tbuckley/cabot-search huggingface dataset:
Phase III Trial of Sunitinib in Combination With Capecitabine Versus Capecitabine Monotherapy for the Treatment of Patients With Pretreated Metastatic Breast Cancer
Authors: John P. Crown, Véronique Diéras, Elzbieta Staroslawska, Denise A. Yardley, Thomas Bachelot, Neville Davidson, Hans Wildiers, Peter A. Fasching, Olivier Capitain, Manuel Ramos, Richard Greil, Francesco Cognetti, George Fountzilas, Maria Blasinska-Morawiec, Cornelia Liedtke, Rolf Kreienberg, Wilson H. Miller, Vanessa Tassell, Xin Huang, Jolanda Paolini, Kenneth A. Kern, Gilles Romieu
Journal: Journal of Clinical Oncology (2013)

Metastatic breast cancer (MBC) remains an incurable illness in the majority of cases, despite major therapeutic advances. This may be related to the ability of breast tumors to induce neoangiogenesis, even in the face of cytotoxic chemotherapy. Sunitinib, an inhibitor of key molecules involved in neoangiogenesis, has an established role in the treatment of metastatic renal cell and other cancers and demonstrated activity in a phase II trial in MBC. We performed a randomized phase III trial comparing sunitinib plus capecitabine (2,000 mg/m2) with single-agent capecitabine (2,500 mg/m2) in patients with heavily pretreated MBC.Eligibility criteria included MBC, prior therapy with anthracyclines and taxanes, one or two prior chemotherapy regimens for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. The primary end point was progression-free survival, for which the study had 90% power to detect a 50% improvement (from 4 to 6 months).A total of 442 patients were randomly assigned. Progression-free survival was not significantly different between the treatment arms, with medians of 5.5 months (95% CI, 4.5 to 6.0) for the sunitinib plus capecitabine arm and 5.9 months (95% CI, 5.4 to 7.6) for the capecitabine monotherapy arm (hazard ratio, 1.22; 95% CI, 0.95 to 1.58; one-sided P = .941). There were no significant differences in response rate or overall survival. Toxicity, except for hand-foot syndrome, was more severe in the combination arm.The addition of sunitinib to capecitabine does not improve the clinical outcome of patients with MBC pretreated with anthracyclines and taxanes.
Prognostic Significance of Disseminated Tumor Cells in the Bone Marrow of Prostate Cancer Patients Treated With Neoadjuvant Hormone Treatment
Authors: Jens Köllermann, Steffen Weikert, Martin Schostak, Carsten Kempkensteffen, Klaus Kleinschmidt, Thomas Rau, Klaus Pantel
Journal: Journal of Clinical Oncology (2008)

To explore whether the presence of occult disseminated tumor cells (DTCs) in the bone marrow before neoadjuvant hormone therapy influences the prognosis of patients with organ confined prostate cancer treated by radical prostatectomy.Pretreatment bone marrow aspirates from 193 cT (1-4) pN0M0 prostate cancer patients submitted to neoadjuvant hormone therapy (mean, 8 months) followed by radical prostatectomy were immunohistochemically evaluated by anticytokeratin antibody A45-B/B3 previously validated for the detection of DTCs. Bone marrow status was compared with established clinical and histopathologic risk parameters. Patients' outcome was evaluated using prostate-specific antigen (PSA) blood serum measurements as surrogate marker for recurrence over a median follow-up of 44 months.DTCs were detected in 44.6% of patients. Bone marrow status neither correlated with tumor grade and stage, nor with the pretreatment PSA risk category (all P values > .05). In the univariate Kaplan-Meier analysis, the presence of DTCs was a significant prognostic factor with respect to poor PSA progression-free survival (log-rank test P = .0035). Using a multivariable piecewise Cox regression model, the presence of DTCs was an independent predictor of PSA relapse (relative risk 1.82; P = .014).The presence of DTCs in the bone marrow of patients with prostate cancer before neoadjuvant hormone therapy and subsequent surgery represents an independent prognostic parameter, suggesting that DTCs may contribute to the failure of current neoadjuvant hormone therapy regimens.
Comprehensive molecular cytogenetic investigation of chromosomal abnormalities in human medulloblastoma cell lines and xenograft
Authors: Naji Aldosari, Rodney N. Wiltshire, Amalia Dutra, Evelin Schrock, Roger E. McLendon, Henry S. Friedman, Darell D. Bigner, Sandra H. Bigner
Journal: Neuro-Oncology (2002)

