GPCR Inhibition in Treating Lymphoma

G protein-coupled receptors (GPCRs) are important classes of cell surface receptors involved in multiple physiological functions. Aberrant expression, upregulation, and mutation of GPCR signaling pathways are frequent in many types of cancers, promoting hyperproliferation, angiogenesis, and metastasis. Recent studies showed that alterations of GPCRs are involved in different lymphoma types. Herein, we review the synthetic strategies to obtain GPCR inhibitors, focusing on CXCR4 inhibitors which represent most of the GPCR inhibitors available in the market or under preclinical investigations for these diseases

Cancer stem cell biomarkers predictive of radiotherapy response in rectal cancer: A systematic review

Background: Rectal cancer (RC) is one of the most commonly diagnosed and particularly challenging tumours to treat due to its location in the pelvis and close proximity to critical genitouri-nary organs. Radiotherapy (RT) is recognised as a key component of therapeutic strategy to treat RC, promoting the downsizing and downstaging of large RCs in neoadjuvant settings, although its therapeutic effect is limited due to radioresistance. Evidence from experimental and clinical studies indicates that the likelihood of achieving local tumour control by RT depends on the complete eradica-tion of cancer stem cells (CSC), a minority subset of tumour cells with stemness properties. Methods: A systematic literature review was conducted by querying two scientific databases (Pubmed and Scopus). The search was restricted to papers published from 2009 to 2021. Results: After assessing the quality and the risk of bias, a total of 11 studies were selected as they mainly focused on biomarkers predictive of RT-response in CSCs isolated from patients affected by RC. Specifically these studies showed that elevated levels of CD133, CD44, ALDH1, Lgr5 and G9a are associated with RT-resistance and poor prognosis. Conclusions: This review aimed to provide an overview of the current scenario of in vitro and in vivo studies evaluating the biomarkers predictive of RT-response in CSCs derived from RC patients

Indication of a fast ejecta fragment in the atomic cloud interacting with the southwestern limb of SN 1006

Context. Supernova remnants interacting with molecular and atomic clouds are interesting X-ray sources for studies of broadband nonthermal emission. X-ray line emission in these systems can be produced by different processes, such as low-energy cosmic rays (LECRs) interacting with the cloud and fast ejecta fragments moving in the cloud. Aims. This paper is aimed at studying the origin of the non-thermal X-ray emission of the southwestern limb of SN 1006 beyond the main shock to determine whether the emission is due to LECRs diffusing in the cloud or to ejecta knots moving into the cloud. Methods. We analyzed the X-ray emission of the southwestern limb of SN 1006, where the remnant interacts with an atomic cloud, using three different X-ray telescopes: NuSTAR, Chandra, and XMM-Newton. We also performed a combined spectro-imaging analysis of this region. Results. Our analysis of the nonthermal X-ray emission of the southwestern limb of SN 1006 interacting with an atomic cloud has led to the detection of an extended X-ray source in the atomic cloud, approximately 2 pc upstream of the shock front. The source is characterized by a hard continuum (described by a power law with photon index Γ ∼ 1.4) and by Ne, Si, and Fe emission lines. The observed flux suggests that the origin of the X-ray emission is not associated with LECRs interacting with the cloud. On the other hand, the spectral properties of the source, together with the detection of an IR counterpart visible with Spitzer-MIPS at 24 μm, are in good agreement with the general expectations for a fast ejecta fragment moving within the atomic cloud. Conclusions. We detected X-ray and IR emission from a possible ejecta fragment, with an approximate radius of 1 × 1017 cm and approximate mass of 10−3 M at about 2 pc out of the shell of SN 1006, in the interaction region between the southwestern limb of the remnant and the atomic cloud

Proteomics signature of autoimmune atrophic gastritis: towards a link with gastric cancer

Background: Autoimmune atrophic gastritis (AAG) is a chronic disease that can progress to gastric cancer (GC). To better understand AAG pathology, this proteomics study investigated gastric proteins whose expression levels are altered in this disease and also in GC. Methods: Using two-dimensional difference gel electrophoresis (2D-DIGE), we compared protein maps of gastric corpus biopsies from AAG patients and controls. Differentially abundant spots (|fold change|≥ 1.5, P < 0.01) were selected and identified by LC-MS/MS. The spots were further assessed in gastric antrum biopsies from AAG patients (without and with Helicobacter pylori infection) and from GC patients and unaffected first-degree relatives of GC patients. Results: 2D-DIGE identified 67 differentially abundant spots, with 28 more and 39 less abundant in AAG-corpus than controls. LC-MS/MS identified these as 53 distinct proteins. The most significant (adjusted P < 0.01) biological process associated with the less abundant proteins was "tricarboxylic acid cycle". Of the 67 spots, 57 were similarly differentially abundant in AAG-antrum biopsies irrespective of H. pylori infection status. The differential abundance was also observed in GC biopsies for 14 of 28 more abundant and 35 of 39 less abundant spots, and in normal gastric biopsies of relatives of GC patients for 6 and 25 spots, respectively. Immunoblotting confirmed the different expression levels of two more abundant proteins (PDIA3, GSTP gene products) and four less abundant proteins (ATP5F1A, PGA3, SDHB, PGC). Conclusion: This study identified a proteomics signature of AAG. Many differential proteins were shared by GC and may be involved in the progression of AAG to GC

320pnab paclitaxel nab p in metastatic breast cancer mbc in elderly patients a real life setting nereide study

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