerative diseases) conditions where high levels of pro-inflammatory cytokines in the nervous system occur pathologically. Our results also suggest that modulation of NFκB-promoted transcription of selective genes could serve as a potential therapeutic target to prevent neuroinflammation-induced neuronal damage.
Hepatitis B virus X protein interacts with β5 subunit of heterotrimeric guanine nucleotide binding protein
Authors: Lwa Siew Hui , Chen Wei Ning 
Published: August 2005

Abstract

Background
To isolate cellular proteins interacting with hepatitis B virus X protein (HBX), from HepG2 cells infected with hepatitis B virus (HBV).

Results
HBV particles were produced in culture medium of HepG2 cells transfected with the mammalian expression vector containing the linear HBV genome, as assessed by commercially available ELISA assay. A cDNA library was made from these cells exposed to HBV. From yeast two hybrid screening with HBX as bait, human guanine nucleotide binding protein β subunit 5L (GNβ5) was isolated from the cDNA library constructed in this study as a new HBX-interacting protein. The HBX-GNβ5 interaction was further supported by mammalian two hybrid assay.

Conclusion
The use of a cDNA library constructed from HBV-transfected HepG2 cells has resulted in the isolation of new cellular proteins interacting with HBX.
L2L: a simple tool for discovering the hidden significance in microarray expression data
Authors: Newman John C , Weiner Alan M 
Published: August 2005

AbstractL2L is a database consisting of lists of differentially expressed genes compiled from published mammalian microarray studies, along with an easy-to-use application for mining the database with the user's own microarray data. As illustrated by re-analysis of a recent study of diabetic nephropathy, L2L identifies novel biological patterns in microarray data, providing insights into the underlying nature of biological processes and disease. L2L is available online at the authors' website [http://depts.washington.edu/l2l/].
Copying clinic letters to psychiatric patients
Authors: Tahir Tayyeb A. , Bisson Jonathan I. , Wilcox Jodie 
Published: August 2005

Aims and MethodTo assess the views of patients and mental health professionals on the practice of copying clinical letters to patients. Patients and professionals from local community mental health teams were asked to complete a questionnaire regarding their views.ResultsThe questionnaires were completed by 51 patients and 40 mental health professionals. Significantly more patients (83%) than staff (37%) thought that copying letters to patients was a good idea (OR=14.56, 95% CI 4.674 –45.158). Many staff appeared concerned that copying letters to patients could result in breakdown of the therapeutic relationship, causing distress and anxiety.Clinical ImplicationsConsiderable work is needed for clinicians to feel comfortable in copying letters to patients. The creation of working groups, including users, carers, managers and clinicians working in the field of mental health, would facilitate the development of guidelines for this practice.
High Rate of Durable Remissions After Treatment of Newly Diagnosed Aggressive Mantle-Cell Lymphoma With Rituximab Plus Hyper-CVAD Alternating With Rituximab Plus High-Dose Methotrexate and Cytarabine
Authors: Romaguera Jorge E. , Fayad Luis , Rodriguez Maria A. , Broglio Kristine R. , Hagemeister Frederick B. , Pro Barbara , McLaughlin Peter , Younes Anas , Samaniego Felipe , Goy Andre , Sarris Andreas H. , Dang Nam H. , Wang Michael , Beasley Virginia , Medeiros L. Jeffrey , Katz Ruth L. , Gagneja Harish , Samuels Barry I. , Smith Terry L. , Cabanillas Fernando F. 
Published: September 2005