Cell lines and xenografts derived from medulloblastomas are useful tools to investigate the chromosomal changes in these tumors. Here we used G-banding, fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), and comparative genomic hybridization to study 4 medulloblastoma cell lines and 1 xenograft. Cell line D-425 Med had a relatively simple karyotype, with a terminal deletion of 10q and amplification of MYC in double-minutes (dmins). FISH demonstrated that an apparent isochromosome (17q) by routine karyotyping was actually an unbalanced translocation between 2 copies of chromosome 17. Cell line D-556 Med also had a simple near-diploid stemline with an unbalanced 1;13 translocation resulting in a gain of 1q, an isochromosome (17q), and dmins. These findings were initially described using routine G-banded preparations, and FISH showed that the dmins were an amplification of MYC and the i(17q) was an isodicentric 17q chromosome. The other finding was confirmed by FISH, SKY, and comparative genomic hybridization. Cell lines D-721 Med and D-581 Med had complex karyotypic patterns that could be completely characterized only when FISH and SKY were used. Xenograft D-690 Med also had a complex pattern that FISH and SKY were helpful in completely elucidating. Interestingly, balanced reciprocal translocations were seen as well as complicated unbalanced translocations and marker chromosomes. Comparative genomic hybridization demonstrated only a deletion of 10q22-10q24, supporting the idea that despite the complexity of the chromosomal rearrangements, minimal alterations in the overall chromosomal content had occurred. This study demonstrates that routine cytogenetic preparations are adequate to describe chromosomal abnormalities in occasional medulloblastoma samples, but a broader spectrum of molecular cytogenetic methods is required to completely analyze most of these tumor samples.
A T-cell HCV vaccine eliciting effective immunity against heterologous virus challenge in chimpanzees
Authors: Antonella Folgori, Stefania Capone, Lionello Ruggeri, Annalisa Meola, Elisabetta Sporeno, Bruno Bruni Ercole, Monica Pezzanera, Rosalba Tafi, Mirko Arcuri, Elena Fattori, Armin Lahm, Alessandra Luzzago, Alessandra Vitelli, Stefano Colloca, Riccardo Cortese, Alfredo Nicosia
Journal: Nature Medicine (2006)
Time-Resolved Imaging Reveals Heterogeneous Landscapes of Nanomolar Ca2+ in Neurons and Astroglia
Authors: Kaiyu Zheng, Lucie Bard, James P. Reynolds, Claire King, Thomas P. Jensen, Alexander V. Gourine, Dmitri A. Rusakov
Journal: Neuron (2015)

