Targeting colorectal cancer with anti-epidermal growth factor receptor antibodies: focus on panitumumab

Panitumumab is a fully humanized monoclonal antibody with a high degree of affinity for the extracellular domain of the epidermal growth factor receptor. Phase II clinical evaluation of this drug, when administered as a single agent, in patients with metastatic colorectal cancer refractory to chemotherapy, demonstrated a modest objective radiographic response rate with acceptable toxicity; the most frequently observed side effect is rash. A randomized phase III study in subjects with chemotherapy-refractory metastatic colorectal cancer documented a progression-free survival advantage in subjects treated with panitumumab plus best supportive care versus best supportive care alone; a difference in survival was not observed, likely due to the high cross over rate. Primary tumor KRAS mutation analysis performed in this study indicated that the benefit was confined to those patients whose tumors did not contain a KRAS mutation. Further studies with panitumumab will be required to develop biomarkers of response and to determine if panitumumab has a role in combination with cytotoxic chemotherapy. This article summarizes the current state-of-the-science knowledge on panitumumab therapy in the treatment of advanced colorectal cancer

What does it mean to use competencies in "praxis" with undergraduate students at Historically Black institutions?

Dialogue concerning competencies in community psychology practice has contributed to the articulation of undergraduate and graduate education in community psychology. This dialogue shares resources in applying community psychology competencies but lacks a voice—Historically Black Colleges and Universities (HBCUs). Historically Black Colleges and Universities have undergraduate courses and graduate programs in community psychology, yet, no one has written on competencies and "praxis" from these settings. This article uses reflective narratives from faculty and undergraduate students to illustrate the use of competencies in community psychology practice with a local community. The context of the institution, emerging from legal segregation in the south, and primarily populated by economically disadvantaged and ethnic minority students, models community inclusion, ecological perspectives, empowerment, value of socio-cultural diversity and reflective practice in a neighborhood revitalization project. Discussion centers on lessons learned and challenges in engaging in praxis across undergraduate settings and HBCUs

What does it mean to use competencies in "praxis" with undergraduate students at Historically Black institutions?

Dialogue concerning competencies in community psychology practice has contributed to the articulation of undergraduate and graduate education in community psychology. This dialogue shares resources in applying community psychology competencies but lacks a voice—Historically Black Colleges and Universities (HBCUs). Historically Black Colleges and Universities have undergraduate courses and graduate programs in community psychology, yet, no one has written on competencies and "praxis" from these settings. This article uses reflective narratives from faculty and undergraduate students to illustrate the use of competencies in community psychology practice with a local community. The context of the institution, emerging from legal segregation in the south, and primarily populated by economically disadvantaged and ethnic minority students, models community inclusion, ecological perspectives, empowerment, value of socio-cultural diversity and reflective practice in a neighborhood revitalization project. Discussion centers on lessons learned and challenges in engaging in praxis across undergraduate settings and HBCUs

A Primer on the Current State-of-the-Science Neoadjuvant and Adjuvant Therapy for Patients with Locally Advanced Rectal Adenocarcinomas

Patients with rectal cancers, due to the unique location of the tumor, have a recurrence pattern distinct from colon cancers. Advances in adjuvant therapy over the last three decades have played an important role in improving patient outcomes. This article serves to review the clinical studies that lay the basis for our current standard-of-care treatment of patients with locally advanced rectal cancer, as well as touch upon future ongoing experimental clinical trials of adjuvant chemoradiation therapy

Selection of optimised ligands by fluorescence-activated bead sorting

The chemistry of aptamers is largely limited to natural nucleotides, and although modifications of nucleic acids can enhance target aptamer affinity, there has not yet been a technology for selecting the right modifications in the right locations out of the vast number of possibilities, because enzymatic amplification does not transmit sequence-specific modification information. Here we show the first method for the selection of specific nucleoside modifications that increase aptamer binding efficacy, using the oncoprotein EGFR as a model target. Using fluorescence-activated bead sorting (FABS), we have successfully selected optimized aptamers from a library of >65 000 variations. Hits were identified by tandem mass spectrometry and validated by using an EGFR binding assay and computational docking studies. Our results provide proof of concept for this novel strategy for the selection of chemically optimised aptamers and offer a new method for rapidly synthesising and screening large aptamer libraries to accelerate diagnostic and drug discovery

The Spatial, Ionization, and Kinematic Conditions of the z=1.39 Damped Ly-alpha Absorber in Q0957+561 A,B

