bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reintroduction of Oxaliplatin Is Associated With Improved Survival in Advanced Colorectal Cancer
Authors: de Gramont Aimery , Buyse Marc , Abrahantes Jose Cortinas , Burzykowski Tomasz , Quinaux Emmanuel , Cervantes Andres , Figer Arie , Lledo Gérard , Flesch Michel , Mineur Laurent , Carola Elisabeth , Etienne Pierre-Luc , Rivera Fernando , Chirivella Isabel , Perez-Staub Nathalie , Louvet Christophe , André Thierry , Tabah-Fisch Isabelle , Tournigand Christophe 
Published: July 2007

Purpose In the OPTIMOX1 trial, previously untreated patients with advanced colorectal cancer were randomly assigned to two different schedules of leucovorin, fluorouracil, and oxaliplatin that were administered until progression in the control arm or in a stop-and-go fashion in the experimental arm. The randomly assigned treatment groups did not differ significantly in terms of response rate, progression-free survival, and overall survival (OS). However, the impact of oxaliplatin reintroduction on OS was potentially masked by the fact that a large number of patients did not receive the planned oxaliplatin reintroduction or received oxaliplatin after second-line therapy in both treatment groups. Patients and Methods A Cox model was fitted with all significant baseline factors plus time-dependent variables reflecting tumor progression, reintroduction of oxaliplatin, and use of second-line irinotecan. A shared frailty model was fitted with all significant baseline factors plus the number of lines of chemotherapy received by the patient and the percentage of patients with oxaliplatin reintroduction in the center. An adjusted hazard ratio (HR) was calculated for three reintroduction classes (1% to 20%, 21% to 40%, and > 40%), using centers with no reintroduction (0%) as the reference group. Results Oxaliplatin reintroduction had an independent and significant impact on OS (HR = 0.56, P = .009). The percentage of patients with oxaliplatin reintroductions also had a significant impact on OS. Centers in which more than 40% of the patients were reintroduced had an adjusted HR for OS of 0.59 compared with centers in which no patient was reintroduced. Conclusion Oxaliplatin reintroduction is associated with improved survival in patients with advanced colorectal cancer.
Survival Prediction in Terminally Ill Cancer Patients by Clinical Estimates, Laboratory Tests, and Self-Rated Anxiety and Depression
Authors: Gripp Stephan , Moeller Sibylle , Bölke Edwin , Schmitt Gerd , Matuschek Christiane , Asgari Sonja , Asgharzadeh Farzin , Roth Stephan , Budach Wilfried , Franz Matthias , Willers Reinhardt 
Published: July 2007

Purpose To study how survival of palliative cancer patients relates to subjective prediction of survival, objective prognostic factors (PFs), and individual psychological coping. Patients and Methods Survival was estimated according to three categories (< 1 month, 1 to 6 months, and > 6 months) by two physicians (A and B) and the institutional tumor board (C) for 216 patients recently referred for palliative radiotherapy. After 6 months, the accuracy of these estimates was assessed. The prognostic relevance of clinical symptoms, performance status, laboratory tests, and self-reported emotional distress (Hospital Anxiety and Depression Scale) was investigated. Results In 61%, 55%, and 63% of the patients, prognoses were correctly estimated by A, B, and C, respectively. κ statistic showed fair agreement of the estimates, which proved to be overly optimistic. Accuracy of the three estimates did not improve with increasing professional experience. In particular, the survival of 96%, 71%, and 87% of patients who died in less than 1 month was overestimated by A, B, and C, respectively. On univariate analysis, 11 of 27 parameters significantly affected survival, namely performance status, primary cancer, fatigue, dyspnea, use of strong analgesics, brain metastases, leukocytosis, lactate dehydrogenase (LDH), depression, and anxiety. On multivariate analysis, colorectal and breast cancer had a favorable prognosis, whereas brain metastases, Karnofsky performance status less than 50%, strong analgesics, dyspnea, LDH, and leukocytosis were associated with a poor prognosis. Conclusion This study revealed that physicians' survival estimates were unreliable, especially in the case of patients near death. Self-reported emotional distress and objective PFs may improve the accuracy of survival estimates.
Tumor Sclerosis but Not Cell Proliferation or Malignancy Grade Is a Prognostic Marker in Advanced-Stage Follicular Lymphoma: The German Low Grade Lymphoma Study Group
Authors: Klapper Wolfram , Hoster Eva , Rölver Lars , Schrader Carsten , Janssen Dirk , Tiemann Markus , Bernd Heinz-Wolfram , Determann Olaf , Hansmann Martin-Leo , Möller Peter , Feller Alfred , Stein Harald , Wacker Hans-Heinrich , Dreyling Martin , Unterhalt Michael , Hiddemann Wolfgang , Ott German 
Published: July 2007

