Cetuximab for treatment of metastatic colorectal cancer

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In vitro and human pharmacoscintigraphic evaluation of an oral 5-ASA delivery system for colonic release

5-aminosalicylic acid (5-ASA) is the most widely used drug for the treatment of ulcerative colitis. The benefits of targeted delivery of 5-ASA to the large intestine are well known, resulting in reduced systemic absorption and increased local concentrations at the disease site. In the present study, a 5-ASA colon delivery system based on the time-dependent strategy, exploiting the relatively consistent small intestinal transit time (SITT), was manufactured and evaluated in vitro as well as in vivo. The system was obtained by successive spray-coating of an immediate-release tablet core with low-viscosity HPMC and Eudragit (R) L. The enteric film was effective in preventing release during the acidic stage of the in vitro test, while the HPMC coating brought about reproducible lag phases prior to release in phosphate buffer medium. A gamma-scintigraphy investigation pointed out that, following administration to fasted and fed volunteers, disintegration of the units never occurred prior to colon arrival. In all cases, a lag time preceded the appearance of the drug and its N-acetyl metabolite in the blood-stream, which was found to correlate with the time of disintegration in a linear mode. The plasma levels of the drug and metabolite as well as their cumulative urinary recovery were relatively low with respect to those reported when 5-ASA is delivered to the small bowel

Engineering 3D Multi-Branched Nanostructures for Ultra- Sensing Applications

The fabrication of plasmonic nanostructures with sub-10 nm gaps supporting extremely large electric field enhancement (hot-spot) has attained great interest over the past years, especially in ultra-sensing applications. The “hot-spot” concept has been successfully implemented in surface-enhanced Raman spectroscopy (SERS) through the extensive exploitation of localized surface plasmon resonances. However, the detection of analyte molecules at ultra-low concentrations, i.e., down to the single/few molecule level, still remains an open challenge due to the poor localization of analyte molecules onto the hot-spot region. On the other hand, three-dimensional nanostructures with multiple branches have been recently introduced, demonstrating breakthrough performances in hot-spot-mediated ultra-sensitive detection. Multi-branched nanostructures support high hot-spot densities with large electromagnetic (EM) fields at the interparticle separations and sharp edges, and exhibit excellent uniformity and morphological homogeneity, thus allowing for unprecedented reproducibility in the SERS signals. 3D multi-branched nanostructures with various configurations are engineered for high hot-spot density SERS substrates, showing an enhancement factor of 1011 with a low detection limit of 1 fM. In this view, multi-branched nanostructures assume enormous importance in analyte detection at ultra-low concentrations, where the superior hot-spot density can promote the identification of probe molecules with increased contrast and spatial resolution

Activity of osimeRTInib in non-small-cell lung Cancer with UNcommon epidermal growth factor receptor mutations: retrospective Observational multicenter study (ARTICUNO)

Background: Osimertinib represents the standard of care for the treatment of advanced non -small -cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor ( EGFR ) mutations, constituting 80%-90% of all EGFR alterations. In the remaining cases, an assorted group of uncommon alterations of EGFR (uEGFR) can be detected, which confer variable sensitivity to previous generations of EGFR inhibitors, overall with lower therapeutic activity. Data on osimertinib in this setting are limited and strongly warranted. Patients and methods: The ARTICUNO study retrospectively evaluated data on osimertinib activity from patients with advanced NSCLC harboring uEGFR treated in 21 clinical centers between August 2017 and March 2023. Data analysis was carried out with a descriptive aim. Investigators collected response data according to RECIST version 1.1 criteria. The median duration of response, progression -free survival (mPFS), and overall survival were estimated by the Kaplan - Meier method. Results: Eighty-six patients harboring uEGFR and treated with osimertinib were identi fi ed. Patients with ' major ' uEGFR, that is, G719X, L861X, and S768I mutations ( n = 51), had an overall response rate (ORR) and mPFS of 50% and 9 months, respectively. Variable outcomes were registered in cases with rarer ' minor ' mutations ( n = 27), with ORR and mPFS of 31% and 4 months, respectively. Among seven patients with exon 20 insertions, ORR was 14%, while the best outcome was registered among patients with compound mutations including at least one classical EGFR mutation ( n = 13). Thirty patients presented brain metastases (BMs) and intracranial ORR and mPFS were 58% and 9 months, respectively. Ampli fi cation of EGFR or MET , TP53 mutations, and EGFR E709K emerged after osimertinib failure in a dataset of 18 patients with available rebiopsy. Conclusion: The ARTICUNO study con fi rms the activity of osimertinib in patients with uEGFR, especially in those with compound uncommon e common mutations, or major uEGFR, even in the presence of BMs. Alterations at the E709 residue of EGFR are associated with resistance to osimertinib

Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility : a Single-Institution Experience

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value. OBJECTIVE: We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s). PATIENTS AND METHODS: From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36-86) and the median number of previous treatment lines was five (range 2-8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%). RESULTS: One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63-3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0-15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80-5.03] vs. 2.13 months [95% CI 1.77-2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17-9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33-10.80] vs. 7.18 months [95% CI 5.63-9.33], respectively, p = 0.06). CONCLUSIONS: This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment

Body appreciation around the world: Measurement invariance of the Body Appreciation Scale-2 (BAS-2) across 65 nations, 40 languages, gender identities, and age.