Highlights•OGB-1 lifetime readout is specific to low [Ca2+] and enables 100 Hz acquisition rate•Neurons and astrocytes maintain uneven landscapes of resting [Ca2+]•Resting [Ca2+] patterns in neurons and astroglia are age and activity dependent•Astroglia in situ split into two sub-groups with respect to their resting [Ca2+]SummaryMaintaining low intracellular calcium is essential to the functioning of brain cells, yet the phenomenology and mechanisms involved remain an enigma. We have advanced a two-photon excitation time-resolved imaging technique, which exploits high sensitivity of the OGB-1 fluorescence lifetime to nanomolar Ca2+ concentration ([Ca2+]) and enables a high data acquisition rate in situ. The [Ca2+] readout is not affected by dye concentration, light scattering, photobleaching, micro-viscosity, temperature, or the main known concomitants of cellular activity. In quiescent tissue, standard whole-cell configuration has little effect on resting [Ca2+] inside neuronal dendrites or inside astroglia dye-filled via gap junctions. Mapping basal [Ca2+] in neurons and astrocytes with submicron resolution unveils heterogeneous concentration landscapes that depend on age and preceding activity. The rich information content represented by such landscapes in acute slices and in vivo promises to unveil the hitherto unexplored, potentially fundamental aspects of brain cell physiology.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJhNDI1NjNmN2RjZjgxNjMzODcxOTA5MDRmMzk3NWVkMSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNzMwNjU0MDU1fQ.IUvCndPrAGgS52XUrrUTM2oyVnVu-SNpHCeX8CxO3CbLGXNSAZs_1A0V5faRPbw3hu4e8TD0c1hBhdRpHLpKRTzLLqrEZGlHRkpBqy9UnP06i8RQark-6KNZEd5FpPvrfuKkgYp8iBwNwlzOc20j14aHKM1_hm64OpjbX1Q7JANYgCyY2RPIQum0r2KRMo8UGdeRLDyERV4RAjN469Cz7m_c-hmmWxjHG9aIt6LME48cv7JPtl9p-QBQ50FmnYwJgJxdgzfXaS958IAWYF5nINuI3BZJEd0xpIqJmGDElCXl6tRwUU7snqgkIDM4g4_N1Y_MMUNNuU3abHjP9X2yHQDownload video (mp4, 56 MB)
Molecular basis of thyrotropin and thyroid hormone action during implantation and early development
Authors: Martina Colicchia, Luisa Campagnolo, Enke Baldini, Salvatore Ulisse, Herbert Valensise, Costanzo Moretti
Journal: Human Reproduction Update (2014)

Implantation and early embryo development are finely regulated processes in which several molecules are involved. Evidence that thyroid hormones (TH: T4 and T3) might be part of this machinery is emerging. An increased demand for TH occurs during gestation, and any alteration in maternal thyroid physiology has significant implications for both maternal and fetal health. Not only overt but also subclinical hypothyroidism is associated with infertility as well as with obstetric complications, including disruptions and disorders of pregnancy, labor, delivery, and troubles in early neonatal life. We searched the PubMed and Google Scholar databases for articles related to TH action on ovary, endometrium, trophoblast maturation and embryo implantation. In addition, articles on the regulation of TH activity at cellular level have been reviewed. The findings are hereby summarized and critically discussed. TH have been shown to influence endometrial, ovarian and placental physiology. TH receptors (TR) and thyrotropin (thyroid-stimulating hormone: TSH) receptors (TSHR) are widely expressed in the feto-maternal unit during implantation, and both the endometrium and the trophoblast might be influenced by TH either directly or through TH effects on the synthesis and activity of implantation-mediating molecules. Interestingly, due to the multiplicity of mechanisms involved in TH action (e.g. differential expression of TR isoforms, heterodimeric receptor partners, interacting cellular proteins, and regulating enzymes), the TH concentration in blood is not always predictive of their cellular availability and activity at both genomic and nongenomic level. In addition to the known role of TH on the hormonal milieu of the ovarian follicle cycle, which is essential for a woman's fertility, evidence is emerging on the importance of TH signaling during implantation and early pregnancy. Based on recent observations, a local action of TH on female reproductive organs and the embryo during implantation appears to be crucial for a successful pregnancy. Furthermore, an imbalance in the spatio-temporal expression of factors involved in TH activity might induce early arrest of pregnancy in women considered as euthyroid, based on their hormonal blood concentration. In conclusion, alterations of the highly regulated local activity of TH may play a crucial, previously underestimated, role in early pregnancy and pregnancy loss. Further studies elucidating this topic should be encouraged.
Identification of the major chemokines that regulate cell influxes in peritoneal dialysis patients.
Authors: J Tekstra, C E Visser, C W Tuk, J J Brouwer-Steenbergen, C W Burger, R T Krediet, R H Beelen
Journal: Journal of the American Society of Nephrology (1996)

