131 research outputs found
Breast conserving surgery versus mastectomy: cancer practice by general surgeons in Iran
BACKGROUND: There appear to be geographical differences in decisions to perform mastectomy or breast conserving surgery for early-stage breast cancer. This study was carried out to evaluate general surgeons' preferences in breast cancer surgery and to assess the factors predicting cancer practice in Iran. METHODS: A structured questionnaire was mailed to 235 general surgeons chosen from the address list of the Iranian Medical Council. The questionnaire elicited information about the general surgeons' characteristics and about their work experience, posts they have held, number of breast cancer operations performed per year, preferences for mastectomy or breast conserving surgery, and the reasons for these preferences. RESULTS: In all, 83 surgeons returned the completed questionnaire. The results indicated that only 19% of the surgeons routinely performed breast conserving surgery (BCS) and this was significantly associated with their breast cancer case load (P < 0.01). There were no associations between BCS practice and the other variables studied. The most frequent reasons for not performing BCS were uncertainty about conservative therapy results (46%), uncertainty about the quality of available radiotherapy services (32%), and the probability of patients' non-compliance in radiotherapy (32%). CONCLUSION: The findings indicate that Iranian surgeons do not routinely perform BCS as the first and the best treatment modality. Further research is recommended to evaluate patients' outcomes after BCS treatment in Iran, with regard to available radiotherapy facilities and cultural factors (patients' compliance)
CXCR4 expression on circulating pan-cytokeratin positive cells is associated with survival in patients with advanced non-small cell lung cancer
<p>Abstract</p> <p>Background</p> <p>The CXC chemokine, CXCL12, and its receptor, CXCR4 promote metastases of a variety of solid tumors, including non-small cell lung cancer (NSCLC). The expression of CXCR4 on tumor cells may represent a critical biomarker for their propensity to metastasize. This study was performed to evaluate the hypothesis that co-expression of pan-cytokeratin and CXCR4 may be a prognostic marker for patients with advanced NSCLC.</p> <p>Methods</p> <p>We evaluated CXCR4 levels on circulating pan-cytokeratin positive cells from patients with NSCLC. NSCLC tumor and metastases were also assessed for the presence of CXCR4.</p> <p>Results</p> <p>Pan-cytokeratin positive cells were increased in the circulation of patients with NSCLC, as compared to normal control subjects. Patients with pan-cytokeratin +/CXCR4+ = 2,500 cells/ml had a significant improvement in median survival when compared with patients with pan-cytokeratin +/CXCR4+ >2,500 cells/ml (not achieved versus 14 weeks). CXCR4 expression was found on NSCLC tumors and at sites of tumor metastasis.</p> <p>Conclusion</p> <p>This study suggests that CXCR4 may be a prognostic marker in NSCLC, and provides hypothesis-generating results, which may be important in determining metastatic potential. In future studies, we will prospectively evaluate the prognostic significance of pan-cytokeratin/CXCR4+ cells, and determine the mechanisms involved in the regulation of CXCR4 expression on tumor cells in a larger patient population.</p
SUMO-Interacting Motifs of Human TRIM5α are Important for Antiviral Activity
Human TRIM5α potently restricts particular strains of murine leukemia viruses
(the so-called N-tropic strains) but not others (the B- or NB-tropic strains)
during early stages of infection. We show that overexpression of SUMO-1 in human
293T cells, but not in mouse MDTF cells, profoundly blocks N-MLV infection. This
block is dependent on the tropism of the incoming virus, as neither B-, NB-, nor
the mutant R110E of N-MLV CA (a B-tropic switch) are affected by SUMO-1
overexpression. The block occurred prior to reverse transcription and could be
abrogated by large amounts of restricted virus. Knockdown of TRIM5α in 293T
SUMO-1-overexpressing cells resulted in ablation of the SUMO-1 antiviral
effects, and this loss of restriction could be restored by expression of a human
TRIM5α shRNA-resistant plasmid. Amino acid sequence analysis of human
TRIM5α revealed a consensus SUMO conjugation site at the N-terminus and
three putative SUMO interacting motifs (SIMs) in the B30.2 domain. Mutations of
the TRIM5α consensus SUMO conjugation site did not affect the antiviral
activity of TRIM5α in any of the cell types tested. Mutation of the SIM
consensus sequences, however, abolished TRIM5α antiviral activity against
N-MLV. Mutation of lysines at a potential site of SUMOylation in the CA region
of the Gag gene reduced the SUMO-1 block and the TRIM5α restriction of
N-MLV. Our data suggest a novel aspect of TRIM5α-mediated restriction, in
which the presence of intact SIMs in TRIM5α, and also the SUMO conjugation
of CA, are required for restriction. We propose that at least a portion of the
antiviral activity of TRIM5α is mediated through the binding of its SIMs to
SUMO-conjugated CA
Final Targeting Strategy for the SDSS-IV APOGEE-2N Survey
APOGEE-2 is a dual-hemisphere, near-infrared (NIR), spectroscopic survey with
the goal of producing a chemo-dynamical mapping of the Milky Way Galaxy. The
targeting for APOGEE-2 is complex and has evolved with time. In this paper, we
present the updates and additions to the initial targeting strategy for
APOGEE-2N presented in Zasowski et al. (2017). These modifications come in two
implementation modes: (i) "Ancillary Science Programs" competitively awarded to
SDSS-IV PIs through proposal calls in 2015 and 2017 for the pursuit of new
scientific avenues outside the main survey, and (ii) an effective 1.5-year
expansion of the survey, known as the Bright Time Extension, made possible
through accrued efficiency gains over the first years of the APOGEE-2N project.