Purpose To determine the response, failure-free survival (FFS), and overall survival rates and toxicity of rituximab plus an intense chemotherapy regimen in patients with previously untreated aggressive mantle-cell lymphoma (MCL). Patients and Methods This was a prospective phase II trial of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD; considered one cycle) alternating every 21 days with rituximab plus high-dose methotrexate-cytarabine (considered one cycle) for a total of six to eight cycles. Results Of 97 assessable patients, 97% responded, and 87% achieved a complete response (CR) or unconfirmed CR. With a median follow-up time of 40 months, the 3-year FFS and overall survival rates were 64% and 82%, respectively, without a plateau in the curves. For the subgroup of patients ≤ 65 years of age, the 3-year FFS rate was 73%. The principal toxicity was hematologic. Five patients died from acute toxicity. Four patients developed treatment-related myelodysplasia/acute myelogenous leukemia, and three patients died while in remission from MCL. A total of eight treatment-related deaths (8%) occurred. Conclusion Rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine is effective in untreated aggressive MCL. Toxicity is significant but expected. Because of the shorter FFS concurrent with significant toxicity in patients more than 65 years of age, this regimen is not recommended as standard therapy for this age subgroup. Larger prospective randomized studies are needed to define the role of this regimen in the treatment of MCL patients compared with existing and new treatment modalities.
Is Leptin a Mediator of Adverse Prognostic Effects of Obesity in Breast Cancer?
Authors: Goodwin Pamela J. , Ennis Marguerite , Fantus I. George , Pritchard Kathleen I. , Trudeau Maureen E. , Koo Jarley , Hood Nicky 
Published: August 2005

Purpose Leptin, an adipocyte-derived cytokine that is elevated in obesity, has been associated with carcinogenesis, tumor migration and invasion, enhancement of angiogenesis, and increased aromatase activity. It has been suggested that leptin may mediate adverse prognostic effects of obesity in breast cancer. Patients and Methods Four hundred seventy-one women with surgically resected T1-3, N0-1, M0 breast cancer were studied. Leptin was assayed in stored fasting blood specimens obtained before adjuvant therapy. Women were followed prospectively for distant disease-free survival (DDFS) and overall survival (OS). Results Patients ranged from 26 to 74 years of age, and staging was as follows: T1 = 262, T2 = 151, T3 = 23, TX = 35, N0 = 323, and N1 = 148. Estrogen receptor was positive in 286 patients, and progesterone receptor was positive in 259 patients. One hundred forty-five patients received adjuvant chemotherapy, 146 received adjuvant tamoxifen, 46 received both, and 134 received neither. Mean leptin was 15.2 ± 10.1 ng/mL. Univariately, leptin was associated with OS (overall P = .049; P = .014 postmenopausal). Leptin was not associated with DDFS overall or in any menopausal subgroup (P ≥ .19). In multivariate Cox modeling, leptin was not significantly associated with DDFS or OS (P = .11 and 0.075, respectively). Adjustment for insulin or body mass index further reduced the association of leptin with outcome. Conclusion Although leptin is strongly correlated with obesity and insulin, we could not show that it is independently associated with prognosis in early-stage breast cancer. Because we cannot rule out modest prognostic effects, we recommend additional research to explore this potential association, particularly in postmenopausal women.
Occurrence of Second Cancers in Patients Treated With Radiotherapy for Rectal Cancer
Authors: Birgisson Helgi , Påhlman Lars , Gunnarsson Ulf , Glimelius Bengt 
Published: August 2005

Purpose To analyze the occurrence of second cancers in patients with rectal cancer treated with external radiotherapy (RT) in addition to surgery. Patients and Methods The analyses were based on the Uppsala Trial (completed in 1985), with patients randomly assigned to preoperative RT to all stages or postoperative RT for stage II and III cancers, and the Swedish Rectal Cancer Trial (completed in 1990), with patients randomly assigned to preoperative RT or surgery alone. Patients from the trials were matched against the Swedish Cancer Registry. Results A total of 115 (7%) of the 1,599 patients developed 122 second cancers. More patients treated with RT developed a second cancer (relative risk [RR], 1.85; 95% CI, 1.23 to 2.78). A significant increased risk for second cancers in the RT group was seen in organs within or adjacent to the irradiated volume (RR, 2.04; 95% CI, 1.10 to 3.79) but not outside the irradiated volume (RR, 1.78; 95% CI, 0.97 to 3.27). For the Swedish Rectal Cancer Trial, 20.3% of the RT patients got either a local recurrence or a second cancer, compared with 30.7% of the non-RT patients (RR, 0.55; 95% CI, 0.44 to 0.70). Conclusion An increased risk of second cancers was found in patients treated with RT in addition to surgery for a rectal cancer, which was mainly explained by an increase in the risk of second cancers in organs within or adjacent to the irradiated volume. However, a favorable effect of radiation seemed to dominate, as shown by the reduced risk of the sum of local recurrences and second cancers.
Randomized Trial Comparing Two Fractionation Schedules for Patients With Localized Prostate Cancer
Authors: Lukka Himu , Hayter Charles , Julian Jim A. , Warde Padraig , Morris W. James , Gospodarowicz Mary , Levine Mark , Sathya Jinka , Choo Richard , Prichard Hugh , Brundage Michael , Kwan Winkle 
Published: August 2005