To investigate which members of the recently discovered family of chemotactic cytokines (chemokines) are important in leukocyte recruitment to a bacterial inflammation site, four different chemokines in the effluent of peritoneal dialysis patients suffering from acute bacterial peritonitis were measured. The presence of two neutrophil-attracting chemokines, interleukin-8 and human melanoma growth-stimulating activity (huGRO alpha), and two monocyte-attracting members of the chemokine superfamily, monocyte chemotactic protein-1 (MCP-1) and regulated on activation normal T cell expressed and secreted (RANTES), was investigated in patient effluents just before, during, and after a peritonitis episode. This was studied in seven peritonitis effluents of five patients by using chemokine-specific enzyme-linked immunosorbent assays. Cell populations in the dialysates were differentiated on cytocentrifuge preparations. The contribution of the detected chemokines to neutrophilic and monocytic cell influxes in the inflamed peritoneal cavity was analyzed by correlating concentrations of chemokines to the relevant cell numbers present in the dialysates of these patients. The detection of the neutrophil-attracting chemokine interleukin-8 during peritonitis was in accordance with other studies. Moreover, a second neutrophil chemoattractant, huGRO alpha, was identified in vivo. Both were elevated during inflammation (P < 0.02) and contributed significantly to the neutrophilic cell influx (P < 0.05). One of the monocyte-attracting chemokines, RANTES, could not be detected in any of the effluents, whereas the other, MCP-1, was significantly elevated during peritonitis (P < 0.02). In contrast to the other chemokines measured, MCP-1 concentration was relatively high in steady-state peritoneal dialysates. An absolute correlation between dialysate MCP-1 concentration and the number of macrophages in these effluents was absent. However, in a 48-well chemotaxis assay, monocyte migration toward peritonitis, as well as steady-state patient dialysates, could be blocked with antibodies to MCP-1. It was concluded, therefore, that MCP-1 is the most important monocyte chemoattractant in peritoneal dialysis steady-state and peritonitis patients; whereas, besides interleukin-8, huGRO alpha was identified as a major neutrophil-attracting chemokine in the peritonitis situation.
Fechner revisited: Towards an inclusive approach to aesthetics
Authors: W. Tecumseh Fitch, Gesche Westphal-Fitch
Journal: Behavioral and Brain Sciences (2013)

Abstract Accepting Bullot &amp; Reber's (B&amp;R's) criteria for art appreciation would confine the study of aesthetics to those works for which historical information is available, mainly post–eighteenth-century Western “high art.” We reject their contention that “correct” artistic understanding is limited to experts with detailed knowledge or education in art, which implies a narrowly elitist conception of aesthetics. Scientific aesthetics must be broadly inclusive.
The Androgen Receptor Negatively Regulates the Expression of c-Met: Implications for a Novel Mechanism of Prostate Cancer Progression
Authors: Meletios Verras, Jane Lee, Hui Xue, Tzu-Huey Li, Yuzhuo Wang, Zijie Sun
Journal: Cancer Research (2007)