For the 23 distinct ancillary programs, we provide descriptions of the
scientific aims, target selection, and how to identify these targets within the
APOGEE-2 sample. The Bright Time Extension permitted changes to the main survey
strategy, the inclusion of new programs in response to scientific discoveries
or to exploit major new datasets not available at the outset of the survey
design, and expansions of existing programs to enhance their scientific success
and reach. After describing the motivations, implementation, and assessment of
these programs, we also leave a summary of lessons learned from nearly a decade
of APOGEE-1 and APOGEE-2 survey operations. A companion paper, Santana et al.
(submitted), provides a complementary presentation of targeting modifications
relevant to APOGEE-2 operations in the Southern Hemisphere.Comment: 59 pages; 11 Figures; 7 Tables; 2 Appendices; Submitted to Journal
and Under Review; Posting to accompany papers using the SDSS-IV/APOGEE-2 Data
Release 17 scheduled for December 202
20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years
The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment
State of the Field: Extreme Precision Radial Velocities
The Second Workshop on Extreme Precision Radial Velocities defined circa 2015
the state of the art Doppler precision and identified the critical path
challenges for reaching 10 cm/s measurement precision. The presentations and
discussion of key issues for instrumentation and data analysis and the workshop
recommendations for achieving this precision are summarized here.
Beginning with the HARPS spectrograph, technological advances for precision
radial velocity measurements have focused on building extremely stable
instruments. To reach still higher precision, future spectrometers will need to
produce even higher fidelity spectra. This should be possible with improved
environmental control, greater stability in the illumination of the
spectrometer optics, better detectors, more precise wavelength calibration, and
broader bandwidth spectra. Key data analysis challenges for the precision
radial velocity community include distinguishing center of mass Keplerian
motion from photospheric velocities, and the proper treatment of telluric
contamination. Success here is coupled to the instrument design, but also
requires the implementation of robust statistical and modeling techniques.
Center of mass velocities produce Doppler shifts that affect every line
identically, while photospheric velocities produce line profile asymmetries
with wavelength and temporal dependencies that are different from Keplerian
signals.
Exoplanets are an important subfield of astronomy and there has been an
impressive rate of discovery over the past two decades. Higher precision radial
velocity measurements are required to serve as a discovery technique for
potentially habitable worlds and to characterize detections from transit
missions. The future of exoplanet science has very different trajectories
depending on the precision that can ultimately be achieved with Doppler
measurements.Comment: 45 pages, 23 Figures, workshop summary proceeding
Are tangles as toxic as they look?
Neurofibrillary tangles are intracellular accumulations of hyperphosphorylated and misfolded tau protein characteristic of Alzheimer's disease and other tauopathies. Classic cross-sectional studies of Alzheimer patient brains showed associations of tangle accumulation with neuronal loss, synapse loss, and dementia, which led to the supposition that tangles are toxic to neurons. More recent advances in imaging techniques and mouse models have allowed the direct exploration of the question of toxicity of aggregated versus soluble tau and have surprisingly challenged the view of tangles as toxic species in the brain. Here, we review these recent experiments on the nature of the toxicity of tau with particular emphasis on our experiments imaging tangles in the intact brain through a cranial window, which allows observation of tangle formation and longitudinal imaging of the fate of tangle-bearing neurons. Neurofibrillary tangles (NFT) were first described in 1906 by Alois Alzheimer based on Bielschowsky silver staining of the brain of his demented patient Auguste D (Alzheimer 1907; Goedert and Spillantini 2006). These intraneuronal aggregates have subsequently been found to be composed primarily of hyperphosphorylated tau protein and are definitive pathological lesions not only in Alzheimer's disease but also in a class of neurodegenerative tauopathies (Goedert et al. 1988; Spires-Jones et al. 2009). NFT pathology in Alzheimer's disease (AD) correlates closely with cognitive decline and synapse and neuronal loss (Braak and Braak 1997; Bretteville and Planel 2008; Congdon and Duff 2008; Mocanu et al. 2008b; Spires-Jones et al. 2009). As a result, NFT have long been considered indicative of impending neuronal cell death. More recent evidence, however, opposes this classical view. Here we review evidence addressing the question of whether NFT cause structural or functional neuronal damage
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