The Body Appreciation Scale-2 (BAS-2) is a widely used measure of a core facet of the positive body image construct. However, extant research concerning measurement invariance of the BAS-2 across a large number of nations remains limited. Here, we utilised the Body Image in Nature (BINS) dataset - with data collected between 2020 and 2022 - to assess measurement invariance of the BAS-2 across 65 nations, 40 languages, gender identities, and age groups. Multi-group confirmatory factor analysis indicated that full scalar invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional BAS-2 model has widespread applicability. There were large differences across nations and languages in latent body appreciation, while differences across gender identities and age groups were negligible-to-small. Additionally, greater body appreciation was significantly associated with higher life satisfaction, being single (versus being married or in a committed relationship), and greater rurality (versus urbanicity). Across a subset of nations where nation-level data were available, greater body appreciation was also significantly associated with greater cultural distance from the United States and greater relative income inequality. These findings suggest that the BAS-2 likely captures a near-universal conceptualisation of the body appreciation construct, which should facilitate further cross-cultural research. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Body appreciation around the world: Measurement invariance of the Body Appreciation Scale-2 (BAS-2) across 65 nations, 40 languages, gender identities, and age

Abstract The Body Appreciation Scale-2 (BAS-2) is a widely used measure of a core facet of the positive body image construct. However, extant research concerning measurement invariance of the BAS-2 across a large number of nations remains limited. Here, we utilised the Body Image in Nature (BINS) dataset – with data collected between 2020 and 2022 – to assess measurement invariance of the BAS-2 across 65 nations, 40 languages, gender identities, and age groups. Multi-group confirmatory factor analysis indicated that full scalar invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional BAS-2 model has widespread applicability. There were large differences across nations and languages in latent body appreciation, while differences across gender identities and age groups were negligible-to-small. Additionally, greater body appreciation was significantly associated with higher life satisfaction, being single (versus being married or in a committed relationship), and greater rurality (versus urbanicity). Across a subset of nations where nation-level data were available, greater body appreciation was also significantly associated with greater cultural distance from the United States and greater relative income inequality. These findings suggest that the BAS-2 likely captures a near-universal conceptualisation of the body appreciation construct, which should facilitate further cross-cultural research

Exposure and connectedness to natural environments: An examination of the measurement invariance of the Nature Exposure Scale (NES) and Connectedness to Nature Scale (CNS) across 65 nations, 40 languages, gender identities, and age groups

Detachment from nature is contributing to the environmental crisis and reversing this trend requires detailed monitoring and targeted interventions to reconnect people to nature. Most tools measuring nature exposure and attachment were developed in high-income countries and little is known about their robustness across national and linguistic groups. Therefore, we used data from the Body Image in Nature Survey to assess measurement invariance of the Nature Exposure Scale (NES) and the Connectedness to Nature Scale (CNS) across 65 nations, 40 languages, gender identities, and age groups (N = 56,968). While multi-group confirmatory factor analysis (MG-CFA) of the NES supported full scalar invariance across gender identities and age groups, only partial scalar invariance was supported across national and linguistic groups. MG-CFA of the CNS also supported full scalar invariance across gender identities and age groups, but only partial scalar invariance of a 7-item version of the CNS across national and linguistic groups. Nation-level associations between NES and CNS scores were negligible, likely reflecting a lack of conceptual clarity over what the NES is measuring. Individual-level associations between both measures and sociodemographic variables were weak. Findings suggest that the CNS-7 may be a useful tool to measure nature connectedness globally, but measures other than the NES may be needed to capture nature exposure cross-culturally

Body appreciation around the world: Measurement invariance of the Body Appreciation Scale-2 (BAS-2) across 65 nations, 40 languages, gender identities, and age

The Body Appreciation Scale-2 (BAS-2) is a widely used measure of a core facet of the positive body image construct. However, extant research concerning measurement invariance of the BAS-2 across a large number of nations remains limited. Here, we utilised the Body Image in Nature (BINS) dataset - with data collected between 2020 and 2022 - to assess measurement invariance of the BAS-2 across 65 nations, 40 languages, gender identities, and age groups. Multi-group confirmatory factor analysis indicated that full scalar invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional BAS-2 model has widespread applicability. There were large differences across nations and languages in latent body appreciation, while differences across gender identities and age groups were negligible-to-small. Additionally, greater body appreciation was significantly associated with higher life satisfaction, being single (versus being married or in a committed relationship), and greater rurality (versus urbanicity). Across a subset of nations where nation-level data were available, greater body appreciation was also significantly associated with greater cultural distance from the United States and greater relative income inequality. These findings suggest that the BAS-2 likely captures a near-universal conceptualisation of the body appreciation construct, which should facilitate further cross-cultural research