Abstract The precise molecular mechanisms by which prostate cancer cells progress from androgen-sensitive to androgen-insensitive status still remain largely unclear. The hepatocyte growth factor/scatter factor (HGF/SF) plays a critical role in the regulation of cell growth, cell motility, morphogenesis, and angiogenesis. The aberrant expression of HGF/SF and its receptor, c-Met, often correlates with poor prognosis in a variety of human malignancies, including prostate cancer. Here, we investigate a potential link between androgen signaling and c-Met expression in prostate cancer cells. First, we showed that the androgen receptor (AR) represses the expression of c-Met in a ligand-dependent manner. Using different c-Met promoter/reporter constructs, we identified that Sp1 induces the transcription of c-Met and that AR can repress the Sp1-induced transcription in prostate cancer cells. Moreover, the data from electrophoretic mobility shift assay showed that AR interferes with the interaction between Sp1 and the functional Sp1 binding site within the c-Met promoter. Furthermore, we tested the effect of AR on c-Met expression in an androgen-insensitive prostate cancer cell line, CWR22Rv1. Finally, the repressive role of androgen signaling on c-Met expression was confirmed in prostate cancer xenografts. The above data indicate a dual role of AR in transcriptional regulation. Although the current androgen ablation therapy can repress the expression of growth-promoting genes that are activated by the AR, it may also attenuate the repressive role of AR on c-Met expression. Therefore, the therapeutic strategies to inhibit the activation of the HGF/c-Met pathway may be of benefit when combined with current androgen ablation treatment. [Cancer Res 2007;67(3):967–75]
Single-Photon Emission Computed Tomography (SPECT)
Authors: B. Leonard Holman
Journal: JAMA (1990)

Single-photon emission computed tomography has received increasing attention as radiopharmaceuticals that reflect perfusion, metabolism, and receptor and cellular function have become widely available. Perfusion single-photon emission computed tomography of the brain provides functional information useful for the diagnosis and management of stroke, dementia, and epilepsy. Single-photon emission computed tomography has been applied to myocardial, skeletal, hepatic, and tumor scintigraphy, resulting in increased diagnostic accuracy over planar imaging because background activity and overlapping tissues interfere far less with activity from the target structure when tomographic techniques are used. Single-photon emission computed tomography is substantially less expensive and far more accessible than positron emission tomography and will become an increasingly attractive alternative for transferring the positron emission tomography technology to routine clinical use. In addition, singlephoton emission computed tomography has unique applications that are increasingly finding their way into the routine practice of clinical nuclear medicine. (<i>JAMA</i>. 1990;263:561-564)
New Lung Cancer Susceptibility Locus Identified: Significance and Implications for Other Genome-Wide Association Studies
Authors: Thomas A. Sellers, Y. Ann Chen
Journal: Cancer Discovery (2012)