Purpose The optimal radiation dose fractionation schedule for localized prostate cancer is unclear. This study was designed to compare two dose fractionation schemes (a shorter 4-week radiation schedule v a longer 6.5-week schedule). Patients and Methods Patients with early-stage (T1 or T2) prostate cancer were randomly assigned to 66 Gy in 33 fractions over 45 days (long arm) or 52.5 Gy in 20 fractions over 28 days (short arm). The study was designed as a noninferiority investigation with a predefined tolerance of −7.5%. The primary outcome was a composite of biochemical or clinical failure (BCF). Secondary outcomes included presence of tumor on prostate biopsy at 2 years, survival, and toxicity. Results From March 1995 to December 1998, 936 men were randomly assigned to treatment; 470 were assigned to the long arm, and 466 were assigned to the short arm. The median follow-up time was 5.7 years. At 5 years, the BCF probability was 52.95% in the long arm and 59.95% in the short arm (difference = −7.0%; 90% CI, −12.6% to −1.4%), favoring the long arm. No difference in 2-year postradiotherapy biopsy or in overall survival was detected between the arms. Acute toxicity was found to be slightly higher in the short arm (11.4%) compared with the long arm (7%; difference = −4.4%; 95% CI, −8.1% to −0.6%); however, late toxicity was similarly low in both arms (3.2%). Conclusion Given the results, we cannot exclude the possibility that the chosen hypofractionated radiation regimen may be inferior to the standard regimen. Further evaluation involving higher dose hypofractionated radiation regimens in contemporary radiation settings is necessary.
Incidence and Prognostic Impact of Amenorrhea During Adjuvant Therapy in High-Risk Premenopausal Breast Cancer: Analysis of a National Cancer Institute of Canada Clinical Trials Group Study—NCIC CTG MA.5
Authors: Parulekar Wendy R. , Day Andrew G. , Ottaway Jon A. , Shepherd Lois E. , Trudeau Maureen E. , Bramwell Vivien , Levine Mark , Pritchard Kathleen I. 
Published: August 2005

Purpose To investigate the therapeutic impact of chemotherapy-induced amenorrhea in premenopausal patients with breast cancer. Patients and Methods We conducted a retrospective cohort study of a National Cancer Institute of Canada Clinical Trials Group phase III trial involving premenopausal patients randomized to receive cyclophosphamide, methotrexate, and fluorouracil (CMF), versus intensive cyclophosphamide, epirubicin, and fluorouracil (CEF). The objectives of our study were to describe the incidence of amenorrhea at 6 and 12 months post-random assignment and to determine the association of amenorrhea with relapse-free and overall survival. Results Data on 442 patients were used in our analyses. Despite the higher cumulative dose of cyclophosphamide in the CMF treatment arm, at 6 months post–random assignment, the rate of amenorrhea was higher in the CEF group (relative risk, 1.2; 95% CI, 1.0 to 1.3), with no difference at 12 months. In the receptor-positive subgroup, 6-month amenorrhea rates were not associated with prognosis. In contrast, amenorrhea at 12 months was significantly associated with relapse-free survival (hazard ratio, 0.51; 95% CI, 0.32 to 0.82; P = .005) and overall survival (hazard ratio, 0.40; 95% CI, 0.22 to 0.72; P = .002). Conclusion Late chemotherapy-induced amenorrhea seems to be associated with improved outcome in patients with premenopausal, receptor-positive breast cancer.
Phase II Multicenter Study of Induction Chemotherapy Followed by Concurrent Efaproxiral (RSR13) and Thoracic Radiotherapy for Patients With Locally Advanced Non–Small-Cell Lung Cancer
Authors: Choy Hak , Nabid Abdenour , Stea Baldassarre , Scott Charles , Roa Wilson , Kleinberg Larry , Ayoub Joseph , Smith Colum , Souhami Luis , Hamburg Solomon , Spanos William , Kreisman Harvey , Boyd Adam P. , Cagnoni Pablo J. , Curran Walter J. 
Published: August 2005