Purpose Follicular lymphoma is an indolent lymphoma with a long median overall survival. However, a considerable number of patients die within the first 2 years after the onset of the disease. Because the treatment options vary with respect to antitumor effect and potential toxic adverse effects, the identification of high-risk patients would be helpful in directing therapeutic decisions in individual patients. Several histopathologic biomarkers for risk stratification have been suggested, but most markers have not been validated in patients treated in prospective trials. Patients and Methods We report a comprehensive approach to evaluate histopathologic biomarkers, including WHO grade, histology, and proliferation and quantitation of immune bystander cells, in 158 patients with nodal advanced-stage follicular lymphoma treated first line within a randomized trial. Results Tumor sclerosis was a significant prognostic marker of poor overall survival that was independent of the Follicular Lymphoma International Prognostic Index (FLIPI). WHO grade, proliferation, and total T-cell or macrophage content were not associated with overall survival. Conclusion The presence of sclerosis within the lymphoma is a marker of poor overall survival that is independent of the FLIPI. The quantification of macrophage or absolute T-cell content, grading, and proliferation are of no help in predicting the outcome of FL. Future studies need to identify surrogate markers for the prognostic immune signatures identified by gene expression profiling. Most importantly, new prognostic markers need to be confirmed in patients treated within prospective trials.
Phase II Trial of Sorafenib Plus Interferon Alfa-2b As First- or Second-Line Therapy in Patients With Metastatic Renal Cell Cancer
Authors: Gollob Jared A. , Rathmell W. Kimryn , Richmond Tina M. , Marino Christine B. , Miller Elizabeth K. , Grigson Gayle , Watkins Catharine , Gu Lin , Peterson Bercedis L. , Wright John J. 
Published: July 2007

Purpose We undertook this study to determine the activity and tolerability of sorafenib administered with interferon alfa-2b (IFN-α-2b) as first- or second-line therapy in metastatic renal cell cancer (RCC). Patients and Methods Between November 2004 and October 2006, 40 patients at two sites were enrolled onto a phase II trial of sorafenib plus IFN-α-2b. Treatment consisted of 8-week cycles of sorafenib 400 mg orally bid plus IFN-α-2b 10 million U subcutaneously three times a week followed by a 2-week break. Patients were eligible to receive additional cycles of therapy until disease progression. Dose reduction of both drugs by 50% was permitted once for toxicity. Results The response rate was 33% (95% CI, 19% to 49%; 13 of 40 patients), including 28% partial responses (n = 11) and 5% complete responses (n = 2). Responses were seen in treatment-naïve and interleukin-2 (IL-2) –treated patients within the first two cycles. The median duration of response was 12 months. With a median follow-up time of 14 months, median progression-free survival time was 10 months (95% CI, 8 to 18 months), and median overall survival time has not yet been reached. Fatigue, anorexia, anemia, diarrhea, hypophosphatemia, rash, nausea, and weight loss were the most common toxicities. Grade 3 toxicities were uncommon but included hypophosphatemia, neutropenia, rash, fatigue, and anemia. Dose reductions were required in 65% of patients. Conclusion The combination of sorafenib and IFN-α-2b has substantial activity in treatment-naïve and IL-2–treated patients with RCC. The toxicity exceeded that of either drug alone, but dose reductions and breaks between cycles allowed for chronic therapy. A larger, randomized trial would determine whether there is any advantage to this regimen compared with sorafenib alone.
Association between Serum Insulin-Like Growth Factor-I Levels and Thyroid Disorders in a Population-Based Study
Authors: Völzke Henry , Friedrich Nele , Schipf Sabine , Haring Robin , Lüdemann Jan , Nauck Matthias , Dörr Marcus , Brabant Georg , Wallaschofski Henri 
Published: August 2007