Abstract Genome-wide association studies have identified more than 150 loci that influence the risk of cancer. In this issue of Cancer Discovery, Shi and colleagues report that a variant in RAD52 is a risk factor for squamous cell lung carcinoma. This work is important not only for its potential implications on control of this dreaded malignancy but also for its methodologic contributions that can advance the field of molecular-genetic epidemiology. Cancer Discovery; 2(2); 110–1. ©2012 AACR. Commentary on Shi et al., p. 131.
Molecular epidemiology of tuberculosis in the Tula area, Central Russia, before the introduction of the Directly Observed Therapy Strategy
Authors: S. Dubiley, A. Ignatova, T. Mukhina, A. Nizova, S. Blagodatskikh, V. Stepanshina, I. Shemyakin
Journal: Clinical Microbiology and Infection (2009)
Deliberate Self-Harm in a Nonclinical Population: Prevalence and Psychological Correlates
Authors: E. David Klonsky, Thomas F. Oltmanns, Eric Turkheimer
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Research on deliberate self-harm (intentionally injuring oneself without suicidal intent) has focused on clinical and forensic populations. Studying only these populations, which typically have serious psychopathology, may lead to inflated estimates of the association between self-harm and psychiatric disorder, as well as of the prevalence of deliberate self-harm. The present study investigated the prevalence and correlates of deliberate self-harm in a large group of nonclinical subjects. METHOD: Participants were 1,986 military recruits, 62% of whom were men, who were participating in a study of peer assessment of personality traits and pathology. Individuals who did and did not report a history of self-harm were compared on measures of personality and psychopathology. RESULTS: Approximately 4% of the participants reported a history of deliberate self-harm. Compared with participants without a history of deliberate self-harm, self-harmers scored higher on self- and peer-report measures of borderline, schizotypal, dependent, and avoidant personality disorder symptoms and reported more symptoms of anxiety and depression. Item-level analyses indicated that peers viewed self-harmers as having strange and intense emotions and a heightened sensitivity to interpersonal rejection. CONCLUSIONS: About one of every 25 members of a large group of relatively high-functioning nonclinical subjects reported a history of self-harm. Self-harmers had more symptoms of several personality disorders than non-self-harmers, and their performance across measures suggested that anxiety plays a prominent role in their psychopathology. Future research should investigate whether psychotherapies or psychiatric medications known to reduce symptoms of anxiety can be effective in treating deliberate self-harm.
Risk and protective factors for thrombosis in systemic lupus erythematosus: results from a large, multi-ethnic cohort
Authors: R Kaiser, C M Cleveland, L A Criswell
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: Few studies have examined thrombosis in systemic lupus erythematosus (SLE), none have included Asian-Americans, and most have had small sample sizes. We analysed risk factors for thrombosis in a large, multi-ethnic SLE cohort. Methods: We studied 1930 SLE subjects, including Caucasians, African-Americans, Asian-Americans and Hispanics. Data were derived from questionnaires and medical records. Documented history of thrombosis was the primary outcome. Explanatory variables included age at SLE diagnosis, gender, ethnicity, disease duration, smoking, antiphospholipid antibody (aPL) status, nephritis and specific medications. Results: Smoking (OR 1.26, p = 0.011), longer disease duration (OR 1.26 per 5 years p = 0.027×10 −7 ), nephritis (OR 1.35, p = 0.036), aPL positivity (OR 3.22, p&lt;10 −9 ) and immunomodulating medication use (OR 1.40, p = 0.011) were statistically significant risk factors for thrombosis. Younger age at SLE onset was protective (OR 0.52 for age ⩽20, p = 0.001). After adjusting for disease severity and incorporating propensity scores, hydroxychloroquine use remained significantly protective for thrombosis (OR 0.62, p = 4.91×10 −4 ). Conclusions: This study confirms that older age at onset, longer disease duration, smoking, aPL positivity, history of nephritis and immunomodulating medication use are risk factors for thrombosis in SLE. These data are the first to confirm in a large and ethnically diverse SLE cohort that hydroxychloroquine use is protective for thrombosis.
Detection of Human Gastric Cancer in Resected Specimens Using a Novel Infrared Fluorescent Anti-Human Carcinoembryonic Antigen Antibody with an Infrared Fluorescence Endoscope in Vitro
Authors: S. Ito, N. Muguruma, Y. Kusaka, M. Tadatsu, K. Inayama, Y. Musashi, M. Yano, T. Bando, H. Honda, I. Shimizu, K. Ii, K. Takesako, H. Takeuchi, S. Shibamura
Journal: Endoscopy (2001)

Background and Study Aims: An indocyanine green derivative (ICG-sulfo-OSu) that can be used as an infrared fluorescent labeling substance suitable for detecting microlesions with an infrared fluorescence endoscope has been developed. The aims of the present study were to develop an infrared fluorescence endoscope and to demonstrate its usefulness in detecting cancerous tissue using an antibody coupled with ICG-sulfo-OSu.
Antigen Availability Determines CD8+ T Cell-Dendritic Cell Interaction Kinetics and Memory Fate Decisions
Authors: Sarah E. Henrickson, Mario Perro, Scott M. Loughhead, Balimkiz Senman, Susanne Stutte, Michael Quigley, Gabriela Alexe, Matteo Iannacone, Michael P. Flynn, Shaida Omid, Jonathan L. Jesneck, Sabrina Imam, Thorsten R. Mempel, Irina B. Mazo, W. Nicholas Haining, Ulrich H. von Andrian
Journal: Immunity (2013)