Purpose Efaproxiral (RSR13) reduces hemoglobin oxygen–binding affinity, facilitates oxygen release, and increases tissue pO2. We conducted a phase II multicenter study that assessed the efficacy and safety of efaproxiral when administered with thoracic radiation therapy (TRT), following induction chemotherapy, for treatment of locally advanced non–small-cell lung cancer (NSCLC). Patients and Methods Fifty-one patients with locally advanced NSCLC were enrolled at 13 sites. Treatment comprised two cycles of paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6), 3 weeks apart, followed by TRT (64 Gy/32 fractions) with concurrent efaproxiral (50 to 100 mg/kg). Survival results were compared with results of study Radiation Therapy Oncology Group (RTOG) 94-10. Results Overall response rate was 75% (37 of 49 patients). Complete and partial response rates were 6% (three of 49 patients) and 69% (34 of 49 patients), respectively. Median survival time (MST) was 20.6 months (95% CI, 14.0 to 24.2); overall survival rates at 1- and 2-years were 67% and 37%, respectively. Survival results were compared with the sequential (S-CRT) and concurrent (C-CRT) chemoradiotherapy arms of RTOG 94-10. MSTs for cases matched by stage, Karnofsky performance status, and age were: RT-010, 20.6 months; S-CRT, 15.1 months; and C-CRT, 17.9 months. Grade 3 to 4 toxicities related to efaproxiral that occurred in more than one patient included transient hypoxemia (19%), radiation pneumonitis (11%), and fatigue (4%). Conclusion Addition of efaproxiral to S-CRT represents a promising approach in NSCLC treatment, and a randomized study should be pursued. The low incidence of grade 3 to 4 toxicities suggests that the use of efaproxiral instead of a cytotoxic agent, as a radiation sensitizer, may be advantageous.
Multicenter Phase II Trial of ABI-007, an Albumin-Bound Paclitaxel, in Women With Metastatic Breast Cancer
Authors: Ibrahim Nuhad K. , Samuels Brian , Page Ray , Doval Dinesh , Patel Kirtikumar M. , Rao S.C. , Nair Madhavan Krishnan , Bhar Paul , Desai Neil , Hortobagyi Gabriel N. 
Published: August 2005

Purpose ABI-007 is a novel nanoparticle, albumin-bound paclitaxel that is free of solvents. This multicenter phase II study was designed to evaluate the efficacy and safety of ABI-007 for the treatment of metastatic breast cancer (MBC). Patients and Methods Sixty-three women with histologically confirmed and measurable MBC received 300 mg/m2 ABI-007 by intravenous infusion over 30 minutes every 3 weeks without premedication. Forty-eight patients received prior chemotherapy; 39 patients received no prior treatment for metastatic disease. Results Overall response rates (complete or partial responses) were 48% (95% CI, 35.3% to 60.0%) for all patients. For patients who received ABI-007 as first-line and greater than first-line therapy for their metastatic disease, the respective response rates were 64% (95% CI, 49.0% to 79.2%) and 21% (95% CI, 7.1% to 42.1%). Median time to disease progression was 26.6 weeks, and median survival was 63.6 weeks. No severe hypersensitivity reactions were reported despite the lack of premedication. Toxicities observed were typical of paclitaxel and included grade 4 neutropenia (24%), grade 3 sensory neuropathy (11%), and grade 4 febrile neutropenia (5%). Patients received a median of six treatment cycles; 16 patients had 25% dose reductions because of toxicities, and two of these patients had subsequent dose reductions. Conclusion ABI-007, the first biologically interactive albumin-bound form of paclitaxel in the nanoparticle state, uses the natural carrier albumin rather than synthetic solvents to deliver paclitaxel and allows for safe administration of high paclitaxel doses without premedication, resulting in significant antitumor activity in patients with MBC, including those receiving the drug as first-line therapy.
Outcome Analysis for Patients With Elevated Serum Tumor Markers at Postchemotherapy Retroperitoneal Lymph Node Dissection
Authors: Beck Stephen D.W. , Foster Richard S. , Bihrle Richard , Einhorn Lawrence H. , Donohue John P. 
Published: August 2005