AbstractObjective: There is current debate on whether serum IGF-I levels are associated with thyroid disorders. The aims of the present study were: 1) to investigate possible associations between serum IGF-I levels and thyroid disorders and 2) to analyze the role of serum IGF binding protein (IGFBP)-3 and TSH levels for these associations.Design: This was a cross-sectional Study of Health in Pomerania.Setting: The study was conducted in the general population of northeast Germany.Subjects: The study population comprised 3662 subjects (1746 women) without history of thyroid disorders.Interventions: No interventions have been performed.Main Outcome Measures: Goiter and thyroid nodules were determined by ultrasound. Serum TSH levels less than 0.25 mIU/liter were considered decreased.Results: Adjusted for major confounders and risk factors for thyroid disorders, subjects with serum IGF-I levels above the upper tertile had higher odds for goiter relative to subjects with serum IGF-I levels below the lower tertile [odds ratio (OR) 1.67; 95% confidence interval (CI) 1.24–2.26 in women; OR 2.04; 95% CI 1.55–2.68 in men]. A similar association was present for thyroid nodules in men (OR 1.64; 95% CI 1.17–2.32) and for decreased serum TSH levels in women (OR 1.65; 95% CI 1.00–2.69). Serum IGFBP-3 levels were not associated with thyroid disorders and did not represent effect modifiers for the association between serum IGF-I levels and the endpoints.Conclusions: We conclude that high serum IGF-I levels are associated with goiter. Whereas high serum IGF-I levels are also related to thyroid nodules in men, they are related to decreased serum TSH levels in women. Serum IGFBP-3 and TSH levels did not modulate these associations.
Insulin-Like Factor 3 Levels in Cord Blood and Serum from Children: Effects of Age, Postnatal Hypothalamic-Pituitary-Gonadal Axis Activation, and Cryptorchidism
Authors: Bay Katrine , Virtanen Helena E. , Hartung Stefan , Ivell Richard , Main Katharina M. , Skakkebaek Niels E. , Andersson Anna-Maria , Toppari Jorma 
Published: August 2007