We examined the sizes of the absorption clouds in a z=1.3911 damped Ly-alpha absorber (DLA) in the double image lensed quasar Q0957+561 A,B (separation 135 pc at the absorber redshift). Using HIRES/Keck spectra, we studied the MgII 2796,2803 doublet, FeII multiplet, and MgI 2853 transition in absorption. We defined six "clouds" in the system of sightline A and seven clouds in the system of sightline B. An examination of the N(v) profiles, using the apparent optical depth method, reveals no clear physical connection between the clouds in A and those in B. The observed column density ratios of all clouds is log[N(MgI)/N(FeII)] ~ -2 across the full velocity range in both systems and also spatially (in both sightlines). This is a remarkable uniformity not seen in Lyman limit systems. The uniformity of the cloud properties suggests that the multiple clouds are not part of a "halo". Based upon photoionization modeling, we constrain the ionization parameters in the range -6.2 < log(U) < -5.1, where the range brackets known abundance ratio and dust depletion patterns. The inferred cloud properties are densities of 2 < n_H < 20 cm^-3, and line of sight sizes of 1 < D < 25 pc. The masses of the clouds in system A are 10 < M/M_sun < 1000 and in system B are 1 < M/M_sun < 60 for spherical clouds. For planar clouds, the upper limits are 400 M_sun and 160 M_sun for A and B, respectively. We favor a model of the absorber in which the DLA region itself is a single cloud in thiscomplex, which could be a parcel of gas in a galactic ISM. A spherical cloud of ~10 pc would be limited to one of the sightlines (A) and imply a covering factor less than 0.1 for the DLA complex. We infer that the DLA cloud properties are consistent with those of lower density, cold clouds in the Galactic interstellar medium.Comment: Accepted for publication in the Astrophysical Journal; final versio

Reirradiation to the abdomen for gastrointestinal malignancies

<p>Abstract</p> <p>Background</p> <p>Reirradiation to the abdomen could potentially play a role in palliation of symptoms or local control in patients with gastrointestinal malignancies. Our goal was to retrospectively determine rates of toxicity, freedom from local progression and overall survival in gastrointestinal cancer patients treated with reirradiation to the abdomen.</p> <p>Methods</p> <p>Between November 2002 and September 2008, 13 patients with a prior history of abdominal radiotherapy (median dose 45 Gy) were treated with reirradiation for recurrent or metastatic gastrointestinal malignancies. The median interval between the two courses of radiotherapy was 26 months. Patients were treated with a hyperfractionated accelerated regimen, using 1.5 Gy fractions twice daily, with a median dose of 30 Gy (range 24-48 Gy). Concurrent chemotherapy was administered to 8 (62%) patients.</p> <p>Results</p> <p>The 1-year rate of freedom from local progression was 50%, and the median duration of freedom from local progression was 14 months. The 1-year rate of overall survival was 62%, and the median duration of overall survival was 14 months. One patient developed grade 3 acute toxicity (abdominal pain and gastrointestinal bleeding), requiring hospitalization during radiotherapy; subsequently, that patient experienced a grade 4 late toxicity (gastrointestinal bleeding). No other patients developed grade 3-4 acute or late toxicity or required hospitalization during radiotherapy.</p> <p>Conclusion</p> <p>Hyperfractionated accelerated reirradiation to the abdomen was well-tolerated with low rates of acute and late toxicity. Reirradiation could play a role in providing a limited duration of local control in gastrointestinal cancer patients with a history of prior abdominal radiotherapy.</p

Growth dynamics of a Bose-Einstein condensate in a dimple trap without cooling

We study the formation of a Bose-Einstein condensate in a cigar-shaped three-dimensional harmonic trap, induced by the controlled addition of an attractive "dimple" potential along the weak axis. In this manner we are able to induce condensation without cooling due to a localized increase in the phase space density. We perform a quantitative analysis of the thermodynamic transformation in both the sudden and adiabatic regimes for a range of dimple widths and depths. We find good agreement with equilibrium calculations based on self-consistent semiclassical Hartree-Fock theory describing the condensate and thermal cloud. We observe there is an optimal dimple depth that results in a maximum in the condensate fraction. We also study the non-equilibrium dynamics of condensate formation in the sudden turn-on regime, finding good agreement for the observed time dependence of the condensate fraction with calculations based on quantum kinetic theory.Comment: v1: 9 pages, 7 figures, submitted to Phys. Rev. A; v2: 10 pages, 8 figures, fixed typos, added references, additional details on experimental procedure, values of phase-space density, new figure and discussion on effects of three-body loss in Appendix B (replaced with published version