PurposeTo evaluate the therapeutic benefit of postchemotherapy retroperitoneal lymph node dissection (PCRPLND) in patients with persistently elevated serum tumor markers.Patients and MethodsOne hundred fourteen patients with metastatic germ cell cancer with elevated serum tumor markers after first-line (50 patients) or second-line chemotherapy (64 patients) who underwent PCRPLND between 1977 and 2000 with a minimum follow-up of 2-years were included in this retrospective study.ResultsThe 5-year overall survival was 53.9%. Sixty-one patients (53.5%) are alive with a medium follow-up of 72 months. Fifty-three patients died of disease, with a medium time to death of 8.0 months. Mean preoperative serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (βHCG) levels were 483 ng/mL and 555 mU/mL, respectively, with no difference in 5-year survival (P = .2). Retroperitoneal pathology revealed germ cell cancer in 53.5% of patients, teratoma in 34.2% of patients, and fibrosis in 12.2% of patients, with 5-year survival rates of 31.4%, 77.5%, and 85.7%, respectively (P < .0001). Predictors of retroperitoneal pathology included an increasing serum AFP or βHCG, βHCG more than 100 ng/mL, redo retroperitoneal lymph node dissection (RPLND), and second-line chemotherapy. Poor prognostic variables by multivariable analysis included βHCG status, serum AFP level, redo RPLND, and germ cell cancer in the resected specimen.ConclusionA subset of patients with elevated serum tumor markers after chemotherapy is curable with surgery. The prognostic factors predictive of outcome in this analysis include an increasing βHCG, serum AFP level, redo RPLND, and germ cell cancer in the resected specimen. These factors, along with clinical and surgical experience, should aid in determining the appropriate integration of surgery and chemotherapy in this population.
Randomized Study on the Efficacy of Cognitive-Behavioral Therapy for Insomnia Secondary to Breast Cancer, Part II: Immunologic Effects
Authors: Savard Josée , Simard Sébastien , Ivers Hans , Morin Charles M. 
Published: August 2005

PurposeCross-sectional studies suggest that clinical insomnia is associated with immune downregulation. However, there is a definite need for experimental studies on this question. The goal of this randomized controlled study was to assess the effect of an 8-week cognitive-behavioral therapy (CBT) for chronic insomnia on immune functioning of breast cancer survivors. Previous analyses of this study showed that CBT was associated with improved sleep and quality of life, and reduced psychological distress.Patients and MethodsFifty-seven women with chronic insomnia secondary to breast cancer were randomly assigned to CBT (n = 27) or to a waiting-list control condition (WLC; n = 30). Peripheral-blood samples were taken at baseline and post-treatment (and postwaiting for WLC patients), as well as at 3-, 6-, and 12-month follow-up for immune measures, including enumeration of blood cell counts (ie, WBCs, monocytes, lymphocytes, CD3+, CD4+, CD8+, and CD16+/CD56+) and cytokine production (ie, interleukin-1-beta [IL-1β] and interferon gamma [IFN-γ]).ResultsPatients treated with CBT had higher secretion of IFN-γ and lower increase of lymphocytes at post-treatment compared with control patients. Pooled data from both treated groups indicated significantly increased levels of IFN-γ and IL-1β from pre- to post-treatment. In addition, significant changes in WBCs, lymphocytes, and IFN-γ were found at follow-up compared with post-treatment.ConclusionThis study provides some support to the hypothesis of a causal relationship between clinical insomnia and immune functioning. Future studies are needed to investigate the clinical impact of such immune alterations.