AbstractContext: The Leydig cell hormone insulin-like factor 3 (INSL3) is important for testicular descent. Currently INSL3 levels in cord blood, in serum throughout childhood, and in relation to congenital cryptorchidism are unknown.Objective: The objective of the study was to characterize INSL3 levels in cord blood during the postnatal activation of the hypothalamic-pituitary-gonadal axis and in later childhood in normal boys and girls and cryptorchid boys.Design and Participants: Serum from 267 3-month-old boys of a prospective study with standardized cryptorchidism classification was analyzed for INSL3 (of these, 99 also had cord blood samples). Testicular position was known in 151 controls and 54 transiently cryptorchid and 62 persistently cryptorchid subjects. Eight infant girls, 26 boys (4.1–10.1 yr), and 13 girls (3.7–8.7 yr) were also included.Outcome Measure: INSL3, age, testicular position, LH, and testosterone were measured.Results: INSL3 levels were significantly higher (P &lt; 0.001) in cord blood and 3-month-old boys as compared with older prepubertal boys. At 3 months of age, INSL3 correlated significantly with LH in healthy boys. Cord blood INSL3 was significantly reduced in persistently cryptorchid boys (P = 0.001), and 3-month-old persistently cryptorchid boys had a significantly increased LH to INSL3 ratio (P = 0.014). INSL3 was unmeasurable in girls at all ages.Conclusions: In boys, early postnatal INSL3 is markedly higher as compared with later childhood, presumably because it is stimulated by the transient postnatal LH peak. INSL3 was unmeasurable in girls at all ages. Reduced cord blood INSL3 and an increased LH to INSL3 ratio at 3 months of age in persistently cryptorchid boys suggest impaired Leydig cell function in cryptorchid boys already in the perinatal period.
Deterioration of Growth Hormone (GH) Response and Anterior Pituitary Function in Young Adults with Childhood-Onset GH Deficiency and Ectopic Posterior Pituitary: A Two-Year Prospective Follow-Up Study
Authors: di Iorgi Natascia , Secco Andrea , Napoli Flavia , Tinelli Carmine , Calcagno Annalisa , Fratangeli Nadia , Ambrosini Linda , Rossi Andrea , Lorini Renata , Maghnie Mohamad 
Published: August 2007

Abstract
Context: The current criteria for definition of partial GHD in young adults are still a subject of debate.
Objectives: The objective of the study was to reinvestigate anterior pituitary function in young adults with congenital childhood-onset GHD associated with structural hypothalamic-pituitary abnormalities and normal GH response at the time of first reassessment of GH secretion.
Design and Setting: This was a prospective explorative study conducted in a university research hospital.
Patients and Methods: Thirteen subjects with a mean age of 17.2 ± 0.7 yr and a peak GH after insulin tolerance test (ITT) higher than 5 μg/liter were recruited from a cohort of 42 patients with childhood-onset GHD and ectopic posterior pituitary at magnetic resonance imaging. GH secretion after ITT and GHRH plus arginine, IGF-I concentration, and body mass index, waist circumference, blood pressure, total cholesterol, and fibrinogen were evaluated at baseline and at 2-yr follow-up.
Results: At mean age of 19.2 ± 0.7 yr, the mean peak GH response decreased significantly after ITT (P = 0.00001) and GHRH plus arginine (P = 0.0001). GH peak values after ITT and GHRH plus arginine were less than 5 and 9 μg/liter in 10 and eight patients, respectively. Additional pituitary defects were documented in eight patients. Significant changes were found in the values of IGF-I sd score (P = 0.0026), waist circumference (P = 0.00001), serum total cholesterol (P = 0.00001), and serum fibrinogen (P = 0.0004).
Conclusions: The results of this study underline the importance of further reassessment of pituitary function in young adults with GHD of childhood-onset and poststimulation GH responses suggestive of partial GHD.
Mammalian Protein-Protein Interaction Trap (MAPPIT) Analysis of STAT5, CIS, and SOCS2 Interactions with the Growth Hormone Receptor
Authors: Uyttendaele Isabel , Lemmens Irma , Verhee Annick , De Smet Anne-Sophie , Vandekerckhove Joël , Lavens Delphine , Peelman Frank , Tavernier Jan 
Published: August 2007

Abstract
Binding of GH to its receptor induces rapid phosphorylation of conserved tyrosine motifs that function as recruitment sites for downstream signaling molecules. Using mammalian protein-protein interaction trap (MAPPIT), a mammalian two-hybrid method, we mapped the binding sites in the GH receptor for signal transducer and activator of transcription 5 (STAT5) a and b and for the negative regulators of cytokine signaling cytokine-inducible Src-homology 2 (SH2)-containing protein (CIS) and suppressor of cytokine signaling 2 (SOCS2). Y534, Y566, and Y627 are the major recruitment sites for STAT5. A non-overlapping recruitment pattern is observed for SOCS2 and CIS with positions Y487 and Y595 as major binding sites, ruling out SOCS-mediated inhibition of STAT5 activation by competition for shared binding sites. More detailed analysis revealed that CIS binding to the Y595, but not to the Y487 motif, depends on both its SH2 domain and the C-terminal part of its SOCS box, with a critical role for the CIS Y253 residue. This functional divergence of the two CIS/SOCS2 recruitment sites is also observed upon substitution of the Y+1 residue by leucine, turning the Y487, but not the Y595 motif into a functional STAT5 recruitment site.
Direct Binding and Activation of Protein Kinase C Isoforms by Aldosterone and 17β-Estradiol
Authors: Alzamora Rodrigo , Brown Laura R. , Harvey Brian J. 
Published: August 2007

AbstractProtein kinase C (PKC) is a signal transduction protein that has been proposed to mediate rapid responses to steroid hormones. Previously, we have shown aldosterone directly activates PKCα whereas 17β-estradiol activates PKCα and PKCδ; however, neither the binding to PKCs nor the mechanism of action has been established. To determine the domains of PKCα and PKCδ involved in binding of aldosterone and 17β-estradiol, glutathione S-transferase fusion recombinant PKCα and PKCδ mutants were used to perform in vitro binding assays with [3H]aldosterone and [3H]17β-estradiol. 17β-Estradiol bound both PKCα and PKCδ but failed to bind PKC mutants lacking a C2 domain. Similarly, aldosterone bound only PKCα and mutants containing C2 domains. Thus, the C2 domain is critical for binding of these hormones. Binding affinities for aldosterone and 17β-estradiol were between 0.5–1.0 nM. Aldosterone and 17β-estradiol competed for binding to PKCα, suggesting they share the same binding site. Phorbol 12,13-dybutyrate did not compete with hormone binding; furthermore, they have an additive effect on PKC activity. EC50 for activation of PKCα and PKCδ by aldosterone and 17β-estradiol was approximately 0.5 nM. Immunoblot analysis using a phospho-PKC antibody revealed that upon binding, PKCα and PKCδ undergo autophosphorylation with an EC50 in the 0.5–1.0 nm range. 17β-Estradiol activated PKCα and PKCδ in estrogen receptor-positive and -negative breast cancer cells (MCF-7 and HCC-38, respectively), suggesting estrogen receptor expression is not required for 17β-estradiol-induced PKC activation. The present results provide first evidence for direct binding and activation of PKCα and PKCδ by steroid hormones and the molecular mechanisms involved.
SRY and the Standoff in Sex Determination
Authors: DiNapoli Leo , Capel Blanche 
Published: August 2007

AbstractSRY was identified as the mammalian sex-determining gene more than 15 yr ago and has been extensively studied since. Although many of the pathways regulating sexual differentiation have been elucidated, direct downstream targets of SRY are still unclear, making a top down approach difficult. However, recent work has demonstrated that the fate of the gonad is actively contested by both male-promoting and female-promoting signals. Sox9 and Fgf9 push gonads towards testis differentiation. These two genes are opposed by Wnt4, and possibly RSPO1, which push gonads toward ovary differentiation. In this review, we will discuss the history of the field, current findings, and exciting new directions in vertebrate sex determination.
Brg1 chromatin remodeling factor is involved in cell growth arrest, apoptosis and senescence of rat mesenchymal stem cells
Authors: Napolitano Marco A. , Cipollaro Marilena , Cascino Antonino , Melone Mariarosa A. B. , Giordano Antonio , Galderisi Umberto 
Published: August 2007

Self-renewal, proliferation and differentiation properties of stem cells are controlled by key transcription factors. However, their activity is modulated by chromatin remodeling factors that operate at the highest hierarchical level. Studies on these factors can be especially important to dissect molecular pathways governing the biology of stem cells. SWI/SNF complexes are adenosine triphosphate (ATP)-dependent chromatin remodeling enzymes that have been shown to be required for cell cycle control, apoptosis and cell differentiation in several biological systems. The aim of our research was to investigate the role of these complexes in the biology of mesenchymal stem cells (MSCs). To this end, in MSCs we caused a forced expression of the ATPase subunit of SWI/SNF (Brg1 – also known as Smarca4) by adenoviral transduction. Forced Brg1 expression induced a significant cell cycle arrest of MSCs in culture. This was associated with a huge increase in apoptosis that reached a peak 3 days after transduction. In addition, we observed signs of senescence in cells having ectopic Brg1 expression. At the molecular level these phenomena were associated with activation of Rb- and p53-related pathways. Inhibition of either p53 or Rb with E1A mutated proteins allowed us to hypothesize that both Rb and p53 are indispensable for Brg1-induced senescence, whereas only p53 seems to play a role in triggering programmed cell death. We also looked at the effects of forced Brg1 expression on canonical MSC differentiation in adipocytes, chondrocytes and osteocytes. Brg1 did not induce cell differentiation per se; however, this protein could contribute, at least in part, to the adipocyte differentiation process.
In conclusion, our results suggest that whereas some ATP-dependent chromatin remodeling factors, such as ISWI complexes, promote stem cell self-renewal and conservation of an uncommitted state, others cause an escape from `stemness' and induction of differentiation along with senescence and cell death phenomena.
Preparation of Calcium Silicate Nanobelts and the In Vitro Behavior in a Simulated Body Fluid
Authors: Ling Huiqin , Liu Qun , Chang Chengkang , Mao Dali 
Published: July 2007

Abstract
Single-crystalline CaSiO3 nanobelts were prepared via a simple solvothermal routine. The synthesized material revealed bioactive response when immersed in a simulated body fluid (SBF) solution, suggesting its potential application as biomedical materials.
TTF–Cytosine Dyad as an Electron-donor Molecule Having Proton-accepting Ability: Formation of Hemiprotonated Cytosine Dimer in I3− Salt
Authors: Miyazaki Eigo , Morita Yasushi , Yakiyama Yumi , Maki Suguru , Umemoto Yoshikazu , Ohmoto Makoto , Nakasuji Kazuhiro 
Published: July 2007

Abstract
A tetrathiafulvalene (TTF) derivative with a cytosine moiety was designed and synthesized as a bi-functional molecule with both electron-donating and proton-accepting abilities. In the crystal of I3− salt, TTF–cytosine dyad formed a hemiprotonated dimer through triple hydrogen-bonds with radical cationic state of the TTF moieties.
Managing Osteoporosis in Patients with Fragility Fractures: Did the British Orthopaedic Association Guidelines Have Any Impact?
Authors: Nixon MF , Ibrahim T , Johari Y , Eltayef S , Hariharan D , Taylor G J 
Published: August 2007

INTRODUCTION The incidence of fragility fractures could double in the next 50 years. Effective treatments for osteoporosis exist and the British Orthopaedic Association (BOA) has guidelines governing how to manage underlying osteoporosis in patients with fragility fractures. This study assessed how well two trauma units treat underlying osteoporosis and whether the BOA guidelines made any impact. PATIENTS AND METHODS Case notes of patients with a fracture of their proximal femur admitted during January and February in 2003, 2004 and 2005 were reviewed. The results were analysed for differences between site and year. RESULTS A total of 602 case notes were reviewed. There was a significant difference in the number of patients discharged on osteoporosis medication between the two sites (27% at LRI, 8% at KGH; P < 0.001), but not between 2003 and 2005 (22% and 16%; P = 0.16). Of the patients started on treatment, 83% were started on calcium and/or vitamin D3 supplements. CONCLUSIONS The number of patients who had their underlying osteoporosis addressed was low and the type of treatment sub-optimal. This suggests the BOA guidelines have not made an impact and further work is required to improve the management of these patients.